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Vitamin D pearls
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Pregnancy can be ‘a vulnerable time’ for developing mental disorders
Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.
“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”
But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.
Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.
Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.
In particular,
“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.
If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.
The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.
So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.
Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.
“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”
Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.
Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.
“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”
But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.
Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.
Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.
In particular,
“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.
If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.
The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.
So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.
Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.
“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”
Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.
Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.
“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”
But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.
Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.
Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.
In particular,
“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.
If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.
The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.
So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.
Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.
“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”
Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.
FROM FOCUS ON NEUROPSYCHIATRY 2020
Weight-loss benefit in diabetes is similar via surgery or diet
The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.
The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.
Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.
“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.
“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.
However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”
“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.
Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”
However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”
Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”
Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
No significant differences in multiple parameters
The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.
Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.
A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity
Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.
After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.
Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.
Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
Study limitations: Small, not randomized, long diabetes duration
The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.
The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.
However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.
He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”
In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.
“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.
Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”
Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.
A version of this article originally appeared on Medscape.com.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity.
The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.
The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.
Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.
“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.
“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.
However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”
“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.
Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”
However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”
Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”
Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
No significant differences in multiple parameters
The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.
Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.
A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity
Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.
After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.
Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.
Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
Study limitations: Small, not randomized, long diabetes duration
The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.
The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.
However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.
He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”
In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.
“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.
Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”
Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.
A version of this article originally appeared on Medscape.com.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity.
The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.
The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.
Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.
“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.
“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.
However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”
“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.
Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”
However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”
Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”
Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
No significant differences in multiple parameters
The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.
Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.
A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity
Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.
After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.
Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.
Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
Study limitations: Small, not randomized, long diabetes duration
The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.
The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.
However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.
He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”
In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.
“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.
Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”
Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.
A version of this article originally appeared on Medscape.com.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity.
Weighing children in school: No good can come of it
The United Kingdom’s National Obesity Forum has apparently decided that returning to school this fall in the middle of a pandemic isn’t stressful enough for kids, and is recommending that its National Child Measurement Programme be expanded to have 4- to 5-year-old and 10- to 11-year-old children weighed when they return to the classroom – and then weighed again in the spring – in a bid to tackle COVID-19–related gains.
It’s difficult to conceive a single plausible mechanism by which this recommendation could be helpful. Given that weight is, by a substantial margin, the No. 1 reported cause of schoolyard bullying, it’s certainly unlikely that children with obesity don’t already know that they have it. It’s also unlikely that they don’t know that obesity confers risks to health, given the near constant drumbeats of concern percussed by the media and public health authorities, and the fact that watching people with obesity be blamed, shamed, and berated for their condition has in the past 2 decades become a regularly repeated prime-time reality show spectacle.
It’s also unlikely, especially in younger grades, to be something within a child’s direct control.
What about the parents? Well, given that they dress their children and that changes in weight affect clothing sizes and fit, they’re already aware if their kids are gaining weight. And like their children, they have been exposed to constant public health alarms around obesity.
Many parents will have seen their time and resources, both real and mental, become significantly impaired during the time of COVID-19, which in turn understandably challenges change. Simply put, permanent intentional behavior change in the name of health requires tremendous privilege and is elusive for many people even during easier times. For non–evidence-based proof of this assertion, simply reflect on all of your own best-laid intentions and plans that might have been good for your health (fitness, relationships, CME, etc.) that you let slide despite probably having far more privilege than the average person.
Then, of course, there is the hugely inconvenient truth that we have yet to see the development of a parent- or child-based educational intervention or directive for weight gain that has shown itself to be beneficial on a population level.
Can something else be done instead?
At this point, we can only speculate about the potential risks associated with school room weigh-ins because randomized controlled trials, thankfully, have not been conducted to explore this area. But I can certainly tell you that I have met many adult patients in my office who traced their lifetime of yo-yo dieting – along with a history of teenage eating disorders, at times – to their well-intentioned physician, school nurse, gym teacher, or parent using a scale to measure their weights. And in doing so, they were teaching that scales measure health, happiness, success, self-worth, and effort.
If governments are concerned about weight gain in children, they need to look to initiatives that will help all children and parents. Weighing them will not somehow inspire parents or kids to discover an as-yet unknown effective childhood obesity treatment. Changes that would be helpful may include:
- Banning food advertisements to children.
- Reforming school cafeteria meals and then ensuring that school meals are made available to children during COVID-19–related school shutdowns.
- Bringing back home economics classes to teach children how to cook (and perhaps doing the same for parents during school off-hours or in community centers).
- Enacting sugar-sweetened beverage taxes and using revenues to fund aforementioned reforms and programs, along with others, which might include the subsidization of fresh produce.
- Reforming front-of-package health claims for foods with questionable nutritional quality.
Given that there is literally no age category in any country on the planet that hasn’t seen rising weights, this is clearly not a disease reflecting a pandemic loss of willpower. Rather, this is a disease of the world’s changing food environments and culture, and until we address both through systemic changes, schemes such as the one being proposed by the UK National Obesity Forum are far more likely to do harm than good.
Yoni Freedhoff is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of “The Diet Fix: Why Diets Fail and How to Make Yours Work.” A version of this article originally appeared on Medscape.com.
The United Kingdom’s National Obesity Forum has apparently decided that returning to school this fall in the middle of a pandemic isn’t stressful enough for kids, and is recommending that its National Child Measurement Programme be expanded to have 4- to 5-year-old and 10- to 11-year-old children weighed when they return to the classroom – and then weighed again in the spring – in a bid to tackle COVID-19–related gains.
It’s difficult to conceive a single plausible mechanism by which this recommendation could be helpful. Given that weight is, by a substantial margin, the No. 1 reported cause of schoolyard bullying, it’s certainly unlikely that children with obesity don’t already know that they have it. It’s also unlikely that they don’t know that obesity confers risks to health, given the near constant drumbeats of concern percussed by the media and public health authorities, and the fact that watching people with obesity be blamed, shamed, and berated for their condition has in the past 2 decades become a regularly repeated prime-time reality show spectacle.
It’s also unlikely, especially in younger grades, to be something within a child’s direct control.
What about the parents? Well, given that they dress their children and that changes in weight affect clothing sizes and fit, they’re already aware if their kids are gaining weight. And like their children, they have been exposed to constant public health alarms around obesity.
Many parents will have seen their time and resources, both real and mental, become significantly impaired during the time of COVID-19, which in turn understandably challenges change. Simply put, permanent intentional behavior change in the name of health requires tremendous privilege and is elusive for many people even during easier times. For non–evidence-based proof of this assertion, simply reflect on all of your own best-laid intentions and plans that might have been good for your health (fitness, relationships, CME, etc.) that you let slide despite probably having far more privilege than the average person.
Then, of course, there is the hugely inconvenient truth that we have yet to see the development of a parent- or child-based educational intervention or directive for weight gain that has shown itself to be beneficial on a population level.
Can something else be done instead?
At this point, we can only speculate about the potential risks associated with school room weigh-ins because randomized controlled trials, thankfully, have not been conducted to explore this area. But I can certainly tell you that I have met many adult patients in my office who traced their lifetime of yo-yo dieting – along with a history of teenage eating disorders, at times – to their well-intentioned physician, school nurse, gym teacher, or parent using a scale to measure their weights. And in doing so, they were teaching that scales measure health, happiness, success, self-worth, and effort.
If governments are concerned about weight gain in children, they need to look to initiatives that will help all children and parents. Weighing them will not somehow inspire parents or kids to discover an as-yet unknown effective childhood obesity treatment. Changes that would be helpful may include:
- Banning food advertisements to children.
- Reforming school cafeteria meals and then ensuring that school meals are made available to children during COVID-19–related school shutdowns.
- Bringing back home economics classes to teach children how to cook (and perhaps doing the same for parents during school off-hours or in community centers).
- Enacting sugar-sweetened beverage taxes and using revenues to fund aforementioned reforms and programs, along with others, which might include the subsidization of fresh produce.
- Reforming front-of-package health claims for foods with questionable nutritional quality.
Given that there is literally no age category in any country on the planet that hasn’t seen rising weights, this is clearly not a disease reflecting a pandemic loss of willpower. Rather, this is a disease of the world’s changing food environments and culture, and until we address both through systemic changes, schemes such as the one being proposed by the UK National Obesity Forum are far more likely to do harm than good.
Yoni Freedhoff is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of “The Diet Fix: Why Diets Fail and How to Make Yours Work.” A version of this article originally appeared on Medscape.com.
The United Kingdom’s National Obesity Forum has apparently decided that returning to school this fall in the middle of a pandemic isn’t stressful enough for kids, and is recommending that its National Child Measurement Programme be expanded to have 4- to 5-year-old and 10- to 11-year-old children weighed when they return to the classroom – and then weighed again in the spring – in a bid to tackle COVID-19–related gains.
It’s difficult to conceive a single plausible mechanism by which this recommendation could be helpful. Given that weight is, by a substantial margin, the No. 1 reported cause of schoolyard bullying, it’s certainly unlikely that children with obesity don’t already know that they have it. It’s also unlikely that they don’t know that obesity confers risks to health, given the near constant drumbeats of concern percussed by the media and public health authorities, and the fact that watching people with obesity be blamed, shamed, and berated for their condition has in the past 2 decades become a regularly repeated prime-time reality show spectacle.
It’s also unlikely, especially in younger grades, to be something within a child’s direct control.
What about the parents? Well, given that they dress their children and that changes in weight affect clothing sizes and fit, they’re already aware if their kids are gaining weight. And like their children, they have been exposed to constant public health alarms around obesity.
Many parents will have seen their time and resources, both real and mental, become significantly impaired during the time of COVID-19, which in turn understandably challenges change. Simply put, permanent intentional behavior change in the name of health requires tremendous privilege and is elusive for many people even during easier times. For non–evidence-based proof of this assertion, simply reflect on all of your own best-laid intentions and plans that might have been good for your health (fitness, relationships, CME, etc.) that you let slide despite probably having far more privilege than the average person.
Then, of course, there is the hugely inconvenient truth that we have yet to see the development of a parent- or child-based educational intervention or directive for weight gain that has shown itself to be beneficial on a population level.
Can something else be done instead?
At this point, we can only speculate about the potential risks associated with school room weigh-ins because randomized controlled trials, thankfully, have not been conducted to explore this area. But I can certainly tell you that I have met many adult patients in my office who traced their lifetime of yo-yo dieting – along with a history of teenage eating disorders, at times – to their well-intentioned physician, school nurse, gym teacher, or parent using a scale to measure their weights. And in doing so, they were teaching that scales measure health, happiness, success, self-worth, and effort.
If governments are concerned about weight gain in children, they need to look to initiatives that will help all children and parents. Weighing them will not somehow inspire parents or kids to discover an as-yet unknown effective childhood obesity treatment. Changes that would be helpful may include:
- Banning food advertisements to children.
- Reforming school cafeteria meals and then ensuring that school meals are made available to children during COVID-19–related school shutdowns.
- Bringing back home economics classes to teach children how to cook (and perhaps doing the same for parents during school off-hours or in community centers).
- Enacting sugar-sweetened beverage taxes and using revenues to fund aforementioned reforms and programs, along with others, which might include the subsidization of fresh produce.
- Reforming front-of-package health claims for foods with questionable nutritional quality.
Given that there is literally no age category in any country on the planet that hasn’t seen rising weights, this is clearly not a disease reflecting a pandemic loss of willpower. Rather, this is a disease of the world’s changing food environments and culture, and until we address both through systemic changes, schemes such as the one being proposed by the UK National Obesity Forum are far more likely to do harm than good.
Yoni Freedhoff is associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute, a nonsurgical weight management center. He is one of Canada’s most outspoken obesity experts and the author of “The Diet Fix: Why Diets Fail and How to Make Yours Work.” A version of this article originally appeared on Medscape.com.
Treat obesity like breast cancer, with empathy, say Canadians
A new Canadian clinical practice guideline for treating adults with obesity emphasizes improving health rather than simply losing weight, among other things.
A summary of the guideline, which was developed by Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons, was published online August 4 in the Canadian Medical Association Journal.
This patient-centered update to the 2006 guidelines is “provocative,” starting with its definition of obesity, co–lead author Sean Wharton, MD, adjunct professor at McMaster University, Hamilton, Ont., said in an interview.
The guideline was authored by more than 60 health care professionals and researchers who assessed more than 500,000 peer-reviewed articles and made 80 key recommendations.
These reflect substantial recent advances in the understanding of obesity. Individuals with obesity (from a patient committee of the Obesity Society) helped to shape the key messages.
“People who live with obesity have been shut out of receiving quality health care because of the biased, deeply flawed misconceptions about what drives obesity and how we can improve health,” Lisa Schaffer, chair of Obesity Canada’s Public Engagement Committee, said in a press release.
“Obesity is widely seen as the result of poor personal decisions, but research tells us it is far more complicated than that. Our hope with the [new] clinical practice guideline is that more health care professionals, health policy makers, benefits providers and people living with obesity will have a better understanding of it, so we can help more of those who need it.”
“Obesity management should be about compassion and empathy, and then everything falls into place,” Dr. Wharton said. “Think of obesity like breast cancer.”
Address the root causes of obesity
The guideline defines obesity as “a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity) that impairs health.”
Aimed at primary care providers, the document stresses that clinicians need to “move beyond simplistic approaches of ‘eat less, move more,’ and address the root drivers of obesity.”
As a first step, doctors should ask a patient for permission to discuss weight (e.g., they can ask: “Would it be all right if we discussed your weight?”) – which demonstrates empathy and can help build patient-provider trust.
Clinicians can still measure body mass index as part of a routine physical examination, but they should also obtain a comprehensive patient history to identify the root causes of any weight gain (which could include genetics or psychological factors such as depression and anxiety), as well as any barriers to managing obesity.
‘Eat less, move more’ is too simple: Employ three pillars
Advice to “eat less and move more is dangerously simplistic,” coauthor Arya M. Sharma, MD, from the University of Alberta, Edmonton, and scientific director of Obesity Canada, said in an interview that “the body fights to put back any lost weight.”
Patients with obesity need “medical nutrition therapy.” For patients at risk for heart disease, that may mean following a Mediterranean diet, Dr. Wharton said.
“Physical activity and medical nutrition therapy are absolutely necessary” to manage obesity, he clarified. As a person loses weight, their body “releases a cascade of neurochemicals and hormones that try to push the weight back up” to the original weight or even higher.
Therefore, to maintain weight loss, people need support from one or more of what he calls the “three pillars” of effective long-term weight loss – pharmacotherapy, bariatric surgery, and cognitive-behavioral therapy – which tempers this cascade of neurochemicals.
Cognitive-behavioral therapy could be given by various health care professionals, he noted. A behavioral strategy to stop snacking, for example, is to wait 5 minutes before eating a desired snack to make sure you still want it.
Similarly, Dr. Sharma noted, “the reason obesity is a chronic disease is that once you’ve gained the weight, your body is not going to want to lose it. That is what I tell all my patients: ‘Your body doesn’t care why you put on the weight, but it does care about keeping it there, and it’s going to fight you’ when you try to maintain weight loss.”
“Clinicians should feel very comfortable” treating obesity as a chronic disease, he added, because they are already treating chronic diseases such as heart, lung, and kidney disease.
Don’t play the blame game: ‘Think of obesity like breast cancer’
Clinicians also need to avoid “shaming and blaming patients with obesity,” said Dr. Sharma.
He noted that many patients have internalized weight bias and blame their excess weight on their lack of willpower. They may not want to talk about weight-loss medications or bariatric surgery because they feel that’s “cheating.”
By thinking of obesity in a similar way to cancer, doctors can help themselves respond to patients in a kinder way. “What would we do with somebody who has breast cancer? We would have compassion. We would talk about surgery to get the lump out and medication to keep the cancer from coming back, and we would engage them in psychological treatment or counseling for some of the challenges they have to face,” Dr. Wharton said.
“The right answer is to treat [obesity] like a disease – with surgery, medication, and psychological intervention,” depending on the individual patient, he added.
The complete guideline is available on the Obesity Canada website.
The study was funded by Obesity Canada, the Canadian Association of Bariatric Physicians and Surgeons, and the Canadian Institutes of Health Research. Dr. Wharton has received honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has received speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.
A version of this article originally appeared on Medscape.com.
A new Canadian clinical practice guideline for treating adults with obesity emphasizes improving health rather than simply losing weight, among other things.
A summary of the guideline, which was developed by Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons, was published online August 4 in the Canadian Medical Association Journal.
This patient-centered update to the 2006 guidelines is “provocative,” starting with its definition of obesity, co–lead author Sean Wharton, MD, adjunct professor at McMaster University, Hamilton, Ont., said in an interview.
The guideline was authored by more than 60 health care professionals and researchers who assessed more than 500,000 peer-reviewed articles and made 80 key recommendations.
These reflect substantial recent advances in the understanding of obesity. Individuals with obesity (from a patient committee of the Obesity Society) helped to shape the key messages.
“People who live with obesity have been shut out of receiving quality health care because of the biased, deeply flawed misconceptions about what drives obesity and how we can improve health,” Lisa Schaffer, chair of Obesity Canada’s Public Engagement Committee, said in a press release.
“Obesity is widely seen as the result of poor personal decisions, but research tells us it is far more complicated than that. Our hope with the [new] clinical practice guideline is that more health care professionals, health policy makers, benefits providers and people living with obesity will have a better understanding of it, so we can help more of those who need it.”
“Obesity management should be about compassion and empathy, and then everything falls into place,” Dr. Wharton said. “Think of obesity like breast cancer.”
Address the root causes of obesity
The guideline defines obesity as “a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity) that impairs health.”
Aimed at primary care providers, the document stresses that clinicians need to “move beyond simplistic approaches of ‘eat less, move more,’ and address the root drivers of obesity.”
As a first step, doctors should ask a patient for permission to discuss weight (e.g., they can ask: “Would it be all right if we discussed your weight?”) – which demonstrates empathy and can help build patient-provider trust.
Clinicians can still measure body mass index as part of a routine physical examination, but they should also obtain a comprehensive patient history to identify the root causes of any weight gain (which could include genetics or psychological factors such as depression and anxiety), as well as any barriers to managing obesity.
‘Eat less, move more’ is too simple: Employ three pillars
Advice to “eat less and move more is dangerously simplistic,” coauthor Arya M. Sharma, MD, from the University of Alberta, Edmonton, and scientific director of Obesity Canada, said in an interview that “the body fights to put back any lost weight.”
Patients with obesity need “medical nutrition therapy.” For patients at risk for heart disease, that may mean following a Mediterranean diet, Dr. Wharton said.
“Physical activity and medical nutrition therapy are absolutely necessary” to manage obesity, he clarified. As a person loses weight, their body “releases a cascade of neurochemicals and hormones that try to push the weight back up” to the original weight or even higher.
Therefore, to maintain weight loss, people need support from one or more of what he calls the “three pillars” of effective long-term weight loss – pharmacotherapy, bariatric surgery, and cognitive-behavioral therapy – which tempers this cascade of neurochemicals.
Cognitive-behavioral therapy could be given by various health care professionals, he noted. A behavioral strategy to stop snacking, for example, is to wait 5 minutes before eating a desired snack to make sure you still want it.
Similarly, Dr. Sharma noted, “the reason obesity is a chronic disease is that once you’ve gained the weight, your body is not going to want to lose it. That is what I tell all my patients: ‘Your body doesn’t care why you put on the weight, but it does care about keeping it there, and it’s going to fight you’ when you try to maintain weight loss.”
“Clinicians should feel very comfortable” treating obesity as a chronic disease, he added, because they are already treating chronic diseases such as heart, lung, and kidney disease.
Don’t play the blame game: ‘Think of obesity like breast cancer’
Clinicians also need to avoid “shaming and blaming patients with obesity,” said Dr. Sharma.
He noted that many patients have internalized weight bias and blame their excess weight on their lack of willpower. They may not want to talk about weight-loss medications or bariatric surgery because they feel that’s “cheating.”
By thinking of obesity in a similar way to cancer, doctors can help themselves respond to patients in a kinder way. “What would we do with somebody who has breast cancer? We would have compassion. We would talk about surgery to get the lump out and medication to keep the cancer from coming back, and we would engage them in psychological treatment or counseling for some of the challenges they have to face,” Dr. Wharton said.
“The right answer is to treat [obesity] like a disease – with surgery, medication, and psychological intervention,” depending on the individual patient, he added.
The complete guideline is available on the Obesity Canada website.
The study was funded by Obesity Canada, the Canadian Association of Bariatric Physicians and Surgeons, and the Canadian Institutes of Health Research. Dr. Wharton has received honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has received speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.
A version of this article originally appeared on Medscape.com.
A new Canadian clinical practice guideline for treating adults with obesity emphasizes improving health rather than simply losing weight, among other things.
A summary of the guideline, which was developed by Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons, was published online August 4 in the Canadian Medical Association Journal.
This patient-centered update to the 2006 guidelines is “provocative,” starting with its definition of obesity, co–lead author Sean Wharton, MD, adjunct professor at McMaster University, Hamilton, Ont., said in an interview.
The guideline was authored by more than 60 health care professionals and researchers who assessed more than 500,000 peer-reviewed articles and made 80 key recommendations.
These reflect substantial recent advances in the understanding of obesity. Individuals with obesity (from a patient committee of the Obesity Society) helped to shape the key messages.
“People who live with obesity have been shut out of receiving quality health care because of the biased, deeply flawed misconceptions about what drives obesity and how we can improve health,” Lisa Schaffer, chair of Obesity Canada’s Public Engagement Committee, said in a press release.
“Obesity is widely seen as the result of poor personal decisions, but research tells us it is far more complicated than that. Our hope with the [new] clinical practice guideline is that more health care professionals, health policy makers, benefits providers and people living with obesity will have a better understanding of it, so we can help more of those who need it.”
“Obesity management should be about compassion and empathy, and then everything falls into place,” Dr. Wharton said. “Think of obesity like breast cancer.”
Address the root causes of obesity
The guideline defines obesity as “a prevalent, complex, progressive and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity) that impairs health.”
Aimed at primary care providers, the document stresses that clinicians need to “move beyond simplistic approaches of ‘eat less, move more,’ and address the root drivers of obesity.”
As a first step, doctors should ask a patient for permission to discuss weight (e.g., they can ask: “Would it be all right if we discussed your weight?”) – which demonstrates empathy and can help build patient-provider trust.
Clinicians can still measure body mass index as part of a routine physical examination, but they should also obtain a comprehensive patient history to identify the root causes of any weight gain (which could include genetics or psychological factors such as depression and anxiety), as well as any barriers to managing obesity.
‘Eat less, move more’ is too simple: Employ three pillars
Advice to “eat less and move more is dangerously simplistic,” coauthor Arya M. Sharma, MD, from the University of Alberta, Edmonton, and scientific director of Obesity Canada, said in an interview that “the body fights to put back any lost weight.”
Patients with obesity need “medical nutrition therapy.” For patients at risk for heart disease, that may mean following a Mediterranean diet, Dr. Wharton said.
“Physical activity and medical nutrition therapy are absolutely necessary” to manage obesity, he clarified. As a person loses weight, their body “releases a cascade of neurochemicals and hormones that try to push the weight back up” to the original weight or even higher.
Therefore, to maintain weight loss, people need support from one or more of what he calls the “three pillars” of effective long-term weight loss – pharmacotherapy, bariatric surgery, and cognitive-behavioral therapy – which tempers this cascade of neurochemicals.
Cognitive-behavioral therapy could be given by various health care professionals, he noted. A behavioral strategy to stop snacking, for example, is to wait 5 minutes before eating a desired snack to make sure you still want it.
Similarly, Dr. Sharma noted, “the reason obesity is a chronic disease is that once you’ve gained the weight, your body is not going to want to lose it. That is what I tell all my patients: ‘Your body doesn’t care why you put on the weight, but it does care about keeping it there, and it’s going to fight you’ when you try to maintain weight loss.”
“Clinicians should feel very comfortable” treating obesity as a chronic disease, he added, because they are already treating chronic diseases such as heart, lung, and kidney disease.
Don’t play the blame game: ‘Think of obesity like breast cancer’
Clinicians also need to avoid “shaming and blaming patients with obesity,” said Dr. Sharma.
He noted that many patients have internalized weight bias and blame their excess weight on their lack of willpower. They may not want to talk about weight-loss medications or bariatric surgery because they feel that’s “cheating.”
By thinking of obesity in a similar way to cancer, doctors can help themselves respond to patients in a kinder way. “What would we do with somebody who has breast cancer? We would have compassion. We would talk about surgery to get the lump out and medication to keep the cancer from coming back, and we would engage them in psychological treatment or counseling for some of the challenges they have to face,” Dr. Wharton said.
“The right answer is to treat [obesity] like a disease – with surgery, medication, and psychological intervention,” depending on the individual patient, he added.
The complete guideline is available on the Obesity Canada website.
The study was funded by Obesity Canada, the Canadian Association of Bariatric Physicians and Surgeons, and the Canadian Institutes of Health Research. Dr. Wharton has received honoraria and travel expenses and has participated in academic advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen. He is the medical director of a medical clinic specializing in weight management and diabetes. Dr. Sharma has received speaker’s bureau and consulting fees from Novo Nordisk, Bausch Pharmaceuticals, and AstraZeneca.
A version of this article originally appeared on Medscape.com.
Weight-loss benefit in diabetes is similar via surgery or diet
The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.
The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.
Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.
“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.
“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.
However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”
“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.
Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”
However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”
Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”
Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
No significant differences in multiple parameters
The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.
Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.
A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity
Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.
After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.
Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.
Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
Study limitations: Small, not randomized, long diabetes duration
The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.
The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.
However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.
He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”
In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.
“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.
Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”
Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.
A version of this article originally appeared on Medscape.com.
The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.
The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.
Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.
“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.
“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.
However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”
“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.
Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”
However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”
Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”
Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
No significant differences in multiple parameters
The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.
Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.
A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity
Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.
After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.
Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.
Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
Study limitations: Small, not randomized, long diabetes duration
The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.
The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.
However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.
He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”
In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.
“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.
Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”
Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.
A version of this article originally appeared on Medscape.com.
The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.
The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.
Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.
“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.
“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.
However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”
“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.
Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”
However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”
Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”
Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
No significant differences in multiple parameters
The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.
Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.
A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity
Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.
After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.
Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.
Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
Study limitations: Small, not randomized, long diabetes duration
The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.
The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.
However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.
He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”
In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.
“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.
Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”
Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.
A version of this article originally appeared on Medscape.com.
Severe obesity ups risk for death in younger men with COVID-19
In a large California health care plan, among patients with COVID-19, men aged 60 years and younger had a much higher risk of dying within 3 weeks of diagnosis if they had severe obesity as opposed to being of normal weight, independently of other risk factors.
reported Sara Y. Tartof, PhD, MPH, Kaiser Permanente Southern California, Pasadena, Calif., and coauthors.
The data “highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention,” they concluded in an article published online Aug. 12 in Annals of Internal Medicine.
This work adds to nearly 300 articles that have shown that severe obesity is associated with an increased risk for morbidity and mortality from COVID-19.
In an accompanying editorial, David A. Kass, MD, said: “Consistency of this new study and prior research should put to rest the contention that obesity is common in severe COVID-19 because it is common in the population.”
Rather, these findings show that “obesity is an important independent risk factor for serious COVID-19 disease,” he pointed out.
On the basis of this evidence, “arguably the hardest question to answer is: What is to be done?” wondered Kass, of Johns Hopkins University, Baltimore.
Although data consistently show that a body mass index >35 kg/m2 is predictive of major health risks, “weight reduction at that level of obesity is difficult and certainly is not achieved rapidly,” Dr. Kass stressed.
“Therefore ... social distancing; altering behaviors to reduce viral exposure and transmission, such as wearing masks; and instituting policies and health care approaches that recognize the potential effects of obesity should be implemented,” he emphasized. “These actions should help and are certainly doable.”
Similarly, Dr. Tartof and colleagues said their “findings also reveal the distressing collision of two pandemics: COVID-19 and obesity.
“As COVID-19 continues to spread unabated, we must focus our immediate efforts on containing the crisis at hand,” they urged.
However, the findings also “underscore the need for future collective efforts to combat the equally devastating, and potentially synergistic, force of the obesity epidemic.”
COVID-19 pandemic collides with obesity epidemic
Previous studies of obesity and COVID-19 were small, did not adjust for multiple confounders, or did not include nonhospitalized patients, Dr. Tartof and coauthors wrote.
Their study included 6,916 members of the Kaiser Permanente Southern California health care plan who were diagnosed with COVID-19 from Feb. 13 to May 2, 2020.
The researchers calculated the risk for death at 21 days after a COVID-19 diagnosis; findings were corrected for age, sex, race/ethnicity, smoking, myocardial infarction, heart failure, peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, renal disease, metastatic tumor or malignancy, other immune disease, hyperlipidemia, hypertension, asthma, organ transplant, and diabetes status.
On the basis of BMI, the patients were classified as being underweight, of normal weight, overweight, or as having class 1, 2, or 3 obesity. BMI of 18.5 to 24 kg/m2 is defined as normal weight.
Class 3 obesity, also called severe obesity, included moderately severe obesity (BMI, 40-44 kg/m2) and extremely severe obesity (≥45 kg/m2).
A little more than half of the patients were women (55%), and more than 50% were Hispanic (54%).
A total of 206 patients (3%) died within 21 days of being diagnosed with COVID-19; of these, 67% had been hospitalized, and 43% had been intubated.
Overall, the COVID-19 patients with moderately severe or extremely severe obesity had a 2.7-fold and 4.2-fold increased risk for death, respectively, within 3 weeks compared with patients of normal weight.
Patients in the other BMI categories did not have a significantly higher risk of dying during follow-up.
However, each decade of increasing age after age 40 was associated with a stepwise increased risk for death within 3 weeks of the COVID-19 diagnosis.
Risk stratified by age and sex
Further analysis showed that, “most strikingly,” among patients aged 60 and younger, those with moderately severe obesity and extremely severe obesity had significant 17-fold and 12-fold higher risks of dying during follow-up, respectively, compared with patients of normal weight, the researchers reported.
In patients older than 60, moderately severe obesity did not confer a significant increased risk for imminent death from COVID-19; extremely severe obesity conferred a smaller, threefold increased risk for this.
“Our finding that severe obesity, particularly among younger patients, eclipses the mortality risk posed by other obesity-related conditions, such as history of myocardial infarction (MI), diabetes, hypertension, or hyperlipidemia, suggests a significant pathophysiologic link between excess adiposity and severe COVID-19 illness,” the researchers noted.
This independent increased risk for death with severe obesity was seen in men but not in women.
Men with moderately severe and extremely severe obesity had significant 4.8-fold and 10-fold higher risks of dying within 3 weeks, respectively, compared with men of normal weight.
“That the risks are higher in younger patients is probably not because obesity is particularly damaging in this age group; it is more likely that other serious comorbidities that evolve later in life take over as dominant risk factors,” Dr. Kass suggested in his editorial.
“That males are particularly affected may reflect their greater visceral adiposity over females, given that this fat is notably proinflammatory and contributes to metabolic and vascular disease,” he added.
“As a cardiologist who studies heart failure,” Dr. Kass wrote, “I am struck by how many of the mechanisms that are mentioned in reviews of obesity risk and heart disease are also mentioned in reviews of obesity and COVID-19.”
The study was funded by Roche-Genentech. Kass has disclosed no relevant financial relationships. Disclosures of the authors are listed in the article.
A version of this article originally appeared on Medscape.com.
In a large California health care plan, among patients with COVID-19, men aged 60 years and younger had a much higher risk of dying within 3 weeks of diagnosis if they had severe obesity as opposed to being of normal weight, independently of other risk factors.
reported Sara Y. Tartof, PhD, MPH, Kaiser Permanente Southern California, Pasadena, Calif., and coauthors.
The data “highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention,” they concluded in an article published online Aug. 12 in Annals of Internal Medicine.
This work adds to nearly 300 articles that have shown that severe obesity is associated with an increased risk for morbidity and mortality from COVID-19.
In an accompanying editorial, David A. Kass, MD, said: “Consistency of this new study and prior research should put to rest the contention that obesity is common in severe COVID-19 because it is common in the population.”
Rather, these findings show that “obesity is an important independent risk factor for serious COVID-19 disease,” he pointed out.
On the basis of this evidence, “arguably the hardest question to answer is: What is to be done?” wondered Kass, of Johns Hopkins University, Baltimore.
Although data consistently show that a body mass index >35 kg/m2 is predictive of major health risks, “weight reduction at that level of obesity is difficult and certainly is not achieved rapidly,” Dr. Kass stressed.
“Therefore ... social distancing; altering behaviors to reduce viral exposure and transmission, such as wearing masks; and instituting policies and health care approaches that recognize the potential effects of obesity should be implemented,” he emphasized. “These actions should help and are certainly doable.”
Similarly, Dr. Tartof and colleagues said their “findings also reveal the distressing collision of two pandemics: COVID-19 and obesity.
“As COVID-19 continues to spread unabated, we must focus our immediate efforts on containing the crisis at hand,” they urged.
However, the findings also “underscore the need for future collective efforts to combat the equally devastating, and potentially synergistic, force of the obesity epidemic.”
COVID-19 pandemic collides with obesity epidemic
Previous studies of obesity and COVID-19 were small, did not adjust for multiple confounders, or did not include nonhospitalized patients, Dr. Tartof and coauthors wrote.
Their study included 6,916 members of the Kaiser Permanente Southern California health care plan who were diagnosed with COVID-19 from Feb. 13 to May 2, 2020.
The researchers calculated the risk for death at 21 days after a COVID-19 diagnosis; findings were corrected for age, sex, race/ethnicity, smoking, myocardial infarction, heart failure, peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, renal disease, metastatic tumor or malignancy, other immune disease, hyperlipidemia, hypertension, asthma, organ transplant, and diabetes status.
On the basis of BMI, the patients were classified as being underweight, of normal weight, overweight, or as having class 1, 2, or 3 obesity. BMI of 18.5 to 24 kg/m2 is defined as normal weight.
Class 3 obesity, also called severe obesity, included moderately severe obesity (BMI, 40-44 kg/m2) and extremely severe obesity (≥45 kg/m2).
A little more than half of the patients were women (55%), and more than 50% were Hispanic (54%).
A total of 206 patients (3%) died within 21 days of being diagnosed with COVID-19; of these, 67% had been hospitalized, and 43% had been intubated.
Overall, the COVID-19 patients with moderately severe or extremely severe obesity had a 2.7-fold and 4.2-fold increased risk for death, respectively, within 3 weeks compared with patients of normal weight.
Patients in the other BMI categories did not have a significantly higher risk of dying during follow-up.
However, each decade of increasing age after age 40 was associated with a stepwise increased risk for death within 3 weeks of the COVID-19 diagnosis.
Risk stratified by age and sex
Further analysis showed that, “most strikingly,” among patients aged 60 and younger, those with moderately severe obesity and extremely severe obesity had significant 17-fold and 12-fold higher risks of dying during follow-up, respectively, compared with patients of normal weight, the researchers reported.
In patients older than 60, moderately severe obesity did not confer a significant increased risk for imminent death from COVID-19; extremely severe obesity conferred a smaller, threefold increased risk for this.
“Our finding that severe obesity, particularly among younger patients, eclipses the mortality risk posed by other obesity-related conditions, such as history of myocardial infarction (MI), diabetes, hypertension, or hyperlipidemia, suggests a significant pathophysiologic link between excess adiposity and severe COVID-19 illness,” the researchers noted.
This independent increased risk for death with severe obesity was seen in men but not in women.
Men with moderately severe and extremely severe obesity had significant 4.8-fold and 10-fold higher risks of dying within 3 weeks, respectively, compared with men of normal weight.
“That the risks are higher in younger patients is probably not because obesity is particularly damaging in this age group; it is more likely that other serious comorbidities that evolve later in life take over as dominant risk factors,” Dr. Kass suggested in his editorial.
“That males are particularly affected may reflect their greater visceral adiposity over females, given that this fat is notably proinflammatory and contributes to metabolic and vascular disease,” he added.
“As a cardiologist who studies heart failure,” Dr. Kass wrote, “I am struck by how many of the mechanisms that are mentioned in reviews of obesity risk and heart disease are also mentioned in reviews of obesity and COVID-19.”
The study was funded by Roche-Genentech. Kass has disclosed no relevant financial relationships. Disclosures of the authors are listed in the article.
A version of this article originally appeared on Medscape.com.
In a large California health care plan, among patients with COVID-19, men aged 60 years and younger had a much higher risk of dying within 3 weeks of diagnosis if they had severe obesity as opposed to being of normal weight, independently of other risk factors.
reported Sara Y. Tartof, PhD, MPH, Kaiser Permanente Southern California, Pasadena, Calif., and coauthors.
The data “highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention,” they concluded in an article published online Aug. 12 in Annals of Internal Medicine.
This work adds to nearly 300 articles that have shown that severe obesity is associated with an increased risk for morbidity and mortality from COVID-19.
In an accompanying editorial, David A. Kass, MD, said: “Consistency of this new study and prior research should put to rest the contention that obesity is common in severe COVID-19 because it is common in the population.”
Rather, these findings show that “obesity is an important independent risk factor for serious COVID-19 disease,” he pointed out.
On the basis of this evidence, “arguably the hardest question to answer is: What is to be done?” wondered Kass, of Johns Hopkins University, Baltimore.
Although data consistently show that a body mass index >35 kg/m2 is predictive of major health risks, “weight reduction at that level of obesity is difficult and certainly is not achieved rapidly,” Dr. Kass stressed.
“Therefore ... social distancing; altering behaviors to reduce viral exposure and transmission, such as wearing masks; and instituting policies and health care approaches that recognize the potential effects of obesity should be implemented,” he emphasized. “These actions should help and are certainly doable.”
Similarly, Dr. Tartof and colleagues said their “findings also reveal the distressing collision of two pandemics: COVID-19 and obesity.
“As COVID-19 continues to spread unabated, we must focus our immediate efforts on containing the crisis at hand,” they urged.
However, the findings also “underscore the need for future collective efforts to combat the equally devastating, and potentially synergistic, force of the obesity epidemic.”
COVID-19 pandemic collides with obesity epidemic
Previous studies of obesity and COVID-19 were small, did not adjust for multiple confounders, or did not include nonhospitalized patients, Dr. Tartof and coauthors wrote.
Their study included 6,916 members of the Kaiser Permanente Southern California health care plan who were diagnosed with COVID-19 from Feb. 13 to May 2, 2020.
The researchers calculated the risk for death at 21 days after a COVID-19 diagnosis; findings were corrected for age, sex, race/ethnicity, smoking, myocardial infarction, heart failure, peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, renal disease, metastatic tumor or malignancy, other immune disease, hyperlipidemia, hypertension, asthma, organ transplant, and diabetes status.
On the basis of BMI, the patients were classified as being underweight, of normal weight, overweight, or as having class 1, 2, or 3 obesity. BMI of 18.5 to 24 kg/m2 is defined as normal weight.
Class 3 obesity, also called severe obesity, included moderately severe obesity (BMI, 40-44 kg/m2) and extremely severe obesity (≥45 kg/m2).
A little more than half of the patients were women (55%), and more than 50% were Hispanic (54%).
A total of 206 patients (3%) died within 21 days of being diagnosed with COVID-19; of these, 67% had been hospitalized, and 43% had been intubated.
Overall, the COVID-19 patients with moderately severe or extremely severe obesity had a 2.7-fold and 4.2-fold increased risk for death, respectively, within 3 weeks compared with patients of normal weight.
Patients in the other BMI categories did not have a significantly higher risk of dying during follow-up.
However, each decade of increasing age after age 40 was associated with a stepwise increased risk for death within 3 weeks of the COVID-19 diagnosis.
Risk stratified by age and sex
Further analysis showed that, “most strikingly,” among patients aged 60 and younger, those with moderately severe obesity and extremely severe obesity had significant 17-fold and 12-fold higher risks of dying during follow-up, respectively, compared with patients of normal weight, the researchers reported.
In patients older than 60, moderately severe obesity did not confer a significant increased risk for imminent death from COVID-19; extremely severe obesity conferred a smaller, threefold increased risk for this.
“Our finding that severe obesity, particularly among younger patients, eclipses the mortality risk posed by other obesity-related conditions, such as history of myocardial infarction (MI), diabetes, hypertension, or hyperlipidemia, suggests a significant pathophysiologic link between excess adiposity and severe COVID-19 illness,” the researchers noted.
This independent increased risk for death with severe obesity was seen in men but not in women.
Men with moderately severe and extremely severe obesity had significant 4.8-fold and 10-fold higher risks of dying within 3 weeks, respectively, compared with men of normal weight.
“That the risks are higher in younger patients is probably not because obesity is particularly damaging in this age group; it is more likely that other serious comorbidities that evolve later in life take over as dominant risk factors,” Dr. Kass suggested in his editorial.
“That males are particularly affected may reflect their greater visceral adiposity over females, given that this fat is notably proinflammatory and contributes to metabolic and vascular disease,” he added.
“As a cardiologist who studies heart failure,” Dr. Kass wrote, “I am struck by how many of the mechanisms that are mentioned in reviews of obesity risk and heart disease are also mentioned in reviews of obesity and COVID-19.”
The study was funded by Roche-Genentech. Kass has disclosed no relevant financial relationships. Disclosures of the authors are listed in the article.
A version of this article originally appeared on Medscape.com.
AHA statement recommends dietary screening at routine checkups
A new scientific statement from the American Heart Association recommends incorporating a rapid diet-screening tool into routine primary care visits to inform dietary counseling and integrating the tool into patients’ electronic health record platforms across all healthcare settings.
The statement authors evaluated 15 existing screening tools and, although they did not recommend a specific tool, they did present advantages and disadvantages of some of the tools and encouraged “critical conversations” among clinicians and other specialists to arrive at a tool that would be most appropriate for use in a particular health care setting.
“The key takeaway is for clinicians to incorporate discussion of dietary patterns into routine preventive care appointments because a suboptimal diet is the No. 1 risk factor for cardiovascular disease,” Maya Vadiveloo, PhD, RD, chair of the statement group, said in an interview.
“We also wanted to touch on the fact the screening tool could be incorporated into the EHR and then used for clinical support and for tracking and monitoring the patient’s dietary patterns over time,” said Dr. Vadiveloo, assistant professor of nutrition and food sciences in the College of Health Science, University of Rhode Island, Kingston.
The statement was published online Aug. 7 in Circulation: Cardiovascular Quality and Outcomes.
Competing demands
Poor dietary quality has “surpassed all other mortality risk factors, accounting for 11 million deaths and about 50% of cardiovascular disease (CVD) deaths globally,” the authors wrote.
Diets deficient in fruits, vegetables, and whole grains and high in red and processed meat, added sugars, sodium, and total energy are the “leading determinants” of the risks for CVD and other conditions, so “strategies that promote holistically healthier dietary patterns to reduce chronic disease risk are of contemporary importance.”
Most clinicians and other members of health care teams “do not currently assess or counsel patients about their food and beverage intake during routine clinical care,” the authors observed.
Reasons for this may include lack of training and knowledge, insufficient time, insufficient integration of nutrition services into health care settings, insufficient reimbursement, and “competing demands during the visit,” they noted.
Dr. Vadiveloo said that an evidence-based rapid screening tool can go a long way toward helping to overcome these barriers.
“Research shows that when primary care practitioners discuss diet with patients, the patients are receptive, but we also know that clinical workloads are already very compressed, and adding another thing to a routine preventive care appointment is challenging,” she said. “So we wanted to look and see if there were already screening tools that showed promise as valid, reliable, reflective of the best science, and easy to incorporate into various types of practice settings.”
Top picks
The authors established “theoretical and practice-based criteria” for an optimal diet screening tool for use in the adult population (aged 20 to 75 years). The tool had to:
- Be developed or used within clinical practice in the past 10 years.
- Be evidence-based, reliable, and valid.
- Assess total dietary pattern rather than focusing on a single food or nutrient.
- Be able to be completed and scored at administration without special knowledge or software.
- Give actionable next steps and support to patients.
- Be able track and monitor dietary change over time.
- Be brief.
- Be useful for chronic disease management.
Of the 15 tools reviewed, the three that met the most theoretical and practice-based validity criteria were the Mediterranean Diet Adherence Screener (MEDAS) and its variations; the modified, shortened Rapid Eating Assessment for Participants (REAP), and the modified version of the Starting the Conversation Tool. However, the authors noted that the Powell and Greenberg Screening Tool was the “least time-intensive.”
One size does not fit all
No single tool will be appropriate for all practice settings, so “we would like clinicians to discuss what will work in their particular setting,” Dr. Vadiveloo emphasized.
For example, should the screening tool be completed by the clinician, a member of the health care team, or the patient? Advantages of a tool completed by clinicians or team members include collection of the information in real time, where it can be used in shared decision-making during the encounter and increased reliability because the screen has been completed by a clinician. On the other hand, the clinician might not be able to prioritize administering the screening tool during a short clinical encounter.
Advantages of a tool completed by the patient via an EHR portal is that the patient may feel less risk of judgment by the clinician or health care professional and patients can complete the screen at their convenience. Disadvantages are limited reach into underserved populations and, potentially, less reliability than clinician-administered tools.
“It is advantageous to have tools that can be administered by multiple members of health care teams to ease the demand on clinicians, if such staff is available, but in other settings, self-administration might be better, so we tried to leave it open-ended,” Dr. Vadiveloo explained.
‘Ideal platform’
“The EHR is the ideal platform to prompt clinicians and other members of the health care team to capture dietary data and deliver dietary advice to patients,” the authors observed.
EHRs allow secure storage of data and also enable access to these data when needed at the point of care. They are also important for documentation purposes.
The authors noted that the use of “myriad EHR platforms and versions of platforms” have created “technical challenges.” They recommended “standardized approaches” for transmitting health data that will “more seamlessly allow rapid diet screeners to be implemented in the EHR.”
They also recommended that the prototypes of rapid diet screeners be tested by end users prior to implementation within particular clinics. “Gathering these data ahead of time can improve the uptake of the application in the real world,” they stated.
Dr. Vadiveloo added that dietary counseling can be conducted by several members of a health care team, such as a dietitian, not just by the physician. Or the patient may need to be referred to a dietitian for counseling and follow-up.
The authors concluded by characterizing the AHA statement as “a call to action ... designed to accelerate efforts to make diet quality assessment an integral part of office-based care delivery by encouraging critical conversations among clinicians, individuals with diet/lifestyle expertise, and specialists in information technology.”
Dr. Vadiveloo has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article originally appeared on Medscape.com.
A new scientific statement from the American Heart Association recommends incorporating a rapid diet-screening tool into routine primary care visits to inform dietary counseling and integrating the tool into patients’ electronic health record platforms across all healthcare settings.
The statement authors evaluated 15 existing screening tools and, although they did not recommend a specific tool, they did present advantages and disadvantages of some of the tools and encouraged “critical conversations” among clinicians and other specialists to arrive at a tool that would be most appropriate for use in a particular health care setting.
“The key takeaway is for clinicians to incorporate discussion of dietary patterns into routine preventive care appointments because a suboptimal diet is the No. 1 risk factor for cardiovascular disease,” Maya Vadiveloo, PhD, RD, chair of the statement group, said in an interview.
“We also wanted to touch on the fact the screening tool could be incorporated into the EHR and then used for clinical support and for tracking and monitoring the patient’s dietary patterns over time,” said Dr. Vadiveloo, assistant professor of nutrition and food sciences in the College of Health Science, University of Rhode Island, Kingston.
The statement was published online Aug. 7 in Circulation: Cardiovascular Quality and Outcomes.
Competing demands
Poor dietary quality has “surpassed all other mortality risk factors, accounting for 11 million deaths and about 50% of cardiovascular disease (CVD) deaths globally,” the authors wrote.
Diets deficient in fruits, vegetables, and whole grains and high in red and processed meat, added sugars, sodium, and total energy are the “leading determinants” of the risks for CVD and other conditions, so “strategies that promote holistically healthier dietary patterns to reduce chronic disease risk are of contemporary importance.”
Most clinicians and other members of health care teams “do not currently assess or counsel patients about their food and beverage intake during routine clinical care,” the authors observed.
Reasons for this may include lack of training and knowledge, insufficient time, insufficient integration of nutrition services into health care settings, insufficient reimbursement, and “competing demands during the visit,” they noted.
Dr. Vadiveloo said that an evidence-based rapid screening tool can go a long way toward helping to overcome these barriers.
“Research shows that when primary care practitioners discuss diet with patients, the patients are receptive, but we also know that clinical workloads are already very compressed, and adding another thing to a routine preventive care appointment is challenging,” she said. “So we wanted to look and see if there were already screening tools that showed promise as valid, reliable, reflective of the best science, and easy to incorporate into various types of practice settings.”
Top picks
The authors established “theoretical and practice-based criteria” for an optimal diet screening tool for use in the adult population (aged 20 to 75 years). The tool had to:
- Be developed or used within clinical practice in the past 10 years.
- Be evidence-based, reliable, and valid.
- Assess total dietary pattern rather than focusing on a single food or nutrient.
- Be able to be completed and scored at administration without special knowledge or software.
- Give actionable next steps and support to patients.
- Be able track and monitor dietary change over time.
- Be brief.
- Be useful for chronic disease management.
Of the 15 tools reviewed, the three that met the most theoretical and practice-based validity criteria were the Mediterranean Diet Adherence Screener (MEDAS) and its variations; the modified, shortened Rapid Eating Assessment for Participants (REAP), and the modified version of the Starting the Conversation Tool. However, the authors noted that the Powell and Greenberg Screening Tool was the “least time-intensive.”
One size does not fit all
No single tool will be appropriate for all practice settings, so “we would like clinicians to discuss what will work in their particular setting,” Dr. Vadiveloo emphasized.
For example, should the screening tool be completed by the clinician, a member of the health care team, or the patient? Advantages of a tool completed by clinicians or team members include collection of the information in real time, where it can be used in shared decision-making during the encounter and increased reliability because the screen has been completed by a clinician. On the other hand, the clinician might not be able to prioritize administering the screening tool during a short clinical encounter.
Advantages of a tool completed by the patient via an EHR portal is that the patient may feel less risk of judgment by the clinician or health care professional and patients can complete the screen at their convenience. Disadvantages are limited reach into underserved populations and, potentially, less reliability than clinician-administered tools.
“It is advantageous to have tools that can be administered by multiple members of health care teams to ease the demand on clinicians, if such staff is available, but in other settings, self-administration might be better, so we tried to leave it open-ended,” Dr. Vadiveloo explained.
‘Ideal platform’
“The EHR is the ideal platform to prompt clinicians and other members of the health care team to capture dietary data and deliver dietary advice to patients,” the authors observed.
EHRs allow secure storage of data and also enable access to these data when needed at the point of care. They are also important for documentation purposes.
The authors noted that the use of “myriad EHR platforms and versions of platforms” have created “technical challenges.” They recommended “standardized approaches” for transmitting health data that will “more seamlessly allow rapid diet screeners to be implemented in the EHR.”
They also recommended that the prototypes of rapid diet screeners be tested by end users prior to implementation within particular clinics. “Gathering these data ahead of time can improve the uptake of the application in the real world,” they stated.
Dr. Vadiveloo added that dietary counseling can be conducted by several members of a health care team, such as a dietitian, not just by the physician. Or the patient may need to be referred to a dietitian for counseling and follow-up.
The authors concluded by characterizing the AHA statement as “a call to action ... designed to accelerate efforts to make diet quality assessment an integral part of office-based care delivery by encouraging critical conversations among clinicians, individuals with diet/lifestyle expertise, and specialists in information technology.”
Dr. Vadiveloo has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article originally appeared on Medscape.com.
A new scientific statement from the American Heart Association recommends incorporating a rapid diet-screening tool into routine primary care visits to inform dietary counseling and integrating the tool into patients’ electronic health record platforms across all healthcare settings.
The statement authors evaluated 15 existing screening tools and, although they did not recommend a specific tool, they did present advantages and disadvantages of some of the tools and encouraged “critical conversations” among clinicians and other specialists to arrive at a tool that would be most appropriate for use in a particular health care setting.
“The key takeaway is for clinicians to incorporate discussion of dietary patterns into routine preventive care appointments because a suboptimal diet is the No. 1 risk factor for cardiovascular disease,” Maya Vadiveloo, PhD, RD, chair of the statement group, said in an interview.
“We also wanted to touch on the fact the screening tool could be incorporated into the EHR and then used for clinical support and for tracking and monitoring the patient’s dietary patterns over time,” said Dr. Vadiveloo, assistant professor of nutrition and food sciences in the College of Health Science, University of Rhode Island, Kingston.
The statement was published online Aug. 7 in Circulation: Cardiovascular Quality and Outcomes.
Competing demands
Poor dietary quality has “surpassed all other mortality risk factors, accounting for 11 million deaths and about 50% of cardiovascular disease (CVD) deaths globally,” the authors wrote.
Diets deficient in fruits, vegetables, and whole grains and high in red and processed meat, added sugars, sodium, and total energy are the “leading determinants” of the risks for CVD and other conditions, so “strategies that promote holistically healthier dietary patterns to reduce chronic disease risk are of contemporary importance.”
Most clinicians and other members of health care teams “do not currently assess or counsel patients about their food and beverage intake during routine clinical care,” the authors observed.
Reasons for this may include lack of training and knowledge, insufficient time, insufficient integration of nutrition services into health care settings, insufficient reimbursement, and “competing demands during the visit,” they noted.
Dr. Vadiveloo said that an evidence-based rapid screening tool can go a long way toward helping to overcome these barriers.
“Research shows that when primary care practitioners discuss diet with patients, the patients are receptive, but we also know that clinical workloads are already very compressed, and adding another thing to a routine preventive care appointment is challenging,” she said. “So we wanted to look and see if there were already screening tools that showed promise as valid, reliable, reflective of the best science, and easy to incorporate into various types of practice settings.”
Top picks
The authors established “theoretical and practice-based criteria” for an optimal diet screening tool for use in the adult population (aged 20 to 75 years). The tool had to:
- Be developed or used within clinical practice in the past 10 years.
- Be evidence-based, reliable, and valid.
- Assess total dietary pattern rather than focusing on a single food or nutrient.
- Be able to be completed and scored at administration without special knowledge or software.
- Give actionable next steps and support to patients.
- Be able track and monitor dietary change over time.
- Be brief.
- Be useful for chronic disease management.
Of the 15 tools reviewed, the three that met the most theoretical and practice-based validity criteria were the Mediterranean Diet Adherence Screener (MEDAS) and its variations; the modified, shortened Rapid Eating Assessment for Participants (REAP), and the modified version of the Starting the Conversation Tool. However, the authors noted that the Powell and Greenberg Screening Tool was the “least time-intensive.”
One size does not fit all
No single tool will be appropriate for all practice settings, so “we would like clinicians to discuss what will work in their particular setting,” Dr. Vadiveloo emphasized.
For example, should the screening tool be completed by the clinician, a member of the health care team, or the patient? Advantages of a tool completed by clinicians or team members include collection of the information in real time, where it can be used in shared decision-making during the encounter and increased reliability because the screen has been completed by a clinician. On the other hand, the clinician might not be able to prioritize administering the screening tool during a short clinical encounter.
Advantages of a tool completed by the patient via an EHR portal is that the patient may feel less risk of judgment by the clinician or health care professional and patients can complete the screen at their convenience. Disadvantages are limited reach into underserved populations and, potentially, less reliability than clinician-administered tools.
“It is advantageous to have tools that can be administered by multiple members of health care teams to ease the demand on clinicians, if such staff is available, but in other settings, self-administration might be better, so we tried to leave it open-ended,” Dr. Vadiveloo explained.
‘Ideal platform’
“The EHR is the ideal platform to prompt clinicians and other members of the health care team to capture dietary data and deliver dietary advice to patients,” the authors observed.
EHRs allow secure storage of data and also enable access to these data when needed at the point of care. They are also important for documentation purposes.
The authors noted that the use of “myriad EHR platforms and versions of platforms” have created “technical challenges.” They recommended “standardized approaches” for transmitting health data that will “more seamlessly allow rapid diet screeners to be implemented in the EHR.”
They also recommended that the prototypes of rapid diet screeners be tested by end users prior to implementation within particular clinics. “Gathering these data ahead of time can improve the uptake of the application in the real world,” they stated.
Dr. Vadiveloo added that dietary counseling can be conducted by several members of a health care team, such as a dietitian, not just by the physician. Or the patient may need to be referred to a dietitian for counseling and follow-up.
The authors concluded by characterizing the AHA statement as “a call to action ... designed to accelerate efforts to make diet quality assessment an integral part of office-based care delivery by encouraging critical conversations among clinicians, individuals with diet/lifestyle expertise, and specialists in information technology.”
Dr. Vadiveloo has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article originally appeared on Medscape.com.
Weight gain persists as HIV-treatment issue
People living with HIV who put on extra pounds and develop metabolic syndrome or related disorders linked in part to certain antiretroviral agents remain a concern today, even as the drugs used to suppress HIV infection have evolved over the decades.
Linkage of HIV treatment with lipodystrophy and insulin resistance or diabetes began in the 1990s with protease inhibitors (Clin Infect Dis. 2000 Jun;30[suppl 2]:s135-42). Several reports over the years also tied any form of effective antiretroviral therapy to weight gain in HIV patients (Antivir Ther. 2012;17[7]:1281-9). More recently, reports have rattled the HIV-treatment community by associating alarmingly high levels of weight gain with a useful and relatively new drug, tenofovir alafenamide fumarate (TAF) – a nucleoside reverse transcriptase inhibitor (NRTI) approved for use in the United States in late 2016, as well as certain agents from an entirely different antiretroviral therapy (ART) class, the integrase strand transfer inhibitors (INSTIs). Both TAF and the INSTIs have come to play major roles in the HIV-treatment landscape, despite relevant and concerning recent weight gain observations with these drugs, such as in a 2019 meta-analysis of eight trials with 5,680 treatment-naive patients who started ART during 2003-2015 (Clin Infect Dis. 2019 Oct 14;doi: 10.1093/cid/ciz999).
“Weight gain is clearly seen in studies of dolutegravir [DTG] or bictegravir [BTG] with TAF,” wrote W.D. Francois Venter, PhD and Andrew Hill, PhD in a recent published commentary on the topic (Lancet HIV. 2020 Jun 1;7[6]:e389-400). Both DTG and BTG are INSTI class members.
“Excessive weight gain, defined as more than 10% over baseline, has recently been observed among people with HIV initiating or switching to regimens incorporating TAF, an INSTI, or both, particularly DTG,” wrote Jordan E. Lake, MD, an HIV specialist at the University of Texas Health Science Center at Houston, in a recent commentary posted online. Women and Black patients “are at even greater risk for excessive weight gain,” Dr. Lake added.
“In recent times, it has emerged that weight gain is more pronounced with the integrase inhibitor class of agents, especially dolutegravir and bictegravir, the so-called second-generation” INSTIs, said Anna Maria Geretti, MD, a professor of clinical infection, microbiology, and immunology at the University of Liverpool, England. ”The effect is more pronounced in women and people of non-White ethnicity, and is of concern because of the associated potential risk of metabolic syndrome, cardiovascular disease, etc.,” Dr. Geretti said in an interview.
The unprecedented susceptibility to weight gain seen recently in non-White women may in part have resulted from the tendency of many earlier treatment trials to have cohorts comprised predominantly of White men, Dr. Venter noted in an interview.
Alarming weight gains reported
Perhaps the most eye-popping example of the potential for weight gain with the combination of TAF with an INSTI came in a recent report from the ADVANCE trial, a randomized, head-to-head comparison of three regimens in 1,053 HIV patients in South Africa. After 144 weeks on a regimen of TAF (Vemlidy), DTG (Tivicay), and FTC (emtricitabine, Emtriva), another NRTI, women gained an averaged of more than 12 kg, compared with their baseline weight, significantly more than in two comparator groups, Simiso Sokhela, MB, reported at the virtual meeting of the International AIDS conference. The women in ADVANCE on the TAF-DTG-FTC regimen also had an 11% rate of incident metabolic syndrome during their first 96 weeks on treatment, compared with rates of 8% among patients on a different form of tenofovir, tenofovir disoproxil fumarate (TDF), along with DTG-FTC, and 5% among those on TDF–EFV (efavirenz, Sustiva)–FTC said Dr. Sokhela, an HIV researcher at Ezintsha, a division of the University of the Witwatersrand in Johannesburg, South Africa.
“We believe that these results support the World Health Organization guidelines that reserve TAF for only patients with osteoporosis or impaired renal function,” Dr. Sokhela said during a press briefing at the conference. The WHO guidelines list the first-line regimen as TDF-DTG-3TC (lamivudine; Epivir) or FTC. “The risk for becoming obese continued to increase after 96 weeks” of chronic use of these drugs, she added.
“All regimens are now brilliant at viral control. Finding the ones that don’t make patients obese or have other long-term side effects is now the priority,” noted Dr. Venter, a professor and HIV researcher at University of the Witwatersrand, head of Ezintsha, and lead investigator of ADVANCE. Clinicians and researchers have recently thought that combining TAF and an INSTI plus FTC or a similar NRTI “would be the ultimate regimen to replace the nonnucleoside reverse transcriptase inhibitors (NNRTIs)” such as EFV, “but now we have a major headache” with unexpectedly high weight gains in some patients, Dr. Venter said.
Weight gains “over 10 kg are unlikely to be acceptable in any circumstances, especially when starting body mass index is already borderline overweight,” wrote Dr. Venter along with Dr. Hill in their commentary. Until recently, many clinicians chalked up weight gain on newly begun ART as a manifestation of the patient’s “return-to-health,” but this interpretation “gives a positive spin to a potentially serious and common side effect,” they added.
More from ADVANCE
The primary efficacy endpoint of ADVANCE was suppression of viral load to less than 50 RNA copies/mL after 48 weeks on treatment, and the result showed that the TAF-DTG-FTC regimen and the TDF-DTG-FTC regimen were each noninferior to the control regimen of TDF-EFV-FTC (New Engl J Med. 2019 Aug 29;381[9]:803-15). Virtually all of the enrolled patients were Black, and 59% were women. Planned follow-up of all patients ran for 96 weeks. After 48 weeks, weight gain among the women averaged 6.4 kg, 3.2 kg, and 1.7 kg in the TAF-DTG, TDF-DTG, and TDF-EFV arms respectively. After 96 weeks, the average weight gains among women were 8.2 kg, 4.6 kg, and 3.2 kg, respectively, in new results reported by Dr. Sokhela at the IAC. Follow-up to 144 weeks was partial and included about a quarter of the enrolled women, with gains averaging 12.3 kg, 7.4 kg, and 5.5 kg respectively. The pattern of weight gain among men tracked the pattern in women, but the magnitude of gain was less. Among men followed for 144 weeks, average gain among those on TAF-DTG-FTC was 7.2 kg, the largest gain seen among men on any regimen and at any follow-up time in the study.
Dr. Sokhela also reported data on body composition analyses, which showed that the weight gains were largely in fat rather than lean tissue, fat accumulation was significantly greater in women than men, and that in both sexes fat accumulated roughly equally in the trunk and on limbs.
An additional analysis looked at the incidence of new-onset obesity among the women who had a normal body mass index at baseline. After 96 weeks, incident obesity occurred in 14% of women on the TAG-DTG-FTC regimen, 8% on TDF-DTG-FTC, and in 2% of women maintained on TDF-EFV-FTC, said Dr. Hill in a separate report at the conference.
Weight starts to weigh in
“I am very mindful of weight gain potential, and I talk to patients about it. It doesn’t determine what regimen I choose for a patient” right now, “but it’s only a matter of time before it starts influencing what we do, particularly if we can achieve efficacy with fewer drugs,” commented Babafemi O. Taiwo, MD, professor of medicine and chief of infectious diseases at Northwestern University in Chicago. “I’ve had some patients show up with a weight gain of 20 kg, and that shouldn’t happen,” he said during a recent online educational session. Dr. Taiwo said his recent practice has been to warn patients about possible weight gain and to urge them to get back in touch with him quickly if it happens.
“Virologic suppression is the most important goal with ART, and the U.S. Department of Health and Human Services currently recommends INSTI-based ART for most PWH [people with HIV],” wrote Dr. Lake in April 2020. “I counsel all PWH initiating ART about the potential for weight gain, and I discuss their current diet and healthy lifestyle habits. I explain to patients that we will monitor their weight, and if weight gain seems more than either of us are comfortable with then we will reassess. Only a small percentage of patients experience excessive weight gain after starting ART.” Dr. Lake also stressed that she had not yet begun to change the regimen a patient is on solely because of weight gain. “We do not know whether this weight gain is reversible,” she noted.
“I do not anticipate that a risk of weight gain at present will dictate a change in guidelines,” said Dr. Geretti. “Drugs such as dolutegravir and bictegravir are very effective, and they are unlikely to cause drug resistance. Further data on the mechanism of weight gain and the reversibility after a change of treatment will help refine drug selection in the near future,” she predicted.
“I consider weight gain when prescribing because my patients hear about this. It’s a side effect that my patients really care about, and I don’t blame them,” said Lisa Hightow-Weidman, MD, a professor and HIV specialist at the University of North Carolina at Chapel Hill, during an on-line educational session. “If you don’t discuss it with a patient and then weight gain happens and the patient finds out [the known risk from their treatment] they may have an issue,” she noted. But weight gain is not a reason to avoid these drugs. “They are great medications in many ways, with once-daily regimens and few side effects.”
Weight gain during pregnancy a special concern
An additional analysis of data from ADVANCE presented at the conference highlighted what the observed weight gain on ART could mean for women who become pregnant while on treatment. Based on a systematic literature review, the ADVANCE investigators calculated the relative risk for six obesity-related pregnancy complications, compared with nonobese women: preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, postpartum hemorrhage, and caesarean delivery. Based on the obesity changes among women on their assigned ART in ADVANCE, the researchers calculated the predicted incidence of these six complications. The analysis showed that for every 1,000 women, those on TAG-DTG-FTC would have an excess of 53 obesity-related pregnancy complications, those on TDF-DTG-FTC would develop 28 excess pregnancy complications, and those on TDG-EFV-FTC would have four excess complications, reported Dr. Hill at the International AIDS conference.
The researchers also ran a similar simulation for the incidence of neonatal complications that could result when mothers are obese because of their ART. The six neonatal complications included in this analysis were small for gestational age, large for gestational age, macrosomia, neonatal death, stillbirth, and neural tube defects. Based on the excess rate of incident obesity, they calculated that for every 1,000 pregnancies women on TAD-DTG-FTC would have 24 additional infants born with one of these complications, women on TDF-DTG-FTC would have an excess of 13 of these events, and women on TDG-EFV-FTC would have an excess of three such obesity-related neonatal complications, Dr. Hill said.
Sorting out the drugs
Results from several additional studies reported at the conference have started trying to discern exactly which ART drugs and regimens pose the greatest weight gain risk and which have the least risk while retaining high efficacy and resistance barriers.
Further evidence implicating any type of ART as a driver of increased weight came from a review of 8,256 adults infected with HIV and members of the Kaiser Permanente health system in three U.S. regions during 2000-2016. Researchers matched these cases using several demographic factors with just under 130,000 members without HIV. Those infected by HIV had half the prevalence of obesity as the matched controls at baseline. During 12 years of follow-up, those infected with HIV had a threefold higher rate of weight gain than those who were uninfected. Annual weight gain averaged 0.06 kg/year among the uninfected people and 0.22 kg/year among those infected with HIV, a statistically significant difference that was consistent regardless of whether people started the study at a normal body mass index, overweight, or obese, reported Michael J. Silverberg, PhD, an epidemiologist with Kaiser Permanente in Oakland, Calif.
Another study tried to focus on the weight gain impact when patients on three-drug ART regimens changed from taking TDF to TAF. This analysis used data collected in the OPERA (Observational Pharmaco-Epidemiology Research & Analysis) longitudinal cohort of about 115,000 U.S. PWH. The observational cohort included nearly 7,000 patients who made a TDF-to-TAF switch, including 3,288 patients who maintained treatment during this switch with an INSTI, 1,454 who maintained a background regimen based on a NNRTI, 1,430 patients who also switched from an INSTI to a different drug, and 747 patients maintained on a boosted dose of a protease inhibitor. All patients were well controlled on their baseline regimen, with at least two consecutive measures showing undetectable viral load.
Patients who maintained their background regimens while changing from TDF to TAF had a 2.0-2.6 kg increase in weight during the 9 months immediately following their switch to TAF, reported Patrick Mallon, MB, a professor of microbial diseases at University College Dublin. Among the patients who both switched to TAF and also switched to treatment with an INSTI, weight gain during the 9 months after the switch averaged 2.6-4.5 kg, depending on which INSTI was started. Patients who switched to treatment with elvitegravir/cobicistat (an INSTI plus a boosting agent) averaged a gain of 2.6 kg during 9 months, those who switched to DTG averaged a 3.1-kg gain, and those who switched to BTG averaged a 4.6-kg increase, Dr. Mallon reported at the conference.
These findings “give us a good sense that the weight gain is real. This is not just overeating or not exercising, but weight changes coincidental with a change in HIV treatment,” commented David Wohl, MD, professor of medicine and site leader of the HIV Prevention and Treatment Clinical Trials Unit at the University of North Carolina at Chapel Hill, during an online educational session.
Contrary to this evidence suggesting a consistent uptick in weight when patients start TAF treatment was a recent report on 629 HIV patients randomized to treatment with TAF-BTG-FTC or abacavir (an NRTI, Ziagen)–DTG-3TC, which found similar weight gains between these two regimens after 144 weeks on treatment (Lancet HIV. 2020 Jun;7[6]:e389-400). This finding had the effect of “strengthening the argument that TAF is simply an innocent bystander” and does not play a central role in weight gain, and supporting the notion that the alternative tenofovir formulation, TDF, differs from TAF by promoting weight loss, Dr. Venter and Dr. Hill suggested in their commentary that accompanied this report.
The new findings from Dr. Mallon raise “serious questions about the way we have moved to TAF as a replacement for TDF, especially because the benefits [from TAF] are for a small subgroup – patients with renal disease or osteoporosis,” Dr. Venter said in an interview. “The question is, will we see weight gain like this” if TAF was combined with a non-INSTI drug? he wondered.
While some study results have suggested a mitigating effect from TDF on weight gain, that wasn’t the case in the AFRICOS (African Cohort Study) study of 1,954 PWH who started treatment with TDF-DTG-FTC (742 patients) or a different three-drug regimen. After a median of 225 days on treatment, those who started on TDF-DTG-FTC had an adjusted, 85% higher rate of developing a high body mass index, compared with patients on a different ART regimen, Julie Ake, MD, reported in a talk at the conference. Her conclusion focused on the possible involvement of DTG: “Consistent with previous reports, dolutegravir was significantly associated with an increased risk of developing high body mass index,” said Dr. Ake, director of the U.S. Military HIV Research Program in Bethesda, Md. and leader of AFRICOS.
A potential workaround to some drugs that cause excessive the weight gain is to just not use them. That was part of the rationale for the TANGO study, which took 741 HIV-infected patients with successful viral suppression on a regimen of TAF-FTC plus one or two additional agents and switched half of them to a TAF-less, two-drug regimen of DTG-FTC. This open-label study’s primary endpoint was noninferiority for viral suppression of the DTG-FTC regimen, compared with patients who stayed on their starting regimen, and the results proved that DTG-FTC was just as effective over 48 weeks for this outcome (Clin Infect Dis. 2020 Jan 6. doi: 10.1093/cid/ciz1243).
At the conference, TANGO’s lead investigator, Jean van Wyk, MD, reported the weight and metabolic effects of the switch. The results showed a similar and small weight gain (on average less than 1 kg) during 48 week follow-up regardless of whether patients remained on their baseline, TAF-containing regimen or switched to DTG-FTC, said Dr. van Wyk, global medical lead for HIV treatment at Viiv Healthcare, the company that markets DTG. About three-quarters of patients in both arms received “boosted” dosages of their drugs, and in this subgroup, patients on DTG-FTC showed statistically significant benefits in several lipid levels, fasting glucose level, and in their degree of insulin resistance. Dr. van Wyk said. These between-group differences were not statistically significant among the “unboosted” patients, and the results failed to show a significant between-group difference in the incidence of metabolic syndrome.
Dr. Venter called these results “exciting,” and noted that he already uses the DTG-FTC two-drug combination “a lot” to treat PWH and renal disease.
A second alternative regimen showcased in a talk at the conference used the three-drug regimen of TDF-FTC plus the NNRTI, DOR (doravirine, Pifeltro). The DRIVE-SHIFT trial enrolled 670 HIV patients with successfully suppressed viral load on conventional regimens who were either switched to TDF-DOR-FTC or maintained on their baseline treatment. After 48 weeks, results confirmed the primary efficacy endpoint of noninferiority for maintenance of suppression with the investigational regimen (J Acquir Immune Defic Syndr. 2019 Aug;81[4]:463-72).
A post-hoc analysis looked at weight changes among these patients after as much as 144 weeks of follow-up. The results showed that patients switched to TDF-DOR-FTC had an average weight increase of 1.2-1.4 kg after more than 2 years on the new regimen, with fewer than 10% of patients having a 10% or greater weight gain with DOR, a “next-generation” NNRTI, reported Princy N. Kumar, MD, professor at Georgetown University and chief of infectious diseases at MedStar Georgetown University Hospital in Washington. “Weight gain was minimal, even over the long term,” she noted.
The tested DOR-based regimen also looks “very exciting,” but the populations it’s been tested have also been largely limited to White men, and limited data exist about the regimen’s performance in pregnant women, commented Dr. Venter. The DRIVE-SHIRT patient cohort was about 85% men, and about three-quarters White.
More weight data needed
HIV-treatment researchers and clinicians seem agreed that weight gain and other metabolic effects from HIV treatment need more assessment and evidence because current data, while suggestive, is also inconclusive.
“Clinical trials are desperately needed to understand the mechanisms of and potential therapeutic options for excessive weight gain on ART,” wrote Dr. Lake in her commentary in April. “While more research is needed,” the new data reported at the virtual International AIDS conference “get us closer to understanding the effects of integrase inhibitors and TAF on weight and the potential metabolic consequences,” she commented as chair of the conference session where these reports occurred.
“Further data on the mechanism of weight gain and its reversibility after a change of treatment will help refine drug selection in the near future,” predicted Dr. Geretti.
“It’s hard to understand physiologically how drugs from such different classes all seem to have weight effects; it’s maddening,” said Dr. Venter. “We need decent studies in all patient populations. That will now be the priority,” he declared. “Patients shouldn’t have to choose” between drugs that most effectively control their HIV infection and drugs that don’t pose a risk for weight gain or metabolic derangements. PWH “should not have to face obesity as their new epidemic,” he wrote with Dr. Hill.
ADVANCE was funded in part by Viiv, the company that markets dolutegravir (Tivicay), and received drugs supplied by Gilead and Viiv. TANGO was sponsored by Viiv. DRIVE-SHIFT was funded by Merck, the company that markets doravirine (Pifeltro). Dr. Lake, Dr. Sokhela, Dr. Ake, and Dr. Kumar had no disclosures, Dr. Venter has received personal fees from Adcock Ingraham, Aspen Healthcare, Johnson and Johnson, Merck, Mylan, Roche, and Viiv. Dr. Hill has received payments from Merck. Dr. Geretti has received honoraria and research funding from Gilead, Jansse, Roche, and Viiv. Dr. Taiwo has had financial relationships with Gilead, Janssen, and Viiv. Dr. Hightow-Weidman has received honoraria from Gilead and Jansse. Dr. Wohl has been a consultant to Gilead, Johnson and Johnson, and Merck. Dr. Silverberg received research funding from Gilead. Dr. Mallon has been an advisor to and speaker on behalf of Bristol-Myers Squibb, Cilag, Gilead, Jansse, Merck Sharp & Dohme, and Viiv. Dr. van Wyk is a Viiv employee.
People living with HIV who put on extra pounds and develop metabolic syndrome or related disorders linked in part to certain antiretroviral agents remain a concern today, even as the drugs used to suppress HIV infection have evolved over the decades.
Linkage of HIV treatment with lipodystrophy and insulin resistance or diabetes began in the 1990s with protease inhibitors (Clin Infect Dis. 2000 Jun;30[suppl 2]:s135-42). Several reports over the years also tied any form of effective antiretroviral therapy to weight gain in HIV patients (Antivir Ther. 2012;17[7]:1281-9). More recently, reports have rattled the HIV-treatment community by associating alarmingly high levels of weight gain with a useful and relatively new drug, tenofovir alafenamide fumarate (TAF) – a nucleoside reverse transcriptase inhibitor (NRTI) approved for use in the United States in late 2016, as well as certain agents from an entirely different antiretroviral therapy (ART) class, the integrase strand transfer inhibitors (INSTIs). Both TAF and the INSTIs have come to play major roles in the HIV-treatment landscape, despite relevant and concerning recent weight gain observations with these drugs, such as in a 2019 meta-analysis of eight trials with 5,680 treatment-naive patients who started ART during 2003-2015 (Clin Infect Dis. 2019 Oct 14;doi: 10.1093/cid/ciz999).
“Weight gain is clearly seen in studies of dolutegravir [DTG] or bictegravir [BTG] with TAF,” wrote W.D. Francois Venter, PhD and Andrew Hill, PhD in a recent published commentary on the topic (Lancet HIV. 2020 Jun 1;7[6]:e389-400). Both DTG and BTG are INSTI class members.
“Excessive weight gain, defined as more than 10% over baseline, has recently been observed among people with HIV initiating or switching to regimens incorporating TAF, an INSTI, or both, particularly DTG,” wrote Jordan E. Lake, MD, an HIV specialist at the University of Texas Health Science Center at Houston, in a recent commentary posted online. Women and Black patients “are at even greater risk for excessive weight gain,” Dr. Lake added.
“In recent times, it has emerged that weight gain is more pronounced with the integrase inhibitor class of agents, especially dolutegravir and bictegravir, the so-called second-generation” INSTIs, said Anna Maria Geretti, MD, a professor of clinical infection, microbiology, and immunology at the University of Liverpool, England. ”The effect is more pronounced in women and people of non-White ethnicity, and is of concern because of the associated potential risk of metabolic syndrome, cardiovascular disease, etc.,” Dr. Geretti said in an interview.
The unprecedented susceptibility to weight gain seen recently in non-White women may in part have resulted from the tendency of many earlier treatment trials to have cohorts comprised predominantly of White men, Dr. Venter noted in an interview.
Alarming weight gains reported
Perhaps the most eye-popping example of the potential for weight gain with the combination of TAF with an INSTI came in a recent report from the ADVANCE trial, a randomized, head-to-head comparison of three regimens in 1,053 HIV patients in South Africa. After 144 weeks on a regimen of TAF (Vemlidy), DTG (Tivicay), and FTC (emtricitabine, Emtriva), another NRTI, women gained an averaged of more than 12 kg, compared with their baseline weight, significantly more than in two comparator groups, Simiso Sokhela, MB, reported at the virtual meeting of the International AIDS conference. The women in ADVANCE on the TAF-DTG-FTC regimen also had an 11% rate of incident metabolic syndrome during their first 96 weeks on treatment, compared with rates of 8% among patients on a different form of tenofovir, tenofovir disoproxil fumarate (TDF), along with DTG-FTC, and 5% among those on TDF–EFV (efavirenz, Sustiva)–FTC said Dr. Sokhela, an HIV researcher at Ezintsha, a division of the University of the Witwatersrand in Johannesburg, South Africa.
“We believe that these results support the World Health Organization guidelines that reserve TAF for only patients with osteoporosis or impaired renal function,” Dr. Sokhela said during a press briefing at the conference. The WHO guidelines list the first-line regimen as TDF-DTG-3TC (lamivudine; Epivir) or FTC. “The risk for becoming obese continued to increase after 96 weeks” of chronic use of these drugs, she added.
“All regimens are now brilliant at viral control. Finding the ones that don’t make patients obese or have other long-term side effects is now the priority,” noted Dr. Venter, a professor and HIV researcher at University of the Witwatersrand, head of Ezintsha, and lead investigator of ADVANCE. Clinicians and researchers have recently thought that combining TAF and an INSTI plus FTC or a similar NRTI “would be the ultimate regimen to replace the nonnucleoside reverse transcriptase inhibitors (NNRTIs)” such as EFV, “but now we have a major headache” with unexpectedly high weight gains in some patients, Dr. Venter said.
Weight gains “over 10 kg are unlikely to be acceptable in any circumstances, especially when starting body mass index is already borderline overweight,” wrote Dr. Venter along with Dr. Hill in their commentary. Until recently, many clinicians chalked up weight gain on newly begun ART as a manifestation of the patient’s “return-to-health,” but this interpretation “gives a positive spin to a potentially serious and common side effect,” they added.
More from ADVANCE
The primary efficacy endpoint of ADVANCE was suppression of viral load to less than 50 RNA copies/mL after 48 weeks on treatment, and the result showed that the TAF-DTG-FTC regimen and the TDF-DTG-FTC regimen were each noninferior to the control regimen of TDF-EFV-FTC (New Engl J Med. 2019 Aug 29;381[9]:803-15). Virtually all of the enrolled patients were Black, and 59% were women. Planned follow-up of all patients ran for 96 weeks. After 48 weeks, weight gain among the women averaged 6.4 kg, 3.2 kg, and 1.7 kg in the TAF-DTG, TDF-DTG, and TDF-EFV arms respectively. After 96 weeks, the average weight gains among women were 8.2 kg, 4.6 kg, and 3.2 kg, respectively, in new results reported by Dr. Sokhela at the IAC. Follow-up to 144 weeks was partial and included about a quarter of the enrolled women, with gains averaging 12.3 kg, 7.4 kg, and 5.5 kg respectively. The pattern of weight gain among men tracked the pattern in women, but the magnitude of gain was less. Among men followed for 144 weeks, average gain among those on TAF-DTG-FTC was 7.2 kg, the largest gain seen among men on any regimen and at any follow-up time in the study.
Dr. Sokhela also reported data on body composition analyses, which showed that the weight gains were largely in fat rather than lean tissue, fat accumulation was significantly greater in women than men, and that in both sexes fat accumulated roughly equally in the trunk and on limbs.
An additional analysis looked at the incidence of new-onset obesity among the women who had a normal body mass index at baseline. After 96 weeks, incident obesity occurred in 14% of women on the TAG-DTG-FTC regimen, 8% on TDF-DTG-FTC, and in 2% of women maintained on TDF-EFV-FTC, said Dr. Hill in a separate report at the conference.
Weight starts to weigh in
“I am very mindful of weight gain potential, and I talk to patients about it. It doesn’t determine what regimen I choose for a patient” right now, “but it’s only a matter of time before it starts influencing what we do, particularly if we can achieve efficacy with fewer drugs,” commented Babafemi O. Taiwo, MD, professor of medicine and chief of infectious diseases at Northwestern University in Chicago. “I’ve had some patients show up with a weight gain of 20 kg, and that shouldn’t happen,” he said during a recent online educational session. Dr. Taiwo said his recent practice has been to warn patients about possible weight gain and to urge them to get back in touch with him quickly if it happens.
“Virologic suppression is the most important goal with ART, and the U.S. Department of Health and Human Services currently recommends INSTI-based ART for most PWH [people with HIV],” wrote Dr. Lake in April 2020. “I counsel all PWH initiating ART about the potential for weight gain, and I discuss their current diet and healthy lifestyle habits. I explain to patients that we will monitor their weight, and if weight gain seems more than either of us are comfortable with then we will reassess. Only a small percentage of patients experience excessive weight gain after starting ART.” Dr. Lake also stressed that she had not yet begun to change the regimen a patient is on solely because of weight gain. “We do not know whether this weight gain is reversible,” she noted.
“I do not anticipate that a risk of weight gain at present will dictate a change in guidelines,” said Dr. Geretti. “Drugs such as dolutegravir and bictegravir are very effective, and they are unlikely to cause drug resistance. Further data on the mechanism of weight gain and the reversibility after a change of treatment will help refine drug selection in the near future,” she predicted.
“I consider weight gain when prescribing because my patients hear about this. It’s a side effect that my patients really care about, and I don’t blame them,” said Lisa Hightow-Weidman, MD, a professor and HIV specialist at the University of North Carolina at Chapel Hill, during an on-line educational session. “If you don’t discuss it with a patient and then weight gain happens and the patient finds out [the known risk from their treatment] they may have an issue,” she noted. But weight gain is not a reason to avoid these drugs. “They are great medications in many ways, with once-daily regimens and few side effects.”
Weight gain during pregnancy a special concern
An additional analysis of data from ADVANCE presented at the conference highlighted what the observed weight gain on ART could mean for women who become pregnant while on treatment. Based on a systematic literature review, the ADVANCE investigators calculated the relative risk for six obesity-related pregnancy complications, compared with nonobese women: preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, postpartum hemorrhage, and caesarean delivery. Based on the obesity changes among women on their assigned ART in ADVANCE, the researchers calculated the predicted incidence of these six complications. The analysis showed that for every 1,000 women, those on TAG-DTG-FTC would have an excess of 53 obesity-related pregnancy complications, those on TDF-DTG-FTC would develop 28 excess pregnancy complications, and those on TDG-EFV-FTC would have four excess complications, reported Dr. Hill at the International AIDS conference.
The researchers also ran a similar simulation for the incidence of neonatal complications that could result when mothers are obese because of their ART. The six neonatal complications included in this analysis were small for gestational age, large for gestational age, macrosomia, neonatal death, stillbirth, and neural tube defects. Based on the excess rate of incident obesity, they calculated that for every 1,000 pregnancies women on TAD-DTG-FTC would have 24 additional infants born with one of these complications, women on TDF-DTG-FTC would have an excess of 13 of these events, and women on TDG-EFV-FTC would have an excess of three such obesity-related neonatal complications, Dr. Hill said.
Sorting out the drugs
Results from several additional studies reported at the conference have started trying to discern exactly which ART drugs and regimens pose the greatest weight gain risk and which have the least risk while retaining high efficacy and resistance barriers.
Further evidence implicating any type of ART as a driver of increased weight came from a review of 8,256 adults infected with HIV and members of the Kaiser Permanente health system in three U.S. regions during 2000-2016. Researchers matched these cases using several demographic factors with just under 130,000 members without HIV. Those infected by HIV had half the prevalence of obesity as the matched controls at baseline. During 12 years of follow-up, those infected with HIV had a threefold higher rate of weight gain than those who were uninfected. Annual weight gain averaged 0.06 kg/year among the uninfected people and 0.22 kg/year among those infected with HIV, a statistically significant difference that was consistent regardless of whether people started the study at a normal body mass index, overweight, or obese, reported Michael J. Silverberg, PhD, an epidemiologist with Kaiser Permanente in Oakland, Calif.
Another study tried to focus on the weight gain impact when patients on three-drug ART regimens changed from taking TDF to TAF. This analysis used data collected in the OPERA (Observational Pharmaco-Epidemiology Research & Analysis) longitudinal cohort of about 115,000 U.S. PWH. The observational cohort included nearly 7,000 patients who made a TDF-to-TAF switch, including 3,288 patients who maintained treatment during this switch with an INSTI, 1,454 who maintained a background regimen based on a NNRTI, 1,430 patients who also switched from an INSTI to a different drug, and 747 patients maintained on a boosted dose of a protease inhibitor. All patients were well controlled on their baseline regimen, with at least two consecutive measures showing undetectable viral load.
Patients who maintained their background regimens while changing from TDF to TAF had a 2.0-2.6 kg increase in weight during the 9 months immediately following their switch to TAF, reported Patrick Mallon, MB, a professor of microbial diseases at University College Dublin. Among the patients who both switched to TAF and also switched to treatment with an INSTI, weight gain during the 9 months after the switch averaged 2.6-4.5 kg, depending on which INSTI was started. Patients who switched to treatment with elvitegravir/cobicistat (an INSTI plus a boosting agent) averaged a gain of 2.6 kg during 9 months, those who switched to DTG averaged a 3.1-kg gain, and those who switched to BTG averaged a 4.6-kg increase, Dr. Mallon reported at the conference.
These findings “give us a good sense that the weight gain is real. This is not just overeating or not exercising, but weight changes coincidental with a change in HIV treatment,” commented David Wohl, MD, professor of medicine and site leader of the HIV Prevention and Treatment Clinical Trials Unit at the University of North Carolina at Chapel Hill, during an online educational session.
Contrary to this evidence suggesting a consistent uptick in weight when patients start TAF treatment was a recent report on 629 HIV patients randomized to treatment with TAF-BTG-FTC or abacavir (an NRTI, Ziagen)–DTG-3TC, which found similar weight gains between these two regimens after 144 weeks on treatment (Lancet HIV. 2020 Jun;7[6]:e389-400). This finding had the effect of “strengthening the argument that TAF is simply an innocent bystander” and does not play a central role in weight gain, and supporting the notion that the alternative tenofovir formulation, TDF, differs from TAF by promoting weight loss, Dr. Venter and Dr. Hill suggested in their commentary that accompanied this report.
The new findings from Dr. Mallon raise “serious questions about the way we have moved to TAF as a replacement for TDF, especially because the benefits [from TAF] are for a small subgroup – patients with renal disease or osteoporosis,” Dr. Venter said in an interview. “The question is, will we see weight gain like this” if TAF was combined with a non-INSTI drug? he wondered.
While some study results have suggested a mitigating effect from TDF on weight gain, that wasn’t the case in the AFRICOS (African Cohort Study) study of 1,954 PWH who started treatment with TDF-DTG-FTC (742 patients) or a different three-drug regimen. After a median of 225 days on treatment, those who started on TDF-DTG-FTC had an adjusted, 85% higher rate of developing a high body mass index, compared with patients on a different ART regimen, Julie Ake, MD, reported in a talk at the conference. Her conclusion focused on the possible involvement of DTG: “Consistent with previous reports, dolutegravir was significantly associated with an increased risk of developing high body mass index,” said Dr. Ake, director of the U.S. Military HIV Research Program in Bethesda, Md. and leader of AFRICOS.
A potential workaround to some drugs that cause excessive the weight gain is to just not use them. That was part of the rationale for the TANGO study, which took 741 HIV-infected patients with successful viral suppression on a regimen of TAF-FTC plus one or two additional agents and switched half of them to a TAF-less, two-drug regimen of DTG-FTC. This open-label study’s primary endpoint was noninferiority for viral suppression of the DTG-FTC regimen, compared with patients who stayed on their starting regimen, and the results proved that DTG-FTC was just as effective over 48 weeks for this outcome (Clin Infect Dis. 2020 Jan 6. doi: 10.1093/cid/ciz1243).
At the conference, TANGO’s lead investigator, Jean van Wyk, MD, reported the weight and metabolic effects of the switch. The results showed a similar and small weight gain (on average less than 1 kg) during 48 week follow-up regardless of whether patients remained on their baseline, TAF-containing regimen or switched to DTG-FTC, said Dr. van Wyk, global medical lead for HIV treatment at Viiv Healthcare, the company that markets DTG. About three-quarters of patients in both arms received “boosted” dosages of their drugs, and in this subgroup, patients on DTG-FTC showed statistically significant benefits in several lipid levels, fasting glucose level, and in their degree of insulin resistance. Dr. van Wyk said. These between-group differences were not statistically significant among the “unboosted” patients, and the results failed to show a significant between-group difference in the incidence of metabolic syndrome.
Dr. Venter called these results “exciting,” and noted that he already uses the DTG-FTC two-drug combination “a lot” to treat PWH and renal disease.
A second alternative regimen showcased in a talk at the conference used the three-drug regimen of TDF-FTC plus the NNRTI, DOR (doravirine, Pifeltro). The DRIVE-SHIFT trial enrolled 670 HIV patients with successfully suppressed viral load on conventional regimens who were either switched to TDF-DOR-FTC or maintained on their baseline treatment. After 48 weeks, results confirmed the primary efficacy endpoint of noninferiority for maintenance of suppression with the investigational regimen (J Acquir Immune Defic Syndr. 2019 Aug;81[4]:463-72).
A post-hoc analysis looked at weight changes among these patients after as much as 144 weeks of follow-up. The results showed that patients switched to TDF-DOR-FTC had an average weight increase of 1.2-1.4 kg after more than 2 years on the new regimen, with fewer than 10% of patients having a 10% or greater weight gain with DOR, a “next-generation” NNRTI, reported Princy N. Kumar, MD, professor at Georgetown University and chief of infectious diseases at MedStar Georgetown University Hospital in Washington. “Weight gain was minimal, even over the long term,” she noted.
The tested DOR-based regimen also looks “very exciting,” but the populations it’s been tested have also been largely limited to White men, and limited data exist about the regimen’s performance in pregnant women, commented Dr. Venter. The DRIVE-SHIRT patient cohort was about 85% men, and about three-quarters White.
More weight data needed
HIV-treatment researchers and clinicians seem agreed that weight gain and other metabolic effects from HIV treatment need more assessment and evidence because current data, while suggestive, is also inconclusive.
“Clinical trials are desperately needed to understand the mechanisms of and potential therapeutic options for excessive weight gain on ART,” wrote Dr. Lake in her commentary in April. “While more research is needed,” the new data reported at the virtual International AIDS conference “get us closer to understanding the effects of integrase inhibitors and TAF on weight and the potential metabolic consequences,” she commented as chair of the conference session where these reports occurred.
“Further data on the mechanism of weight gain and its reversibility after a change of treatment will help refine drug selection in the near future,” predicted Dr. Geretti.
“It’s hard to understand physiologically how drugs from such different classes all seem to have weight effects; it’s maddening,” said Dr. Venter. “We need decent studies in all patient populations. That will now be the priority,” he declared. “Patients shouldn’t have to choose” between drugs that most effectively control their HIV infection and drugs that don’t pose a risk for weight gain or metabolic derangements. PWH “should not have to face obesity as their new epidemic,” he wrote with Dr. Hill.
ADVANCE was funded in part by Viiv, the company that markets dolutegravir (Tivicay), and received drugs supplied by Gilead and Viiv. TANGO was sponsored by Viiv. DRIVE-SHIFT was funded by Merck, the company that markets doravirine (Pifeltro). Dr. Lake, Dr. Sokhela, Dr. Ake, and Dr. Kumar had no disclosures, Dr. Venter has received personal fees from Adcock Ingraham, Aspen Healthcare, Johnson and Johnson, Merck, Mylan, Roche, and Viiv. Dr. Hill has received payments from Merck. Dr. Geretti has received honoraria and research funding from Gilead, Jansse, Roche, and Viiv. Dr. Taiwo has had financial relationships with Gilead, Janssen, and Viiv. Dr. Hightow-Weidman has received honoraria from Gilead and Jansse. Dr. Wohl has been a consultant to Gilead, Johnson and Johnson, and Merck. Dr. Silverberg received research funding from Gilead. Dr. Mallon has been an advisor to and speaker on behalf of Bristol-Myers Squibb, Cilag, Gilead, Jansse, Merck Sharp & Dohme, and Viiv. Dr. van Wyk is a Viiv employee.
People living with HIV who put on extra pounds and develop metabolic syndrome or related disorders linked in part to certain antiretroviral agents remain a concern today, even as the drugs used to suppress HIV infection have evolved over the decades.
Linkage of HIV treatment with lipodystrophy and insulin resistance or diabetes began in the 1990s with protease inhibitors (Clin Infect Dis. 2000 Jun;30[suppl 2]:s135-42). Several reports over the years also tied any form of effective antiretroviral therapy to weight gain in HIV patients (Antivir Ther. 2012;17[7]:1281-9). More recently, reports have rattled the HIV-treatment community by associating alarmingly high levels of weight gain with a useful and relatively new drug, tenofovir alafenamide fumarate (TAF) – a nucleoside reverse transcriptase inhibitor (NRTI) approved for use in the United States in late 2016, as well as certain agents from an entirely different antiretroviral therapy (ART) class, the integrase strand transfer inhibitors (INSTIs). Both TAF and the INSTIs have come to play major roles in the HIV-treatment landscape, despite relevant and concerning recent weight gain observations with these drugs, such as in a 2019 meta-analysis of eight trials with 5,680 treatment-naive patients who started ART during 2003-2015 (Clin Infect Dis. 2019 Oct 14;doi: 10.1093/cid/ciz999).
“Weight gain is clearly seen in studies of dolutegravir [DTG] or bictegravir [BTG] with TAF,” wrote W.D. Francois Venter, PhD and Andrew Hill, PhD in a recent published commentary on the topic (Lancet HIV. 2020 Jun 1;7[6]:e389-400). Both DTG and BTG are INSTI class members.
“Excessive weight gain, defined as more than 10% over baseline, has recently been observed among people with HIV initiating or switching to regimens incorporating TAF, an INSTI, or both, particularly DTG,” wrote Jordan E. Lake, MD, an HIV specialist at the University of Texas Health Science Center at Houston, in a recent commentary posted online. Women and Black patients “are at even greater risk for excessive weight gain,” Dr. Lake added.
“In recent times, it has emerged that weight gain is more pronounced with the integrase inhibitor class of agents, especially dolutegravir and bictegravir, the so-called second-generation” INSTIs, said Anna Maria Geretti, MD, a professor of clinical infection, microbiology, and immunology at the University of Liverpool, England. ”The effect is more pronounced in women and people of non-White ethnicity, and is of concern because of the associated potential risk of metabolic syndrome, cardiovascular disease, etc.,” Dr. Geretti said in an interview.
The unprecedented susceptibility to weight gain seen recently in non-White women may in part have resulted from the tendency of many earlier treatment trials to have cohorts comprised predominantly of White men, Dr. Venter noted in an interview.
Alarming weight gains reported
Perhaps the most eye-popping example of the potential for weight gain with the combination of TAF with an INSTI came in a recent report from the ADVANCE trial, a randomized, head-to-head comparison of three regimens in 1,053 HIV patients in South Africa. After 144 weeks on a regimen of TAF (Vemlidy), DTG (Tivicay), and FTC (emtricitabine, Emtriva), another NRTI, women gained an averaged of more than 12 kg, compared with their baseline weight, significantly more than in two comparator groups, Simiso Sokhela, MB, reported at the virtual meeting of the International AIDS conference. The women in ADVANCE on the TAF-DTG-FTC regimen also had an 11% rate of incident metabolic syndrome during their first 96 weeks on treatment, compared with rates of 8% among patients on a different form of tenofovir, tenofovir disoproxil fumarate (TDF), along with DTG-FTC, and 5% among those on TDF–EFV (efavirenz, Sustiva)–FTC said Dr. Sokhela, an HIV researcher at Ezintsha, a division of the University of the Witwatersrand in Johannesburg, South Africa.
“We believe that these results support the World Health Organization guidelines that reserve TAF for only patients with osteoporosis or impaired renal function,” Dr. Sokhela said during a press briefing at the conference. The WHO guidelines list the first-line regimen as TDF-DTG-3TC (lamivudine; Epivir) or FTC. “The risk for becoming obese continued to increase after 96 weeks” of chronic use of these drugs, she added.
“All regimens are now brilliant at viral control. Finding the ones that don’t make patients obese or have other long-term side effects is now the priority,” noted Dr. Venter, a professor and HIV researcher at University of the Witwatersrand, head of Ezintsha, and lead investigator of ADVANCE. Clinicians and researchers have recently thought that combining TAF and an INSTI plus FTC or a similar NRTI “would be the ultimate regimen to replace the nonnucleoside reverse transcriptase inhibitors (NNRTIs)” such as EFV, “but now we have a major headache” with unexpectedly high weight gains in some patients, Dr. Venter said.
Weight gains “over 10 kg are unlikely to be acceptable in any circumstances, especially when starting body mass index is already borderline overweight,” wrote Dr. Venter along with Dr. Hill in their commentary. Until recently, many clinicians chalked up weight gain on newly begun ART as a manifestation of the patient’s “return-to-health,” but this interpretation “gives a positive spin to a potentially serious and common side effect,” they added.
More from ADVANCE
The primary efficacy endpoint of ADVANCE was suppression of viral load to less than 50 RNA copies/mL after 48 weeks on treatment, and the result showed that the TAF-DTG-FTC regimen and the TDF-DTG-FTC regimen were each noninferior to the control regimen of TDF-EFV-FTC (New Engl J Med. 2019 Aug 29;381[9]:803-15). Virtually all of the enrolled patients were Black, and 59% were women. Planned follow-up of all patients ran for 96 weeks. After 48 weeks, weight gain among the women averaged 6.4 kg, 3.2 kg, and 1.7 kg in the TAF-DTG, TDF-DTG, and TDF-EFV arms respectively. After 96 weeks, the average weight gains among women were 8.2 kg, 4.6 kg, and 3.2 kg, respectively, in new results reported by Dr. Sokhela at the IAC. Follow-up to 144 weeks was partial and included about a quarter of the enrolled women, with gains averaging 12.3 kg, 7.4 kg, and 5.5 kg respectively. The pattern of weight gain among men tracked the pattern in women, but the magnitude of gain was less. Among men followed for 144 weeks, average gain among those on TAF-DTG-FTC was 7.2 kg, the largest gain seen among men on any regimen and at any follow-up time in the study.
Dr. Sokhela also reported data on body composition analyses, which showed that the weight gains were largely in fat rather than lean tissue, fat accumulation was significantly greater in women than men, and that in both sexes fat accumulated roughly equally in the trunk and on limbs.
An additional analysis looked at the incidence of new-onset obesity among the women who had a normal body mass index at baseline. After 96 weeks, incident obesity occurred in 14% of women on the TAG-DTG-FTC regimen, 8% on TDF-DTG-FTC, and in 2% of women maintained on TDF-EFV-FTC, said Dr. Hill in a separate report at the conference.
Weight starts to weigh in
“I am very mindful of weight gain potential, and I talk to patients about it. It doesn’t determine what regimen I choose for a patient” right now, “but it’s only a matter of time before it starts influencing what we do, particularly if we can achieve efficacy with fewer drugs,” commented Babafemi O. Taiwo, MD, professor of medicine and chief of infectious diseases at Northwestern University in Chicago. “I’ve had some patients show up with a weight gain of 20 kg, and that shouldn’t happen,” he said during a recent online educational session. Dr. Taiwo said his recent practice has been to warn patients about possible weight gain and to urge them to get back in touch with him quickly if it happens.
“Virologic suppression is the most important goal with ART, and the U.S. Department of Health and Human Services currently recommends INSTI-based ART for most PWH [people with HIV],” wrote Dr. Lake in April 2020. “I counsel all PWH initiating ART about the potential for weight gain, and I discuss their current diet and healthy lifestyle habits. I explain to patients that we will monitor their weight, and if weight gain seems more than either of us are comfortable with then we will reassess. Only a small percentage of patients experience excessive weight gain after starting ART.” Dr. Lake also stressed that she had not yet begun to change the regimen a patient is on solely because of weight gain. “We do not know whether this weight gain is reversible,” she noted.
“I do not anticipate that a risk of weight gain at present will dictate a change in guidelines,” said Dr. Geretti. “Drugs such as dolutegravir and bictegravir are very effective, and they are unlikely to cause drug resistance. Further data on the mechanism of weight gain and the reversibility after a change of treatment will help refine drug selection in the near future,” she predicted.
“I consider weight gain when prescribing because my patients hear about this. It’s a side effect that my patients really care about, and I don’t blame them,” said Lisa Hightow-Weidman, MD, a professor and HIV specialist at the University of North Carolina at Chapel Hill, during an on-line educational session. “If you don’t discuss it with a patient and then weight gain happens and the patient finds out [the known risk from their treatment] they may have an issue,” she noted. But weight gain is not a reason to avoid these drugs. “They are great medications in many ways, with once-daily regimens and few side effects.”
Weight gain during pregnancy a special concern
An additional analysis of data from ADVANCE presented at the conference highlighted what the observed weight gain on ART could mean for women who become pregnant while on treatment. Based on a systematic literature review, the ADVANCE investigators calculated the relative risk for six obesity-related pregnancy complications, compared with nonobese women: preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, postpartum hemorrhage, and caesarean delivery. Based on the obesity changes among women on their assigned ART in ADVANCE, the researchers calculated the predicted incidence of these six complications. The analysis showed that for every 1,000 women, those on TAG-DTG-FTC would have an excess of 53 obesity-related pregnancy complications, those on TDF-DTG-FTC would develop 28 excess pregnancy complications, and those on TDG-EFV-FTC would have four excess complications, reported Dr. Hill at the International AIDS conference.
The researchers also ran a similar simulation for the incidence of neonatal complications that could result when mothers are obese because of their ART. The six neonatal complications included in this analysis were small for gestational age, large for gestational age, macrosomia, neonatal death, stillbirth, and neural tube defects. Based on the excess rate of incident obesity, they calculated that for every 1,000 pregnancies women on TAD-DTG-FTC would have 24 additional infants born with one of these complications, women on TDF-DTG-FTC would have an excess of 13 of these events, and women on TDG-EFV-FTC would have an excess of three such obesity-related neonatal complications, Dr. Hill said.
Sorting out the drugs
Results from several additional studies reported at the conference have started trying to discern exactly which ART drugs and regimens pose the greatest weight gain risk and which have the least risk while retaining high efficacy and resistance barriers.
Further evidence implicating any type of ART as a driver of increased weight came from a review of 8,256 adults infected with HIV and members of the Kaiser Permanente health system in three U.S. regions during 2000-2016. Researchers matched these cases using several demographic factors with just under 130,000 members without HIV. Those infected by HIV had half the prevalence of obesity as the matched controls at baseline. During 12 years of follow-up, those infected with HIV had a threefold higher rate of weight gain than those who were uninfected. Annual weight gain averaged 0.06 kg/year among the uninfected people and 0.22 kg/year among those infected with HIV, a statistically significant difference that was consistent regardless of whether people started the study at a normal body mass index, overweight, or obese, reported Michael J. Silverberg, PhD, an epidemiologist with Kaiser Permanente in Oakland, Calif.
Another study tried to focus on the weight gain impact when patients on three-drug ART regimens changed from taking TDF to TAF. This analysis used data collected in the OPERA (Observational Pharmaco-Epidemiology Research & Analysis) longitudinal cohort of about 115,000 U.S. PWH. The observational cohort included nearly 7,000 patients who made a TDF-to-TAF switch, including 3,288 patients who maintained treatment during this switch with an INSTI, 1,454 who maintained a background regimen based on a NNRTI, 1,430 patients who also switched from an INSTI to a different drug, and 747 patients maintained on a boosted dose of a protease inhibitor. All patients were well controlled on their baseline regimen, with at least two consecutive measures showing undetectable viral load.
Patients who maintained their background regimens while changing from TDF to TAF had a 2.0-2.6 kg increase in weight during the 9 months immediately following their switch to TAF, reported Patrick Mallon, MB, a professor of microbial diseases at University College Dublin. Among the patients who both switched to TAF and also switched to treatment with an INSTI, weight gain during the 9 months after the switch averaged 2.6-4.5 kg, depending on which INSTI was started. Patients who switched to treatment with elvitegravir/cobicistat (an INSTI plus a boosting agent) averaged a gain of 2.6 kg during 9 months, those who switched to DTG averaged a 3.1-kg gain, and those who switched to BTG averaged a 4.6-kg increase, Dr. Mallon reported at the conference.
These findings “give us a good sense that the weight gain is real. This is not just overeating or not exercising, but weight changes coincidental with a change in HIV treatment,” commented David Wohl, MD, professor of medicine and site leader of the HIV Prevention and Treatment Clinical Trials Unit at the University of North Carolina at Chapel Hill, during an online educational session.
Contrary to this evidence suggesting a consistent uptick in weight when patients start TAF treatment was a recent report on 629 HIV patients randomized to treatment with TAF-BTG-FTC or abacavir (an NRTI, Ziagen)–DTG-3TC, which found similar weight gains between these two regimens after 144 weeks on treatment (Lancet HIV. 2020 Jun;7[6]:e389-400). This finding had the effect of “strengthening the argument that TAF is simply an innocent bystander” and does not play a central role in weight gain, and supporting the notion that the alternative tenofovir formulation, TDF, differs from TAF by promoting weight loss, Dr. Venter and Dr. Hill suggested in their commentary that accompanied this report.
The new findings from Dr. Mallon raise “serious questions about the way we have moved to TAF as a replacement for TDF, especially because the benefits [from TAF] are for a small subgroup – patients with renal disease or osteoporosis,” Dr. Venter said in an interview. “The question is, will we see weight gain like this” if TAF was combined with a non-INSTI drug? he wondered.
While some study results have suggested a mitigating effect from TDF on weight gain, that wasn’t the case in the AFRICOS (African Cohort Study) study of 1,954 PWH who started treatment with TDF-DTG-FTC (742 patients) or a different three-drug regimen. After a median of 225 days on treatment, those who started on TDF-DTG-FTC had an adjusted, 85% higher rate of developing a high body mass index, compared with patients on a different ART regimen, Julie Ake, MD, reported in a talk at the conference. Her conclusion focused on the possible involvement of DTG: “Consistent with previous reports, dolutegravir was significantly associated with an increased risk of developing high body mass index,” said Dr. Ake, director of the U.S. Military HIV Research Program in Bethesda, Md. and leader of AFRICOS.
A potential workaround to some drugs that cause excessive the weight gain is to just not use them. That was part of the rationale for the TANGO study, which took 741 HIV-infected patients with successful viral suppression on a regimen of TAF-FTC plus one or two additional agents and switched half of them to a TAF-less, two-drug regimen of DTG-FTC. This open-label study’s primary endpoint was noninferiority for viral suppression of the DTG-FTC regimen, compared with patients who stayed on their starting regimen, and the results proved that DTG-FTC was just as effective over 48 weeks for this outcome (Clin Infect Dis. 2020 Jan 6. doi: 10.1093/cid/ciz1243).
At the conference, TANGO’s lead investigator, Jean van Wyk, MD, reported the weight and metabolic effects of the switch. The results showed a similar and small weight gain (on average less than 1 kg) during 48 week follow-up regardless of whether patients remained on their baseline, TAF-containing regimen or switched to DTG-FTC, said Dr. van Wyk, global medical lead for HIV treatment at Viiv Healthcare, the company that markets DTG. About three-quarters of patients in both arms received “boosted” dosages of their drugs, and in this subgroup, patients on DTG-FTC showed statistically significant benefits in several lipid levels, fasting glucose level, and in their degree of insulin resistance. Dr. van Wyk said. These between-group differences were not statistically significant among the “unboosted” patients, and the results failed to show a significant between-group difference in the incidence of metabolic syndrome.
Dr. Venter called these results “exciting,” and noted that he already uses the DTG-FTC two-drug combination “a lot” to treat PWH and renal disease.
A second alternative regimen showcased in a talk at the conference used the three-drug regimen of TDF-FTC plus the NNRTI, DOR (doravirine, Pifeltro). The DRIVE-SHIFT trial enrolled 670 HIV patients with successfully suppressed viral load on conventional regimens who were either switched to TDF-DOR-FTC or maintained on their baseline treatment. After 48 weeks, results confirmed the primary efficacy endpoint of noninferiority for maintenance of suppression with the investigational regimen (J Acquir Immune Defic Syndr. 2019 Aug;81[4]:463-72).
A post-hoc analysis looked at weight changes among these patients after as much as 144 weeks of follow-up. The results showed that patients switched to TDF-DOR-FTC had an average weight increase of 1.2-1.4 kg after more than 2 years on the new regimen, with fewer than 10% of patients having a 10% or greater weight gain with DOR, a “next-generation” NNRTI, reported Princy N. Kumar, MD, professor at Georgetown University and chief of infectious diseases at MedStar Georgetown University Hospital in Washington. “Weight gain was minimal, even over the long term,” she noted.
The tested DOR-based regimen also looks “very exciting,” but the populations it’s been tested have also been largely limited to White men, and limited data exist about the regimen’s performance in pregnant women, commented Dr. Venter. The DRIVE-SHIRT patient cohort was about 85% men, and about three-quarters White.
More weight data needed
HIV-treatment researchers and clinicians seem agreed that weight gain and other metabolic effects from HIV treatment need more assessment and evidence because current data, while suggestive, is also inconclusive.
“Clinical trials are desperately needed to understand the mechanisms of and potential therapeutic options for excessive weight gain on ART,” wrote Dr. Lake in her commentary in April. “While more research is needed,” the new data reported at the virtual International AIDS conference “get us closer to understanding the effects of integrase inhibitors and TAF on weight and the potential metabolic consequences,” she commented as chair of the conference session where these reports occurred.
“Further data on the mechanism of weight gain and its reversibility after a change of treatment will help refine drug selection in the near future,” predicted Dr. Geretti.
“It’s hard to understand physiologically how drugs from such different classes all seem to have weight effects; it’s maddening,” said Dr. Venter. “We need decent studies in all patient populations. That will now be the priority,” he declared. “Patients shouldn’t have to choose” between drugs that most effectively control their HIV infection and drugs that don’t pose a risk for weight gain or metabolic derangements. PWH “should not have to face obesity as their new epidemic,” he wrote with Dr. Hill.
ADVANCE was funded in part by Viiv, the company that markets dolutegravir (Tivicay), and received drugs supplied by Gilead and Viiv. TANGO was sponsored by Viiv. DRIVE-SHIFT was funded by Merck, the company that markets doravirine (Pifeltro). Dr. Lake, Dr. Sokhela, Dr. Ake, and Dr. Kumar had no disclosures, Dr. Venter has received personal fees from Adcock Ingraham, Aspen Healthcare, Johnson and Johnson, Merck, Mylan, Roche, and Viiv. Dr. Hill has received payments from Merck. Dr. Geretti has received honoraria and research funding from Gilead, Jansse, Roche, and Viiv. Dr. Taiwo has had financial relationships with Gilead, Janssen, and Viiv. Dr. Hightow-Weidman has received honoraria from Gilead and Jansse. Dr. Wohl has been a consultant to Gilead, Johnson and Johnson, and Merck. Dr. Silverberg received research funding from Gilead. Dr. Mallon has been an advisor to and speaker on behalf of Bristol-Myers Squibb, Cilag, Gilead, Jansse, Merck Sharp & Dohme, and Viiv. Dr. van Wyk is a Viiv employee.
FROM AIDS 2020
How high a priority is bariatric surgery during COVID-19?
The ASMBS statement, “Safer Through Surgery,” was published online in Surgery for Obesity and Related Diseases by the ASMBS executive committee.
It is a reaction to the fact that some U.S. states have placed metabolic and bariatric surgery in the same low-priority category as cosmetic surgery as examples of “elective” procedures that should be among the last to be restarted when pandemic restrictions are eased.
Rather, ASMBS argues, although obesity surgery must be postponed along with other nonemergency procedures when surges in the novel coronavirus make them unsafe, such operations should be resumed as soon as possible along with other medically necessary procedures.
“Metabolic and bariatric surgery is NOT elective. Metabolic and bariatric surgery is medically necessary and the best treatment for those with the life-threatening and life-limiting disease of severe obesity,” the statement says.
And obesity itself is a major risk factor for worse COVID-19 outcomes, ASMBS President Matt Hutter, MD, told Medscape Medical News, noting that individuals with obesity are “more likely to be in [intensive care units].”
“Mortality rates are higher, even in young patients. And [obesity] ... is associated with other comorbidities including diabetes and heart disease...We know the clock is ticking for some folks. For those with early diabetes, the sooner the [bariatric] surgery the more likely it is [for diabetes] to go into remission.”
Because the pandemic may be around for a while, “If we can make people [with obesity] safer ... because they’ve had surgery ... they may be better off,” should they get COVID-19 later, he pointed out.
Hutter noted that the ASMBS recorded a series of webinars, archived on the society’s website, with panels discussing in-depth issues to consider in prioritizing patients when restarting metabolic and bariatric surgery.
There are some differences of opinion, such as whether the sickest patients should be the first to have the surgeries upon reopening, or whether those individuals might be worse off if they contract COVID-19 in the perioperative setting.
“I don’t think there’s a right or wrong answer, but I think we have to figure out what’s right for the individual patient, considering their specific risks of having versus not having surgery, of waiting 1 month, 2 months, or 6 months. One thing we do know is that obesity is a significant disease.”
‘Before, during, and after COVID, obesity itself remains an epidemic’
Asked to comment on the ASMBS stance, Obesity Society president Lee M. Kaplan, MD, PhD, sent Medscape Medical News a statement.
“We do not fully understand which aspects of obesity pathophysiology ... are most responsible for the adverse COVID-19 outcomes, nor do we know the degree to which reduced access to care, social isolation, and other social and environmental determinants of health disproportionately affect COVID-19 patients with obesity,” he noted.
“At this early stage, we have not yet determined the impact of weight loss and various types of antiobesity therapies on these risks.”
Nonetheless, Kaplan said, “the extended COVID-19 pandemic underscores the importance of increasing, not diminishing, our commitment to understanding and treating obesity, using all available, evidence-based therapies, including lifestyle modification, antiobesity medications, bariatric surgery, and combinations thereof.”
As all health care delivery is being reorganized around the pandemic, Kaplan added: “Rethinking and changing our approach to obesity needs to be a central feature of this process.
“Before, during, and after COVID, obesity itself remains an epidemic. Its high global prevalence, increasing severity, and profound impact on all aspects of health and disease require that it be addressed more universally within the health care system, with the same commitment afforded to other chronic diseases.”
Obesity treatment isn’t generally considered an emergency, he noted, “because obesity is a chronic disease, whose adverse health effects often accumulate slowly and insidiously. Its generally slow progression allows for careful and coordinated care planning, and advanced scheduling of therapeutic interventions, including surgery. These characteristics, however, should not lead us to infer that treating obesity itself is optional.”
Hutter has reported receiving honoraria from Ethicon and Medtronic, and is a consultant for Vicarious Surgical and Sigilon Therapeutics. Kaplan has reported consulting for Boehringer Ingelheim, Fractyl, Gelesis, GI Dynamics, Johnson & Johnson, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, the National Institutes of Health, and the Department of State.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity.
This article first appeared on Medscape.com.
The ASMBS statement, “Safer Through Surgery,” was published online in Surgery for Obesity and Related Diseases by the ASMBS executive committee.
It is a reaction to the fact that some U.S. states have placed metabolic and bariatric surgery in the same low-priority category as cosmetic surgery as examples of “elective” procedures that should be among the last to be restarted when pandemic restrictions are eased.
Rather, ASMBS argues, although obesity surgery must be postponed along with other nonemergency procedures when surges in the novel coronavirus make them unsafe, such operations should be resumed as soon as possible along with other medically necessary procedures.
“Metabolic and bariatric surgery is NOT elective. Metabolic and bariatric surgery is medically necessary and the best treatment for those with the life-threatening and life-limiting disease of severe obesity,” the statement says.
And obesity itself is a major risk factor for worse COVID-19 outcomes, ASMBS President Matt Hutter, MD, told Medscape Medical News, noting that individuals with obesity are “more likely to be in [intensive care units].”
“Mortality rates are higher, even in young patients. And [obesity] ... is associated with other comorbidities including diabetes and heart disease...We know the clock is ticking for some folks. For those with early diabetes, the sooner the [bariatric] surgery the more likely it is [for diabetes] to go into remission.”
Because the pandemic may be around for a while, “If we can make people [with obesity] safer ... because they’ve had surgery ... they may be better off,” should they get COVID-19 later, he pointed out.
Hutter noted that the ASMBS recorded a series of webinars, archived on the society’s website, with panels discussing in-depth issues to consider in prioritizing patients when restarting metabolic and bariatric surgery.
There are some differences of opinion, such as whether the sickest patients should be the first to have the surgeries upon reopening, or whether those individuals might be worse off if they contract COVID-19 in the perioperative setting.
“I don’t think there’s a right or wrong answer, but I think we have to figure out what’s right for the individual patient, considering their specific risks of having versus not having surgery, of waiting 1 month, 2 months, or 6 months. One thing we do know is that obesity is a significant disease.”
‘Before, during, and after COVID, obesity itself remains an epidemic’
Asked to comment on the ASMBS stance, Obesity Society president Lee M. Kaplan, MD, PhD, sent Medscape Medical News a statement.
“We do not fully understand which aspects of obesity pathophysiology ... are most responsible for the adverse COVID-19 outcomes, nor do we know the degree to which reduced access to care, social isolation, and other social and environmental determinants of health disproportionately affect COVID-19 patients with obesity,” he noted.
“At this early stage, we have not yet determined the impact of weight loss and various types of antiobesity therapies on these risks.”
Nonetheless, Kaplan said, “the extended COVID-19 pandemic underscores the importance of increasing, not diminishing, our commitment to understanding and treating obesity, using all available, evidence-based therapies, including lifestyle modification, antiobesity medications, bariatric surgery, and combinations thereof.”
As all health care delivery is being reorganized around the pandemic, Kaplan added: “Rethinking and changing our approach to obesity needs to be a central feature of this process.
“Before, during, and after COVID, obesity itself remains an epidemic. Its high global prevalence, increasing severity, and profound impact on all aspects of health and disease require that it be addressed more universally within the health care system, with the same commitment afforded to other chronic diseases.”
Obesity treatment isn’t generally considered an emergency, he noted, “because obesity is a chronic disease, whose adverse health effects often accumulate slowly and insidiously. Its generally slow progression allows for careful and coordinated care planning, and advanced scheduling of therapeutic interventions, including surgery. These characteristics, however, should not lead us to infer that treating obesity itself is optional.”
Hutter has reported receiving honoraria from Ethicon and Medtronic, and is a consultant for Vicarious Surgical and Sigilon Therapeutics. Kaplan has reported consulting for Boehringer Ingelheim, Fractyl, Gelesis, GI Dynamics, Johnson & Johnson, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, the National Institutes of Health, and the Department of State.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity.
This article first appeared on Medscape.com.
The ASMBS statement, “Safer Through Surgery,” was published online in Surgery for Obesity and Related Diseases by the ASMBS executive committee.
It is a reaction to the fact that some U.S. states have placed metabolic and bariatric surgery in the same low-priority category as cosmetic surgery as examples of “elective” procedures that should be among the last to be restarted when pandemic restrictions are eased.
Rather, ASMBS argues, although obesity surgery must be postponed along with other nonemergency procedures when surges in the novel coronavirus make them unsafe, such operations should be resumed as soon as possible along with other medically necessary procedures.
“Metabolic and bariatric surgery is NOT elective. Metabolic and bariatric surgery is medically necessary and the best treatment for those with the life-threatening and life-limiting disease of severe obesity,” the statement says.
And obesity itself is a major risk factor for worse COVID-19 outcomes, ASMBS President Matt Hutter, MD, told Medscape Medical News, noting that individuals with obesity are “more likely to be in [intensive care units].”
“Mortality rates are higher, even in young patients. And [obesity] ... is associated with other comorbidities including diabetes and heart disease...We know the clock is ticking for some folks. For those with early diabetes, the sooner the [bariatric] surgery the more likely it is [for diabetes] to go into remission.”
Because the pandemic may be around for a while, “If we can make people [with obesity] safer ... because they’ve had surgery ... they may be better off,” should they get COVID-19 later, he pointed out.
Hutter noted that the ASMBS recorded a series of webinars, archived on the society’s website, with panels discussing in-depth issues to consider in prioritizing patients when restarting metabolic and bariatric surgery.
There are some differences of opinion, such as whether the sickest patients should be the first to have the surgeries upon reopening, or whether those individuals might be worse off if they contract COVID-19 in the perioperative setting.
“I don’t think there’s a right or wrong answer, but I think we have to figure out what’s right for the individual patient, considering their specific risks of having versus not having surgery, of waiting 1 month, 2 months, or 6 months. One thing we do know is that obesity is a significant disease.”
‘Before, during, and after COVID, obesity itself remains an epidemic’
Asked to comment on the ASMBS stance, Obesity Society president Lee M. Kaplan, MD, PhD, sent Medscape Medical News a statement.
“We do not fully understand which aspects of obesity pathophysiology ... are most responsible for the adverse COVID-19 outcomes, nor do we know the degree to which reduced access to care, social isolation, and other social and environmental determinants of health disproportionately affect COVID-19 patients with obesity,” he noted.
“At this early stage, we have not yet determined the impact of weight loss and various types of antiobesity therapies on these risks.”
Nonetheless, Kaplan said, “the extended COVID-19 pandemic underscores the importance of increasing, not diminishing, our commitment to understanding and treating obesity, using all available, evidence-based therapies, including lifestyle modification, antiobesity medications, bariatric surgery, and combinations thereof.”
As all health care delivery is being reorganized around the pandemic, Kaplan added: “Rethinking and changing our approach to obesity needs to be a central feature of this process.
“Before, during, and after COVID, obesity itself remains an epidemic. Its high global prevalence, increasing severity, and profound impact on all aspects of health and disease require that it be addressed more universally within the health care system, with the same commitment afforded to other chronic diseases.”
Obesity treatment isn’t generally considered an emergency, he noted, “because obesity is a chronic disease, whose adverse health effects often accumulate slowly and insidiously. Its generally slow progression allows for careful and coordinated care planning, and advanced scheduling of therapeutic interventions, including surgery. These characteristics, however, should not lead us to infer that treating obesity itself is optional.”
Hutter has reported receiving honoraria from Ethicon and Medtronic, and is a consultant for Vicarious Surgical and Sigilon Therapeutics. Kaplan has reported consulting for Boehringer Ingelheim, Fractyl, Gelesis, GI Dynamics, Johnson & Johnson, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, the National Institutes of Health, and the Department of State.
The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity.
This article first appeared on Medscape.com.