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Weight-loss drug lorcaserin’s glycemic effects revealed
BERLIN – Lower rates of incident type 2 diabetes mellitus (T2DM) and improved glycemic control were two of the metabolic effects seen with the appetite-suppressant drug lorcaserin versus placebo on top of existing lifestyle management measures in a large-scale trial of more than 12,000 overweight or obese individuals with established cardiovascular disease or T2DM and other cardiovascular risk factors.
In the CAMELLIA-TIMI 61 trial, treatment with a twice-daily, 10-mg dose of lorcaserin for a median of 3.3 years was associated with a significant 19% reduction in the risk of incident T2DM in participants with prediabetes, compared with placebo (8.5% vs. 10.3%; hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .038). The reduction in the risk of incident T2DM was even greater (23%) in people without diabetes at baseline (6.7% lorcaserin vs. 8.4% placebo; HR, 0.77; 95% CI, 0.63-0.94; P = .012).
Furthermore, in patients with T2DM who had a mean baseline glycated hemoglobin (HbA1c) of 7%, an absolute 0.33% reduction was seen at 1 year between the lorcaserin and placebo groups, with more modest but still significant between-group reductions (–0.09% and –0.08%) in individuals with prediabetes or normoglycemia (all P less than .0001). When baseline HbA1c levels were higher in patients with T2DM (8%), greater net reductions (0.52%) versus placebo were seen (P less than .0001).
These were some of the metabolic findings, published online in the Lancet to coincide with their presentation at the annual meeting of the European Association for the Study of Diabetes, that add to those already released from the CAMELLIA-TIMI 61 trial on cardiovascular safety, lead author and TIMI (Thrombolysis in Myocardial Infarction) group investigator Erin A. Bohula May, MD, observed during a press conference.
The cardiovascular safety data were presented at the 2018 annual congress of the European Society for Cardiology in August and published in the New England Journal of Medicine. These showed no increase with lorcaserin versus placebo in the risk of achieving a major cardiovascular endpoint (MACE) of cardiovascular death, MI, or stroke (HR, 0.99; 95% CI, 0.85-1.14; P less than .001 for noninferiority). There was also no difference between groups in the cumulative incidence of MACE+, which included heart failure, hospitalization for unstable angina, and the need for coronary revascularization (HR, 0.97; 95% CI, 0.87-1.07; P = .55 for superiority).
“We know that weight loss can improve cardiovascular and glycemic risk factors, but it’s difficult to achieve and maintain, and weight-loss agents are guideline-recommended adjuncts to lifestyle modification,” said Dr. Bohula May, who is a cardiovascular medicine and critical care specialist at Brigham and Women’s Hospital in Boston.
“However, prior to this study no agent had convincingly demonstrated cardiovascular safety in a rigorous clinical outcomes study,” she said, noting that several agents, such as the now-withdrawn rimonabant (Acomplia/Zimulti) and sibutramine (Meridia), had been shown to precipitate cardiovascular or psychiatric events, which led the Food and Drug Administration to mandate that all weight-loss drugs be assessed for cardiovascular safety. Lorcaserin (Belviq) is a centrally acting 5-HT2C agonist that works by decreasing appetite and was approved by the FDA in 2012 but is not currently available in Europe.
Long-term data on the effects of weight-loss agents on glycemic parameters were limited, hence the remit of the CAMELLIA-TIMI 61 trial was to assess both the cardiovascular and metabolic safety of lorcaserin. The drug was used on a background of lifestyle modification in 6,000 obese or overweight individuals at high risk of cardiovascular events. A further 6,000 individuals received placebo.
“Lorcaserin induced and maintained weight loss across the glycemic categories,” said coauthor and TIMI group investigator Benjamin Scirica, MD, also of Brigham and Women’s Hospital, who presented the metabolic data during a scientific session at the EASD meeting. Specifically, there was a net weight loss beyond that seen with placebo of 2.6 kg, 2.8 kg, and 3.3 kg in individuals with T2DM, prediabetes, and normoglycemia, respectively.
“Roughly 40% of patients with lorcaserin achieved a 5% weight loss, and about 14%-18% achieved a 10% weight loss across the glycemic categories,” Dr. Scirica reported. The corresponding values for the placebo-treated patients were 17%-18% and 4%-7%.
Naveed Sattar, MD, the independent commentator for the trial, noted the weight-loss reduction seen “was modest in the context of this trial, but I think the important point was that it was sustained. Sustained weight loss is difficult, and it was sustained on top of lifestyle and on top of the other drugs, and that is important.”
However, Dr. Sattar, who is professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow (Scotland), also observed that “as night follows day, glycemic improvements follow weight loss.” So, did the glycemic parameters improve purely because of the weight loss? While there is some preclinical evidence that lorcaserin may have an effect outside of its weight-lowering effects, Dr. Sattar felt this was unlikely to be clinically significant in itself.
“Obesity is probably the biggest challenge we have in the medical profession. We’ve got excellent cholesterol-lowering, blood pressure–lowering, and diabetes drugs. Yet obesity and complications are rising worldwide” and “safe weight-loss drugs remain sparse,” Dr. Sattar said.
He suggested that lorcaserin may well have an adjunctive place in the current treatment paradigm, but that place is probably “down the line” after other measures with greater weight-reducing effects or proven cardiovascular benefits were used. Not only are lifestyle modification approaches improving, Dr. Sattar said, but there are also over-the-counter options such as orlistat (Xenical), metformin, sodium-glucose cotransporter 2 inhibitors, glucagonlike peptide receptor–1 agonists, and bariatric surgery that are likely to be used first.
“This is a fantastically well done trial, we needed it,” Dr. Sattar said. However, because there was modest weight loss and no real cardiovascular benefit (but also no cardiovascular safety concern) he called the results “a bust” saying that “we have to take them at face value for what they are.”
Dr. Sattar noted that his “gut feeling at the moment is that the clinical role for lorcaserin is probably, at best, a down-the-line adjunct in those who are still obese for additional weight reduction on top of other drugs and lifestyle modifications, particularly in those who are ‘super responders.’ ” This is so long as the safety signals remain strong and there are quality of life benefits, he added.
The study was designed by the TIMI Study Group in conjunction with the executive committee and the trial sponsor, Eisai. Dr. Bohula May and Dr. Scirica reported receiving grants from Eisai, during the conduct of the study. Dr. Sattar reported grant support from Boehringer Ingelheim, and being part of an advisory board or speaker’s bureau for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Novo Nordisk, and Sanofi.
SOURCES: Bohula May EA et al. Lancet. 2018 Oct 4. doi: 10.1016/S0140-6736(18)32328-6; Bohula May EA et al. N Engl J Med. 2018; 379:1107-17; Sattar N. EASD 2018, Session S33.
BERLIN – Lower rates of incident type 2 diabetes mellitus (T2DM) and improved glycemic control were two of the metabolic effects seen with the appetite-suppressant drug lorcaserin versus placebo on top of existing lifestyle management measures in a large-scale trial of more than 12,000 overweight or obese individuals with established cardiovascular disease or T2DM and other cardiovascular risk factors.
In the CAMELLIA-TIMI 61 trial, treatment with a twice-daily, 10-mg dose of lorcaserin for a median of 3.3 years was associated with a significant 19% reduction in the risk of incident T2DM in participants with prediabetes, compared with placebo (8.5% vs. 10.3%; hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .038). The reduction in the risk of incident T2DM was even greater (23%) in people without diabetes at baseline (6.7% lorcaserin vs. 8.4% placebo; HR, 0.77; 95% CI, 0.63-0.94; P = .012).
Furthermore, in patients with T2DM who had a mean baseline glycated hemoglobin (HbA1c) of 7%, an absolute 0.33% reduction was seen at 1 year between the lorcaserin and placebo groups, with more modest but still significant between-group reductions (–0.09% and –0.08%) in individuals with prediabetes or normoglycemia (all P less than .0001). When baseline HbA1c levels were higher in patients with T2DM (8%), greater net reductions (0.52%) versus placebo were seen (P less than .0001).
These were some of the metabolic findings, published online in the Lancet to coincide with their presentation at the annual meeting of the European Association for the Study of Diabetes, that add to those already released from the CAMELLIA-TIMI 61 trial on cardiovascular safety, lead author and TIMI (Thrombolysis in Myocardial Infarction) group investigator Erin A. Bohula May, MD, observed during a press conference.
The cardiovascular safety data were presented at the 2018 annual congress of the European Society for Cardiology in August and published in the New England Journal of Medicine. These showed no increase with lorcaserin versus placebo in the risk of achieving a major cardiovascular endpoint (MACE) of cardiovascular death, MI, or stroke (HR, 0.99; 95% CI, 0.85-1.14; P less than .001 for noninferiority). There was also no difference between groups in the cumulative incidence of MACE+, which included heart failure, hospitalization for unstable angina, and the need for coronary revascularization (HR, 0.97; 95% CI, 0.87-1.07; P = .55 for superiority).
“We know that weight loss can improve cardiovascular and glycemic risk factors, but it’s difficult to achieve and maintain, and weight-loss agents are guideline-recommended adjuncts to lifestyle modification,” said Dr. Bohula May, who is a cardiovascular medicine and critical care specialist at Brigham and Women’s Hospital in Boston.
“However, prior to this study no agent had convincingly demonstrated cardiovascular safety in a rigorous clinical outcomes study,” she said, noting that several agents, such as the now-withdrawn rimonabant (Acomplia/Zimulti) and sibutramine (Meridia), had been shown to precipitate cardiovascular or psychiatric events, which led the Food and Drug Administration to mandate that all weight-loss drugs be assessed for cardiovascular safety. Lorcaserin (Belviq) is a centrally acting 5-HT2C agonist that works by decreasing appetite and was approved by the FDA in 2012 but is not currently available in Europe.
Long-term data on the effects of weight-loss agents on glycemic parameters were limited, hence the remit of the CAMELLIA-TIMI 61 trial was to assess both the cardiovascular and metabolic safety of lorcaserin. The drug was used on a background of lifestyle modification in 6,000 obese or overweight individuals at high risk of cardiovascular events. A further 6,000 individuals received placebo.
“Lorcaserin induced and maintained weight loss across the glycemic categories,” said coauthor and TIMI group investigator Benjamin Scirica, MD, also of Brigham and Women’s Hospital, who presented the metabolic data during a scientific session at the EASD meeting. Specifically, there was a net weight loss beyond that seen with placebo of 2.6 kg, 2.8 kg, and 3.3 kg in individuals with T2DM, prediabetes, and normoglycemia, respectively.
“Roughly 40% of patients with lorcaserin achieved a 5% weight loss, and about 14%-18% achieved a 10% weight loss across the glycemic categories,” Dr. Scirica reported. The corresponding values for the placebo-treated patients were 17%-18% and 4%-7%.
Naveed Sattar, MD, the independent commentator for the trial, noted the weight-loss reduction seen “was modest in the context of this trial, but I think the important point was that it was sustained. Sustained weight loss is difficult, and it was sustained on top of lifestyle and on top of the other drugs, and that is important.”
However, Dr. Sattar, who is professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow (Scotland), also observed that “as night follows day, glycemic improvements follow weight loss.” So, did the glycemic parameters improve purely because of the weight loss? While there is some preclinical evidence that lorcaserin may have an effect outside of its weight-lowering effects, Dr. Sattar felt this was unlikely to be clinically significant in itself.
“Obesity is probably the biggest challenge we have in the medical profession. We’ve got excellent cholesterol-lowering, blood pressure–lowering, and diabetes drugs. Yet obesity and complications are rising worldwide” and “safe weight-loss drugs remain sparse,” Dr. Sattar said.
He suggested that lorcaserin may well have an adjunctive place in the current treatment paradigm, but that place is probably “down the line” after other measures with greater weight-reducing effects or proven cardiovascular benefits were used. Not only are lifestyle modification approaches improving, Dr. Sattar said, but there are also over-the-counter options such as orlistat (Xenical), metformin, sodium-glucose cotransporter 2 inhibitors, glucagonlike peptide receptor–1 agonists, and bariatric surgery that are likely to be used first.
“This is a fantastically well done trial, we needed it,” Dr. Sattar said. However, because there was modest weight loss and no real cardiovascular benefit (but also no cardiovascular safety concern) he called the results “a bust” saying that “we have to take them at face value for what they are.”
Dr. Sattar noted that his “gut feeling at the moment is that the clinical role for lorcaserin is probably, at best, a down-the-line adjunct in those who are still obese for additional weight reduction on top of other drugs and lifestyle modifications, particularly in those who are ‘super responders.’ ” This is so long as the safety signals remain strong and there are quality of life benefits, he added.
The study was designed by the TIMI Study Group in conjunction with the executive committee and the trial sponsor, Eisai. Dr. Bohula May and Dr. Scirica reported receiving grants from Eisai, during the conduct of the study. Dr. Sattar reported grant support from Boehringer Ingelheim, and being part of an advisory board or speaker’s bureau for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Novo Nordisk, and Sanofi.
SOURCES: Bohula May EA et al. Lancet. 2018 Oct 4. doi: 10.1016/S0140-6736(18)32328-6; Bohula May EA et al. N Engl J Med. 2018; 379:1107-17; Sattar N. EASD 2018, Session S33.
BERLIN – Lower rates of incident type 2 diabetes mellitus (T2DM) and improved glycemic control were two of the metabolic effects seen with the appetite-suppressant drug lorcaserin versus placebo on top of existing lifestyle management measures in a large-scale trial of more than 12,000 overweight or obese individuals with established cardiovascular disease or T2DM and other cardiovascular risk factors.
In the CAMELLIA-TIMI 61 trial, treatment with a twice-daily, 10-mg dose of lorcaserin for a median of 3.3 years was associated with a significant 19% reduction in the risk of incident T2DM in participants with prediabetes, compared with placebo (8.5% vs. 10.3%; hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .038). The reduction in the risk of incident T2DM was even greater (23%) in people without diabetes at baseline (6.7% lorcaserin vs. 8.4% placebo; HR, 0.77; 95% CI, 0.63-0.94; P = .012).
Furthermore, in patients with T2DM who had a mean baseline glycated hemoglobin (HbA1c) of 7%, an absolute 0.33% reduction was seen at 1 year between the lorcaserin and placebo groups, with more modest but still significant between-group reductions (–0.09% and –0.08%) in individuals with prediabetes or normoglycemia (all P less than .0001). When baseline HbA1c levels were higher in patients with T2DM (8%), greater net reductions (0.52%) versus placebo were seen (P less than .0001).
These were some of the metabolic findings, published online in the Lancet to coincide with their presentation at the annual meeting of the European Association for the Study of Diabetes, that add to those already released from the CAMELLIA-TIMI 61 trial on cardiovascular safety, lead author and TIMI (Thrombolysis in Myocardial Infarction) group investigator Erin A. Bohula May, MD, observed during a press conference.
The cardiovascular safety data were presented at the 2018 annual congress of the European Society for Cardiology in August and published in the New England Journal of Medicine. These showed no increase with lorcaserin versus placebo in the risk of achieving a major cardiovascular endpoint (MACE) of cardiovascular death, MI, or stroke (HR, 0.99; 95% CI, 0.85-1.14; P less than .001 for noninferiority). There was also no difference between groups in the cumulative incidence of MACE+, which included heart failure, hospitalization for unstable angina, and the need for coronary revascularization (HR, 0.97; 95% CI, 0.87-1.07; P = .55 for superiority).
“We know that weight loss can improve cardiovascular and glycemic risk factors, but it’s difficult to achieve and maintain, and weight-loss agents are guideline-recommended adjuncts to lifestyle modification,” said Dr. Bohula May, who is a cardiovascular medicine and critical care specialist at Brigham and Women’s Hospital in Boston.
“However, prior to this study no agent had convincingly demonstrated cardiovascular safety in a rigorous clinical outcomes study,” she said, noting that several agents, such as the now-withdrawn rimonabant (Acomplia/Zimulti) and sibutramine (Meridia), had been shown to precipitate cardiovascular or psychiatric events, which led the Food and Drug Administration to mandate that all weight-loss drugs be assessed for cardiovascular safety. Lorcaserin (Belviq) is a centrally acting 5-HT2C agonist that works by decreasing appetite and was approved by the FDA in 2012 but is not currently available in Europe.
Long-term data on the effects of weight-loss agents on glycemic parameters were limited, hence the remit of the CAMELLIA-TIMI 61 trial was to assess both the cardiovascular and metabolic safety of lorcaserin. The drug was used on a background of lifestyle modification in 6,000 obese or overweight individuals at high risk of cardiovascular events. A further 6,000 individuals received placebo.
“Lorcaserin induced and maintained weight loss across the glycemic categories,” said coauthor and TIMI group investigator Benjamin Scirica, MD, also of Brigham and Women’s Hospital, who presented the metabolic data during a scientific session at the EASD meeting. Specifically, there was a net weight loss beyond that seen with placebo of 2.6 kg, 2.8 kg, and 3.3 kg in individuals with T2DM, prediabetes, and normoglycemia, respectively.
“Roughly 40% of patients with lorcaserin achieved a 5% weight loss, and about 14%-18% achieved a 10% weight loss across the glycemic categories,” Dr. Scirica reported. The corresponding values for the placebo-treated patients were 17%-18% and 4%-7%.
Naveed Sattar, MD, the independent commentator for the trial, noted the weight-loss reduction seen “was modest in the context of this trial, but I think the important point was that it was sustained. Sustained weight loss is difficult, and it was sustained on top of lifestyle and on top of the other drugs, and that is important.”
However, Dr. Sattar, who is professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow (Scotland), also observed that “as night follows day, glycemic improvements follow weight loss.” So, did the glycemic parameters improve purely because of the weight loss? While there is some preclinical evidence that lorcaserin may have an effect outside of its weight-lowering effects, Dr. Sattar felt this was unlikely to be clinically significant in itself.
“Obesity is probably the biggest challenge we have in the medical profession. We’ve got excellent cholesterol-lowering, blood pressure–lowering, and diabetes drugs. Yet obesity and complications are rising worldwide” and “safe weight-loss drugs remain sparse,” Dr. Sattar said.
He suggested that lorcaserin may well have an adjunctive place in the current treatment paradigm, but that place is probably “down the line” after other measures with greater weight-reducing effects or proven cardiovascular benefits were used. Not only are lifestyle modification approaches improving, Dr. Sattar said, but there are also over-the-counter options such as orlistat (Xenical), metformin, sodium-glucose cotransporter 2 inhibitors, glucagonlike peptide receptor–1 agonists, and bariatric surgery that are likely to be used first.
“This is a fantastically well done trial, we needed it,” Dr. Sattar said. However, because there was modest weight loss and no real cardiovascular benefit (but also no cardiovascular safety concern) he called the results “a bust” saying that “we have to take them at face value for what they are.”
Dr. Sattar noted that his “gut feeling at the moment is that the clinical role for lorcaserin is probably, at best, a down-the-line adjunct in those who are still obese for additional weight reduction on top of other drugs and lifestyle modifications, particularly in those who are ‘super responders.’ ” This is so long as the safety signals remain strong and there are quality of life benefits, he added.
The study was designed by the TIMI Study Group in conjunction with the executive committee and the trial sponsor, Eisai. Dr. Bohula May and Dr. Scirica reported receiving grants from Eisai, during the conduct of the study. Dr. Sattar reported grant support from Boehringer Ingelheim, and being part of an advisory board or speaker’s bureau for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Novo Nordisk, and Sanofi.
SOURCES: Bohula May EA et al. Lancet. 2018 Oct 4. doi: 10.1016/S0140-6736(18)32328-6; Bohula May EA et al. N Engl J Med. 2018; 379:1107-17; Sattar N. EASD 2018, Session S33.
REPORTING FROM EASD 2018
Key clinical point: Lorcaserin is an adjunctive treatment to lifestyle modification for chronic weight management that may improve metabolic health.
Major finding: A total of 8.5% of lorcaserin-treated individuals with prediabetes versus 10.3% of placebo-treated individuals developed incident type 2 diabetes mellitus at 1 year (hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .038).
Study details: A randomized, double-blind, placebo-controlled trial of 12,000 overweight or obese individuals with established cardiovascular disease, established or no type 2 diabetes mellitus, and other cardiovascular risk factors.
Disclosures: The study was designed by the Thrombolysis in Myocardial Infarction Study Group in conjunction with the executive committee and the trial sponsor, Eisai. Dr. Bohula May and Dr. Scirica reported receiving grants from Eisai, during the conduct of the study. Dr. Sattar reported grant support from Boehringer Ingelheim and being part of an advisory board or speaker’s bureau for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Novo Nordisk, and Sanofi.
Sources: Bohula May EA et al. Lancet. 2018. doi: 10.1016/S0140-6736(18)32328-6; Bohula May EA et al. N Engl J Med. 2018;379:1107-17; Sattar N. EASD 2018, Session S33.
Task force advises behavioral intervention for obese adults
The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.
Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.
The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m2 or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.
The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.
The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.
“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.
The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.
In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.
The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.
Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.
Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.
The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.
The researchers and Task Force members had no relevant financial conflicts to disclose.
SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.
In the USPSTF Recommendation Statement on Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults the Task Force updates their 2012 statement and recommends that patients with obesity be referred for intensive, multicomponent behavioral weight loss interventions and weight loss maintenance. Reiterating the importance of intensive behavioral and lifestyle support is to be commended and should be the cornerstone of treatment for people with overweight disorders. As thoughtfully discussed in accompanying editorials by Haire-Joshu, Hill-Briggs, and Yanovski, moving from recommendation to reality will require access to high-quality programs for patients of all socioeconomic and ethnic backgrounds, less restrictive reimbursement for services, and broader involvement of the public health and food industry sectors.
However, the task force recommendations were limited in scope: they pertained to people with obesity defined as a BMI greater than 30 kg/m2, to those without diagnosed obesity-associated disorders, and to patients seen in a primary care setting. This lessens the impact of the report for a disease which continues to be epidemic in the United States. Leaving out the overweight pre-obese in whom efforts toward prevention are essential, as well as people with obesity who have coexisting comorbidities restricts the recommendations to one slice of the large obesity pie. As more high-quality data pertaining to a broader range of people impacted by overweight disorders become available, more expansive guidelines for treatment will be important.
Furthermore, while behavioral weight loss interventions are meaningful, they fall short for many in bringing about sustained efficacy. The primary care setting should include referral for appropriate patients to be evaluated for combined multidisciplinary behavioral and surgical, endoscopic, or pharmacologic therapies that can improve clinical outcomes for those refractory to behavioral weight loss interventions alone. Finally, tackling the obesity epidemic requires that health care providers across a broad range of specialties become involved in a coordinated effort to help our patients. As digestive disease specialists treating a myriad of obesity-related diseases from fatty liver to colorectal cancer, we too need to help address the underlying disease by providing obesity therapy within our practices or making referrals for its multidisciplinary treatment.
Sarah Streett, MD, AGAF, clinical associate professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine, Stanford, Calif. She has no relevant disclosures.
In the USPSTF Recommendation Statement on Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults the Task Force updates their 2012 statement and recommends that patients with obesity be referred for intensive, multicomponent behavioral weight loss interventions and weight loss maintenance. Reiterating the importance of intensive behavioral and lifestyle support is to be commended and should be the cornerstone of treatment for people with overweight disorders. As thoughtfully discussed in accompanying editorials by Haire-Joshu, Hill-Briggs, and Yanovski, moving from recommendation to reality will require access to high-quality programs for patients of all socioeconomic and ethnic backgrounds, less restrictive reimbursement for services, and broader involvement of the public health and food industry sectors.
However, the task force recommendations were limited in scope: they pertained to people with obesity defined as a BMI greater than 30 kg/m2, to those without diagnosed obesity-associated disorders, and to patients seen in a primary care setting. This lessens the impact of the report for a disease which continues to be epidemic in the United States. Leaving out the overweight pre-obese in whom efforts toward prevention are essential, as well as people with obesity who have coexisting comorbidities restricts the recommendations to one slice of the large obesity pie. As more high-quality data pertaining to a broader range of people impacted by overweight disorders become available, more expansive guidelines for treatment will be important.
Furthermore, while behavioral weight loss interventions are meaningful, they fall short for many in bringing about sustained efficacy. The primary care setting should include referral for appropriate patients to be evaluated for combined multidisciplinary behavioral and surgical, endoscopic, or pharmacologic therapies that can improve clinical outcomes for those refractory to behavioral weight loss interventions alone. Finally, tackling the obesity epidemic requires that health care providers across a broad range of specialties become involved in a coordinated effort to help our patients. As digestive disease specialists treating a myriad of obesity-related diseases from fatty liver to colorectal cancer, we too need to help address the underlying disease by providing obesity therapy within our practices or making referrals for its multidisciplinary treatment.
Sarah Streett, MD, AGAF, clinical associate professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine, Stanford, Calif. She has no relevant disclosures.
In the USPSTF Recommendation Statement on Behavioral Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults the Task Force updates their 2012 statement and recommends that patients with obesity be referred for intensive, multicomponent behavioral weight loss interventions and weight loss maintenance. Reiterating the importance of intensive behavioral and lifestyle support is to be commended and should be the cornerstone of treatment for people with overweight disorders. As thoughtfully discussed in accompanying editorials by Haire-Joshu, Hill-Briggs, and Yanovski, moving from recommendation to reality will require access to high-quality programs for patients of all socioeconomic and ethnic backgrounds, less restrictive reimbursement for services, and broader involvement of the public health and food industry sectors.
However, the task force recommendations were limited in scope: they pertained to people with obesity defined as a BMI greater than 30 kg/m2, to those without diagnosed obesity-associated disorders, and to patients seen in a primary care setting. This lessens the impact of the report for a disease which continues to be epidemic in the United States. Leaving out the overweight pre-obese in whom efforts toward prevention are essential, as well as people with obesity who have coexisting comorbidities restricts the recommendations to one slice of the large obesity pie. As more high-quality data pertaining to a broader range of people impacted by overweight disorders become available, more expansive guidelines for treatment will be important.
Furthermore, while behavioral weight loss interventions are meaningful, they fall short for many in bringing about sustained efficacy. The primary care setting should include referral for appropriate patients to be evaluated for combined multidisciplinary behavioral and surgical, endoscopic, or pharmacologic therapies that can improve clinical outcomes for those refractory to behavioral weight loss interventions alone. Finally, tackling the obesity epidemic requires that health care providers across a broad range of specialties become involved in a coordinated effort to help our patients. As digestive disease specialists treating a myriad of obesity-related diseases from fatty liver to colorectal cancer, we too need to help address the underlying disease by providing obesity therapy within our practices or making referrals for its multidisciplinary treatment.
Sarah Streett, MD, AGAF, clinical associate professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine, Stanford, Calif. She has no relevant disclosures.
The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.
Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.
The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m2 or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.
The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.
The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.
“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.
The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.
In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.
The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.
Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.
Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.
The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.
The researchers and Task Force members had no relevant financial conflicts to disclose.
SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.
The U.S. Preventive Services Task Force advises clinicians to refer or offer intensive behavioral weight-loss interventions to obese adults, according to an updated recommendation statement published in JAMA.
Obesity affects more than one-third of U.S. adults, according to federal statistics. It carries increased risk for comorbidities including heart disease, diabetes, and various cancers, as well as increased risk of death among adults younger than 65 years, noted lead author Susan J. Curry, PhD, of the University of Iowa, Iowa City, and members of the Task Force.
The B recommendation applies to obese adults; obesity was defined as a body mass index of 30 kg/m2 or higher. The evidence review focused on interventions for weight loss and weight maintenance that could be provided in primary care or referred from primary care, such as nutrition counseling, exercise strategies, and goal setting.
The Task Force found adequate evidence that behavior-based weight-loss interventions improved weight, reduced incidence of type 2 diabetes, and helped maintain weight loss after interventions ended.
The Task Force found small to no evidence of harm associated with any of the behavioral weight-loss interventions, which included group sessions, personal sessions, print-based interventions, and technology-based interventions (such as text messages). Although interventions that combined drug therapy with behavioral intervention resulted in greater weight loss over 12-18 months, compared with behavioral interventions alone, the attrition rates were high and data on weight-loss maintenance after discontinuation of the drugs were limited, the Task Force noted.
“As a result, the USPSTF encourages clinicians to promote behavioral interventions as the primary focus of effective interventions for weight loss in adults,” they wrote.
The Task Force acknowledged the need for future research in subgroups and to explore whether factors such as genetics and untreated conditions are barriers to behavior-based weight loss interventions.
In the evidence review published in JAMA, Erin S. LeBlanc, MD, of Kaiser Permanente in Portland, Ore., and her colleagues reviewed data from 122 randomized, controlled trials including more than 62,000 persons and 2 observational studies including more than 209,000 persons.
The researchers found behavioral interventions were associated with greater weight loss and less risk of developing diabetes, compared with control interventions.
Intensive behavioral interventions included counseling patients about healthy eating, encouraging physical activity, setting weight and health goals, and assisting with weight monitoring. The interventions ranged from text messaging to in-person sessions for individuals or groups. The average absolute weight loss in the trials included in the review ranged from –0.5 kg to –9.3 kg (–1.1 lb to –20.5 lb) for intervention patients and from +1.4 kg to –5.6 kg (+3.1 lb to –12.3 lb) in controls.
Limitations of the review included a lack of data on population subgroups and a lack of long-term data on weight and health outcomes, the researchers noted. However, the results support the value of behavior-based therapy for obesity treatment.
The final recommendation is consistent with the 2018 draft recommendation and updates the 2012 final recommendation on obesity management.
The researchers and Task Force members had no relevant financial conflicts to disclose.
SOURCE: U.S. Preventive Services Task Force. JAMA. 2018;320(11):1163-71. doi: 10.1001/jama.2018.13022.
FROM JAMA
Increased incidence of GI, colorectal cancers seen in young, obese patients
PHILADELPHIA – Researchers have identified a link between obesity and an increased incidence rate of gastrointestinal (GI) cancers in younger patients as well as an increased rate of colorectal, esophageal, and pancreatic cancer resections in obese patients of various ages, according to an award-winning presentation at the annual meeting of the American College of Gastroenterology.
“These findings strengthen a contributing role of obesity in etiology as well as increasing incidence of these cancers, and call for more efforts targeting obesity,” Hisham Hussan, MD, assistant professor at The Ohio State University Wexner Medical Center in Columbus, stated in his presentation.
The abstract, presented by Dr. Hussan, received an American College of Gastroenterology Category Award in the subject of obesity. He noted in his presentation that the obesity rate in U.S. adults exceeded 37% in 2014. In addition, the temporal changes of obesity-related GI cancers with regard to age-specific groups are not known, he said.
“There’s sufficient evidence linking obesity to certain [GI cancers], such as esophagus, colon, pancreas, and gastric,” Dr. Hussan said. “However, the impact of rising obesity prevalence on the incidence of these obesity-related GI cancers is unknown.”
Dr. Hussan and his colleagues sought to investigate the incidence of obesity-related GI cancers by age group as well as whether there was an association between obesity-related GI cancers in both obese and nonobese patients.
“Our hypothesis is that the incidence of some obesity-related GI cancers is rising in some age groups, and we suspect that this corresponds with increasing rates of obese patients undergoing these cancerous resections,” he said in his presentation.
The researchers evaluated cancer incidence trends in the Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2013 as well as obesity trends from 91,116 obese patients (7.16%) and 1,181,127 nonobese patients (92.84%) in the National Inpatient Sample (NIS) database who underwent cancer resection surgeries. Of these, 93.1% of patients underwent colorectal and 4.4% of patients underwent gastric cancer resections. Patients were considered obese if they had a body mass index of at least 30 kg/m2. The researchers examined annual trends for incidence rates of obesity-related GI cancers by age group and obesity-related GI cancer resection by age and obesity, using a joinpoint regression analysis to determine the percentage change per year.
In patients aged between 20 and 49 years, the incidence of colorectal cancer increased by 1.5% compared with a decrease of 1.5% in patients aged between 50 and 64 years old, a 3.8% decrease in patients aged 65-74 years, and a 3.9% decrease in patients who were a minimum of 75 years old. Gastric cancer incidence also increased by 0.7% in patients aged between 20 and 49 years compared with a 0.5%, 1.1%, and 1.8% decrease among patients who were aged 50-64 years, 65-74 years, and at least 75 years, respectively. There was an increased cancer incidence among patients in the 20- to 49-year-old age group (0.8%), 50- to 64-year-old age group (1.0%), 65- to 74-year-old age group (0.7%), and the 75-and-older group (1.0%). Esophageal cancer was associated with a decreased incidence in the 20- to 49-year-old group (1.8%), 50- to 64-year-old group (1.1%), 65- to 74-year-old age group (1.2%), and the 75-and-older group (0.7%)
For obese patients who underwent colorectal cancer resection, there was a 13.1% increase in the 18- to 49-year-old group, a 10.3% increase in the 50- to 64-year-old group, an 11.3% increase in the 65- to 74-year-old group, and a 12.8% increase in the 75-year-or-older group, compared with an overall decreased incidence in the nonobese group. There was an increased rate of pancreatic cancer resections for obese patients in the 50-to 64-year-old group (26.9%) and 65- to 74-year-old group (27.6%), compared with nonobese patients. Patients in the 18- to 49-year-old group (11.2%), 50- to 64-year-old group (14.6%), and 65- to 74-year-old group (25.7%) also had a higher incidence of esophageal cancer resections.
The limitations of the study included defining BMI at the time of surgery, which does not account for weight loss due to cachexia, and relying on ICD-9 codes for obesity, which “may not be reliable in some cases.
“However, we [saw] an increase in obese patients who come for resection, so it could have probably been more pronounced if we had accounted for obesity at the earlier age before diagnosis,” he added.
Dr. Hussan reports no relevant conflicts of interest.
SOURCE: Hussan H. ACG 2018, Presentation 34.
PHILADELPHIA – Researchers have identified a link between obesity and an increased incidence rate of gastrointestinal (GI) cancers in younger patients as well as an increased rate of colorectal, esophageal, and pancreatic cancer resections in obese patients of various ages, according to an award-winning presentation at the annual meeting of the American College of Gastroenterology.
“These findings strengthen a contributing role of obesity in etiology as well as increasing incidence of these cancers, and call for more efforts targeting obesity,” Hisham Hussan, MD, assistant professor at The Ohio State University Wexner Medical Center in Columbus, stated in his presentation.
The abstract, presented by Dr. Hussan, received an American College of Gastroenterology Category Award in the subject of obesity. He noted in his presentation that the obesity rate in U.S. adults exceeded 37% in 2014. In addition, the temporal changes of obesity-related GI cancers with regard to age-specific groups are not known, he said.
“There’s sufficient evidence linking obesity to certain [GI cancers], such as esophagus, colon, pancreas, and gastric,” Dr. Hussan said. “However, the impact of rising obesity prevalence on the incidence of these obesity-related GI cancers is unknown.”
Dr. Hussan and his colleagues sought to investigate the incidence of obesity-related GI cancers by age group as well as whether there was an association between obesity-related GI cancers in both obese and nonobese patients.
“Our hypothesis is that the incidence of some obesity-related GI cancers is rising in some age groups, and we suspect that this corresponds with increasing rates of obese patients undergoing these cancerous resections,” he said in his presentation.
The researchers evaluated cancer incidence trends in the Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2013 as well as obesity trends from 91,116 obese patients (7.16%) and 1,181,127 nonobese patients (92.84%) in the National Inpatient Sample (NIS) database who underwent cancer resection surgeries. Of these, 93.1% of patients underwent colorectal and 4.4% of patients underwent gastric cancer resections. Patients were considered obese if they had a body mass index of at least 30 kg/m2. The researchers examined annual trends for incidence rates of obesity-related GI cancers by age group and obesity-related GI cancer resection by age and obesity, using a joinpoint regression analysis to determine the percentage change per year.
In patients aged between 20 and 49 years, the incidence of colorectal cancer increased by 1.5% compared with a decrease of 1.5% in patients aged between 50 and 64 years old, a 3.8% decrease in patients aged 65-74 years, and a 3.9% decrease in patients who were a minimum of 75 years old. Gastric cancer incidence also increased by 0.7% in patients aged between 20 and 49 years compared with a 0.5%, 1.1%, and 1.8% decrease among patients who were aged 50-64 years, 65-74 years, and at least 75 years, respectively. There was an increased cancer incidence among patients in the 20- to 49-year-old age group (0.8%), 50- to 64-year-old age group (1.0%), 65- to 74-year-old age group (0.7%), and the 75-and-older group (1.0%). Esophageal cancer was associated with a decreased incidence in the 20- to 49-year-old group (1.8%), 50- to 64-year-old group (1.1%), 65- to 74-year-old age group (1.2%), and the 75-and-older group (0.7%)
For obese patients who underwent colorectal cancer resection, there was a 13.1% increase in the 18- to 49-year-old group, a 10.3% increase in the 50- to 64-year-old group, an 11.3% increase in the 65- to 74-year-old group, and a 12.8% increase in the 75-year-or-older group, compared with an overall decreased incidence in the nonobese group. There was an increased rate of pancreatic cancer resections for obese patients in the 50-to 64-year-old group (26.9%) and 65- to 74-year-old group (27.6%), compared with nonobese patients. Patients in the 18- to 49-year-old group (11.2%), 50- to 64-year-old group (14.6%), and 65- to 74-year-old group (25.7%) also had a higher incidence of esophageal cancer resections.
The limitations of the study included defining BMI at the time of surgery, which does not account for weight loss due to cachexia, and relying on ICD-9 codes for obesity, which “may not be reliable in some cases.
“However, we [saw] an increase in obese patients who come for resection, so it could have probably been more pronounced if we had accounted for obesity at the earlier age before diagnosis,” he added.
Dr. Hussan reports no relevant conflicts of interest.
SOURCE: Hussan H. ACG 2018, Presentation 34.
PHILADELPHIA – Researchers have identified a link between obesity and an increased incidence rate of gastrointestinal (GI) cancers in younger patients as well as an increased rate of colorectal, esophageal, and pancreatic cancer resections in obese patients of various ages, according to an award-winning presentation at the annual meeting of the American College of Gastroenterology.
“These findings strengthen a contributing role of obesity in etiology as well as increasing incidence of these cancers, and call for more efforts targeting obesity,” Hisham Hussan, MD, assistant professor at The Ohio State University Wexner Medical Center in Columbus, stated in his presentation.
The abstract, presented by Dr. Hussan, received an American College of Gastroenterology Category Award in the subject of obesity. He noted in his presentation that the obesity rate in U.S. adults exceeded 37% in 2014. In addition, the temporal changes of obesity-related GI cancers with regard to age-specific groups are not known, he said.
“There’s sufficient evidence linking obesity to certain [GI cancers], such as esophagus, colon, pancreas, and gastric,” Dr. Hussan said. “However, the impact of rising obesity prevalence on the incidence of these obesity-related GI cancers is unknown.”
Dr. Hussan and his colleagues sought to investigate the incidence of obesity-related GI cancers by age group as well as whether there was an association between obesity-related GI cancers in both obese and nonobese patients.
“Our hypothesis is that the incidence of some obesity-related GI cancers is rising in some age groups, and we suspect that this corresponds with increasing rates of obese patients undergoing these cancerous resections,” he said in his presentation.
The researchers evaluated cancer incidence trends in the Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2013 as well as obesity trends from 91,116 obese patients (7.16%) and 1,181,127 nonobese patients (92.84%) in the National Inpatient Sample (NIS) database who underwent cancer resection surgeries. Of these, 93.1% of patients underwent colorectal and 4.4% of patients underwent gastric cancer resections. Patients were considered obese if they had a body mass index of at least 30 kg/m2. The researchers examined annual trends for incidence rates of obesity-related GI cancers by age group and obesity-related GI cancer resection by age and obesity, using a joinpoint regression analysis to determine the percentage change per year.
In patients aged between 20 and 49 years, the incidence of colorectal cancer increased by 1.5% compared with a decrease of 1.5% in patients aged between 50 and 64 years old, a 3.8% decrease in patients aged 65-74 years, and a 3.9% decrease in patients who were a minimum of 75 years old. Gastric cancer incidence also increased by 0.7% in patients aged between 20 and 49 years compared with a 0.5%, 1.1%, and 1.8% decrease among patients who were aged 50-64 years, 65-74 years, and at least 75 years, respectively. There was an increased cancer incidence among patients in the 20- to 49-year-old age group (0.8%), 50- to 64-year-old age group (1.0%), 65- to 74-year-old age group (0.7%), and the 75-and-older group (1.0%). Esophageal cancer was associated with a decreased incidence in the 20- to 49-year-old group (1.8%), 50- to 64-year-old group (1.1%), 65- to 74-year-old age group (1.2%), and the 75-and-older group (0.7%)
For obese patients who underwent colorectal cancer resection, there was a 13.1% increase in the 18- to 49-year-old group, a 10.3% increase in the 50- to 64-year-old group, an 11.3% increase in the 65- to 74-year-old group, and a 12.8% increase in the 75-year-or-older group, compared with an overall decreased incidence in the nonobese group. There was an increased rate of pancreatic cancer resections for obese patients in the 50-to 64-year-old group (26.9%) and 65- to 74-year-old group (27.6%), compared with nonobese patients. Patients in the 18- to 49-year-old group (11.2%), 50- to 64-year-old group (14.6%), and 65- to 74-year-old group (25.7%) also had a higher incidence of esophageal cancer resections.
The limitations of the study included defining BMI at the time of surgery, which does not account for weight loss due to cachexia, and relying on ICD-9 codes for obesity, which “may not be reliable in some cases.
“However, we [saw] an increase in obese patients who come for resection, so it could have probably been more pronounced if we had accounted for obesity at the earlier age before diagnosis,” he added.
Dr. Hussan reports no relevant conflicts of interest.
SOURCE: Hussan H. ACG 2018, Presentation 34.
REPORTING FROM ACG 2018
Key clinical point: There is a higher incidence of colorectal and gastric cancer among obese patients under 50 years old.
Major finding: Obese patients of all age ranges had a higher rate of colorectal cancer resections, obese patients 75 and younger had a significantly higher incidence of esophageal cancer resections, and obese patients aged between 50 and 74 years had a higher rate of pancreatic resections, compared with nonobese patients.
Study details: A database analysis of cancer incidence trends in the Surveillance, Epidemiology, and End Results database and patient cancer incidence and obesity trends in the National Inpatient Sample database between 2002 and 2013.
Disclosures: Dr. Hussan reports no conflicts of interest.
Source: Hussan H. ACG 2018, Presentation 34.
Obesity paradox extends to PE patients
SAN ANTONIO – compared with those who are not obese, according to results of a retrospective analysis covering 13 years and nearly 2 million PE discharges.
The obese patients in the analysis had a lower mortality risk, despite receiving more thrombolytics and mechanical intubation, said investigator Zubair Khan, MD, an internal medicine resident at the University of Toledo (Ohio) Medical Center.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “When we initiated the study, we did not expect this result.”
The association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions including stable heart failure, coronary artery disease, unstable angina, MI, and also in some PE studies, Dr. Khan said.
The study by Dr. Khan and his colleagues, based on the National Inpatient Sample (NIS) database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. They included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but had an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P less than .001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P less than .001), as was chronic lung disease and chronic liver disease, he noted in his presentation.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P less than .001) and mechanical ventilation (5.8% vs. 4%; P less than .001), and more frequently had cardiogenic shock (0.65% vs. 0.45%; P less than .001), he said.
The obese PE patients were more often female, black, and younger than 65 years of age, it was reported.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014, Dr. Khan added.
The paradoxically lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan told attendees at the meeting.
“I think it’s a rich area for more and further research, especially in basic science,” Dr. Khan said.
Dr. Khan and his coauthors disclosed that they had no relationships relevant to the study.
SOURCE: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
SAN ANTONIO – compared with those who are not obese, according to results of a retrospective analysis covering 13 years and nearly 2 million PE discharges.
The obese patients in the analysis had a lower mortality risk, despite receiving more thrombolytics and mechanical intubation, said investigator Zubair Khan, MD, an internal medicine resident at the University of Toledo (Ohio) Medical Center.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “When we initiated the study, we did not expect this result.”
The association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions including stable heart failure, coronary artery disease, unstable angina, MI, and also in some PE studies, Dr. Khan said.
The study by Dr. Khan and his colleagues, based on the National Inpatient Sample (NIS) database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. They included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but had an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P less than .001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P less than .001), as was chronic lung disease and chronic liver disease, he noted in his presentation.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P less than .001) and mechanical ventilation (5.8% vs. 4%; P less than .001), and more frequently had cardiogenic shock (0.65% vs. 0.45%; P less than .001), he said.
The obese PE patients were more often female, black, and younger than 65 years of age, it was reported.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014, Dr. Khan added.
The paradoxically lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan told attendees at the meeting.
“I think it’s a rich area for more and further research, especially in basic science,” Dr. Khan said.
Dr. Khan and his coauthors disclosed that they had no relationships relevant to the study.
SOURCE: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
SAN ANTONIO – compared with those who are not obese, according to results of a retrospective analysis covering 13 years and nearly 2 million PE discharges.
The obese patients in the analysis had a lower mortality risk, despite receiving more thrombolytics and mechanical intubation, said investigator Zubair Khan, MD, an internal medicine resident at the University of Toledo (Ohio) Medical Center.
“Surprisingly, the mortality of PE was significantly less in obese patients,” Dr. Khan said in a podium presentation at the annual meeting of the American College of Chest Physicians. “When we initiated the study, we did not expect this result.”
The association between obesity and lower mortality, sometimes called the “obesity paradox,” has been observed in studies of other chronic health conditions including stable heart failure, coronary artery disease, unstable angina, MI, and also in some PE studies, Dr. Khan said.
The study by Dr. Khan and his colleagues, based on the National Inpatient Sample (NIS) database, included adults with a primary discharge diagnosis of PE between 2002 and 2014. They included 1,959,018 PE discharges, of which 312,770 (16%) had an underlying obesity diagnosis.
Obese PE patients had more risk factors and more severe disease but had an overall mortality of 2.2%, compared with 3.7% in PE patients without obesity (P less than .001), Dr. Khan reported.
Hypertension was significantly more prevalent in the obese PE patients (65% vs. 50.5%; P less than .001), as was chronic lung disease and chronic liver disease, he noted in his presentation.
Obese patients more often received thrombolytics (3.6% vs. 1.9%; P less than .001) and mechanical ventilation (5.8% vs. 4%; P less than .001), and more frequently had cardiogenic shock (0.65% vs. 0.45%; P less than .001), he said.
The obese PE patients were more often female, black, and younger than 65 years of age, it was reported.
Notably, the prevalence of obesity in PE patients more than doubled over the course of the study period, from 10.2% in 2002 to 22.6% in 2014, Dr. Khan added.
The paradoxically lower mortality in obese patients might be explained by increased levels of endocannabinoids, which have shown protective effects in rat and mouse studies, Dr. Khan told attendees at the meeting.
“I think it’s a rich area for more and further research, especially in basic science,” Dr. Khan said.
Dr. Khan and his coauthors disclosed that they had no relationships relevant to the study.
SOURCE: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
REPORTING FROM CHEST 2018
Key clinical point: The obesity paradox observed in other chronic conditions held true in this study of patients with pulmonary embolism (PE).
Major finding: Obese PE patients had more risk factors and more severe disease, but an overall mortality of 2.2% vs 3.7% in nonobese PE patients.
Study details: Retrospective analysis of the National Inpatient Sample (NIS) database including almost 2 million individuals with a primary discharge diagnosis of PE.
Disclosures: Study authors had no disclosures.
Source: Khan Z et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.919.
Reducing asthma, COPD exacerbations in obese patients
SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.
Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.
The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.
Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.
Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).
In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.
In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.
Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.
In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV1 improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV1 after 2 months.
Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.
In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.
In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.
The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.
Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.
Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.
SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.
Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.
The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.
Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.
Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).
In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.
In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.
Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.
In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV1 improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV1 after 2 months.
Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.
In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.
In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.
The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.
Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.
Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.
SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.
Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.
The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.
Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.
Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).
In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.
In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.
Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.
In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV1 improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV1 after 2 months.
Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.
In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.
In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.
The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.
Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.
Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.
REPORTING FROM CHEST 2018
Gastric banding, metformin “equal” for slowing early T2DM progression
BERLIN – Gastric banding surgery and metformin produce similar improvements in insulin sensitivity and parameters indicative of preserved beta-cell function in patients with impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes mellitus (T2DM), according to the results of a study conducted by the Restoring Insulin Secretion (RISE) Consortium.
“Both interventions resulted in about 50% improvements in insulin sensitivity at 1 year, which was attenuated at 2 years,” reported study investigator Thomas Buchanan, MD, of the University of Southern California, Los Angeles, at the annual meeting of the European Association for the Study of Diabetes.
“The beta-cell responses fell in a pattern that maintained relatively, but not perfectly, stable compensation for insulin resistance,” he added.
Although glucose levels improved “only slightly,” he said, “acute compensation to glucose improved significantly with gastric banding and beta-cell compensation at maximal stimulation fell significantly with metformin.”
Results of the BetaFat (Beta Cell Restoration through Fat Mitigation) study, which are now published online in Diabetes Care, also showed that greater weight loss could be achieved with surgery versus metformin, with a 8.9 kg difference between the groups at 2 years (10.6 vs. 1.7 kg, respectively, P less than .01).
HDL cholesterol levels also rose with both interventions, and gastric banding resulted in a greater effect on very low–density lipoprotein cholesterol and triglycerides, as well as serum ALT, Dr. Buchanan said.
The BetaFat study is one of three “proof-of principle” studies currently being conducted by the RISE Consortium in patients with IGT, sometimes called prediabetes, and T2DM, explained Steven E. Kahn, MB, ChB, the chair for the RISE studies.
The other two multicenter, randomized trials being conducted by the RISE Consortium are looking at the effects of medications on preserving beta-cell function in pediatric/adolescent (10-19 years) and adult (21-65 years) populations with IGT or mild, recently diagnosed T2DM. The design, and some results, of these trials can be viewed on a dedicated section of the Diabetes Care website.
Beta-cell function is being assessed using “state-of-the-art” methods; the coprimary endpoint of the surgery versus metformin study was the steady state C-peptide level and acute C-peptide response at maximal glycemia measured using a hyperglycemic “clamp.”
The goal of the RISE studies is to test different approaches to preserve beta-cell function. It is designed to answer the question of which is more effective in this setting: sustained weight loss through gastric banding such as in the BetaFat study or medication.
Patients were eligible for inclusion in the study if they were aged 21-65 years, had a body mass index of 30-40 kg/m2, and had IGT or a diagnosis of T2DM within the past year for which they had received no diabetes medication at recruitment.
A total of 88 individuals were randomized with exactly half undergoing gastric banding. This consisted of a gastric band placed laparoscopically and adjusted every 2 months for the first year, and then every 3 months for the following year depending on symptoms and weight change.
Normoglycemia was observed in none of the study subjects at baseline but in 22% and 15% of those who had gastric banding or metformin, respectively, at 2 years (P = .66).
As for tolerability, five patients who underwent gastric banding experienced serious adverse events, of which two were caused by band slippage and three were caused other reasons. In the metformin arm, there were two serious adverse events, both unrelated to the medication.
“Gastric banding and metformin offered approximately equal approaches for improving insulin sensitivity in adults with mild to moderate obesity and impaired glucose tolerance or early, mild type 2 diabetes,” Dr. Buchanan concluded. “The predominant beta-cell response was a reduction in secretion to maintain a relatively constant compensation for insulin resistance, with only a small improvement in glucose. Whether these interventions will have different effects on beta-cell function over the long-term remains to be determined.”
Commenting on the study, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University (England), noted that the changes in the lipid and liver parameters were important. Fasting plasma triglyceride levels fell from 1.3 mmol/L at baseline to 1.1 mmol/L at 2 years with surgery but stayed more or less the same with metformin (1.23 mmol/L and 1.28 mmol/L; P less than .009 comparing surgery and metformin groups at 2 years). Change in ALT levels were also significant comparing baseline values with results at 2 years, decreasing in the surgical group to a greater extent than in the metformin groups.
“There’s a really important message here, the predictors of a better response to the weight loss [i.e. changes in triglycerides and liver enzymes] are all there,” Dr. Taylor observed. “RISE has looked at 2 years of this effect, but the conversion to type 2 diabetes is probably going to happen over a longer time course.”
He added that “although the primary outcome measure of change in insulin secretion was not achieved, the writing is on the wall. These people, provided they maintain their weight loss, are likely to succeed. We see all the hallmarks of a successful outcome for the weight loss group – remove the primary driver for type 2 diabetes, and that group is on track.”
The RISE Consortium conducted the BetaFat study. The RISE Consortium is supported by grants from the National Institutes for Health. Further support came from the Department of Veterans Affairs, Kaiser Permanente Southern California, the American Diabetes Association, and Allergan. Additional donations of supplies were provided by Allergan, Apollo Endosurgery, Abbott, and Novo Nordisk. Dr. Buchanan reported receiving research funding from Allergan and Apollo Endosurgery. Dr. Taylor had no conflicts of interest.
SOURCES: Buchanan T et al. EASD 2018, Session S09; Xiang AH et al. Diabetes Care. 2018 Oct; dc181662.
BERLIN – Gastric banding surgery and metformin produce similar improvements in insulin sensitivity and parameters indicative of preserved beta-cell function in patients with impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes mellitus (T2DM), according to the results of a study conducted by the Restoring Insulin Secretion (RISE) Consortium.
“Both interventions resulted in about 50% improvements in insulin sensitivity at 1 year, which was attenuated at 2 years,” reported study investigator Thomas Buchanan, MD, of the University of Southern California, Los Angeles, at the annual meeting of the European Association for the Study of Diabetes.
“The beta-cell responses fell in a pattern that maintained relatively, but not perfectly, stable compensation for insulin resistance,” he added.
Although glucose levels improved “only slightly,” he said, “acute compensation to glucose improved significantly with gastric banding and beta-cell compensation at maximal stimulation fell significantly with metformin.”
Results of the BetaFat (Beta Cell Restoration through Fat Mitigation) study, which are now published online in Diabetes Care, also showed that greater weight loss could be achieved with surgery versus metformin, with a 8.9 kg difference between the groups at 2 years (10.6 vs. 1.7 kg, respectively, P less than .01).
HDL cholesterol levels also rose with both interventions, and gastric banding resulted in a greater effect on very low–density lipoprotein cholesterol and triglycerides, as well as serum ALT, Dr. Buchanan said.
The BetaFat study is one of three “proof-of principle” studies currently being conducted by the RISE Consortium in patients with IGT, sometimes called prediabetes, and T2DM, explained Steven E. Kahn, MB, ChB, the chair for the RISE studies.
The other two multicenter, randomized trials being conducted by the RISE Consortium are looking at the effects of medications on preserving beta-cell function in pediatric/adolescent (10-19 years) and adult (21-65 years) populations with IGT or mild, recently diagnosed T2DM. The design, and some results, of these trials can be viewed on a dedicated section of the Diabetes Care website.
Beta-cell function is being assessed using “state-of-the-art” methods; the coprimary endpoint of the surgery versus metformin study was the steady state C-peptide level and acute C-peptide response at maximal glycemia measured using a hyperglycemic “clamp.”
The goal of the RISE studies is to test different approaches to preserve beta-cell function. It is designed to answer the question of which is more effective in this setting: sustained weight loss through gastric banding such as in the BetaFat study or medication.
Patients were eligible for inclusion in the study if they were aged 21-65 years, had a body mass index of 30-40 kg/m2, and had IGT or a diagnosis of T2DM within the past year for which they had received no diabetes medication at recruitment.
A total of 88 individuals were randomized with exactly half undergoing gastric banding. This consisted of a gastric band placed laparoscopically and adjusted every 2 months for the first year, and then every 3 months for the following year depending on symptoms and weight change.
Normoglycemia was observed in none of the study subjects at baseline but in 22% and 15% of those who had gastric banding or metformin, respectively, at 2 years (P = .66).
As for tolerability, five patients who underwent gastric banding experienced serious adverse events, of which two were caused by band slippage and three were caused other reasons. In the metformin arm, there were two serious adverse events, both unrelated to the medication.
“Gastric banding and metformin offered approximately equal approaches for improving insulin sensitivity in adults with mild to moderate obesity and impaired glucose tolerance or early, mild type 2 diabetes,” Dr. Buchanan concluded. “The predominant beta-cell response was a reduction in secretion to maintain a relatively constant compensation for insulin resistance, with only a small improvement in glucose. Whether these interventions will have different effects on beta-cell function over the long-term remains to be determined.”
Commenting on the study, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University (England), noted that the changes in the lipid and liver parameters were important. Fasting plasma triglyceride levels fell from 1.3 mmol/L at baseline to 1.1 mmol/L at 2 years with surgery but stayed more or less the same with metformin (1.23 mmol/L and 1.28 mmol/L; P less than .009 comparing surgery and metformin groups at 2 years). Change in ALT levels were also significant comparing baseline values with results at 2 years, decreasing in the surgical group to a greater extent than in the metformin groups.
“There’s a really important message here, the predictors of a better response to the weight loss [i.e. changes in triglycerides and liver enzymes] are all there,” Dr. Taylor observed. “RISE has looked at 2 years of this effect, but the conversion to type 2 diabetes is probably going to happen over a longer time course.”
He added that “although the primary outcome measure of change in insulin secretion was not achieved, the writing is on the wall. These people, provided they maintain their weight loss, are likely to succeed. We see all the hallmarks of a successful outcome for the weight loss group – remove the primary driver for type 2 diabetes, and that group is on track.”
The RISE Consortium conducted the BetaFat study. The RISE Consortium is supported by grants from the National Institutes for Health. Further support came from the Department of Veterans Affairs, Kaiser Permanente Southern California, the American Diabetes Association, and Allergan. Additional donations of supplies were provided by Allergan, Apollo Endosurgery, Abbott, and Novo Nordisk. Dr. Buchanan reported receiving research funding from Allergan and Apollo Endosurgery. Dr. Taylor had no conflicts of interest.
SOURCES: Buchanan T et al. EASD 2018, Session S09; Xiang AH et al. Diabetes Care. 2018 Oct; dc181662.
BERLIN – Gastric banding surgery and metformin produce similar improvements in insulin sensitivity and parameters indicative of preserved beta-cell function in patients with impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes mellitus (T2DM), according to the results of a study conducted by the Restoring Insulin Secretion (RISE) Consortium.
“Both interventions resulted in about 50% improvements in insulin sensitivity at 1 year, which was attenuated at 2 years,” reported study investigator Thomas Buchanan, MD, of the University of Southern California, Los Angeles, at the annual meeting of the European Association for the Study of Diabetes.
“The beta-cell responses fell in a pattern that maintained relatively, but not perfectly, stable compensation for insulin resistance,” he added.
Although glucose levels improved “only slightly,” he said, “acute compensation to glucose improved significantly with gastric banding and beta-cell compensation at maximal stimulation fell significantly with metformin.”
Results of the BetaFat (Beta Cell Restoration through Fat Mitigation) study, which are now published online in Diabetes Care, also showed that greater weight loss could be achieved with surgery versus metformin, with a 8.9 kg difference between the groups at 2 years (10.6 vs. 1.7 kg, respectively, P less than .01).
HDL cholesterol levels also rose with both interventions, and gastric banding resulted in a greater effect on very low–density lipoprotein cholesterol and triglycerides, as well as serum ALT, Dr. Buchanan said.
The BetaFat study is one of three “proof-of principle” studies currently being conducted by the RISE Consortium in patients with IGT, sometimes called prediabetes, and T2DM, explained Steven E. Kahn, MB, ChB, the chair for the RISE studies.
The other two multicenter, randomized trials being conducted by the RISE Consortium are looking at the effects of medications on preserving beta-cell function in pediatric/adolescent (10-19 years) and adult (21-65 years) populations with IGT or mild, recently diagnosed T2DM. The design, and some results, of these trials can be viewed on a dedicated section of the Diabetes Care website.
Beta-cell function is being assessed using “state-of-the-art” methods; the coprimary endpoint of the surgery versus metformin study was the steady state C-peptide level and acute C-peptide response at maximal glycemia measured using a hyperglycemic “clamp.”
The goal of the RISE studies is to test different approaches to preserve beta-cell function. It is designed to answer the question of which is more effective in this setting: sustained weight loss through gastric banding such as in the BetaFat study or medication.
Patients were eligible for inclusion in the study if they were aged 21-65 years, had a body mass index of 30-40 kg/m2, and had IGT or a diagnosis of T2DM within the past year for which they had received no diabetes medication at recruitment.
A total of 88 individuals were randomized with exactly half undergoing gastric banding. This consisted of a gastric band placed laparoscopically and adjusted every 2 months for the first year, and then every 3 months for the following year depending on symptoms and weight change.
Normoglycemia was observed in none of the study subjects at baseline but in 22% and 15% of those who had gastric banding or metformin, respectively, at 2 years (P = .66).
As for tolerability, five patients who underwent gastric banding experienced serious adverse events, of which two were caused by band slippage and three were caused other reasons. In the metformin arm, there were two serious adverse events, both unrelated to the medication.
“Gastric banding and metformin offered approximately equal approaches for improving insulin sensitivity in adults with mild to moderate obesity and impaired glucose tolerance or early, mild type 2 diabetes,” Dr. Buchanan concluded. “The predominant beta-cell response was a reduction in secretion to maintain a relatively constant compensation for insulin resistance, with only a small improvement in glucose. Whether these interventions will have different effects on beta-cell function over the long-term remains to be determined.”
Commenting on the study, Roy Taylor, MD, professor of medicine and metabolism at Newcastle University (England), noted that the changes in the lipid and liver parameters were important. Fasting plasma triglyceride levels fell from 1.3 mmol/L at baseline to 1.1 mmol/L at 2 years with surgery but stayed more or less the same with metformin (1.23 mmol/L and 1.28 mmol/L; P less than .009 comparing surgery and metformin groups at 2 years). Change in ALT levels were also significant comparing baseline values with results at 2 years, decreasing in the surgical group to a greater extent than in the metformin groups.
“There’s a really important message here, the predictors of a better response to the weight loss [i.e. changes in triglycerides and liver enzymes] are all there,” Dr. Taylor observed. “RISE has looked at 2 years of this effect, but the conversion to type 2 diabetes is probably going to happen over a longer time course.”
He added that “although the primary outcome measure of change in insulin secretion was not achieved, the writing is on the wall. These people, provided they maintain their weight loss, are likely to succeed. We see all the hallmarks of a successful outcome for the weight loss group – remove the primary driver for type 2 diabetes, and that group is on track.”
The RISE Consortium conducted the BetaFat study. The RISE Consortium is supported by grants from the National Institutes for Health. Further support came from the Department of Veterans Affairs, Kaiser Permanente Southern California, the American Diabetes Association, and Allergan. Additional donations of supplies were provided by Allergan, Apollo Endosurgery, Abbott, and Novo Nordisk. Dr. Buchanan reported receiving research funding from Allergan and Apollo Endosurgery. Dr. Taylor had no conflicts of interest.
SOURCES: Buchanan T et al. EASD 2018, Session S09; Xiang AH et al. Diabetes Care. 2018 Oct; dc181662.
REPORTING FROM EASD 2018
Key clinical point: Over 2 years, gastric banding surgery and metformin produced similar improvements in insulin sensitivity and parameters suggestive of preserved beta-cell function in patients with prediabetes or early type 2 diabetes.
Major finding: Around a 50% improvement in insulin sensitivity was seen in both study groups at 1 year with attenuation of the effect at 2 years.
Study details: The BetaFat study included 88 obese adults with impaired glucose tolerance or newly diagnosed early type 2 diabetes.
Disclosures: The study was part of the RISE studies, which are supported by grants from the National Institutes for Health. Further support comes from the Department of Veterans Affairs, Kaiser Permanente Southern California, the American Diabetes Association, and Allergan. Additional donations of supplies are provided by Allergan, Apollo Endosurgery, Abbott Laboratories, and Novo Nordisk. Dr. Buchanan reported research funding from Allergan and Apollo Endosurgery. Dr. Taylor had no conflicts of interest.
Sources: Buchanan T et al. EASD 2018, Session S09; Xiang AH et al. Diabetes Care. 2018 Oct; dc181662.
Obesity in early childhood promotes obese adolescence
Most obese adolescents first became obese between the ages of 2 and 6 years, based on data from approximately 50,000 children in Germany.
Identifying periods of weight gain in childhood can help develop intervention and prevention strategies to reduce the risk of obesity in adolescence, wrote Mandy Geserick, MSc, of the University of Leipzig, Germany, and her colleagues in the New England Journal of Medicine.
To assess the timing of weight gain in early childhood, the researchers reviewed data from a German patient registry designed to monitor growth data. The study population included 51,505 children who had at least one visit to a pediatrician between birth and age 14 years and a second visit between age 15 and 19 years.
Overall, the probability of being overweight or obese in adolescence was 29% among children who gained more weight in the preschool years, between the ages of 2 and 6 years (defined as a change in body mass index [BMI] of 0.2 or more to less than 2.0), compared with 20% among children whose preschool weight remained stable (defined as a change in BMI of more than −0.2 to less than 0.2) – a relative risk of 1.43.
“A total of 83% of the children with obesity at the age of 4 were overweight or obese in adolescence, and only 17% returned to a normal weight,” they wrote. In addition, 44% of children who were born large for gestational age were overweight or obese in adolescence.
“A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before 6 years of age, even in the absence of obesity,” the researchers wrote.
The study findings were limited by several factors including the variation in the number of visits, the lack of data on many children beyond the age of 14 years, and the lack of data on parental weight and perinatal risk factors associated with obesity, the researchers noted. However, the results were strengthened by the large, population-based design, and support the study hypothesis that obesity develops in early childhood and, once present, persists into adolescence.
“The specific dynamics and patterns of BMI in this early childhood period, rather than the absolute BMI, appear to be important factors in identifying children at risk for obesity later in life,” the researchers wrote. “It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period.”
The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
SOURCE: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
Most normal-weight children remained in the normal range throughout childhood, but the association between obesity by the age of 5 years and obese adolescence is a “new and important” finding, Michael S. Freemark, MD, wrote in an accompanying editorial (N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMe1811305).
Although body mass index (BMI) generally decreases by age 5-6 years before increasing through adolescence, data from previous studies have shown that “an early or exaggerated ‘adiposity rebound’ portends an increased risk of obesity in later childhood and adolescence,” he wrote.
In this study, BMI increase between age 2 and 6 years was the strongest predictor of obesity in adolescence. Although the study was not designed to show causality, the results support the idea of a window of opportunity for intervention for children at increased risk for obesity, Dr. Freemark wrote. “The finding that the risk of adolescent obesity manifests by 3 to 5 years of age suggests that nutritional counseling should be considered when exaggerated weight gain persists or emerges after 2 years of age; it would be of value to test the efficacy of early dietary intervention in an appropriate trial.
“Counseling could be applied preemptively for families in which the parents are overweight, particularly if there is a history of maternal diabetes or smoking,” he added.
Dr. Freemark is affiliated with the division of pediatric endocrinology and diabetes at Duke University, Durham, N.C. He disclosed grants from Rhythm Pharmaceuticals, the American Heart Association, and the Humanitarian Innovation Fund and European Commission, as well as personal fees from Springer Publishing outside the submitted work.
Most normal-weight children remained in the normal range throughout childhood, but the association between obesity by the age of 5 years and obese adolescence is a “new and important” finding, Michael S. Freemark, MD, wrote in an accompanying editorial (N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMe1811305).
Although body mass index (BMI) generally decreases by age 5-6 years before increasing through adolescence, data from previous studies have shown that “an early or exaggerated ‘adiposity rebound’ portends an increased risk of obesity in later childhood and adolescence,” he wrote.
In this study, BMI increase between age 2 and 6 years was the strongest predictor of obesity in adolescence. Although the study was not designed to show causality, the results support the idea of a window of opportunity for intervention for children at increased risk for obesity, Dr. Freemark wrote. “The finding that the risk of adolescent obesity manifests by 3 to 5 years of age suggests that nutritional counseling should be considered when exaggerated weight gain persists or emerges after 2 years of age; it would be of value to test the efficacy of early dietary intervention in an appropriate trial.
“Counseling could be applied preemptively for families in which the parents are overweight, particularly if there is a history of maternal diabetes or smoking,” he added.
Dr. Freemark is affiliated with the division of pediatric endocrinology and diabetes at Duke University, Durham, N.C. He disclosed grants from Rhythm Pharmaceuticals, the American Heart Association, and the Humanitarian Innovation Fund and European Commission, as well as personal fees from Springer Publishing outside the submitted work.
Most normal-weight children remained in the normal range throughout childhood, but the association between obesity by the age of 5 years and obese adolescence is a “new and important” finding, Michael S. Freemark, MD, wrote in an accompanying editorial (N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMe1811305).
Although body mass index (BMI) generally decreases by age 5-6 years before increasing through adolescence, data from previous studies have shown that “an early or exaggerated ‘adiposity rebound’ portends an increased risk of obesity in later childhood and adolescence,” he wrote.
In this study, BMI increase between age 2 and 6 years was the strongest predictor of obesity in adolescence. Although the study was not designed to show causality, the results support the idea of a window of opportunity for intervention for children at increased risk for obesity, Dr. Freemark wrote. “The finding that the risk of adolescent obesity manifests by 3 to 5 years of age suggests that nutritional counseling should be considered when exaggerated weight gain persists or emerges after 2 years of age; it would be of value to test the efficacy of early dietary intervention in an appropriate trial.
“Counseling could be applied preemptively for families in which the parents are overweight, particularly if there is a history of maternal diabetes or smoking,” he added.
Dr. Freemark is affiliated with the division of pediatric endocrinology and diabetes at Duke University, Durham, N.C. He disclosed grants from Rhythm Pharmaceuticals, the American Heart Association, and the Humanitarian Innovation Fund and European Commission, as well as personal fees from Springer Publishing outside the submitted work.
Most obese adolescents first became obese between the ages of 2 and 6 years, based on data from approximately 50,000 children in Germany.
Identifying periods of weight gain in childhood can help develop intervention and prevention strategies to reduce the risk of obesity in adolescence, wrote Mandy Geserick, MSc, of the University of Leipzig, Germany, and her colleagues in the New England Journal of Medicine.
To assess the timing of weight gain in early childhood, the researchers reviewed data from a German patient registry designed to monitor growth data. The study population included 51,505 children who had at least one visit to a pediatrician between birth and age 14 years and a second visit between age 15 and 19 years.
Overall, the probability of being overweight or obese in adolescence was 29% among children who gained more weight in the preschool years, between the ages of 2 and 6 years (defined as a change in body mass index [BMI] of 0.2 or more to less than 2.0), compared with 20% among children whose preschool weight remained stable (defined as a change in BMI of more than −0.2 to less than 0.2) – a relative risk of 1.43.
“A total of 83% of the children with obesity at the age of 4 were overweight or obese in adolescence, and only 17% returned to a normal weight,” they wrote. In addition, 44% of children who were born large for gestational age were overweight or obese in adolescence.
“A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before 6 years of age, even in the absence of obesity,” the researchers wrote.
The study findings were limited by several factors including the variation in the number of visits, the lack of data on many children beyond the age of 14 years, and the lack of data on parental weight and perinatal risk factors associated with obesity, the researchers noted. However, the results were strengthened by the large, population-based design, and support the study hypothesis that obesity develops in early childhood and, once present, persists into adolescence.
“The specific dynamics and patterns of BMI in this early childhood period, rather than the absolute BMI, appear to be important factors in identifying children at risk for obesity later in life,” the researchers wrote. “It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period.”
The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
SOURCE: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
Most obese adolescents first became obese between the ages of 2 and 6 years, based on data from approximately 50,000 children in Germany.
Identifying periods of weight gain in childhood can help develop intervention and prevention strategies to reduce the risk of obesity in adolescence, wrote Mandy Geserick, MSc, of the University of Leipzig, Germany, and her colleagues in the New England Journal of Medicine.
To assess the timing of weight gain in early childhood, the researchers reviewed data from a German patient registry designed to monitor growth data. The study population included 51,505 children who had at least one visit to a pediatrician between birth and age 14 years and a second visit between age 15 and 19 years.
Overall, the probability of being overweight or obese in adolescence was 29% among children who gained more weight in the preschool years, between the ages of 2 and 6 years (defined as a change in body mass index [BMI] of 0.2 or more to less than 2.0), compared with 20% among children whose preschool weight remained stable (defined as a change in BMI of more than −0.2 to less than 0.2) – a relative risk of 1.43.
“A total of 83% of the children with obesity at the age of 4 were overweight or obese in adolescence, and only 17% returned to a normal weight,” they wrote. In addition, 44% of children who were born large for gestational age were overweight or obese in adolescence.
“A practical clinical implication of our study results would be surveillance for BMI acceleration, which should be recognized before 6 years of age, even in the absence of obesity,” the researchers wrote.
The study findings were limited by several factors including the variation in the number of visits, the lack of data on many children beyond the age of 14 years, and the lack of data on parental weight and perinatal risk factors associated with obesity, the researchers noted. However, the results were strengthened by the large, population-based design, and support the study hypothesis that obesity develops in early childhood and, once present, persists into adolescence.
“The specific dynamics and patterns of BMI in this early childhood period, rather than the absolute BMI, appear to be important factors in identifying children at risk for obesity later in life,” the researchers wrote. “It is therefore important for health care professionals, educational staff, and parents to become more sensitive to this critical time period.”
The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
SOURCE: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Of children who were obese at age 4 years, 83% were overweight or obese in adolescence.
Study details: The data come from a retrospective study of 51,505 children in Germany.
Disclosures: The study was supported by the German Research Council for the Clinical Research Center; the Federal Ministry of Education and Research; and the University of Leipzig, which was supported by the European Union, the European Regional Development Fund, and the Free State of Saxony within the framework of the excellence initiative. The CrescNet registry infrastructure was supported by grants from Hexal, Novo Nordisk, Merck Serono, Lilly Deutschland, Pfizer, and Ipsen Pharma. Dr. Geserick had no financial conflicts to report.
Source: Geserick M et al. N Engl J Med. 2018 Oct 3. doi: 10.1056/NEJMoa1803527.
Web-based lifestyle program aids in weight loss for NAFLD patients
A web-based intervention for management of nonalcoholic fatty liver disease – which researchers said may help reach busy or remote patients not able to attend in-person sessions – had a similar number of patients reach a target weight-loss goal of at least 10% of body weight, compared with a group-based intervention.
“The use of web education in the management of noncommunicable diseases has long been suggested, considering the huge number of cases at risk and patients’ needs,” wrote Arianna Mazzotti, MD, of the department of medical and surgical sciences, Alma Mater University, Bologna, Italy, and her colleagues. Their report was published in the Journal of Hepatology.
“The majority of cases are in an age range where job constraints make it difficult to implement a systematic face-to-face or group approach, whereas the eHealth procedures may keep the contact between patients and therapists without disrupting normal daily living.”
Dr. Mazzotti and her colleagues studied 716 patients with nonalcoholic fatty liver disease (NAFLD) at the university between January 2010 and December 2015 who attended either a web-based NAFLD intervention (278 patients) or an in-person, group-based lifestyle modification program (438 patients). Patients in the web-based intervention tended to be younger males with a higher education level, similar mean body mass index (33 kg/m2), and significantly lower blood pressure and rates of type 2 diabetes mellitus. The primary outcome included weight loss of at least 10%; secondary outcomes included changes in weight, changes in lifestyle, surrogate markers of steatosis and fibrosis, and alanine aminotransferase (ALT) within normal limits, researchers said.
The group-based program consisted of five 2-hour weekly sessions counseling patients on diet and physical activity, whereas the web-based intervention reproduced these sessions in addition to questionnaires, “highly interactive” slides, examples, and games as well as a mechanism to ask questions. Regardless of intervention, patients attended a 6-month in-person follow-up where they received treatment and reinforcement for comorbidities such as type 2 diabetes mellitus.
In the web-based intervention, 76% of patients attended the 6-month follow-up, 58% attended the 12-month follow-up, and 43% attended the 24-month follow-up, compared with 87%, 80%, and 69% of patients in the group-based intervention, respectively. Patients in the web-based intervention had a significantly decreased intake of calories after 6 months (273 kcal/day vs. 193 kcal/day; P = .006) compared with the group-based intervention. Physical activity significantly increased at 6 months for both groups, but there were no significant differences between groups.
Body weight decreased for the web-based intervention by 3.4% at 6 months, 4.9% at 12 months, and 5.5% at 24 months, compared with 3.1% at 6 months, 4.0% at 12 months, and 4.2% at 24 months in the group-based intervention. There was a nearly two-point reduction in body mass index for both groups, with 20% of web-based intervention patients and 15% of group-based intervention patients achieving the 10% weight-loss target; and, when the researchers performed a logistic regression analysis, the web-based intervention group was not associated with less short- and long-term 10% weight reduction after attrition rates and confounders were adjusted for.
At 24-month follow-up, the researchers found a decrease in ALT levels by an average of 22 ± 32 mU/mL, with the web-based intervention group having normalized ALT levels in 18% of cases at 6 months, 32% at 12 months, and 35% at 24 months, compared with 16% of cases at 6 months, 22% of cases at 12 months, and 29% of cases at 24 months in the group-based intervention. Compared with the group-based intervention, there was a higher reduction in fatty liver index scores at 12-month follow-up (71.3 vs. 78.0; P less than .001) and 24-month follow-up (68.9 vs. 76.3; P = .002) for the web-based intervention group. The researchers noted NAFLD fibrosis score and Fib-4 scores were reduced in both groups.
“The [web-based intervention] program might be extended to other units and/or general practitioners, increasing its impact in the community in prevention and treatment of progressive NAFLD,” Dr. Mazzotti and her colleagues wrote. “It might also be superimposed to drug treatment in the most severe cases, with possible additive effects.”
This study was supported by a grant from the European Community Seventh Framework Program. The authors report no relevant conflicts of interest.
*This story was updated on 10/4/2018.
SOURCE: Mazzotti A et al. J Hepatol. 2018 Oct 2. doi: 10.1016/j.jhep.2018.07.013.
A web-based intervention for management of nonalcoholic fatty liver disease – which researchers said may help reach busy or remote patients not able to attend in-person sessions – had a similar number of patients reach a target weight-loss goal of at least 10% of body weight, compared with a group-based intervention.
“The use of web education in the management of noncommunicable diseases has long been suggested, considering the huge number of cases at risk and patients’ needs,” wrote Arianna Mazzotti, MD, of the department of medical and surgical sciences, Alma Mater University, Bologna, Italy, and her colleagues. Their report was published in the Journal of Hepatology.
“The majority of cases are in an age range where job constraints make it difficult to implement a systematic face-to-face or group approach, whereas the eHealth procedures may keep the contact between patients and therapists without disrupting normal daily living.”
Dr. Mazzotti and her colleagues studied 716 patients with nonalcoholic fatty liver disease (NAFLD) at the university between January 2010 and December 2015 who attended either a web-based NAFLD intervention (278 patients) or an in-person, group-based lifestyle modification program (438 patients). Patients in the web-based intervention tended to be younger males with a higher education level, similar mean body mass index (33 kg/m2), and significantly lower blood pressure and rates of type 2 diabetes mellitus. The primary outcome included weight loss of at least 10%; secondary outcomes included changes in weight, changes in lifestyle, surrogate markers of steatosis and fibrosis, and alanine aminotransferase (ALT) within normal limits, researchers said.
The group-based program consisted of five 2-hour weekly sessions counseling patients on diet and physical activity, whereas the web-based intervention reproduced these sessions in addition to questionnaires, “highly interactive” slides, examples, and games as well as a mechanism to ask questions. Regardless of intervention, patients attended a 6-month in-person follow-up where they received treatment and reinforcement for comorbidities such as type 2 diabetes mellitus.
In the web-based intervention, 76% of patients attended the 6-month follow-up, 58% attended the 12-month follow-up, and 43% attended the 24-month follow-up, compared with 87%, 80%, and 69% of patients in the group-based intervention, respectively. Patients in the web-based intervention had a significantly decreased intake of calories after 6 months (273 kcal/day vs. 193 kcal/day; P = .006) compared with the group-based intervention. Physical activity significantly increased at 6 months for both groups, but there were no significant differences between groups.
Body weight decreased for the web-based intervention by 3.4% at 6 months, 4.9% at 12 months, and 5.5% at 24 months, compared with 3.1% at 6 months, 4.0% at 12 months, and 4.2% at 24 months in the group-based intervention. There was a nearly two-point reduction in body mass index for both groups, with 20% of web-based intervention patients and 15% of group-based intervention patients achieving the 10% weight-loss target; and, when the researchers performed a logistic regression analysis, the web-based intervention group was not associated with less short- and long-term 10% weight reduction after attrition rates and confounders were adjusted for.
At 24-month follow-up, the researchers found a decrease in ALT levels by an average of 22 ± 32 mU/mL, with the web-based intervention group having normalized ALT levels in 18% of cases at 6 months, 32% at 12 months, and 35% at 24 months, compared with 16% of cases at 6 months, 22% of cases at 12 months, and 29% of cases at 24 months in the group-based intervention. Compared with the group-based intervention, there was a higher reduction in fatty liver index scores at 12-month follow-up (71.3 vs. 78.0; P less than .001) and 24-month follow-up (68.9 vs. 76.3; P = .002) for the web-based intervention group. The researchers noted NAFLD fibrosis score and Fib-4 scores were reduced in both groups.
“The [web-based intervention] program might be extended to other units and/or general practitioners, increasing its impact in the community in prevention and treatment of progressive NAFLD,” Dr. Mazzotti and her colleagues wrote. “It might also be superimposed to drug treatment in the most severe cases, with possible additive effects.”
This study was supported by a grant from the European Community Seventh Framework Program. The authors report no relevant conflicts of interest.
*This story was updated on 10/4/2018.
SOURCE: Mazzotti A et al. J Hepatol. 2018 Oct 2. doi: 10.1016/j.jhep.2018.07.013.
A web-based intervention for management of nonalcoholic fatty liver disease – which researchers said may help reach busy or remote patients not able to attend in-person sessions – had a similar number of patients reach a target weight-loss goal of at least 10% of body weight, compared with a group-based intervention.
“The use of web education in the management of noncommunicable diseases has long been suggested, considering the huge number of cases at risk and patients’ needs,” wrote Arianna Mazzotti, MD, of the department of medical and surgical sciences, Alma Mater University, Bologna, Italy, and her colleagues. Their report was published in the Journal of Hepatology.
“The majority of cases are in an age range where job constraints make it difficult to implement a systematic face-to-face or group approach, whereas the eHealth procedures may keep the contact between patients and therapists without disrupting normal daily living.”
Dr. Mazzotti and her colleagues studied 716 patients with nonalcoholic fatty liver disease (NAFLD) at the university between January 2010 and December 2015 who attended either a web-based NAFLD intervention (278 patients) or an in-person, group-based lifestyle modification program (438 patients). Patients in the web-based intervention tended to be younger males with a higher education level, similar mean body mass index (33 kg/m2), and significantly lower blood pressure and rates of type 2 diabetes mellitus. The primary outcome included weight loss of at least 10%; secondary outcomes included changes in weight, changes in lifestyle, surrogate markers of steatosis and fibrosis, and alanine aminotransferase (ALT) within normal limits, researchers said.
The group-based program consisted of five 2-hour weekly sessions counseling patients on diet and physical activity, whereas the web-based intervention reproduced these sessions in addition to questionnaires, “highly interactive” slides, examples, and games as well as a mechanism to ask questions. Regardless of intervention, patients attended a 6-month in-person follow-up where they received treatment and reinforcement for comorbidities such as type 2 diabetes mellitus.
In the web-based intervention, 76% of patients attended the 6-month follow-up, 58% attended the 12-month follow-up, and 43% attended the 24-month follow-up, compared with 87%, 80%, and 69% of patients in the group-based intervention, respectively. Patients in the web-based intervention had a significantly decreased intake of calories after 6 months (273 kcal/day vs. 193 kcal/day; P = .006) compared with the group-based intervention. Physical activity significantly increased at 6 months for both groups, but there were no significant differences between groups.
Body weight decreased for the web-based intervention by 3.4% at 6 months, 4.9% at 12 months, and 5.5% at 24 months, compared with 3.1% at 6 months, 4.0% at 12 months, and 4.2% at 24 months in the group-based intervention. There was a nearly two-point reduction in body mass index for both groups, with 20% of web-based intervention patients and 15% of group-based intervention patients achieving the 10% weight-loss target; and, when the researchers performed a logistic regression analysis, the web-based intervention group was not associated with less short- and long-term 10% weight reduction after attrition rates and confounders were adjusted for.
At 24-month follow-up, the researchers found a decrease in ALT levels by an average of 22 ± 32 mU/mL, with the web-based intervention group having normalized ALT levels in 18% of cases at 6 months, 32% at 12 months, and 35% at 24 months, compared with 16% of cases at 6 months, 22% of cases at 12 months, and 29% of cases at 24 months in the group-based intervention. Compared with the group-based intervention, there was a higher reduction in fatty liver index scores at 12-month follow-up (71.3 vs. 78.0; P less than .001) and 24-month follow-up (68.9 vs. 76.3; P = .002) for the web-based intervention group. The researchers noted NAFLD fibrosis score and Fib-4 scores were reduced in both groups.
“The [web-based intervention] program might be extended to other units and/or general practitioners, increasing its impact in the community in prevention and treatment of progressive NAFLD,” Dr. Mazzotti and her colleagues wrote. “It might also be superimposed to drug treatment in the most severe cases, with possible additive effects.”
This study was supported by a grant from the European Community Seventh Framework Program. The authors report no relevant conflicts of interest.
*This story was updated on 10/4/2018.
SOURCE: Mazzotti A et al. J Hepatol. 2018 Oct 2. doi: 10.1016/j.jhep.2018.07.013.
FROM THE JOURNAL OF HEPATOLOGY
Key clinical point: A web-based lifestyle modification intervention was similarly effective as a group intervention in reducing weight for patients with nonalcoholic fatty liver disease.
Major finding: In the web-based intervention, body weight decreased by 3.4% at 6 months, 4.9% at 12 months, and 5.5% at 24 months, compared with 3.1% at 6 months, 4.0% at 12 months, and 4.2% at 24 months in the group-based intervention. A similar number of patients in both groups achieved the 10% weight-loss target.
Study details: An observational study of 716 patients participating in web-based or group nonalcoholic fatty liver disease interventions at the University of Bologna between January 2010 and December 2015.
Disclosures: The European Community Seventh Framework Program supported the study. The authors report no conflicts of interest.
Source: Mazzotti A et al. J Hepatol. 2018 Oct 2. doi: 10.1016/j.jhep.2018.07.013.
The devil is in the headlines
“Breast Milk From Bottle May Not Be As Beneficial As Feeding Directly From The Breast, Researchers Say.” This was the headline on the AAP Daily Briefing that was sent to American Academy of Pediatrics members on Sept 25, 2018.
I suspect that this finding doesn’t surprise you. I can imagine a dozen factors that could make bottled breast milk less advantageous for a baby than milk received directly from the mother’s breast. Antibodies might adhere to the glass surface. A few degrees above or below body temperature could interfere with gastric emptying. Or a temptation to focus on the level in the bottle and inadvertently overfeed could inflate the baby’s body mass index at 3 months, as was found in the study published online in the September 2018 issue of Pediatrics (“Infant Feeding and Weight Gain: Separating Breast Milk From Breastfeeding and Formula From Food”).
I agree that the title of the actual paper is rather dry; it’s a scientific research paper. But the distillation chosen by the folks at AAP Daily Briefing seems ill advised. They were not alone. CCN-Health chose “Breastfeeding better for babies’ weight gain than pumping, new study says” (Michael Nedelman, Sept. 24, 2018). HealthDay News headlined its story with “Milk straight from breast best for baby’s weight” (Sept. 24, 2018).
The articles themselves were well balanced and accurately described this research based on more than 2,500 Canadian mother-infant dyads. But not everyone – including mothers who are struggling with or considering breastfeeding – reads beyond the headlines. How many realize that “better for babies’ weight gain” means a slower weight gain? For the mother who has found that, for a variety of reasons, pumping is the only way she can provide her baby the benefits of breast milk, what these headlines suggest is another blow to her already fragile sense of self-worth.
This research article is excellent and should be read by all of us who counsel young families. It suggests that one of the contributors to our epidemic of childhood obesity may be that bottle-feeding discourages the infant’s own self-regulation skills. It should prompt us to ask every parent who is bottle-feeding his or her baby – regardless of what is in the bottle – exactly how they decide how much to put in the bottle and how long a feeding takes. Even if we are comfortable with the infant’s weight gain, we should caution parents to be more aware of the baby’s cues that he or she has had enough. Not every baby provides cues that are obvious, and parents may need our coaching in deciding how much to feed. This research paper also suggests that as long as breastfeeding was continued, introduction of solids as early as 5 months was not associated with an unhealthy BMI trajectory.
Unfortunately, the reporting of this research article is another example of the hazards of the explosive growth of the Internet. There really is no reason to keep the results of well-crafted research from the lay public, particularly if they are explained in common sense language. However, this places a burden of responsibility on the editors of websites to consider the damage that can be done by a poorly chosen headline.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
“Breast Milk From Bottle May Not Be As Beneficial As Feeding Directly From The Breast, Researchers Say.” This was the headline on the AAP Daily Briefing that was sent to American Academy of Pediatrics members on Sept 25, 2018.
I suspect that this finding doesn’t surprise you. I can imagine a dozen factors that could make bottled breast milk less advantageous for a baby than milk received directly from the mother’s breast. Antibodies might adhere to the glass surface. A few degrees above or below body temperature could interfere with gastric emptying. Or a temptation to focus on the level in the bottle and inadvertently overfeed could inflate the baby’s body mass index at 3 months, as was found in the study published online in the September 2018 issue of Pediatrics (“Infant Feeding and Weight Gain: Separating Breast Milk From Breastfeeding and Formula From Food”).
I agree that the title of the actual paper is rather dry; it’s a scientific research paper. But the distillation chosen by the folks at AAP Daily Briefing seems ill advised. They were not alone. CCN-Health chose “Breastfeeding better for babies’ weight gain than pumping, new study says” (Michael Nedelman, Sept. 24, 2018). HealthDay News headlined its story with “Milk straight from breast best for baby’s weight” (Sept. 24, 2018).
The articles themselves were well balanced and accurately described this research based on more than 2,500 Canadian mother-infant dyads. But not everyone – including mothers who are struggling with or considering breastfeeding – reads beyond the headlines. How many realize that “better for babies’ weight gain” means a slower weight gain? For the mother who has found that, for a variety of reasons, pumping is the only way she can provide her baby the benefits of breast milk, what these headlines suggest is another blow to her already fragile sense of self-worth.
This research article is excellent and should be read by all of us who counsel young families. It suggests that one of the contributors to our epidemic of childhood obesity may be that bottle-feeding discourages the infant’s own self-regulation skills. It should prompt us to ask every parent who is bottle-feeding his or her baby – regardless of what is in the bottle – exactly how they decide how much to put in the bottle and how long a feeding takes. Even if we are comfortable with the infant’s weight gain, we should caution parents to be more aware of the baby’s cues that he or she has had enough. Not every baby provides cues that are obvious, and parents may need our coaching in deciding how much to feed. This research paper also suggests that as long as breastfeeding was continued, introduction of solids as early as 5 months was not associated with an unhealthy BMI trajectory.
Unfortunately, the reporting of this research article is another example of the hazards of the explosive growth of the Internet. There really is no reason to keep the results of well-crafted research from the lay public, particularly if they are explained in common sense language. However, this places a burden of responsibility on the editors of websites to consider the damage that can be done by a poorly chosen headline.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
“Breast Milk From Bottle May Not Be As Beneficial As Feeding Directly From The Breast, Researchers Say.” This was the headline on the AAP Daily Briefing that was sent to American Academy of Pediatrics members on Sept 25, 2018.
I suspect that this finding doesn’t surprise you. I can imagine a dozen factors that could make bottled breast milk less advantageous for a baby than milk received directly from the mother’s breast. Antibodies might adhere to the glass surface. A few degrees above or below body temperature could interfere with gastric emptying. Or a temptation to focus on the level in the bottle and inadvertently overfeed could inflate the baby’s body mass index at 3 months, as was found in the study published online in the September 2018 issue of Pediatrics (“Infant Feeding and Weight Gain: Separating Breast Milk From Breastfeeding and Formula From Food”).
I agree that the title of the actual paper is rather dry; it’s a scientific research paper. But the distillation chosen by the folks at AAP Daily Briefing seems ill advised. They were not alone. CCN-Health chose “Breastfeeding better for babies’ weight gain than pumping, new study says” (Michael Nedelman, Sept. 24, 2018). HealthDay News headlined its story with “Milk straight from breast best for baby’s weight” (Sept. 24, 2018).
The articles themselves were well balanced and accurately described this research based on more than 2,500 Canadian mother-infant dyads. But not everyone – including mothers who are struggling with or considering breastfeeding – reads beyond the headlines. How many realize that “better for babies’ weight gain” means a slower weight gain? For the mother who has found that, for a variety of reasons, pumping is the only way she can provide her baby the benefits of breast milk, what these headlines suggest is another blow to her already fragile sense of self-worth.
This research article is excellent and should be read by all of us who counsel young families. It suggests that one of the contributors to our epidemic of childhood obesity may be that bottle-feeding discourages the infant’s own self-regulation skills. It should prompt us to ask every parent who is bottle-feeding his or her baby – regardless of what is in the bottle – exactly how they decide how much to put in the bottle and how long a feeding takes. Even if we are comfortable with the infant’s weight gain, we should caution parents to be more aware of the baby’s cues that he or she has had enough. Not every baby provides cues that are obvious, and parents may need our coaching in deciding how much to feed. This research paper also suggests that as long as breastfeeding was continued, introduction of solids as early as 5 months was not associated with an unhealthy BMI trajectory.
Unfortunately, the reporting of this research article is another example of the hazards of the explosive growth of the Internet. There really is no reason to keep the results of well-crafted research from the lay public, particularly if they are explained in common sense language. However, this places a burden of responsibility on the editors of websites to consider the damage that can be done by a poorly chosen headline.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Breast cancer risk in type 2 diabetes related to adiposity
ORLANDO – findings from meta-analyses suggest.
In one meta-analysis of data from 21 prospective studies with a total of nearly 15.2 million women, 325,117 breast cancer cases, and a mean follow-up time of 8 years (nearly 33 million person-years), the risk of breast cancer was significantly greater among patients with diabetes than it was among patients without diabetes (summary relative risk, 1.11), Maria Bota reported at the annual scientific sessions of the American Diabetes Association.
However, there was substantial unexplained heterogeneity of results across the individual studies (I2 = 82%), said Ms. Bota, a faculty member at the International Prevention Research Institute, Lyon, France.
“When the analysis was restricted to the 12 studies that adjusted for [body mass index], the summary relative risk decreased to 1.09 and the heterogeneity also decreased to a moderate value of 32%; when the analysis was restricted to the 9 studies that did not adjust for BMI, the summary relative risk increased to 1.14 again, and the heterogeneity increased even more to 91%,” she said.
In an analysis that combined the results of the nine studies that did not adjust for BMI along with crude relative risks from studies that reported both crude and BMI-adjusted relative risks (17 studies in all), the SRR was 1.12, and heterogeneity among the studies was high at 84%.
Additionally, an analysis by menopausal status based on four studies that reported breast cancer in both pre- and postmenopausal women showed SRRs for breast cancer of 0.97 (a 3% decrease in risk) and 1.14 among diabetic vs. nondiabetic premenopausal women and postmenopausal women, respectively, she said, noting that heterogeneity was low (I2 = 0%) among the premenopausal breast cancer study groups and high (I2 = 70%) among the postmenopausal study groups.
The findings provide evidence for a moderately increased risk of breast cancer in women with T2DM, Ms. Bota said.
“However, the effect of the adjustment or lack of adjustment on the heterogeneity suggests that the higher risk of breast cancer in women with diabetes may not be due to diabetes itself, but to adiposity,” she said, adding that “this hypothesis is equally supported by our subgroup analysis according to menopausal status because we saw that the risk of breast cancer was only associated with diabetes in postmenopausal women and this pattern resembles the pattern of the risk of breast cancer associated with adiposity, which is also only increased in postmenopausal women.”
This study was limited by insufficient data for investigating the sources of heterogeneity, she said.
“Therefore we propose ... future pooled analyses based on individual data from good quality prospective studies in order to increase the study power and to do some detailed analysis of the links between adiposity, diabetes, and breast cancer,” she concluded, adding that new studies to examine those relationships only in premenopausal women are also needed
In a separate meta-analysis, she and her colleagues, including Peter Boyle, PhD, president of the International Prevention Research Institute, assessed the association between insulin treatment and breast cancer risk in patients with diabetes.
“The long-acting insulin analogues glargine and detemir have been shown in some studies to be associated with increased risk of breast cancer, and other studies have shown no association between the use of these two compounds and the risk of breast cancer,” Dr. Boyle said in a separate presentation at the ADA meeting. “It was important to sort out a little bit what was going on in the literature.”
Overall, the meta-analysis of data from 12 longitudinal cohort studies – including more than 6,000 cases of breast cancer – showed a slight increase in breast cancer risk in patients taking long-acting insulin (SRR, 1.13) with “a relatively reasonable” level of heterogeneity (I2 = 23%).
“But we see that the story is not that simple,” he said.
For example, some studies included only patients who were prescribed insulin for the first time after the study began (new users), some included only patients who were prescribed insulin before the study began (prevalent users), and some included both (ever users), which may have introduced bias in the results, he explained.
Studies of glargine included 4,168 breast cancer cases over a total of 1,418,743 person-years of observation, and studies of detemir included fewer than 2,047 breast cancer cases (not all studies reported case numbers). Among both new users of glargine and detemir, the SRR was 1.12, suggesting no real association between either glargine or detemir use and breast cancer, he said.
“One important take-home message is that you have to be careful that these pharmaco-epidemiological studies, even when working with the same database, may have conflicting results ... so we still need more robust standards in methods for [such] studies,” he concluded.
Ms. Bota reported having no disclosures. The study presented by Dr. Boyle was funded by Sanofi. Dr. Boyle is president of a charity that has received donations from Pfizer, Roche, Novartis, and Lilly.
SOURCE: Bota M. ADA 2018, Abstract 180-OR; Boyle P. ADA 2018, Abstract 133-OR.
ORLANDO – findings from meta-analyses suggest.
In one meta-analysis of data from 21 prospective studies with a total of nearly 15.2 million women, 325,117 breast cancer cases, and a mean follow-up time of 8 years (nearly 33 million person-years), the risk of breast cancer was significantly greater among patients with diabetes than it was among patients without diabetes (summary relative risk, 1.11), Maria Bota reported at the annual scientific sessions of the American Diabetes Association.
However, there was substantial unexplained heterogeneity of results across the individual studies (I2 = 82%), said Ms. Bota, a faculty member at the International Prevention Research Institute, Lyon, France.
“When the analysis was restricted to the 12 studies that adjusted for [body mass index], the summary relative risk decreased to 1.09 and the heterogeneity also decreased to a moderate value of 32%; when the analysis was restricted to the 9 studies that did not adjust for BMI, the summary relative risk increased to 1.14 again, and the heterogeneity increased even more to 91%,” she said.
In an analysis that combined the results of the nine studies that did not adjust for BMI along with crude relative risks from studies that reported both crude and BMI-adjusted relative risks (17 studies in all), the SRR was 1.12, and heterogeneity among the studies was high at 84%.
Additionally, an analysis by menopausal status based on four studies that reported breast cancer in both pre- and postmenopausal women showed SRRs for breast cancer of 0.97 (a 3% decrease in risk) and 1.14 among diabetic vs. nondiabetic premenopausal women and postmenopausal women, respectively, she said, noting that heterogeneity was low (I2 = 0%) among the premenopausal breast cancer study groups and high (I2 = 70%) among the postmenopausal study groups.
The findings provide evidence for a moderately increased risk of breast cancer in women with T2DM, Ms. Bota said.
“However, the effect of the adjustment or lack of adjustment on the heterogeneity suggests that the higher risk of breast cancer in women with diabetes may not be due to diabetes itself, but to adiposity,” she said, adding that “this hypothesis is equally supported by our subgroup analysis according to menopausal status because we saw that the risk of breast cancer was only associated with diabetes in postmenopausal women and this pattern resembles the pattern of the risk of breast cancer associated with adiposity, which is also only increased in postmenopausal women.”
This study was limited by insufficient data for investigating the sources of heterogeneity, she said.
“Therefore we propose ... future pooled analyses based on individual data from good quality prospective studies in order to increase the study power and to do some detailed analysis of the links between adiposity, diabetes, and breast cancer,” she concluded, adding that new studies to examine those relationships only in premenopausal women are also needed
In a separate meta-analysis, she and her colleagues, including Peter Boyle, PhD, president of the International Prevention Research Institute, assessed the association between insulin treatment and breast cancer risk in patients with diabetes.
“The long-acting insulin analogues glargine and detemir have been shown in some studies to be associated with increased risk of breast cancer, and other studies have shown no association between the use of these two compounds and the risk of breast cancer,” Dr. Boyle said in a separate presentation at the ADA meeting. “It was important to sort out a little bit what was going on in the literature.”
Overall, the meta-analysis of data from 12 longitudinal cohort studies – including more than 6,000 cases of breast cancer – showed a slight increase in breast cancer risk in patients taking long-acting insulin (SRR, 1.13) with “a relatively reasonable” level of heterogeneity (I2 = 23%).
“But we see that the story is not that simple,” he said.
For example, some studies included only patients who were prescribed insulin for the first time after the study began (new users), some included only patients who were prescribed insulin before the study began (prevalent users), and some included both (ever users), which may have introduced bias in the results, he explained.
Studies of glargine included 4,168 breast cancer cases over a total of 1,418,743 person-years of observation, and studies of detemir included fewer than 2,047 breast cancer cases (not all studies reported case numbers). Among both new users of glargine and detemir, the SRR was 1.12, suggesting no real association between either glargine or detemir use and breast cancer, he said.
“One important take-home message is that you have to be careful that these pharmaco-epidemiological studies, even when working with the same database, may have conflicting results ... so we still need more robust standards in methods for [such] studies,” he concluded.
Ms. Bota reported having no disclosures. The study presented by Dr. Boyle was funded by Sanofi. Dr. Boyle is president of a charity that has received donations from Pfizer, Roche, Novartis, and Lilly.
SOURCE: Bota M. ADA 2018, Abstract 180-OR; Boyle P. ADA 2018, Abstract 133-OR.
ORLANDO – findings from meta-analyses suggest.
In one meta-analysis of data from 21 prospective studies with a total of nearly 15.2 million women, 325,117 breast cancer cases, and a mean follow-up time of 8 years (nearly 33 million person-years), the risk of breast cancer was significantly greater among patients with diabetes than it was among patients without diabetes (summary relative risk, 1.11), Maria Bota reported at the annual scientific sessions of the American Diabetes Association.
However, there was substantial unexplained heterogeneity of results across the individual studies (I2 = 82%), said Ms. Bota, a faculty member at the International Prevention Research Institute, Lyon, France.
“When the analysis was restricted to the 12 studies that adjusted for [body mass index], the summary relative risk decreased to 1.09 and the heterogeneity also decreased to a moderate value of 32%; when the analysis was restricted to the 9 studies that did not adjust for BMI, the summary relative risk increased to 1.14 again, and the heterogeneity increased even more to 91%,” she said.
In an analysis that combined the results of the nine studies that did not adjust for BMI along with crude relative risks from studies that reported both crude and BMI-adjusted relative risks (17 studies in all), the SRR was 1.12, and heterogeneity among the studies was high at 84%.
Additionally, an analysis by menopausal status based on four studies that reported breast cancer in both pre- and postmenopausal women showed SRRs for breast cancer of 0.97 (a 3% decrease in risk) and 1.14 among diabetic vs. nondiabetic premenopausal women and postmenopausal women, respectively, she said, noting that heterogeneity was low (I2 = 0%) among the premenopausal breast cancer study groups and high (I2 = 70%) among the postmenopausal study groups.
The findings provide evidence for a moderately increased risk of breast cancer in women with T2DM, Ms. Bota said.
“However, the effect of the adjustment or lack of adjustment on the heterogeneity suggests that the higher risk of breast cancer in women with diabetes may not be due to diabetes itself, but to adiposity,” she said, adding that “this hypothesis is equally supported by our subgroup analysis according to menopausal status because we saw that the risk of breast cancer was only associated with diabetes in postmenopausal women and this pattern resembles the pattern of the risk of breast cancer associated with adiposity, which is also only increased in postmenopausal women.”
This study was limited by insufficient data for investigating the sources of heterogeneity, she said.
“Therefore we propose ... future pooled analyses based on individual data from good quality prospective studies in order to increase the study power and to do some detailed analysis of the links between adiposity, diabetes, and breast cancer,” she concluded, adding that new studies to examine those relationships only in premenopausal women are also needed
In a separate meta-analysis, she and her colleagues, including Peter Boyle, PhD, president of the International Prevention Research Institute, assessed the association between insulin treatment and breast cancer risk in patients with diabetes.
“The long-acting insulin analogues glargine and detemir have been shown in some studies to be associated with increased risk of breast cancer, and other studies have shown no association between the use of these two compounds and the risk of breast cancer,” Dr. Boyle said in a separate presentation at the ADA meeting. “It was important to sort out a little bit what was going on in the literature.”
Overall, the meta-analysis of data from 12 longitudinal cohort studies – including more than 6,000 cases of breast cancer – showed a slight increase in breast cancer risk in patients taking long-acting insulin (SRR, 1.13) with “a relatively reasonable” level of heterogeneity (I2 = 23%).
“But we see that the story is not that simple,” he said.
For example, some studies included only patients who were prescribed insulin for the first time after the study began (new users), some included only patients who were prescribed insulin before the study began (prevalent users), and some included both (ever users), which may have introduced bias in the results, he explained.
Studies of glargine included 4,168 breast cancer cases over a total of 1,418,743 person-years of observation, and studies of detemir included fewer than 2,047 breast cancer cases (not all studies reported case numbers). Among both new users of glargine and detemir, the SRR was 1.12, suggesting no real association between either glargine or detemir use and breast cancer, he said.
“One important take-home message is that you have to be careful that these pharmaco-epidemiological studies, even when working with the same database, may have conflicting results ... so we still need more robust standards in methods for [such] studies,” he concluded.
Ms. Bota reported having no disclosures. The study presented by Dr. Boyle was funded by Sanofi. Dr. Boyle is president of a charity that has received donations from Pfizer, Roche, Novartis, and Lilly.
SOURCE: Bota M. ADA 2018, Abstract 180-OR; Boyle P. ADA 2018, Abstract 133-OR.
REPORTING FROM ADA 2018
Key clinical point: Adiposity accounts for the increased risk of breast cancer among women with diabetes.
Major finding: An analysis of 12 studies that adjusted for BMI showed a summary relative risk for breast cancer of 1.09 in diabetic versus nondiabetic women, with moderate study heterogeneity.
Study details: Meta-analyses including 21 and 12 studies, respectively.
Disclosures: Ms. Bota reported having no disclosures. The study presented by Dr. Boyle was funded by Sanofi. Dr. Boyle is president of a charity that has received donations from Pfizer, Roche, Novartis, and Lilly.
Source: Bota M. ADA 2018, Abstract 180-OR; Boyle P. ADA 2018, Abstract 133-OR.