User login
GLP-1 RAs Reduce Early-Onset CRC Risk in Patients With Type 2 Diabetes
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
FROM ACG 2024
Should the Body Roundness Index Replace BMI?
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
In daily practice, physicians need a quick and simple way to assess whether a patient’s weight presents a health risk. For decades, the body mass index (BMI) has been used for this purpose, with calculations based on height and weight. Despite its convenience, BMI has faced increasing criticism.
According to experts, BRI may more accurately identify people with high levels of visceral fat than BMI. It’s well documented that abdominal fat is strongly linked to higher risks for obesity-related diseases.
Studies Support BRI
Several studies have suggested that BRI could be a valuable tool for assessing health risks. In June of this year, researchers from China reported a significant U-shaped association between BRI and overall mortality in a paper published in JAMA Network Open. People with very low or very high BRI had an increased risk for death, noted Xiaoqian Zhang, MD, from Beijing University of Chinese Medicine, Beijing, China, and his colleagues.
A study published in September in the Journal of the American Heart Association showed that elevated BRI over several years was associated with an increased risk for cardiovascular diseases. “The BRI can be included as a predictive factor for cardiovascular disease incidence,” stated the authors, led by Man Yang, MD, from Nanjing Medical University in Nanjing, China.
Why Replace BMI?
Why is a replacement for BMI necessary? When asked by this news organization, Manfred Müller, MD, senior professor at the Institute of Human Nutrition and Food Science at the University of Kiel, in Germany, explained: “BMI was designed to provide a simple value that was as independent of body size as possible, that could detect obesity and estimate related disease risks. But scientifically, BMI has always been a very crude measure to characterize disease risks.”
Müller was part of a research group led by US mathematician Diana Thomas, PhD, who, at the time, worked at Montclair State University, Montclair, New Jersey, and now holds a position at the US Military Academy at West Point, in New York. The group developed and published the BRI in 2013.
BMI Classifies Bodybuilders as Obese
The researchers justified their search for a “better” anthropometric measure with two aspects of BMI that still constitute the main points of criticism of the widely used index today:
BMI incorrectly classifies individuals with significant muscle mass, like bodybuilders, as obese, as it doesn’t distinguish between fat and muscle mass.
BMI provides no information about fat distribution in the body — whether it’s concentrated in the hips or the abdomen, for example.
In practice, this means that a person with a normal BMI could already have prediabetes, high blood pressure, and high cholesterol, which might go undetected if no further investigations are conducted based solely on their BMI.
The BRI aims to solve this problem. As the name suggests, this index seeks to capture a person’s “roundness.” The formula for calculating BRI includes waist circumference and height but excludes body weight:
BRI = 364.2 − 365.5 × √(1 − [Waist circumference in cm/2π]²/[0.5 × Height in cm]²)
In their 2013 article, Thomas, Müller, and colleagues wrote that it still needed to be proven whether their newly developed index correlated with mortality and the risk for cardiovascular and metabolic diseases — and whether it was sufficiently better than BMI to justify the more complex calculation.
Could BRI Replace BMI?
Opinions differ on whether the BRI should replace the BMI. Zhang’s team concluded that the BRI needs to be validated in additional independent cohorts. If it does, it could become a practical screening tool in patient care.
Yang’s research group is optimistic about the BRI’s future: “The longitudinal trajectory of the BRI could be used as a novel indicator of cardiovascular disease risk, which provides a new possibility for cardiovascular disease prevention,” they wrote.
However, even BRI Co-creator Thomas has concerns. “Our entire medical system has been built around the BMI,” she told JAMA, referring to factors such as children’s growth charts and dosage recommendations for medications. That cannot be changed overnight.
Any anthropometric measure intended to replace BMI would need to be rigorously validated across all age groups, genders, and ethnicities. The impact of interventions such as bariatric surgery, diet, and exercise on the new measure would also need to be demonstrated.
Anthropometric Measures Only for Clinical Use
Even if BRI proves to be a “better” metric than BMI for patient care, Müller believes it would be no more suitable for research than BMI. “Regardless of the anthropometric measure, these are practical tools for everyday use,” he stressed.
“A high BRI, like a high BMI, is a risk factor — similar to high blood pressure, high cholesterol levels, or smoking — but it is not a disease,” he added. “In practice, as a physician, I know that a patient with a high BMI or BRI has an increased risk. I need to pay attention to that patient.”
Problems arise when indices like BMI or BRI are used in research. “These ‘invented’ anthropometric measures have no biological basis, which can harm obesity research,” Müller emphasized.
He cited the example of genetic research into obesity, which seeks to identify associations between specific genetic patterns and BMI values. “Why should weight in kilograms divided by height in meters squared be genetically determined?” he asked. “These measures are human-made constructs that have nothing to do with biology.”
Müller believes that the use of BMI has created a “gray area in obesity research” that may account for many of the “unexplained” phenomena in this field.
The BMI Might Be Responsible for the ‘Healthy Obese’
One such phenomenon is the much-discussed “healthy obese,” referring to individuals with a BMI over 30 who do not have high blood sugar, high blood pressure, metabolic disorders, or elevated uric acid levels. “It’s speculated that it must be due to genetic factors, but in reality, the classification is simply wrong,” Müller said.
According to Müller, research should rely on other methods to determine obesity or relevant fat. For example, to assess diabetes risk, liver fat needs to be measured through enzyme tests, ultrasonography, CT, or MRI.
Visceral fat is also important in assessing cardiometabolic risk. “In the doctor’s office, it’s acceptable to estimate this by looking at waist circumference or even BRI. But for research, that’s inadequate,” noted Müller. Direct measurement of trunk fat with dual-energy x-ray absorptiometry or visceral fat with CT or MRI is needed.
“You always have to distinguish between research and patient care. In daily practice, measures like BRI or BMI are sufficient for assessing cardiometabolic risk. But in research, they are not,” Müller explained. To accurately study the disease risks associated with obesity, one must be aware that “with BMI, you cannot create scientifically valid patient or population groups because this value is far too imprecise.”
This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Thyroid Cancer Overdiagnosis Continues Despite Cautions
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a recently published global study.
The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.
Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.
Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.
Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.
“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”
Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.
This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.
Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.
“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
Persisting Problem
Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.
The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”
“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.
In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.
If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.
In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.
“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.
“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.
The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.
“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.
In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
New Thinking on Thyroid Cancer
There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.
“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”
The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.
Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.
“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.
Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.
“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.
Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.
“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”
Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.
“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”
This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
American Diabetes Association Advises on Hospital CGM Use
, based in part on data collected during the COVID-19 pandemic.
The statement, Consensus Considerations and Good Practice Points for Use of Continuous Glucose Monitoring Systems in Hospital Settings, was published on October 25, 2024, in Diabetes Care.
“This is something that requires close collaboration with many groups in the hospital ... There needs to be really good guidance within the hospital as to when it can be used, in which patients, and what checks and balances need to be in place,” statement lead author Julie L.V. Shaw, PhD, Laboratory Director at Renfrew Victoria Hospital and St. Francis Memorial Hospital, Ottawa, Ontario, Canada, told this news organization.
CGM use in the outpatient setting continues to grow, among people with type 2 as well as type 1 diabetes. The devices are worn on the body for up to 15 days via a subcutaneously-inserted sensor that detects glucose in interstitial fluid every 1-15 minutes. The readings generally track with blood glucose levels, although discrepancies can occur and may be even more relevant in hospital settings.
About 1 in 4 hospitalized patients have diabetes and/or hyperglycemia. During the COVID-19 pandemic, the US Food and Drug Administration (FDA) and Health Canada temporarily authorized the use of CGM systems in hospitals to supplement point-of-care glucose testing, as an emergency measure to reduce healthcare worker exposure and preserve personal protective equipment. That FDA authorization expired on November 7, 2023, and currently hospital CGM use in the United States is technically off-label, although it is often allowed for patients who already use CGM systems.
The new statement summarizes clinical study data and also addresses the potential benefits of CGM systems for inpatients, existing guidance, analytical and clinical evaluation of CGM performance, safety factors, staff training, clinical workflow, and hospital policies. Also covered are issues around quality assurance, integration of CGM data into electronic health records, cost considerations, and barriers to implementation.
The “good practice points for consideration” in the document are as follows:
- If healthcare professionals want to use CGM systems beyond their intended use, eg, to replace or reduce point-of-care glucose measurements, analytical and clinical performance should be assessed.
- The Clinical and Laboratory Standards Institute (CLSI) 2nd Edition of POCT05 — Performance Metrics for Continuous Interstitial Glucose Monitoring provides helpful guidance.
- Potential interferences that preclude patients from being eligible for CGM should be noted, and staff must be aware that CGM can’t be used for clinical decision-making in these patients.
- A CGM system and/or inpatient glycemia management committee should oversee the development and implementation of hospital-approved policies and procedures for CGM use in the hospital. This committee should have representatives from nursing leadership, physician leadership (e.g., endocrinologists, internal medicine specialists, hospitalists), laboratory, information services, hospital administration, pharmacy, and risk management/legal.
- Policies for patient-owned and hospital-owned CGM devices should be developed, and staff should be trained in their use.
“During the pandemic, there was a lot of research on CGM use in the hospital setting, so we could look at how it works and was it safe. I think we have some good data to show where it can be used,” said Shaw, who also heads the Division of Biochemistry at the Ottawa Hospital. She added, “There’s quite a bit we still don’t know, but I think with some guidance in place about when not to use it, there are certainly patient populations who could benefit from it in the hospital setting.”
Shaw had no disclosures. Another author is general manager and medical director of the Institute for Diabetes Technology (IfDT), which carries out clinical studies, eg, with medical devices for diabetes therapy, on its own initiative and on behalf of various companies. Another author is an IfDT employee. Other authors have received speakers’ honoraria or consulting fees in the last 3 years from Abbott, Berlin-Chemie, BOYDSense, Dexcom, Lilly Deutschland, Novo Nordisk, Perfood, PharmaSens, Roche, Sinocare, Terumo, and Ypsomed.
A version of this article appeared on Medscape.com.
, based in part on data collected during the COVID-19 pandemic.
The statement, Consensus Considerations and Good Practice Points for Use of Continuous Glucose Monitoring Systems in Hospital Settings, was published on October 25, 2024, in Diabetes Care.
“This is something that requires close collaboration with many groups in the hospital ... There needs to be really good guidance within the hospital as to when it can be used, in which patients, and what checks and balances need to be in place,” statement lead author Julie L.V. Shaw, PhD, Laboratory Director at Renfrew Victoria Hospital and St. Francis Memorial Hospital, Ottawa, Ontario, Canada, told this news organization.
CGM use in the outpatient setting continues to grow, among people with type 2 as well as type 1 diabetes. The devices are worn on the body for up to 15 days via a subcutaneously-inserted sensor that detects glucose in interstitial fluid every 1-15 minutes. The readings generally track with blood glucose levels, although discrepancies can occur and may be even more relevant in hospital settings.
About 1 in 4 hospitalized patients have diabetes and/or hyperglycemia. During the COVID-19 pandemic, the US Food and Drug Administration (FDA) and Health Canada temporarily authorized the use of CGM systems in hospitals to supplement point-of-care glucose testing, as an emergency measure to reduce healthcare worker exposure and preserve personal protective equipment. That FDA authorization expired on November 7, 2023, and currently hospital CGM use in the United States is technically off-label, although it is often allowed for patients who already use CGM systems.
The new statement summarizes clinical study data and also addresses the potential benefits of CGM systems for inpatients, existing guidance, analytical and clinical evaluation of CGM performance, safety factors, staff training, clinical workflow, and hospital policies. Also covered are issues around quality assurance, integration of CGM data into electronic health records, cost considerations, and barriers to implementation.
The “good practice points for consideration” in the document are as follows:
- If healthcare professionals want to use CGM systems beyond their intended use, eg, to replace or reduce point-of-care glucose measurements, analytical and clinical performance should be assessed.
- The Clinical and Laboratory Standards Institute (CLSI) 2nd Edition of POCT05 — Performance Metrics for Continuous Interstitial Glucose Monitoring provides helpful guidance.
- Potential interferences that preclude patients from being eligible for CGM should be noted, and staff must be aware that CGM can’t be used for clinical decision-making in these patients.
- A CGM system and/or inpatient glycemia management committee should oversee the development and implementation of hospital-approved policies and procedures for CGM use in the hospital. This committee should have representatives from nursing leadership, physician leadership (e.g., endocrinologists, internal medicine specialists, hospitalists), laboratory, information services, hospital administration, pharmacy, and risk management/legal.
- Policies for patient-owned and hospital-owned CGM devices should be developed, and staff should be trained in their use.
“During the pandemic, there was a lot of research on CGM use in the hospital setting, so we could look at how it works and was it safe. I think we have some good data to show where it can be used,” said Shaw, who also heads the Division of Biochemistry at the Ottawa Hospital. She added, “There’s quite a bit we still don’t know, but I think with some guidance in place about when not to use it, there are certainly patient populations who could benefit from it in the hospital setting.”
Shaw had no disclosures. Another author is general manager and medical director of the Institute for Diabetes Technology (IfDT), which carries out clinical studies, eg, with medical devices for diabetes therapy, on its own initiative and on behalf of various companies. Another author is an IfDT employee. Other authors have received speakers’ honoraria or consulting fees in the last 3 years from Abbott, Berlin-Chemie, BOYDSense, Dexcom, Lilly Deutschland, Novo Nordisk, Perfood, PharmaSens, Roche, Sinocare, Terumo, and Ypsomed.
A version of this article appeared on Medscape.com.
, based in part on data collected during the COVID-19 pandemic.
The statement, Consensus Considerations and Good Practice Points for Use of Continuous Glucose Monitoring Systems in Hospital Settings, was published on October 25, 2024, in Diabetes Care.
“This is something that requires close collaboration with many groups in the hospital ... There needs to be really good guidance within the hospital as to when it can be used, in which patients, and what checks and balances need to be in place,” statement lead author Julie L.V. Shaw, PhD, Laboratory Director at Renfrew Victoria Hospital and St. Francis Memorial Hospital, Ottawa, Ontario, Canada, told this news organization.
CGM use in the outpatient setting continues to grow, among people with type 2 as well as type 1 diabetes. The devices are worn on the body for up to 15 days via a subcutaneously-inserted sensor that detects glucose in interstitial fluid every 1-15 minutes. The readings generally track with blood glucose levels, although discrepancies can occur and may be even more relevant in hospital settings.
About 1 in 4 hospitalized patients have diabetes and/or hyperglycemia. During the COVID-19 pandemic, the US Food and Drug Administration (FDA) and Health Canada temporarily authorized the use of CGM systems in hospitals to supplement point-of-care glucose testing, as an emergency measure to reduce healthcare worker exposure and preserve personal protective equipment. That FDA authorization expired on November 7, 2023, and currently hospital CGM use in the United States is technically off-label, although it is often allowed for patients who already use CGM systems.
The new statement summarizes clinical study data and also addresses the potential benefits of CGM systems for inpatients, existing guidance, analytical and clinical evaluation of CGM performance, safety factors, staff training, clinical workflow, and hospital policies. Also covered are issues around quality assurance, integration of CGM data into electronic health records, cost considerations, and barriers to implementation.
The “good practice points for consideration” in the document are as follows:
- If healthcare professionals want to use CGM systems beyond their intended use, eg, to replace or reduce point-of-care glucose measurements, analytical and clinical performance should be assessed.
- The Clinical and Laboratory Standards Institute (CLSI) 2nd Edition of POCT05 — Performance Metrics for Continuous Interstitial Glucose Monitoring provides helpful guidance.
- Potential interferences that preclude patients from being eligible for CGM should be noted, and staff must be aware that CGM can’t be used for clinical decision-making in these patients.
- A CGM system and/or inpatient glycemia management committee should oversee the development and implementation of hospital-approved policies and procedures for CGM use in the hospital. This committee should have representatives from nursing leadership, physician leadership (e.g., endocrinologists, internal medicine specialists, hospitalists), laboratory, information services, hospital administration, pharmacy, and risk management/legal.
- Policies for patient-owned and hospital-owned CGM devices should be developed, and staff should be trained in their use.
“During the pandemic, there was a lot of research on CGM use in the hospital setting, so we could look at how it works and was it safe. I think we have some good data to show where it can be used,” said Shaw, who also heads the Division of Biochemistry at the Ottawa Hospital. She added, “There’s quite a bit we still don’t know, but I think with some guidance in place about when not to use it, there are certainly patient populations who could benefit from it in the hospital setting.”
Shaw had no disclosures. Another author is general manager and medical director of the Institute for Diabetes Technology (IfDT), which carries out clinical studies, eg, with medical devices for diabetes therapy, on its own initiative and on behalf of various companies. Another author is an IfDT employee. Other authors have received speakers’ honoraria or consulting fees in the last 3 years from Abbott, Berlin-Chemie, BOYDSense, Dexcom, Lilly Deutschland, Novo Nordisk, Perfood, PharmaSens, Roche, Sinocare, Terumo, and Ypsomed.
A version of this article appeared on Medscape.com.
Cardiovascular Disease 2050: No, GLP-1s Won’t Save the Day
This transcript has been edited for clarity .
Robert A. Harrington, MD: I’m here in London at the European Society of Cardiology meetings, at theheart.org | Medscape Cardiology booth, using the meetings as an opportunity to meet with colleagues to talk about recent things that they’ve been writing about.
Today I’m joined by a good friend and colleague, Dr. Dhruv Kazi from Beth Israel Deaconess in Boston. Thanks for joining us.
Dhruv S. Kazi, MD, MS: Thank you for having me.
Harrington: Dr. Kazi is an associate professor of medicine at Harvard Medical School. He’s also the associate director of the Smith Center, which is an outcomes research center at the Beth Israel Deaconess. Thanks for joining us.
Kazi: Excited to be here.
Harrington: The topic I think you know that I want to discuss is a really important paper. There are two papers. They’re part of the American Heart Association’s 100th anniversary celebration, if you will. Many of the papers looked back at where science taken us.
With your coauthor, Karen Joynt Maddox, your papers are looking forward. They’re about the burden of cardiovascular disease in 2050. One paper really focused on what I would call the clinical and public health issues. Yours is focused on the economics. Is that a good description?
Kazi: Perfect.
Harrington: Tell us what you, Karen, and the other writers set out to do. What were you asked to do?
Kazi: As you know, the American Heart Association is entering its second century. Part of this was an exercise to say, where will the country be in 2050, which is a long enough time horizon for us to start planning for the future.
We looked back and said, if prior trends remain the same, where will we be in 2050, accounting for changes in demographics, changes in the composition of the population, and knowing that some of the cardiovascular risk factors are getting worse?
Harrington: For me, what was really striking is that, when I first saw the title and read “2050,” I thought, Oh, that’s a long way away. Then as I started reading it, I realized that this is not so far away.
Kazi: Absolutely.
Harrington: If we’re going to make a difference, it might take us 25 years.
Kazi: Especially if we set ourselves ambitious goals, we›re going to have to dig deep. Business-as-usual is not going to get us there.
Harrington: No. What I think has happened is we›ve spent so much time taking care of acute illness. Case fatality rates are fantastic. I was actually making the comment yesterday to a colleague that when I was an intern, the 30-day death rate from acute myocardial infarction was about 20%.
Kazi: Oh, wow.
Harrington: Now it’s 5%. That’s a big difference in a career.
Trends in the Wrong Direction
Kazi: There are fundamental trends. The decline in case fatalities is a really positive development, and I would hope that, going forward, that would continue. Those are risk-adjusted death rates and what is happening is that risk is going up. This is a function of the fact that the US population is aging; 2030 will be the first year that all the baby boomers will be over the age of 65.
By the mid-2030s, we’ll have more adults over the age of 65 than kids. That aging of the population is going to increase risk. The second is — and this is a positive development — we are a more diverse population, but the populations that are minoritized have higher cardiovascular risk, for a variety of reasons.
As the population of Asian Americans increases and doubles, in fact, as the population of Hispanic Americans doubles, we’re going to see an increase in risk related to cardiovascular disease. The third is that, over the past decade, there are some risk factors that are going in the wrong direction.
Harrington: Let’s talk about that because that’s humbling. I’m involved, as you know, with the American Heart Association, as are you. Despite all the work on Life’s Simple 7 and now Life’s Essential 8, we still have some issues.
Kazi: The big ones that come to mind are hypertension, diabetes, and obesity, all of which are trending in the wrong direction. Hypertension, we were gaining traction; and then over the past decade, we’ve slipped again. As you know, national blood pressure control rates have declined in many populations.
Harrington: Rather substantially.
Kazi: Substantially so, which has implications, in particular, for stroke rates in the future and stroke rates in young adults in the future. Obesity is a problem that we have very little control over. We’re already at 40% on average, which means that some populations are already in the 60% range.
Harrington: We also have obesity in kids — the burden, I’ll call it, of obesity. It’s not that you become obese in your thirties or your forties; you›re becoming obese as a teenager or even younger.
Kazi: Exactly. Since the 1990s, obesity in US adults has doubled, but obesity in US children has quadrupled. It’s starting from a lower base, but it’s very much an escalating problem.
Harrington: Diabetes is tightly linked to it but not totally explained.
Kazi: Exactly. The increase in diabetes is largely driven by obesity, but it›s probably also driven by changes in diet and lifestyle that don›t go through obesity.
Harrington: Yeah, it’s interesting. I think I have this figure correctly. It used to be rare that you saw a child with type 2 diabetes or what we call type 2 diabetes.
Kazi: Yeah.
Harrington: Now, the vast majority of kids with diabetes have type 2 diabetes.
Kazi: In the adolescents/young adults age group, most of it is type 2.
Harrington: Diabetes going up, obesity up, hypertension not well controlled, smoking combustible cigarettes way down.
Kazi: Yeah.
Harrington: Cholesterol levels. I was surprised. Cholesterol looked better. You said — because I was at a meeting where somebody asked you — that’s not explained by treatment.
Kazi: No, it’s not, at least going back to the ‘70s, but likely even sooner. I think that can only be attributed to substantial dietary changes. We are consuming less fat and less trans-fat. It’s possible that those collectively are improving our cholesterol levels, possibly at the expense of our glucose levels, because we basically substituted fats in our diet with more carbs at a population level.
Cigarettes and Vaping
Harrington: Some things certainly trend in the right direction but others in a really difficult direction. It’s going to lead to pretty large changes in risk for coronary disease, atrial fibrillation, and heart failure.
Kazi: I want to go back to the tobacco point. There are definitely marked declines in tobacco, still tightly related to income in the country. You see much higher prevalence of tobacco use in lower-income populations, but it’s unclear to me where it’s going in kids. We know that combustible tobacco use is going down but e-cigarettes went up. What that leads to over the next 30 years is unclear to me.
Harrington: That is a really important comment that’s worth sidebarring. The vaping use has been a terrible epidemic among our high schoolers. What is that going to lead to? Is it going to lead to the use of combustible cigarettes and we’re going to see that go back up? It remains to be seen.
Kazi: Yes, it remains to be seen. Going back to your point about this change in risk factors and this change in demographics, both aging and becoming a more diverse population means that we have large increases in some healthcare conditions.
Coronary heart disease goes up some, there›s a big jump in stroke — nearly a doubling in stroke — which is related to hypertension, obesity, an aging population, and a more diverse population. There are changes in stroke in the young, and atrial fibrillation related to, again, hypertension. We’re seeing these projections, and with them come these pretty large projections in changes in healthcare spending.
Healthcare Spending Not Sustainable
Harrington: Big. I mean, it’s not sustainable. Give the audience the number — it’s pretty frightening.
Kazi: We’re talking about a quadrupling of healthcare costs related to cardiovascular disease over 25 years. We’ve gotten used to the narrative that healthcare in the US is expensive and drugs are expensive, but this is an enormous problem — an unsustainable problem, like you called it.
It’s a doubling as a proportion of the economy. I was looking this up this morning. If the US healthcare economy were its own economy, it would be the fourth largest economy in the world.
Harrington: Healthcare as it is today, is it 21% of our economy?
Kazi: It’s 17% now. If it were its own economy, it would be the fourth largest in the world. We are spending more on healthcare than all but two other countries’ total economies. It’s kind of crazy.
Harrington: We’re talking about a quadrupling.
Kazi: Within that, the cardiovascular piece is a big piece, and we›re talking about a quadrupling.
Harrington: That’s both direct and indirect costs.
Kazi: The quadrupling of costs is just the direct costs. Indirect costs, for the listeners, refer to costs unrelated to healthcare but changes in productivity, either because people are disabled and unable to participate fully in the workforce or they die early.
The productivity costs are also increased substantially as a result. If you look at both healthcare and productivity, that goes up threefold. These are very large changes.
Harrington: Let’s now get to what we can do about it. I made the comment to you when I first read the papers that I was very depressed. Then, after I went through my Kübler-Ross stages of depression, death, and dying, I came to acceptance.
What are we going to do about it? This is a focus on policy, but also a focus on how we deliver healthcare, how we think about healthcare, and how we develop drugs and devices.
The drug question is going to be the one the audience is thinking about. They say, well, what about GLP-1 agonists? Aren’t those going to save the day?
Kazi: Yes and no. I’ll say that, early in my career, I used to be very attracted to simple solutions to complex problems. I’ve come to realize that simple solutions are elegant, attractive, and wrong. We›re dealing with a very complex issue and I think we’re going to need a multipronged approach.
The way I think about it is that there was a group of people who are at very high risk today. How do we help those individuals? Then how do we help the future generation so that they’re not dealing with the projections that we’re talking about.
My colleague, Karen Joynt Maddox, who led one of the papers, as you mentioned, has an elegant line in the paper where she says projections are not destiny. These are things we can change.
Harrington: If nothing changes, this is what it’s going to look like.
Kazi: This is where we’re headed.
Harrington: We can change. We’ve got some time to change, but we don’t have forever.
Kazi: Yes, exactly. We picked the 25-year timeline instead of a “let’s plan for the next century” timeline because we want something concrete and actionable. It’s close enough to be meaningful but far enough to give us the runway we need to act.
Harrington: Give me two things from the policy perspective, because it’s mostly policy.
Kazi: There are policy and clinical interventions. From the policy perspective, if I had to list two things, one is expansion of access to care. As we talk about this big increase in the burden of disease and risk factors, if you have a large proportion of your population that has hypertension or diabetes, you’re going to have to expand access to care to ensure that people get treated so they can get access to this care before they develop the complications that we worry about, like stroke and heart disease, that are very expensive to treat downstream.
The second, more broadly related to access to care, is the access to medications that are effective. You bring up GLP-1s. I think we need a real strategy for how we can give people access to GLP-1s at a price that is affordable to individuals but also affordable to the health system, and to help them stay on the drugs.
GLP-1s are transformative in what they do for weight loss and for diabetes, but more than 50% of people who start one are off it at 12 months. There’s something fundamentally wrong about how we’re delivering GLP-1s today. It’s not just about the cost of the drugs but the support system people need to stay on.
Harrington: I’ve made the comment, in many forms now, that we know the drugs work. We have to figure out how to use them.
Kazi: Exactly, yes.
Harrington: Using them includes chronicity. This is a chronic condition. Some people can come off the drugs, but many can’t. We’re going to have to figure this out, and maybe the newer generations of drugs will help us address what people call the off-ramping. How are we going to do that? I think you’re spot-on. Those are critically important questions.
Kazi: As we looked at this modeling, I’ll tell you — I had a come-to-Jesus moment where I was like, there is no way to fix cardiovascular disease in the US without going through obesity and diabetes. We have to address obesity in the US. We can’t just treat our way out of it. Obesity is fundamentally a food problem and we’ve got to engage again with food policy in a meaningful way.
Harrington: As you know, with the American Heart Association, we›re doing a large amount of work now on food as medicine and food is medicine. We are trying to figure out what the levers are that we can pull to actually help people eat healthier diets.
Kazi: Yes. Rather than framing it as an individual choice that people are eating poorly, it’s, how do we make healthy diets the default in the environment?
Harrington: This is where you get to the children as well.
Kazi: Exactly.
Harrington: I could talk about this all day. I’ve had the benefit of reading the papers now a few times and talking to you on several occasions. Thank you for joining us.
Kazi: Thank you.
Dr. Harrington, Stephen and Suzanne Weiss Dean, Weill Cornell Medicine; Provost for Medical Affairs, Cornell University, New York, NY, disclosed ties with Baim Institute (DSMB); CSL (RCT Executive Committee); Janssen (RCT Char), NHLBI (RCT Executive Committee, DSMB Chair); PCORI (RCT Co-Chair); DCRI, Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; and Cytokinetics. Dr. Kazi, Associate Director, Smith Center for Outcomes Research, Associate Professor, Department of Medicine (Cardiology), Harvard Medical School, Director, Department of Cardiac Critical Care Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, has disclosed receiving a research grant from Boston Scientific (grant to examine the economics of stroke prevention).
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity .
Robert A. Harrington, MD: I’m here in London at the European Society of Cardiology meetings, at theheart.org | Medscape Cardiology booth, using the meetings as an opportunity to meet with colleagues to talk about recent things that they’ve been writing about.
Today I’m joined by a good friend and colleague, Dr. Dhruv Kazi from Beth Israel Deaconess in Boston. Thanks for joining us.
Dhruv S. Kazi, MD, MS: Thank you for having me.
Harrington: Dr. Kazi is an associate professor of medicine at Harvard Medical School. He’s also the associate director of the Smith Center, which is an outcomes research center at the Beth Israel Deaconess. Thanks for joining us.
Kazi: Excited to be here.
Harrington: The topic I think you know that I want to discuss is a really important paper. There are two papers. They’re part of the American Heart Association’s 100th anniversary celebration, if you will. Many of the papers looked back at where science taken us.
With your coauthor, Karen Joynt Maddox, your papers are looking forward. They’re about the burden of cardiovascular disease in 2050. One paper really focused on what I would call the clinical and public health issues. Yours is focused on the economics. Is that a good description?
Kazi: Perfect.
Harrington: Tell us what you, Karen, and the other writers set out to do. What were you asked to do?
Kazi: As you know, the American Heart Association is entering its second century. Part of this was an exercise to say, where will the country be in 2050, which is a long enough time horizon for us to start planning for the future.
We looked back and said, if prior trends remain the same, where will we be in 2050, accounting for changes in demographics, changes in the composition of the population, and knowing that some of the cardiovascular risk factors are getting worse?
Harrington: For me, what was really striking is that, when I first saw the title and read “2050,” I thought, Oh, that’s a long way away. Then as I started reading it, I realized that this is not so far away.
Kazi: Absolutely.
Harrington: If we’re going to make a difference, it might take us 25 years.
Kazi: Especially if we set ourselves ambitious goals, we›re going to have to dig deep. Business-as-usual is not going to get us there.
Harrington: No. What I think has happened is we›ve spent so much time taking care of acute illness. Case fatality rates are fantastic. I was actually making the comment yesterday to a colleague that when I was an intern, the 30-day death rate from acute myocardial infarction was about 20%.
Kazi: Oh, wow.
Harrington: Now it’s 5%. That’s a big difference in a career.
Trends in the Wrong Direction
Kazi: There are fundamental trends. The decline in case fatalities is a really positive development, and I would hope that, going forward, that would continue. Those are risk-adjusted death rates and what is happening is that risk is going up. This is a function of the fact that the US population is aging; 2030 will be the first year that all the baby boomers will be over the age of 65.
By the mid-2030s, we’ll have more adults over the age of 65 than kids. That aging of the population is going to increase risk. The second is — and this is a positive development — we are a more diverse population, but the populations that are minoritized have higher cardiovascular risk, for a variety of reasons.
As the population of Asian Americans increases and doubles, in fact, as the population of Hispanic Americans doubles, we’re going to see an increase in risk related to cardiovascular disease. The third is that, over the past decade, there are some risk factors that are going in the wrong direction.
Harrington: Let’s talk about that because that’s humbling. I’m involved, as you know, with the American Heart Association, as are you. Despite all the work on Life’s Simple 7 and now Life’s Essential 8, we still have some issues.
Kazi: The big ones that come to mind are hypertension, diabetes, and obesity, all of which are trending in the wrong direction. Hypertension, we were gaining traction; and then over the past decade, we’ve slipped again. As you know, national blood pressure control rates have declined in many populations.
Harrington: Rather substantially.
Kazi: Substantially so, which has implications, in particular, for stroke rates in the future and stroke rates in young adults in the future. Obesity is a problem that we have very little control over. We’re already at 40% on average, which means that some populations are already in the 60% range.
Harrington: We also have obesity in kids — the burden, I’ll call it, of obesity. It’s not that you become obese in your thirties or your forties; you›re becoming obese as a teenager or even younger.
Kazi: Exactly. Since the 1990s, obesity in US adults has doubled, but obesity in US children has quadrupled. It’s starting from a lower base, but it’s very much an escalating problem.
Harrington: Diabetes is tightly linked to it but not totally explained.
Kazi: Exactly. The increase in diabetes is largely driven by obesity, but it›s probably also driven by changes in diet and lifestyle that don›t go through obesity.
Harrington: Yeah, it’s interesting. I think I have this figure correctly. It used to be rare that you saw a child with type 2 diabetes or what we call type 2 diabetes.
Kazi: Yeah.
Harrington: Now, the vast majority of kids with diabetes have type 2 diabetes.
Kazi: In the adolescents/young adults age group, most of it is type 2.
Harrington: Diabetes going up, obesity up, hypertension not well controlled, smoking combustible cigarettes way down.
Kazi: Yeah.
Harrington: Cholesterol levels. I was surprised. Cholesterol looked better. You said — because I was at a meeting where somebody asked you — that’s not explained by treatment.
Kazi: No, it’s not, at least going back to the ‘70s, but likely even sooner. I think that can only be attributed to substantial dietary changes. We are consuming less fat and less trans-fat. It’s possible that those collectively are improving our cholesterol levels, possibly at the expense of our glucose levels, because we basically substituted fats in our diet with more carbs at a population level.
Cigarettes and Vaping
Harrington: Some things certainly trend in the right direction but others in a really difficult direction. It’s going to lead to pretty large changes in risk for coronary disease, atrial fibrillation, and heart failure.
Kazi: I want to go back to the tobacco point. There are definitely marked declines in tobacco, still tightly related to income in the country. You see much higher prevalence of tobacco use in lower-income populations, but it’s unclear to me where it’s going in kids. We know that combustible tobacco use is going down but e-cigarettes went up. What that leads to over the next 30 years is unclear to me.
Harrington: That is a really important comment that’s worth sidebarring. The vaping use has been a terrible epidemic among our high schoolers. What is that going to lead to? Is it going to lead to the use of combustible cigarettes and we’re going to see that go back up? It remains to be seen.
Kazi: Yes, it remains to be seen. Going back to your point about this change in risk factors and this change in demographics, both aging and becoming a more diverse population means that we have large increases in some healthcare conditions.
Coronary heart disease goes up some, there›s a big jump in stroke — nearly a doubling in stroke — which is related to hypertension, obesity, an aging population, and a more diverse population. There are changes in stroke in the young, and atrial fibrillation related to, again, hypertension. We’re seeing these projections, and with them come these pretty large projections in changes in healthcare spending.
Healthcare Spending Not Sustainable
Harrington: Big. I mean, it’s not sustainable. Give the audience the number — it’s pretty frightening.
Kazi: We’re talking about a quadrupling of healthcare costs related to cardiovascular disease over 25 years. We’ve gotten used to the narrative that healthcare in the US is expensive and drugs are expensive, but this is an enormous problem — an unsustainable problem, like you called it.
It’s a doubling as a proportion of the economy. I was looking this up this morning. If the US healthcare economy were its own economy, it would be the fourth largest economy in the world.
Harrington: Healthcare as it is today, is it 21% of our economy?
Kazi: It’s 17% now. If it were its own economy, it would be the fourth largest in the world. We are spending more on healthcare than all but two other countries’ total economies. It’s kind of crazy.
Harrington: We’re talking about a quadrupling.
Kazi: Within that, the cardiovascular piece is a big piece, and we›re talking about a quadrupling.
Harrington: That’s both direct and indirect costs.
Kazi: The quadrupling of costs is just the direct costs. Indirect costs, for the listeners, refer to costs unrelated to healthcare but changes in productivity, either because people are disabled and unable to participate fully in the workforce or they die early.
The productivity costs are also increased substantially as a result. If you look at both healthcare and productivity, that goes up threefold. These are very large changes.
Harrington: Let’s now get to what we can do about it. I made the comment to you when I first read the papers that I was very depressed. Then, after I went through my Kübler-Ross stages of depression, death, and dying, I came to acceptance.
What are we going to do about it? This is a focus on policy, but also a focus on how we deliver healthcare, how we think about healthcare, and how we develop drugs and devices.
The drug question is going to be the one the audience is thinking about. They say, well, what about GLP-1 agonists? Aren’t those going to save the day?
Kazi: Yes and no. I’ll say that, early in my career, I used to be very attracted to simple solutions to complex problems. I’ve come to realize that simple solutions are elegant, attractive, and wrong. We›re dealing with a very complex issue and I think we’re going to need a multipronged approach.
The way I think about it is that there was a group of people who are at very high risk today. How do we help those individuals? Then how do we help the future generation so that they’re not dealing with the projections that we’re talking about.
My colleague, Karen Joynt Maddox, who led one of the papers, as you mentioned, has an elegant line in the paper where she says projections are not destiny. These are things we can change.
Harrington: If nothing changes, this is what it’s going to look like.
Kazi: This is where we’re headed.
Harrington: We can change. We’ve got some time to change, but we don’t have forever.
Kazi: Yes, exactly. We picked the 25-year timeline instead of a “let’s plan for the next century” timeline because we want something concrete and actionable. It’s close enough to be meaningful but far enough to give us the runway we need to act.
Harrington: Give me two things from the policy perspective, because it’s mostly policy.
Kazi: There are policy and clinical interventions. From the policy perspective, if I had to list two things, one is expansion of access to care. As we talk about this big increase in the burden of disease and risk factors, if you have a large proportion of your population that has hypertension or diabetes, you’re going to have to expand access to care to ensure that people get treated so they can get access to this care before they develop the complications that we worry about, like stroke and heart disease, that are very expensive to treat downstream.
The second, more broadly related to access to care, is the access to medications that are effective. You bring up GLP-1s. I think we need a real strategy for how we can give people access to GLP-1s at a price that is affordable to individuals but also affordable to the health system, and to help them stay on the drugs.
GLP-1s are transformative in what they do for weight loss and for diabetes, but more than 50% of people who start one are off it at 12 months. There’s something fundamentally wrong about how we’re delivering GLP-1s today. It’s not just about the cost of the drugs but the support system people need to stay on.
Harrington: I’ve made the comment, in many forms now, that we know the drugs work. We have to figure out how to use them.
Kazi: Exactly, yes.
Harrington: Using them includes chronicity. This is a chronic condition. Some people can come off the drugs, but many can’t. We’re going to have to figure this out, and maybe the newer generations of drugs will help us address what people call the off-ramping. How are we going to do that? I think you’re spot-on. Those are critically important questions.
Kazi: As we looked at this modeling, I’ll tell you — I had a come-to-Jesus moment where I was like, there is no way to fix cardiovascular disease in the US without going through obesity and diabetes. We have to address obesity in the US. We can’t just treat our way out of it. Obesity is fundamentally a food problem and we’ve got to engage again with food policy in a meaningful way.
Harrington: As you know, with the American Heart Association, we›re doing a large amount of work now on food as medicine and food is medicine. We are trying to figure out what the levers are that we can pull to actually help people eat healthier diets.
Kazi: Yes. Rather than framing it as an individual choice that people are eating poorly, it’s, how do we make healthy diets the default in the environment?
Harrington: This is where you get to the children as well.
Kazi: Exactly.
Harrington: I could talk about this all day. I’ve had the benefit of reading the papers now a few times and talking to you on several occasions. Thank you for joining us.
Kazi: Thank you.
Dr. Harrington, Stephen and Suzanne Weiss Dean, Weill Cornell Medicine; Provost for Medical Affairs, Cornell University, New York, NY, disclosed ties with Baim Institute (DSMB); CSL (RCT Executive Committee); Janssen (RCT Char), NHLBI (RCT Executive Committee, DSMB Chair); PCORI (RCT Co-Chair); DCRI, Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; and Cytokinetics. Dr. Kazi, Associate Director, Smith Center for Outcomes Research, Associate Professor, Department of Medicine (Cardiology), Harvard Medical School, Director, Department of Cardiac Critical Care Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, has disclosed receiving a research grant from Boston Scientific (grant to examine the economics of stroke prevention).
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity .
Robert A. Harrington, MD: I’m here in London at the European Society of Cardiology meetings, at theheart.org | Medscape Cardiology booth, using the meetings as an opportunity to meet with colleagues to talk about recent things that they’ve been writing about.
Today I’m joined by a good friend and colleague, Dr. Dhruv Kazi from Beth Israel Deaconess in Boston. Thanks for joining us.
Dhruv S. Kazi, MD, MS: Thank you for having me.
Harrington: Dr. Kazi is an associate professor of medicine at Harvard Medical School. He’s also the associate director of the Smith Center, which is an outcomes research center at the Beth Israel Deaconess. Thanks for joining us.
Kazi: Excited to be here.
Harrington: The topic I think you know that I want to discuss is a really important paper. There are two papers. They’re part of the American Heart Association’s 100th anniversary celebration, if you will. Many of the papers looked back at where science taken us.
With your coauthor, Karen Joynt Maddox, your papers are looking forward. They’re about the burden of cardiovascular disease in 2050. One paper really focused on what I would call the clinical and public health issues. Yours is focused on the economics. Is that a good description?
Kazi: Perfect.
Harrington: Tell us what you, Karen, and the other writers set out to do. What were you asked to do?
Kazi: As you know, the American Heart Association is entering its second century. Part of this was an exercise to say, where will the country be in 2050, which is a long enough time horizon for us to start planning for the future.
We looked back and said, if prior trends remain the same, where will we be in 2050, accounting for changes in demographics, changes in the composition of the population, and knowing that some of the cardiovascular risk factors are getting worse?
Harrington: For me, what was really striking is that, when I first saw the title and read “2050,” I thought, Oh, that’s a long way away. Then as I started reading it, I realized that this is not so far away.
Kazi: Absolutely.
Harrington: If we’re going to make a difference, it might take us 25 years.
Kazi: Especially if we set ourselves ambitious goals, we›re going to have to dig deep. Business-as-usual is not going to get us there.
Harrington: No. What I think has happened is we›ve spent so much time taking care of acute illness. Case fatality rates are fantastic. I was actually making the comment yesterday to a colleague that when I was an intern, the 30-day death rate from acute myocardial infarction was about 20%.
Kazi: Oh, wow.
Harrington: Now it’s 5%. That’s a big difference in a career.
Trends in the Wrong Direction
Kazi: There are fundamental trends. The decline in case fatalities is a really positive development, and I would hope that, going forward, that would continue. Those are risk-adjusted death rates and what is happening is that risk is going up. This is a function of the fact that the US population is aging; 2030 will be the first year that all the baby boomers will be over the age of 65.
By the mid-2030s, we’ll have more adults over the age of 65 than kids. That aging of the population is going to increase risk. The second is — and this is a positive development — we are a more diverse population, but the populations that are minoritized have higher cardiovascular risk, for a variety of reasons.
As the population of Asian Americans increases and doubles, in fact, as the population of Hispanic Americans doubles, we’re going to see an increase in risk related to cardiovascular disease. The third is that, over the past decade, there are some risk factors that are going in the wrong direction.
Harrington: Let’s talk about that because that’s humbling. I’m involved, as you know, with the American Heart Association, as are you. Despite all the work on Life’s Simple 7 and now Life’s Essential 8, we still have some issues.
Kazi: The big ones that come to mind are hypertension, diabetes, and obesity, all of which are trending in the wrong direction. Hypertension, we were gaining traction; and then over the past decade, we’ve slipped again. As you know, national blood pressure control rates have declined in many populations.
Harrington: Rather substantially.
Kazi: Substantially so, which has implications, in particular, for stroke rates in the future and stroke rates in young adults in the future. Obesity is a problem that we have very little control over. We’re already at 40% on average, which means that some populations are already in the 60% range.
Harrington: We also have obesity in kids — the burden, I’ll call it, of obesity. It’s not that you become obese in your thirties or your forties; you›re becoming obese as a teenager or even younger.
Kazi: Exactly. Since the 1990s, obesity in US adults has doubled, but obesity in US children has quadrupled. It’s starting from a lower base, but it’s very much an escalating problem.
Harrington: Diabetes is tightly linked to it but not totally explained.
Kazi: Exactly. The increase in diabetes is largely driven by obesity, but it›s probably also driven by changes in diet and lifestyle that don›t go through obesity.
Harrington: Yeah, it’s interesting. I think I have this figure correctly. It used to be rare that you saw a child with type 2 diabetes or what we call type 2 diabetes.
Kazi: Yeah.
Harrington: Now, the vast majority of kids with diabetes have type 2 diabetes.
Kazi: In the adolescents/young adults age group, most of it is type 2.
Harrington: Diabetes going up, obesity up, hypertension not well controlled, smoking combustible cigarettes way down.
Kazi: Yeah.
Harrington: Cholesterol levels. I was surprised. Cholesterol looked better. You said — because I was at a meeting where somebody asked you — that’s not explained by treatment.
Kazi: No, it’s not, at least going back to the ‘70s, but likely even sooner. I think that can only be attributed to substantial dietary changes. We are consuming less fat and less trans-fat. It’s possible that those collectively are improving our cholesterol levels, possibly at the expense of our glucose levels, because we basically substituted fats in our diet with more carbs at a population level.
Cigarettes and Vaping
Harrington: Some things certainly trend in the right direction but others in a really difficult direction. It’s going to lead to pretty large changes in risk for coronary disease, atrial fibrillation, and heart failure.
Kazi: I want to go back to the tobacco point. There are definitely marked declines in tobacco, still tightly related to income in the country. You see much higher prevalence of tobacco use in lower-income populations, but it’s unclear to me where it’s going in kids. We know that combustible tobacco use is going down but e-cigarettes went up. What that leads to over the next 30 years is unclear to me.
Harrington: That is a really important comment that’s worth sidebarring. The vaping use has been a terrible epidemic among our high schoolers. What is that going to lead to? Is it going to lead to the use of combustible cigarettes and we’re going to see that go back up? It remains to be seen.
Kazi: Yes, it remains to be seen. Going back to your point about this change in risk factors and this change in demographics, both aging and becoming a more diverse population means that we have large increases in some healthcare conditions.
Coronary heart disease goes up some, there›s a big jump in stroke — nearly a doubling in stroke — which is related to hypertension, obesity, an aging population, and a more diverse population. There are changes in stroke in the young, and atrial fibrillation related to, again, hypertension. We’re seeing these projections, and with them come these pretty large projections in changes in healthcare spending.
Healthcare Spending Not Sustainable
Harrington: Big. I mean, it’s not sustainable. Give the audience the number — it’s pretty frightening.
Kazi: We’re talking about a quadrupling of healthcare costs related to cardiovascular disease over 25 years. We’ve gotten used to the narrative that healthcare in the US is expensive and drugs are expensive, but this is an enormous problem — an unsustainable problem, like you called it.
It’s a doubling as a proportion of the economy. I was looking this up this morning. If the US healthcare economy were its own economy, it would be the fourth largest economy in the world.
Harrington: Healthcare as it is today, is it 21% of our economy?
Kazi: It’s 17% now. If it were its own economy, it would be the fourth largest in the world. We are spending more on healthcare than all but two other countries’ total economies. It’s kind of crazy.
Harrington: We’re talking about a quadrupling.
Kazi: Within that, the cardiovascular piece is a big piece, and we›re talking about a quadrupling.
Harrington: That’s both direct and indirect costs.
Kazi: The quadrupling of costs is just the direct costs. Indirect costs, for the listeners, refer to costs unrelated to healthcare but changes in productivity, either because people are disabled and unable to participate fully in the workforce or they die early.
The productivity costs are also increased substantially as a result. If you look at both healthcare and productivity, that goes up threefold. These are very large changes.
Harrington: Let’s now get to what we can do about it. I made the comment to you when I first read the papers that I was very depressed. Then, after I went through my Kübler-Ross stages of depression, death, and dying, I came to acceptance.
What are we going to do about it? This is a focus on policy, but also a focus on how we deliver healthcare, how we think about healthcare, and how we develop drugs and devices.
The drug question is going to be the one the audience is thinking about. They say, well, what about GLP-1 agonists? Aren’t those going to save the day?
Kazi: Yes and no. I’ll say that, early in my career, I used to be very attracted to simple solutions to complex problems. I’ve come to realize that simple solutions are elegant, attractive, and wrong. We›re dealing with a very complex issue and I think we’re going to need a multipronged approach.
The way I think about it is that there was a group of people who are at very high risk today. How do we help those individuals? Then how do we help the future generation so that they’re not dealing with the projections that we’re talking about.
My colleague, Karen Joynt Maddox, who led one of the papers, as you mentioned, has an elegant line in the paper where she says projections are not destiny. These are things we can change.
Harrington: If nothing changes, this is what it’s going to look like.
Kazi: This is where we’re headed.
Harrington: We can change. We’ve got some time to change, but we don’t have forever.
Kazi: Yes, exactly. We picked the 25-year timeline instead of a “let’s plan for the next century” timeline because we want something concrete and actionable. It’s close enough to be meaningful but far enough to give us the runway we need to act.
Harrington: Give me two things from the policy perspective, because it’s mostly policy.
Kazi: There are policy and clinical interventions. From the policy perspective, if I had to list two things, one is expansion of access to care. As we talk about this big increase in the burden of disease and risk factors, if you have a large proportion of your population that has hypertension or diabetes, you’re going to have to expand access to care to ensure that people get treated so they can get access to this care before they develop the complications that we worry about, like stroke and heart disease, that are very expensive to treat downstream.
The second, more broadly related to access to care, is the access to medications that are effective. You bring up GLP-1s. I think we need a real strategy for how we can give people access to GLP-1s at a price that is affordable to individuals but also affordable to the health system, and to help them stay on the drugs.
GLP-1s are transformative in what they do for weight loss and for diabetes, but more than 50% of people who start one are off it at 12 months. There’s something fundamentally wrong about how we’re delivering GLP-1s today. It’s not just about the cost of the drugs but the support system people need to stay on.
Harrington: I’ve made the comment, in many forms now, that we know the drugs work. We have to figure out how to use them.
Kazi: Exactly, yes.
Harrington: Using them includes chronicity. This is a chronic condition. Some people can come off the drugs, but many can’t. We’re going to have to figure this out, and maybe the newer generations of drugs will help us address what people call the off-ramping. How are we going to do that? I think you’re spot-on. Those are critically important questions.
Kazi: As we looked at this modeling, I’ll tell you — I had a come-to-Jesus moment where I was like, there is no way to fix cardiovascular disease in the US without going through obesity and diabetes. We have to address obesity in the US. We can’t just treat our way out of it. Obesity is fundamentally a food problem and we’ve got to engage again with food policy in a meaningful way.
Harrington: As you know, with the American Heart Association, we›re doing a large amount of work now on food as medicine and food is medicine. We are trying to figure out what the levers are that we can pull to actually help people eat healthier diets.
Kazi: Yes. Rather than framing it as an individual choice that people are eating poorly, it’s, how do we make healthy diets the default in the environment?
Harrington: This is where you get to the children as well.
Kazi: Exactly.
Harrington: I could talk about this all day. I’ve had the benefit of reading the papers now a few times and talking to you on several occasions. Thank you for joining us.
Kazi: Thank you.
Dr. Harrington, Stephen and Suzanne Weiss Dean, Weill Cornell Medicine; Provost for Medical Affairs, Cornell University, New York, NY, disclosed ties with Baim Institute (DSMB); CSL (RCT Executive Committee); Janssen (RCT Char), NHLBI (RCT Executive Committee, DSMB Chair); PCORI (RCT Co-Chair); DCRI, Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; and Cytokinetics. Dr. Kazi, Associate Director, Smith Center for Outcomes Research, Associate Professor, Department of Medicine (Cardiology), Harvard Medical School, Director, Department of Cardiac Critical Care Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, has disclosed receiving a research grant from Boston Scientific (grant to examine the economics of stroke prevention).
A version of this article appeared on Medscape.com.
Humans and Carbs: A Complicated 800,000-Year Relationship
Trying to reduce your carbohydrate intake means going against nearly a million years of evolution.
Humans are among a few species with multiple copies of certain genes that help us break down starch — carbs like potatoes, beans, corn, and grains — so that we can turn it into energy our bodies can use.
However, it’s been difficult for researchers to pinpoint when in human history we acquired multiple copies of these genes because they’re in a region of the genome that’s hard to sequence.
A recent study published in Science suggests that humans may have developed multiple copies of the gene for amylase — an enzyme that’s the first step in starch digestion — over 800,000 years ago, long before the agricultural revolution. This genetic change could have helped us adapt to eating starchy foods.
The study shows how “what your ancestors ate thousands of years ago could be affecting our genetics today,” said Kelsey Jorgensen, PhD, a biological anthropologist at The University of Kansas, Lawrence, who was not involved in the study.
The double-edged sword has sharpened over all those centuries. On one hand, the human body needs and craves carbs to function. On the other hand, our modern-day consumption of carbs, especially calorie-dense/nutritionally-barren processed carbs, has long since passed “healthy.”
How Researchers Found Our Carb-Lover Gene
The enzyme amylase turns complex carbs into maltose, a sweet-tasting sugar that is made of two glucose molecules linked together. We make two kinds of amylases: Salivary amylase that breaks down carbs in our mouths and pancreatic amylase that is secreted into our small intestines.
Modern humans have multiple copies of both amylases. Past research showed that human populations with diets high in starch can have up to nine copies of the gene for salivary amylase, called AMY1.
To pinpoint when in human history we acquired multiple copies of AMY1, the new study utilized novel techniques, called optical genome mapping and long-read sequencing, to sequence and analyze the genes. They sequenced 98 modern-day samples and 68 ancient DNA samples, including one from a Siberian person who lived 45,000 years ago.
The ancient DNA data in the study allowed the researchers to track how the number of amylase genes changed over time, said George Perry, PhD, an anthropological geneticist at The Pennsylvania State University-University Park (he was not involved in the study).
Based on the sequencing, the team analyzed changes in the genes in their samples to gauge evolutionary timelines. Perry noted that this was a “very clever approach to estimating the amylase copy number mutation rate, which in turn can really help in testing evolutionary hypotheses.”
The researchers found that even before farming, hunter-gatherers had between four and eight AMY1 genes in their cells. This suggests that people across Eurasia already had a number of these genes long before they started growing crops. (Recent research indicates that Neanderthals also ate starchy foods.)
“Even archaic hominins had these [genetic] variations and that indicates that they were consuming starch,” said Feyza Yilmaz, PhD, an associate computational scientist at The Jackson Laboratory in Bar Harbor, Maine, and a lead author of the study.
However, 4000 years ago, after the agricultural revolution, the research indicates that there were even more AMY1 copies acquired. Yilmaz noted, “with the advance of agriculture, we see an increase in high amylase copy number haplotypes. So genetic variation goes hand in hand with adaptation to the environment.”
A previous study showed that species that share an environment with humans, such as dogs and pigs, also have copy number variation of amylase genes, said Yilmaz, indicating a link between genome changes and an increase in starch consumption.
Potential Health Impacts on Modern Humans
The duplications in the AMY1 gene could have allowed humans to better digest starches. And it’s conceivable that having more copies of the gene means being able to break down starches even more efficiently, and those with more copies “may be more prone to having high blood sugar, prediabetes, that sort of thing,” Jorgensen said.
Whether those with more AMY1 genes have more health risks is an active area of research. “Researchers tested whether there’s a correlation between AMY1 gene copies and diabetes or BMI [body mass index]. And so far, some studies show that there is indeed correlation, but other studies show that there is no correlation at all,” said Yilmaz.
Yilmaz pointed out that only 5 or 10% of carb digestion happens in our mouths, the rest occurs in our small intestine, plus there are many other factors involved in eating and metabolism.
“I am really looking forward to seeing studies which truly figure out the connection between AMY1 copy number and metabolic health and also what type of factors play a role in metabolic health,” said Yilmaz.
It’s also possible that having more AMY1 copies could lead to more carb cravings as the enzyme creates a type of sugar in our mouths. “Previous studies show that there’s a correlation between AMY1 copy number and also the amylase enzyme levels, so the faster we process the starch, the taste [of starches] will be sweeter,” said Yilmaz.
However, the link between cravings and copy numbers isn’t clear. And we don’t exactly know what came first — did the starch in humans’ diet lead to more copies of amylase genes, or did the copies of the amylase genes drive cravings that lead us to cultivate more carbs? We’ll need more research to find out.
How Will Today’s Processed Carbs Affect Our Genes Tomorrow?
As our diet changes to increasingly include processed carbs, what will happen to our AMY1 genes is fuzzy. “I don’t know what this could do to our genomes in the next 1000 years or more than 1000 years,” Yilmaz noted, but she said from the evidence it seems as though we may have peaked in AMY1 copies.
Jorgensen noted that this research is focused on a European population. She wonders whether the pattern of AMY1 duplication will be repeated in other populations “because the rise of starch happened first in the Middle East and then Europe and then later in the Americas,” she said.
“There’s individual variation and then there’s population-wide variation,” Jorgensen pointed out. She speculates that the historical diet of different cultures could explain population-based variations in AMY1 genes — it’s something future research could investigate. Other populations may also experience genetic changes as much of the world shifts to a more carb-heavy Western diet.
Overall, this research adds to the growing evidence that humans have a long history of loving carbs — for better and, at least over our most recent history and immediate future, for worse.
A version of this article appeared on Medscape.com.
Trying to reduce your carbohydrate intake means going against nearly a million years of evolution.
Humans are among a few species with multiple copies of certain genes that help us break down starch — carbs like potatoes, beans, corn, and grains — so that we can turn it into energy our bodies can use.
However, it’s been difficult for researchers to pinpoint when in human history we acquired multiple copies of these genes because they’re in a region of the genome that’s hard to sequence.
A recent study published in Science suggests that humans may have developed multiple copies of the gene for amylase — an enzyme that’s the first step in starch digestion — over 800,000 years ago, long before the agricultural revolution. This genetic change could have helped us adapt to eating starchy foods.
The study shows how “what your ancestors ate thousands of years ago could be affecting our genetics today,” said Kelsey Jorgensen, PhD, a biological anthropologist at The University of Kansas, Lawrence, who was not involved in the study.
The double-edged sword has sharpened over all those centuries. On one hand, the human body needs and craves carbs to function. On the other hand, our modern-day consumption of carbs, especially calorie-dense/nutritionally-barren processed carbs, has long since passed “healthy.”
How Researchers Found Our Carb-Lover Gene
The enzyme amylase turns complex carbs into maltose, a sweet-tasting sugar that is made of two glucose molecules linked together. We make two kinds of amylases: Salivary amylase that breaks down carbs in our mouths and pancreatic amylase that is secreted into our small intestines.
Modern humans have multiple copies of both amylases. Past research showed that human populations with diets high in starch can have up to nine copies of the gene for salivary amylase, called AMY1.
To pinpoint when in human history we acquired multiple copies of AMY1, the new study utilized novel techniques, called optical genome mapping and long-read sequencing, to sequence and analyze the genes. They sequenced 98 modern-day samples and 68 ancient DNA samples, including one from a Siberian person who lived 45,000 years ago.
The ancient DNA data in the study allowed the researchers to track how the number of amylase genes changed over time, said George Perry, PhD, an anthropological geneticist at The Pennsylvania State University-University Park (he was not involved in the study).
Based on the sequencing, the team analyzed changes in the genes in their samples to gauge evolutionary timelines. Perry noted that this was a “very clever approach to estimating the amylase copy number mutation rate, which in turn can really help in testing evolutionary hypotheses.”
The researchers found that even before farming, hunter-gatherers had between four and eight AMY1 genes in their cells. This suggests that people across Eurasia already had a number of these genes long before they started growing crops. (Recent research indicates that Neanderthals also ate starchy foods.)
“Even archaic hominins had these [genetic] variations and that indicates that they were consuming starch,” said Feyza Yilmaz, PhD, an associate computational scientist at The Jackson Laboratory in Bar Harbor, Maine, and a lead author of the study.
However, 4000 years ago, after the agricultural revolution, the research indicates that there were even more AMY1 copies acquired. Yilmaz noted, “with the advance of agriculture, we see an increase in high amylase copy number haplotypes. So genetic variation goes hand in hand with adaptation to the environment.”
A previous study showed that species that share an environment with humans, such as dogs and pigs, also have copy number variation of amylase genes, said Yilmaz, indicating a link between genome changes and an increase in starch consumption.
Potential Health Impacts on Modern Humans
The duplications in the AMY1 gene could have allowed humans to better digest starches. And it’s conceivable that having more copies of the gene means being able to break down starches even more efficiently, and those with more copies “may be more prone to having high blood sugar, prediabetes, that sort of thing,” Jorgensen said.
Whether those with more AMY1 genes have more health risks is an active area of research. “Researchers tested whether there’s a correlation between AMY1 gene copies and diabetes or BMI [body mass index]. And so far, some studies show that there is indeed correlation, but other studies show that there is no correlation at all,” said Yilmaz.
Yilmaz pointed out that only 5 or 10% of carb digestion happens in our mouths, the rest occurs in our small intestine, plus there are many other factors involved in eating and metabolism.
“I am really looking forward to seeing studies which truly figure out the connection between AMY1 copy number and metabolic health and also what type of factors play a role in metabolic health,” said Yilmaz.
It’s also possible that having more AMY1 copies could lead to more carb cravings as the enzyme creates a type of sugar in our mouths. “Previous studies show that there’s a correlation between AMY1 copy number and also the amylase enzyme levels, so the faster we process the starch, the taste [of starches] will be sweeter,” said Yilmaz.
However, the link between cravings and copy numbers isn’t clear. And we don’t exactly know what came first — did the starch in humans’ diet lead to more copies of amylase genes, or did the copies of the amylase genes drive cravings that lead us to cultivate more carbs? We’ll need more research to find out.
How Will Today’s Processed Carbs Affect Our Genes Tomorrow?
As our diet changes to increasingly include processed carbs, what will happen to our AMY1 genes is fuzzy. “I don’t know what this could do to our genomes in the next 1000 years or more than 1000 years,” Yilmaz noted, but she said from the evidence it seems as though we may have peaked in AMY1 copies.
Jorgensen noted that this research is focused on a European population. She wonders whether the pattern of AMY1 duplication will be repeated in other populations “because the rise of starch happened first in the Middle East and then Europe and then later in the Americas,” she said.
“There’s individual variation and then there’s population-wide variation,” Jorgensen pointed out. She speculates that the historical diet of different cultures could explain population-based variations in AMY1 genes — it’s something future research could investigate. Other populations may also experience genetic changes as much of the world shifts to a more carb-heavy Western diet.
Overall, this research adds to the growing evidence that humans have a long history of loving carbs — for better and, at least over our most recent history and immediate future, for worse.
A version of this article appeared on Medscape.com.
Trying to reduce your carbohydrate intake means going against nearly a million years of evolution.
Humans are among a few species with multiple copies of certain genes that help us break down starch — carbs like potatoes, beans, corn, and grains — so that we can turn it into energy our bodies can use.
However, it’s been difficult for researchers to pinpoint when in human history we acquired multiple copies of these genes because they’re in a region of the genome that’s hard to sequence.
A recent study published in Science suggests that humans may have developed multiple copies of the gene for amylase — an enzyme that’s the first step in starch digestion — over 800,000 years ago, long before the agricultural revolution. This genetic change could have helped us adapt to eating starchy foods.
The study shows how “what your ancestors ate thousands of years ago could be affecting our genetics today,” said Kelsey Jorgensen, PhD, a biological anthropologist at The University of Kansas, Lawrence, who was not involved in the study.
The double-edged sword has sharpened over all those centuries. On one hand, the human body needs and craves carbs to function. On the other hand, our modern-day consumption of carbs, especially calorie-dense/nutritionally-barren processed carbs, has long since passed “healthy.”
How Researchers Found Our Carb-Lover Gene
The enzyme amylase turns complex carbs into maltose, a sweet-tasting sugar that is made of two glucose molecules linked together. We make two kinds of amylases: Salivary amylase that breaks down carbs in our mouths and pancreatic amylase that is secreted into our small intestines.
Modern humans have multiple copies of both amylases. Past research showed that human populations with diets high in starch can have up to nine copies of the gene for salivary amylase, called AMY1.
To pinpoint when in human history we acquired multiple copies of AMY1, the new study utilized novel techniques, called optical genome mapping and long-read sequencing, to sequence and analyze the genes. They sequenced 98 modern-day samples and 68 ancient DNA samples, including one from a Siberian person who lived 45,000 years ago.
The ancient DNA data in the study allowed the researchers to track how the number of amylase genes changed over time, said George Perry, PhD, an anthropological geneticist at The Pennsylvania State University-University Park (he was not involved in the study).
Based on the sequencing, the team analyzed changes in the genes in their samples to gauge evolutionary timelines. Perry noted that this was a “very clever approach to estimating the amylase copy number mutation rate, which in turn can really help in testing evolutionary hypotheses.”
The researchers found that even before farming, hunter-gatherers had between four and eight AMY1 genes in their cells. This suggests that people across Eurasia already had a number of these genes long before they started growing crops. (Recent research indicates that Neanderthals also ate starchy foods.)
“Even archaic hominins had these [genetic] variations and that indicates that they were consuming starch,” said Feyza Yilmaz, PhD, an associate computational scientist at The Jackson Laboratory in Bar Harbor, Maine, and a lead author of the study.
However, 4000 years ago, after the agricultural revolution, the research indicates that there were even more AMY1 copies acquired. Yilmaz noted, “with the advance of agriculture, we see an increase in high amylase copy number haplotypes. So genetic variation goes hand in hand with adaptation to the environment.”
A previous study showed that species that share an environment with humans, such as dogs and pigs, also have copy number variation of amylase genes, said Yilmaz, indicating a link between genome changes and an increase in starch consumption.
Potential Health Impacts on Modern Humans
The duplications in the AMY1 gene could have allowed humans to better digest starches. And it’s conceivable that having more copies of the gene means being able to break down starches even more efficiently, and those with more copies “may be more prone to having high blood sugar, prediabetes, that sort of thing,” Jorgensen said.
Whether those with more AMY1 genes have more health risks is an active area of research. “Researchers tested whether there’s a correlation between AMY1 gene copies and diabetes or BMI [body mass index]. And so far, some studies show that there is indeed correlation, but other studies show that there is no correlation at all,” said Yilmaz.
Yilmaz pointed out that only 5 or 10% of carb digestion happens in our mouths, the rest occurs in our small intestine, plus there are many other factors involved in eating and metabolism.
“I am really looking forward to seeing studies which truly figure out the connection between AMY1 copy number and metabolic health and also what type of factors play a role in metabolic health,” said Yilmaz.
It’s also possible that having more AMY1 copies could lead to more carb cravings as the enzyme creates a type of sugar in our mouths. “Previous studies show that there’s a correlation between AMY1 copy number and also the amylase enzyme levels, so the faster we process the starch, the taste [of starches] will be sweeter,” said Yilmaz.
However, the link between cravings and copy numbers isn’t clear. And we don’t exactly know what came first — did the starch in humans’ diet lead to more copies of amylase genes, or did the copies of the amylase genes drive cravings that lead us to cultivate more carbs? We’ll need more research to find out.
How Will Today’s Processed Carbs Affect Our Genes Tomorrow?
As our diet changes to increasingly include processed carbs, what will happen to our AMY1 genes is fuzzy. “I don’t know what this could do to our genomes in the next 1000 years or more than 1000 years,” Yilmaz noted, but she said from the evidence it seems as though we may have peaked in AMY1 copies.
Jorgensen noted that this research is focused on a European population. She wonders whether the pattern of AMY1 duplication will be repeated in other populations “because the rise of starch happened first in the Middle East and then Europe and then later in the Americas,” she said.
“There’s individual variation and then there’s population-wide variation,” Jorgensen pointed out. She speculates that the historical diet of different cultures could explain population-based variations in AMY1 genes — it’s something future research could investigate. Other populations may also experience genetic changes as much of the world shifts to a more carb-heavy Western diet.
Overall, this research adds to the growing evidence that humans have a long history of loving carbs — for better and, at least over our most recent history and immediate future, for worse.
A version of this article appeared on Medscape.com.
Does Exercise Intensity Modulate Ghrelin?
TOPLINE:
METHODOLOGY:
- Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
- To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
- Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2peak) test to determine the exercise intensity.
- Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2peak).
- Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.
TAKEAWAY:
- Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
- Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
- Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
- Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
IN PRACTICE:
“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”
SOURCE:
This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.
LIMITATIONS:
The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.
DISCLOSURES:
The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
- To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
- Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2peak) test to determine the exercise intensity.
- Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2peak).
- Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.
TAKEAWAY:
- Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
- Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
- Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
- Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
IN PRACTICE:
“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”
SOURCE:
This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.
LIMITATIONS:
The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.
DISCLOSURES:
The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
- To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
- Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2peak) test to determine the exercise intensity.
- Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2peak).
- Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.
TAKEAWAY:
- Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
- Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
- Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
- Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
IN PRACTICE:
“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”
SOURCE:
This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.
LIMITATIONS:
The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.
DISCLOSURES:
The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
A 51-year-old woman presented for a routine full body skin exam after vacationing in Hawaii.
Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.
Palmar creases, subungual surfaces, sites of trauma, and joint spaces (including the knees, spine, elbows, and shoulders) are commonly affected. Hair depletes in the pubic area and axillary vaults. Nevi may also appear darker. In patients with autoimmune adrenalitis, vitiligo may be seen secondary to autoimmune destruction of melanocytes.
Diagnosis may be difficult in the early stages, but historical findings of fatigue and clinical findings of hyperpigmentation in classic areas may prompt appropriate lab screening workup. It is essential to determine whether adrenal insufficiency is primary or secondary. Evaluation of decreased cortisol production, determination of whether production is ACTH-dependent or -independent, and evaluation for the underlying causes of adrenal dysfunction are important. Lab screening includes morning serum cortisol, morning ACTH (cosyntropin) stimulation test, fasting CBC with differential, and CMP to evaluate for normocytic normochromic anemia, hyponatremia, hyperkalemia, hypoglycemia, plasma renin/aldosterone ratio, and 21-hydroxylase autoantibodies.
Management strategies of primary adrenal insufficiency require corticosteroid supplementation and multidisciplinary collaboration with endocrinology. If untreated, primary adrenal insufficiency can be fatal. Adrenal crisis is a critical condition following a precipitating event, such as GI infection, fever, acute stress, and/or untreated adrenal or pituitary disorders. Clinical findings include acute shock with hypotension, nausea, vomiting, abdominal pain, back or leg pain, and a change in mental status. In this scenario, increasing the dose of corticosteroid supplementation is essential for reducing mortality.
Upon examining this patient’s new skin findings of hyperpigmentation and discussing her fatigue, primary adrenal insufficiency was suspected. With further prompting, the patient reported an ICU hospitalization several months prior because of sepsis originating from a peritonsillar abscess. With these clinical and historical findings, preliminary workup was conducted by dermatology, which included morning cortisol level, ACTH, CBC with differential, CMP, plasma renin-aldosterone ratio, and 21-hydroxylase autoantibodies. Work up demonstrated a low morning cortisol level of 1.3 mcg/dL, an elevated ACTH of 2,739 pg/mL, and positive 21-hydroxylase autoantibodies. The patient was urgently referred to endocrinology and started on oral hydrocortisone. Her fatigue immediately improved, and at 1-year follow-up with dermatology, her mucocutaneous hyperpigmentation had subsided dramatically.
Dermatologists can play a major role in the early diagnosis of primary adrenal insufficiency, which is essential for reducing patient morbidity and mortality. Skin findings on full body skin exams can clue in dermatologists for ordering preliminary workup to expedite care for these patients.
The case and photos were submitted by Dr. Akhiyat, Scripps Clinic Medical Group, La Jolla, California. Donna Bilu Martin, MD, edited the column.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
J Am Acad Dermatol. 2014 May;70(5):Supplement 1AB118. doi: 10.1016/j.jaad.2014.01.491.
Michels A, Michels N. Am Fam Physician. 2014 Apr 1;89(7):563-568.
Kauzman A et al. J Can Dent Assoc. 2004 Nov;70(10):682-683.
Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.
Palmar creases, subungual surfaces, sites of trauma, and joint spaces (including the knees, spine, elbows, and shoulders) are commonly affected. Hair depletes in the pubic area and axillary vaults. Nevi may also appear darker. In patients with autoimmune adrenalitis, vitiligo may be seen secondary to autoimmune destruction of melanocytes.
Diagnosis may be difficult in the early stages, but historical findings of fatigue and clinical findings of hyperpigmentation in classic areas may prompt appropriate lab screening workup. It is essential to determine whether adrenal insufficiency is primary or secondary. Evaluation of decreased cortisol production, determination of whether production is ACTH-dependent or -independent, and evaluation for the underlying causes of adrenal dysfunction are important. Lab screening includes morning serum cortisol, morning ACTH (cosyntropin) stimulation test, fasting CBC with differential, and CMP to evaluate for normocytic normochromic anemia, hyponatremia, hyperkalemia, hypoglycemia, plasma renin/aldosterone ratio, and 21-hydroxylase autoantibodies.
Management strategies of primary adrenal insufficiency require corticosteroid supplementation and multidisciplinary collaboration with endocrinology. If untreated, primary adrenal insufficiency can be fatal. Adrenal crisis is a critical condition following a precipitating event, such as GI infection, fever, acute stress, and/or untreated adrenal or pituitary disorders. Clinical findings include acute shock with hypotension, nausea, vomiting, abdominal pain, back or leg pain, and a change in mental status. In this scenario, increasing the dose of corticosteroid supplementation is essential for reducing mortality.
Upon examining this patient’s new skin findings of hyperpigmentation and discussing her fatigue, primary adrenal insufficiency was suspected. With further prompting, the patient reported an ICU hospitalization several months prior because of sepsis originating from a peritonsillar abscess. With these clinical and historical findings, preliminary workup was conducted by dermatology, which included morning cortisol level, ACTH, CBC with differential, CMP, plasma renin-aldosterone ratio, and 21-hydroxylase autoantibodies. Work up demonstrated a low morning cortisol level of 1.3 mcg/dL, an elevated ACTH of 2,739 pg/mL, and positive 21-hydroxylase autoantibodies. The patient was urgently referred to endocrinology and started on oral hydrocortisone. Her fatigue immediately improved, and at 1-year follow-up with dermatology, her mucocutaneous hyperpigmentation had subsided dramatically.
Dermatologists can play a major role in the early diagnosis of primary adrenal insufficiency, which is essential for reducing patient morbidity and mortality. Skin findings on full body skin exams can clue in dermatologists for ordering preliminary workup to expedite care for these patients.
The case and photos were submitted by Dr. Akhiyat, Scripps Clinic Medical Group, La Jolla, California. Donna Bilu Martin, MD, edited the column.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
J Am Acad Dermatol. 2014 May;70(5):Supplement 1AB118. doi: 10.1016/j.jaad.2014.01.491.
Michels A, Michels N. Am Fam Physician. 2014 Apr 1;89(7):563-568.
Kauzman A et al. J Can Dent Assoc. 2004 Nov;70(10):682-683.
Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.
Palmar creases, subungual surfaces, sites of trauma, and joint spaces (including the knees, spine, elbows, and shoulders) are commonly affected. Hair depletes in the pubic area and axillary vaults. Nevi may also appear darker. In patients with autoimmune adrenalitis, vitiligo may be seen secondary to autoimmune destruction of melanocytes.
Diagnosis may be difficult in the early stages, but historical findings of fatigue and clinical findings of hyperpigmentation in classic areas may prompt appropriate lab screening workup. It is essential to determine whether adrenal insufficiency is primary or secondary. Evaluation of decreased cortisol production, determination of whether production is ACTH-dependent or -independent, and evaluation for the underlying causes of adrenal dysfunction are important. Lab screening includes morning serum cortisol, morning ACTH (cosyntropin) stimulation test, fasting CBC with differential, and CMP to evaluate for normocytic normochromic anemia, hyponatremia, hyperkalemia, hypoglycemia, plasma renin/aldosterone ratio, and 21-hydroxylase autoantibodies.
Management strategies of primary adrenal insufficiency require corticosteroid supplementation and multidisciplinary collaboration with endocrinology. If untreated, primary adrenal insufficiency can be fatal. Adrenal crisis is a critical condition following a precipitating event, such as GI infection, fever, acute stress, and/or untreated adrenal or pituitary disorders. Clinical findings include acute shock with hypotension, nausea, vomiting, abdominal pain, back or leg pain, and a change in mental status. In this scenario, increasing the dose of corticosteroid supplementation is essential for reducing mortality.
Upon examining this patient’s new skin findings of hyperpigmentation and discussing her fatigue, primary adrenal insufficiency was suspected. With further prompting, the patient reported an ICU hospitalization several months prior because of sepsis originating from a peritonsillar abscess. With these clinical and historical findings, preliminary workup was conducted by dermatology, which included morning cortisol level, ACTH, CBC with differential, CMP, plasma renin-aldosterone ratio, and 21-hydroxylase autoantibodies. Work up demonstrated a low morning cortisol level of 1.3 mcg/dL, an elevated ACTH of 2,739 pg/mL, and positive 21-hydroxylase autoantibodies. The patient was urgently referred to endocrinology and started on oral hydrocortisone. Her fatigue immediately improved, and at 1-year follow-up with dermatology, her mucocutaneous hyperpigmentation had subsided dramatically.
Dermatologists can play a major role in the early diagnosis of primary adrenal insufficiency, which is essential for reducing patient morbidity and mortality. Skin findings on full body skin exams can clue in dermatologists for ordering preliminary workup to expedite care for these patients.
The case and photos were submitted by Dr. Akhiyat, Scripps Clinic Medical Group, La Jolla, California. Donna Bilu Martin, MD, edited the column.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.
References
J Am Acad Dermatol. 2014 May;70(5):Supplement 1AB118. doi: 10.1016/j.jaad.2014.01.491.
Michels A, Michels N. Am Fam Physician. 2014 Apr 1;89(7):563-568.
Kauzman A et al. J Can Dent Assoc. 2004 Nov;70(10):682-683.
Help Your Patients Reap the Benefits of Plant-Based Diets
Research pooled from nearly 100 studies has indicated that people who adhere to a vegan diet (ie, completely devoid of animal products) or a vegetarian diet (ie, devoid of meat, but may include dairy and eggs) are able to ward off some chronic diseases, such as cardiovascular disease, optimize glycemic control, and decrease their risk for cancer compared with those who consume omnivorous diets.
Vegan and vegetarian diets, or flexitarian diets — which are less reliant on animal protein than the standard US diet but do not completely exclude meat, fish, eggs, or dairy — may promote homeostasis and decrease inflammation by providing more fiber, antioxidants, and unsaturated fatty acids than the typical Western diet.
Inflammation and Obesity
Adipose tissue is a major producer of pro-inflammatory cytokines like interleukin (IL)-6, whose presence then triggers a rush of acute-phase reactants such as C-reactive protein (CRP) by the liver. This process develops into chronic low-grade inflammation that can increase a person’s chances of developing diabetes, cardiovascular disease, kidney disease, metabolic syndrome, and related complications.
Adopting a plant-based diet can improve markers of chronic low-grade inflammation that can lead to chronic disease and worsen existent chronic disease. A meta-analysis of 29 studies encompassing nearly 2700 participants found that initiation of a plant-based diet showed significant improvement in CRP, IL-6, and soluble intercellular adhesion molecule 1.
If we want to prevent these inflammatory disease states and their complications, the obvious response is to counsel patients to avoid excessive weight gain or to lose weight if obesity is their baseline. This can be tough for some patients, but it is nonetheless an important step in chronic disease prevention and management.
Plant-Based Diet for Type 2 Diabetes
According to a review of nine studies of patients living with type 2 diabetes who adhered to a plant-based diet, all but one found that this approach led to significantly lower A1c values than those seen in control groups. Six of the included studies reported that participants were able to decrease or discontinue medications for the management of diabetes. Researchers across all included studies also noted a decrease in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increased weight loss in participants in each intervention group.
Such improvements are probably the result of the increase in fiber intake that occurs with a plant-based diet. A high-fiber diet is known to promote improved glucose and lipid metabolism as well as weight loss.
It is also worth noting that participants in the intervention groups also experienced improvements in depression and less chronic pain than did those in the control groups.
Plant-Based Diet for Chronic Kidney Disease (CKD)
Although the use of a plant-based diet in the prevention of CKD is well documented, adopting such diets for the treatment of CKD may intimidate both patients and practitioners owing to the high potassium and phosphorus content of many fruits and vegetables.
However, research indicates that the bioavailability of both potassium and phosphorus is lower in plant-based, whole foods than in preservatives and the highly processed food items that incorporate them. This makes a plant-based diet more viable than previously thought.
Diets rich in vegetables, whole grains, nuts, and legumes have been shown to decrease dietary acid load, both preventing and treating metabolic acidosis. Such diets have also been shown to decrease blood pressure and the risk for a decline in estimated glomerular filtration rate. This type of diet would also prioritize the unsaturated fatty acids and fiber-rich proteins such as avocados, beans, and nuts shown to improve dyslipidemia, which may occur alongside CKD.
Realistic Options for Patients on Medical Diets
There is one question that I always seem to get from when recommending a plant-based diet: “These patients already have so many restrictions. Why would you add more?” And my answer is also always the same: I don’t.
I rarely, if ever, recommend completely cutting out any food item or food group. Instead, I ask the patient to increase their intake of plant-based foods and only limit highly processed foods and fatty meats. By shifting a patient’s focus to beans; nuts; and low-carbohydrate, high-fiber fruits and vegetables, I am often opening up a whole new world of possibilities.
Instead of a sandwich with low-sodium turkey and cheese on white bread with a side of unsalted pretzels, I recommend a caprese salad with blueberries and almonds or a Southwest salad with black beans, corn, and avocado. I don’t encourage my patients to skip the foods that they love, but instead to only think about all the delicious plant-based options that will provide them with more than just calories.
Meat, dairy, seafood, and eggs can certainly be a part of a healthy diet, but what if our chronically ill patients, especially those with diabetes, had more options than just grilled chicken and green beans for every meal? What if we focus on decreasing dietary restrictions, incorporating a variety of nourishing foods, and educating our patients, instead of on portion control and moderation?
This is how I choose to incorporate plant-based diets into my practice to treat and prevent these chronic inflammatory conditions and promote sustainable, realistic change in my clients’ health.
Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Research pooled from nearly 100 studies has indicated that people who adhere to a vegan diet (ie, completely devoid of animal products) or a vegetarian diet (ie, devoid of meat, but may include dairy and eggs) are able to ward off some chronic diseases, such as cardiovascular disease, optimize glycemic control, and decrease their risk for cancer compared with those who consume omnivorous diets.
Vegan and vegetarian diets, or flexitarian diets — which are less reliant on animal protein than the standard US diet but do not completely exclude meat, fish, eggs, or dairy — may promote homeostasis and decrease inflammation by providing more fiber, antioxidants, and unsaturated fatty acids than the typical Western diet.
Inflammation and Obesity
Adipose tissue is a major producer of pro-inflammatory cytokines like interleukin (IL)-6, whose presence then triggers a rush of acute-phase reactants such as C-reactive protein (CRP) by the liver. This process develops into chronic low-grade inflammation that can increase a person’s chances of developing diabetes, cardiovascular disease, kidney disease, metabolic syndrome, and related complications.
Adopting a plant-based diet can improve markers of chronic low-grade inflammation that can lead to chronic disease and worsen existent chronic disease. A meta-analysis of 29 studies encompassing nearly 2700 participants found that initiation of a plant-based diet showed significant improvement in CRP, IL-6, and soluble intercellular adhesion molecule 1.
If we want to prevent these inflammatory disease states and their complications, the obvious response is to counsel patients to avoid excessive weight gain or to lose weight if obesity is their baseline. This can be tough for some patients, but it is nonetheless an important step in chronic disease prevention and management.
Plant-Based Diet for Type 2 Diabetes
According to a review of nine studies of patients living with type 2 diabetes who adhered to a plant-based diet, all but one found that this approach led to significantly lower A1c values than those seen in control groups. Six of the included studies reported that participants were able to decrease or discontinue medications for the management of diabetes. Researchers across all included studies also noted a decrease in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increased weight loss in participants in each intervention group.
Such improvements are probably the result of the increase in fiber intake that occurs with a plant-based diet. A high-fiber diet is known to promote improved glucose and lipid metabolism as well as weight loss.
It is also worth noting that participants in the intervention groups also experienced improvements in depression and less chronic pain than did those in the control groups.
Plant-Based Diet for Chronic Kidney Disease (CKD)
Although the use of a plant-based diet in the prevention of CKD is well documented, adopting such diets for the treatment of CKD may intimidate both patients and practitioners owing to the high potassium and phosphorus content of many fruits and vegetables.
However, research indicates that the bioavailability of both potassium and phosphorus is lower in plant-based, whole foods than in preservatives and the highly processed food items that incorporate them. This makes a plant-based diet more viable than previously thought.
Diets rich in vegetables, whole grains, nuts, and legumes have been shown to decrease dietary acid load, both preventing and treating metabolic acidosis. Such diets have also been shown to decrease blood pressure and the risk for a decline in estimated glomerular filtration rate. This type of diet would also prioritize the unsaturated fatty acids and fiber-rich proteins such as avocados, beans, and nuts shown to improve dyslipidemia, which may occur alongside CKD.
Realistic Options for Patients on Medical Diets
There is one question that I always seem to get from when recommending a plant-based diet: “These patients already have so many restrictions. Why would you add more?” And my answer is also always the same: I don’t.
I rarely, if ever, recommend completely cutting out any food item or food group. Instead, I ask the patient to increase their intake of plant-based foods and only limit highly processed foods and fatty meats. By shifting a patient’s focus to beans; nuts; and low-carbohydrate, high-fiber fruits and vegetables, I am often opening up a whole new world of possibilities.
Instead of a sandwich with low-sodium turkey and cheese on white bread with a side of unsalted pretzels, I recommend a caprese salad with blueberries and almonds or a Southwest salad with black beans, corn, and avocado. I don’t encourage my patients to skip the foods that they love, but instead to only think about all the delicious plant-based options that will provide them with more than just calories.
Meat, dairy, seafood, and eggs can certainly be a part of a healthy diet, but what if our chronically ill patients, especially those with diabetes, had more options than just grilled chicken and green beans for every meal? What if we focus on decreasing dietary restrictions, incorporating a variety of nourishing foods, and educating our patients, instead of on portion control and moderation?
This is how I choose to incorporate plant-based diets into my practice to treat and prevent these chronic inflammatory conditions and promote sustainable, realistic change in my clients’ health.
Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Research pooled from nearly 100 studies has indicated that people who adhere to a vegan diet (ie, completely devoid of animal products) or a vegetarian diet (ie, devoid of meat, but may include dairy and eggs) are able to ward off some chronic diseases, such as cardiovascular disease, optimize glycemic control, and decrease their risk for cancer compared with those who consume omnivorous diets.
Vegan and vegetarian diets, or flexitarian diets — which are less reliant on animal protein than the standard US diet but do not completely exclude meat, fish, eggs, or dairy — may promote homeostasis and decrease inflammation by providing more fiber, antioxidants, and unsaturated fatty acids than the typical Western diet.
Inflammation and Obesity
Adipose tissue is a major producer of pro-inflammatory cytokines like interleukin (IL)-6, whose presence then triggers a rush of acute-phase reactants such as C-reactive protein (CRP) by the liver. This process develops into chronic low-grade inflammation that can increase a person’s chances of developing diabetes, cardiovascular disease, kidney disease, metabolic syndrome, and related complications.
Adopting a plant-based diet can improve markers of chronic low-grade inflammation that can lead to chronic disease and worsen existent chronic disease. A meta-analysis of 29 studies encompassing nearly 2700 participants found that initiation of a plant-based diet showed significant improvement in CRP, IL-6, and soluble intercellular adhesion molecule 1.
If we want to prevent these inflammatory disease states and their complications, the obvious response is to counsel patients to avoid excessive weight gain or to lose weight if obesity is their baseline. This can be tough for some patients, but it is nonetheless an important step in chronic disease prevention and management.
Plant-Based Diet for Type 2 Diabetes
According to a review of nine studies of patients living with type 2 diabetes who adhered to a plant-based diet, all but one found that this approach led to significantly lower A1c values than those seen in control groups. Six of the included studies reported that participants were able to decrease or discontinue medications for the management of diabetes. Researchers across all included studies also noted a decrease in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increased weight loss in participants in each intervention group.
Such improvements are probably the result of the increase in fiber intake that occurs with a plant-based diet. A high-fiber diet is known to promote improved glucose and lipid metabolism as well as weight loss.
It is also worth noting that participants in the intervention groups also experienced improvements in depression and less chronic pain than did those in the control groups.
Plant-Based Diet for Chronic Kidney Disease (CKD)
Although the use of a plant-based diet in the prevention of CKD is well documented, adopting such diets for the treatment of CKD may intimidate both patients and practitioners owing to the high potassium and phosphorus content of many fruits and vegetables.
However, research indicates that the bioavailability of both potassium and phosphorus is lower in plant-based, whole foods than in preservatives and the highly processed food items that incorporate them. This makes a plant-based diet more viable than previously thought.
Diets rich in vegetables, whole grains, nuts, and legumes have been shown to decrease dietary acid load, both preventing and treating metabolic acidosis. Such diets have also been shown to decrease blood pressure and the risk for a decline in estimated glomerular filtration rate. This type of diet would also prioritize the unsaturated fatty acids and fiber-rich proteins such as avocados, beans, and nuts shown to improve dyslipidemia, which may occur alongside CKD.
Realistic Options for Patients on Medical Diets
There is one question that I always seem to get from when recommending a plant-based diet: “These patients already have so many restrictions. Why would you add more?” And my answer is also always the same: I don’t.
I rarely, if ever, recommend completely cutting out any food item or food group. Instead, I ask the patient to increase their intake of plant-based foods and only limit highly processed foods and fatty meats. By shifting a patient’s focus to beans; nuts; and low-carbohydrate, high-fiber fruits and vegetables, I am often opening up a whole new world of possibilities.
Instead of a sandwich with low-sodium turkey and cheese on white bread with a side of unsalted pretzels, I recommend a caprese salad with blueberries and almonds or a Southwest salad with black beans, corn, and avocado. I don’t encourage my patients to skip the foods that they love, but instead to only think about all the delicious plant-based options that will provide them with more than just calories.
Meat, dairy, seafood, and eggs can certainly be a part of a healthy diet, but what if our chronically ill patients, especially those with diabetes, had more options than just grilled chicken and green beans for every meal? What if we focus on decreasing dietary restrictions, incorporating a variety of nourishing foods, and educating our patients, instead of on portion control and moderation?
This is how I choose to incorporate plant-based diets into my practice to treat and prevent these chronic inflammatory conditions and promote sustainable, realistic change in my clients’ health.
Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Can Restricting Carbohydrates Cut the Need for Medication in T2D?
, new research suggests.
In the 12-week study of 57 people with T2D who were not using insulin, C-peptide levels were significantly higher among those randomized to receive a low-carbohydrate diet (~9% of total calories) vs a higher-carbohydrate diet (~55%). The results were published online on October 22, 2024, in The Journal of Clinical Endocrinology & Metabolism.
“While other studies have demonstrated metabolic health benefits of low-carb diets, our results are the first to show that dietary carbohydrate restriction can improve beta-cell function ... Furthermore, the carbohydrate-restricted diet improved insulin secretion in African American patients to a much greater extent than in Caucasian Americans,” study author Marian L. Yurchishin, MS, Department of Nutrition Sciences, The University of Alabama, Birmingham, Alabama, told Medscape Medical News.
Yurchishin added, “Our data suggests that a carbohydrate-restricted diet provides the opportunity to improve beta-cell function without the need for medication use or weight loss. This approach may be more appealing and effective for some persons with T2D, particularly in patients of African descent.”
At the same time, she clarified, “Our research should not be interpreted to mean that a carbohydrate-restricted diet can replace medical therapy in those who need it, especially patients at risk of cardiovascular disease, heart failure, or chronic kidney disease…or when medications are needed to achieve A1c targets.”
Asked to comment, Alison B. Evert, RDN, CDCES, former (now retired) manager of the Nutrition and Diabetes Education Programs at the University of Washington Medicine Primary Care, Kirkland, Washington, expressed some caveats about the findings, noting “I doubt this approach would be sustainable for the average person.”
Evert also pointed out that the amount of fat in the carbohydrate-restricted diet — 65% of energy vs just 20% of energy with the higher-carbohydrate diet — was “extremely high ... essentially a keto diet,” and that in the real-world people might not receive education on heart-healthy fat intake. Moreover, she noted that the study’s use of grocery delivery to the participants with instructions for food preparation “is not a real-world situation either.”
Low-Carbohydrate Diet Increased C-Peptide Levels
The study participants were all either African American or European American. All had been diagnosed with T2D within the past 10 years, with average 4.9 years in the carbohydrate-restricted group vs 3.0 years in the higher-carbohydrate group. The two diets contained approximately the same number of calories.
All their medications were discontinued 1-2 weeks prior to baseline testing.
A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide response to glucose at baseline and after 12 weeks of following the diets. First-phase beta-cell response to glucose was assessed at 30 minutes, insulin sensitivity was evaluated at 2 hours, and maximal beta-cell response to arginine was evaluated after another 30 minutes.
Oral glucose tolerance tests were also conducted at baseline and at 12 weeks to determine the disposition index (DI), a marker of beta-cell function that factors in both C-peptide and insulin sensitivity.
Of 65 participants enrolled, eight discontinued the study, most due to non-adherence. At 12 weeks, the acute C-peptide response from baseline was twice as high with the carbohydrate-restricted diet than with the higher-carbohydrate diet (P < .05). This difference was significant among the 37 African Americans (110% greater; P < .01) but not for the 20 European Americans.
Evert said that because people have typically lost at least 50% of their beta-cell function at the time of T2D diagnosis, “it is helpful to have return of first phase response, but long-term discontinuation of medications that also have cardioprotective function seems short sighted in this patient population.”
The overall maximal C-peptide response was 22% greater with the carbohydrate-restricted diet (P < .05), this time only significant in the European Americans (48%; P < .01) but not the African Americans.
In the combined group, the DI was 32% greater with the carbohydrate-restricted diet (P < .05) but only significantly so in the African American participants (48%; P < .01); however, no DI changes were seen with the higher-carbohydrate diet in the European American participants.
Regarding the racial differences, Yurchishin explained “Research supports the contention that the pathophysiology of T2D differs can differ among races based on genetic factors and environmental interactions that affect beta-cell function. For example, T2D onset in African Americans may be less related to obesity and insulin resistance than it is in European Americans and depend on alterations in beta-cell function to a larger degree. While sociocultural factors do influence T2D risk, other studies have also shown that there are inherent biological differences in the mechanisms that lead to beta-cell failure between races that warrant further investigation.”
In their paper, Yurchishin and colleagues concluded, “With the caveat that carbohydrate restriction may be difficult for some patients, such a diet may allow patients with mild T2D to discontinue medication and enjoy eating meals and snacks that meet their energy needs while improving beta-cell function, an outcome that cannot be achieved with medication.”
Evert commented, “I think it is a bit subjective to say that people following a 9% carb intake ‘will enjoy eating their meals and snacks that meet their energy needs.’ Guess they would enjoy as long as they choose very high fat, low carb foods.”
The research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the UAB Nutrition Obesity Research Center, and the UAB Diabetes Research Center. Yurchishin was supported by the National Heart, Lung, and Blood Institute. Evert had no disclosures.
A version of this article appeared on Medscape.com.
, new research suggests.
In the 12-week study of 57 people with T2D who were not using insulin, C-peptide levels were significantly higher among those randomized to receive a low-carbohydrate diet (~9% of total calories) vs a higher-carbohydrate diet (~55%). The results were published online on October 22, 2024, in The Journal of Clinical Endocrinology & Metabolism.
“While other studies have demonstrated metabolic health benefits of low-carb diets, our results are the first to show that dietary carbohydrate restriction can improve beta-cell function ... Furthermore, the carbohydrate-restricted diet improved insulin secretion in African American patients to a much greater extent than in Caucasian Americans,” study author Marian L. Yurchishin, MS, Department of Nutrition Sciences, The University of Alabama, Birmingham, Alabama, told Medscape Medical News.
Yurchishin added, “Our data suggests that a carbohydrate-restricted diet provides the opportunity to improve beta-cell function without the need for medication use or weight loss. This approach may be more appealing and effective for some persons with T2D, particularly in patients of African descent.”
At the same time, she clarified, “Our research should not be interpreted to mean that a carbohydrate-restricted diet can replace medical therapy in those who need it, especially patients at risk of cardiovascular disease, heart failure, or chronic kidney disease…or when medications are needed to achieve A1c targets.”
Asked to comment, Alison B. Evert, RDN, CDCES, former (now retired) manager of the Nutrition and Diabetes Education Programs at the University of Washington Medicine Primary Care, Kirkland, Washington, expressed some caveats about the findings, noting “I doubt this approach would be sustainable for the average person.”
Evert also pointed out that the amount of fat in the carbohydrate-restricted diet — 65% of energy vs just 20% of energy with the higher-carbohydrate diet — was “extremely high ... essentially a keto diet,” and that in the real-world people might not receive education on heart-healthy fat intake. Moreover, she noted that the study’s use of grocery delivery to the participants with instructions for food preparation “is not a real-world situation either.”
Low-Carbohydrate Diet Increased C-Peptide Levels
The study participants were all either African American or European American. All had been diagnosed with T2D within the past 10 years, with average 4.9 years in the carbohydrate-restricted group vs 3.0 years in the higher-carbohydrate group. The two diets contained approximately the same number of calories.
All their medications were discontinued 1-2 weeks prior to baseline testing.
A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide response to glucose at baseline and after 12 weeks of following the diets. First-phase beta-cell response to glucose was assessed at 30 minutes, insulin sensitivity was evaluated at 2 hours, and maximal beta-cell response to arginine was evaluated after another 30 minutes.
Oral glucose tolerance tests were also conducted at baseline and at 12 weeks to determine the disposition index (DI), a marker of beta-cell function that factors in both C-peptide and insulin sensitivity.
Of 65 participants enrolled, eight discontinued the study, most due to non-adherence. At 12 weeks, the acute C-peptide response from baseline was twice as high with the carbohydrate-restricted diet than with the higher-carbohydrate diet (P < .05). This difference was significant among the 37 African Americans (110% greater; P < .01) but not for the 20 European Americans.
Evert said that because people have typically lost at least 50% of their beta-cell function at the time of T2D diagnosis, “it is helpful to have return of first phase response, but long-term discontinuation of medications that also have cardioprotective function seems short sighted in this patient population.”
The overall maximal C-peptide response was 22% greater with the carbohydrate-restricted diet (P < .05), this time only significant in the European Americans (48%; P < .01) but not the African Americans.
In the combined group, the DI was 32% greater with the carbohydrate-restricted diet (P < .05) but only significantly so in the African American participants (48%; P < .01); however, no DI changes were seen with the higher-carbohydrate diet in the European American participants.
Regarding the racial differences, Yurchishin explained “Research supports the contention that the pathophysiology of T2D differs can differ among races based on genetic factors and environmental interactions that affect beta-cell function. For example, T2D onset in African Americans may be less related to obesity and insulin resistance than it is in European Americans and depend on alterations in beta-cell function to a larger degree. While sociocultural factors do influence T2D risk, other studies have also shown that there are inherent biological differences in the mechanisms that lead to beta-cell failure between races that warrant further investigation.”
In their paper, Yurchishin and colleagues concluded, “With the caveat that carbohydrate restriction may be difficult for some patients, such a diet may allow patients with mild T2D to discontinue medication and enjoy eating meals and snacks that meet their energy needs while improving beta-cell function, an outcome that cannot be achieved with medication.”
Evert commented, “I think it is a bit subjective to say that people following a 9% carb intake ‘will enjoy eating their meals and snacks that meet their energy needs.’ Guess they would enjoy as long as they choose very high fat, low carb foods.”
The research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the UAB Nutrition Obesity Research Center, and the UAB Diabetes Research Center. Yurchishin was supported by the National Heart, Lung, and Blood Institute. Evert had no disclosures.
A version of this article appeared on Medscape.com.
, new research suggests.
In the 12-week study of 57 people with T2D who were not using insulin, C-peptide levels were significantly higher among those randomized to receive a low-carbohydrate diet (~9% of total calories) vs a higher-carbohydrate diet (~55%). The results were published online on October 22, 2024, in The Journal of Clinical Endocrinology & Metabolism.
“While other studies have demonstrated metabolic health benefits of low-carb diets, our results are the first to show that dietary carbohydrate restriction can improve beta-cell function ... Furthermore, the carbohydrate-restricted diet improved insulin secretion in African American patients to a much greater extent than in Caucasian Americans,” study author Marian L. Yurchishin, MS, Department of Nutrition Sciences, The University of Alabama, Birmingham, Alabama, told Medscape Medical News.
Yurchishin added, “Our data suggests that a carbohydrate-restricted diet provides the opportunity to improve beta-cell function without the need for medication use or weight loss. This approach may be more appealing and effective for some persons with T2D, particularly in patients of African descent.”
At the same time, she clarified, “Our research should not be interpreted to mean that a carbohydrate-restricted diet can replace medical therapy in those who need it, especially patients at risk of cardiovascular disease, heart failure, or chronic kidney disease…or when medications are needed to achieve A1c targets.”
Asked to comment, Alison B. Evert, RDN, CDCES, former (now retired) manager of the Nutrition and Diabetes Education Programs at the University of Washington Medicine Primary Care, Kirkland, Washington, expressed some caveats about the findings, noting “I doubt this approach would be sustainable for the average person.”
Evert also pointed out that the amount of fat in the carbohydrate-restricted diet — 65% of energy vs just 20% of energy with the higher-carbohydrate diet — was “extremely high ... essentially a keto diet,” and that in the real-world people might not receive education on heart-healthy fat intake. Moreover, she noted that the study’s use of grocery delivery to the participants with instructions for food preparation “is not a real-world situation either.”
Low-Carbohydrate Diet Increased C-Peptide Levels
The study participants were all either African American or European American. All had been diagnosed with T2D within the past 10 years, with average 4.9 years in the carbohydrate-restricted group vs 3.0 years in the higher-carbohydrate group. The two diets contained approximately the same number of calories.
All their medications were discontinued 1-2 weeks prior to baseline testing.
A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide response to glucose at baseline and after 12 weeks of following the diets. First-phase beta-cell response to glucose was assessed at 30 minutes, insulin sensitivity was evaluated at 2 hours, and maximal beta-cell response to arginine was evaluated after another 30 minutes.
Oral glucose tolerance tests were also conducted at baseline and at 12 weeks to determine the disposition index (DI), a marker of beta-cell function that factors in both C-peptide and insulin sensitivity.
Of 65 participants enrolled, eight discontinued the study, most due to non-adherence. At 12 weeks, the acute C-peptide response from baseline was twice as high with the carbohydrate-restricted diet than with the higher-carbohydrate diet (P < .05). This difference was significant among the 37 African Americans (110% greater; P < .01) but not for the 20 European Americans.
Evert said that because people have typically lost at least 50% of their beta-cell function at the time of T2D diagnosis, “it is helpful to have return of first phase response, but long-term discontinuation of medications that also have cardioprotective function seems short sighted in this patient population.”
The overall maximal C-peptide response was 22% greater with the carbohydrate-restricted diet (P < .05), this time only significant in the European Americans (48%; P < .01) but not the African Americans.
In the combined group, the DI was 32% greater with the carbohydrate-restricted diet (P < .05) but only significantly so in the African American participants (48%; P < .01); however, no DI changes were seen with the higher-carbohydrate diet in the European American participants.
Regarding the racial differences, Yurchishin explained “Research supports the contention that the pathophysiology of T2D differs can differ among races based on genetic factors and environmental interactions that affect beta-cell function. For example, T2D onset in African Americans may be less related to obesity and insulin resistance than it is in European Americans and depend on alterations in beta-cell function to a larger degree. While sociocultural factors do influence T2D risk, other studies have also shown that there are inherent biological differences in the mechanisms that lead to beta-cell failure between races that warrant further investigation.”
In their paper, Yurchishin and colleagues concluded, “With the caveat that carbohydrate restriction may be difficult for some patients, such a diet may allow patients with mild T2D to discontinue medication and enjoy eating meals and snacks that meet their energy needs while improving beta-cell function, an outcome that cannot be achieved with medication.”
Evert commented, “I think it is a bit subjective to say that people following a 9% carb intake ‘will enjoy eating their meals and snacks that meet their energy needs.’ Guess they would enjoy as long as they choose very high fat, low carb foods.”
The research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the UAB Nutrition Obesity Research Center, and the UAB Diabetes Research Center. Yurchishin was supported by the National Heart, Lung, and Blood Institute. Evert had no disclosures.
A version of this article appeared on Medscape.com.