Obesity

A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.

In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.

The new findings were published online in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.

Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Dr. Hoe told this news organization in an interview.

“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
 

Zeroing in on Those at Greatest Risk for Type 2 Diabetes

Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.

And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.

The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.

“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Dr. Hoe said.

Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
 

Large Database Allows for Detailed Findings

The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.

Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P < .001).

Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.

The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.

In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.

The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.

Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islanders.

“We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk,” Dr. Hoe told this news organization.

This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Dr. Hoe and his coauthors had no further disclosures.

A version of this article appeared on Medscape.com.

A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.

In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.

The new findings were published online in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.

Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Dr. Hoe told this news organization in an interview.

“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
 

Zeroing in on Those at Greatest Risk for Type 2 Diabetes

Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.

And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.

The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.

“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Dr. Hoe said.

Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
 

Large Database Allows for Detailed Findings

The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.

Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P < .001).

Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.

The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.

In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.

The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.

Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islanders.

“We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk,” Dr. Hoe told this news organization.

This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Dr. Hoe and his coauthors had no further disclosures.

A version of this article appeared on Medscape.com.

A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.

In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.

The new findings were published online in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.

Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Dr. Hoe told this news organization in an interview.

“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
 

Zeroing in on Those at Greatest Risk for Type 2 Diabetes

Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.

And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.

The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.

“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Dr. Hoe said.

Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
 

Large Database Allows for Detailed Findings

The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.

Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P < .001).

Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.

The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.

In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.

The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.

Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islanders.

“We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk,” Dr. Hoe told this news organization.

This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Dr. Hoe and his coauthors had no further disclosures.

A version of this article appeared on Medscape.com.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

Intake of protein, especially from plants, in middle age is associated with higher odds of healthy aging and positive mental and physical health status in older women, a recent analysis of the Nurses’ Health Study (NHS) data suggests.

The study is said to be the first to examine the long-term impact of midlife protein consumption on later health status.

Writing in the American Journal of Clinical Nutrition, a team led by Andres V. Ardisson Korat, DSc, a nutritional epidemiologist at the USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts, found the following midlife protein–related odds ratios (ORs) for later healthy aging measured at ages 70-93.

For each 3% energy increment from various protein sources:

• 1.05 (95% confidence interval, 1.01-1.10) for total protein
• 1.07 (1.02-1.11) for animal protein
• 1.14 (1.06-1.23) for dairy protein
• 1.38 (1.24-1.54) for plant protein 

In substitution analyses, significant positive associations were observed for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein — with increased ORs for healthy aging of 1.22-1.58 for each 3% of energy replacement.

On the measure of physical function, for example, replacing calories from all macronutrient variables with equivalent calories from plant protein was associated with 20%-60% higher odds of having no physical function limitations. Plant protein was also associated with higher odds for good mental status.

“Other studies have looked at protein intake in older adults, but we felt midlife was a more relevant etiological window,” Dr. Ardisson Korat said in an interview. “Our findings generally align, however, with those of protein intake in older populations, which have shown that protein can reduce the risk of frailty.”

He added that the benefits of protein, especially from plant sources, would likely apply to men as well and increasing plant protein intake is not difficult. “If you want a snack during the day, eat a handful of nuts instead of potato chips,” he advised. And eating several meals a week featuring beans, peas, lentils, tofu, whole grains, or seeds is an easy way to boost dietary plant protein, which comes with health-promoting soluble and insoluble fiber as well as antioxidant and anti-inflammatory polyphenols and other phytochemicals.

Conversely, plant but not animal protein consumption in older adulthood was linked to a lower risk of frailty in a previous NHS trial.

Higher plant protein intake was associated with a better probability of achieving healthy aging defined by changes in functional impairments, self-reported health/vitality, mental health, and use of health services in the Spanish Seniors-Estudio Sobre Nutricion y Riesgo Cardiovascular.

In contrast, animal protein intake in middle adulthood has been linked to an increased risk of premature death from chronic diseases driven by cardiovascular disease mortality.

The present findings are consistent with those observed for protein intakes in older adulthood, Dr. Ardisson Korat said.

“This study underscores the health advantages for midlife adults consuming adequate dietary protein — particularly plant protein — as one component of pursuing a healthy lifestyle,” said Douglas R. Dirschl, MD, chair of orthopedic surgery at Baylor College of Medicine in Houston, Texas. Most Americans consume adequate amounts of protein, but according to Dr. Dirschl, who treats many older patients for osteoporotic fractures and other musculoskeletal conditions, many US diets are subpar in this nutrient.

While protein is essential for bone and muscle formation and maintenance, “a surprising number of Americans are protein deficient, even those who seem hale and are overweight,” he said.


 

Dietary Recommendations for Midlife Patients

Physicians should therefore advise midlife patients to meet or perhaps modestly exceed the recommended dietary allowance (RDA) for protein of 0.8 g/kg per day and to make plant protein a substantial component of daily dietary protein intake, Dr. Dirschl said.

Luke D. Kim, MD, MEd, a geriatrician at the Cleveland Clinic in Cleveland, Ohio, noted that patients with lower socioeconomic status or with difficulty in day-to-day functioning are likely to have suboptimal protein intake. Such patients may need encouragement to eat more protein. “But we should keep in mind that showing a higher associated odds ratio of better health with increased protein take does not mean causality,” he said.

According to Rachel L. Amdur, MD, an internist at Northwestern Medicine in Chicago, Illinois, the long-term follow-up data from the NHS are uniquely helpful. “Middle-aged persons may think they no longer need much dietary protein and need to be reminded. Sometimes eating carbohydrates is just easier,” she said in an interview. Physicians need to asses and counsel patients on nutrition at all stages of life. “As I tell my patients, it’s best to think of your future self now.”

In agreement is Louis J. Morledge, MD, an internist at Northwell Health in New York City. “I firmly counsel my patients about adequate and often increased protein intake in middle life. But this is always within a larger framework of overall nutritional health.” He added that middle-aged persons often find themselves “stuck in food ruts,” and one of his clinical focuses is to advise patients about the importance of healthier food choices so they can better adjust to mental, emotional, physical, and skeletal changes as they age.
 

Study Details

The NHS analysis drew on prospective data from 48,762 nurses under age 60 in 1984. Total protein, animal protein, dairy protein, and plant protein were derived from validated food-frequency questionnaires.

Adjusting for lifestyle, demographics, and health status, the investigators identified 3721 (7.6% of cohort) eligible participants. The mean age of participants at baseline was 48.6 years; 38.6% had body mass indexes (BMI; in kg/m²) greater than 25; 22.9% were current smokers; and 88.2% were married.

Healthy aging was defined as freedom from 11 major chronic diseases, good mental health, and no impairments in cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. Diseases/treatments included cancer, type 2 diabetes, myocardial infarction, coronary artery bypass graft or coronary angioplasty, congestive heart failure, stroke, kidney failure, chronic obstructive pulmonary disease, Parkinson disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Mean total protein consumption as a percentage of energy was 18.3% (standard deviation 3%), slightly higher than the average 16% in the US diet. Of this, 13.3% derived from animals, 3.6% from dairy products, and 4.9% from plants.

Total protein intake was positively associated with higher education levels, being physically active, higher BMI, and a baseline history of hypertension and hypercholesterolemia. Conversely, total protein intake was inversely associated with intakes of total carbohydrates, nuts, alcohol, and sugar-sweetened beverages.

The associations between protein intake and healthy aging are complex and not fully understood, the authors stated.
 

Effects of Protein Intake

In studies of older adult populations lower protein intake has been associated with lean mass loss. Animal protein supplementation studies in older adults have shown lean mass gains potentially related to amino acid composition.

In terms of mechanisms, evidence suggests that protein-related activation of the rapamycin complex 1 pathway may play a role, the authors suggested. The activity of this signaling pathway decreases with age.

Rapamycin, a compound used to prevent organ transplant rejection, has been associated with delayed aging. In the body, dietary protein and exercise activate this pathway, thereby stimulating muscle protein synthesis and possibly improving physical function.

As for the differential associations of plant and animal protein on the chronic disease domain of the healthy aging phenotype, Dr. Ardisson Korat and coauthors said plant protein has been associated with favorable levels of important risk factors for cardiometabolic diseases, such as reduced LDL cholesterol, lower blood pressure, and insulin sensitivity, as well as decreased levels of proinflammatory markers.

Conversely, total and animal protein intakes have been positively associated with concentrations of insulin-like growth factor 1, which is implicated in the growth of malignant cells in breast and prostate tissue.

This study is the first step in evaluating the long-term health effect of protein intake in midlife, the relevant development window for most chronic conditions, the NHS study authors said. More research is needed, however, to corroborate the study findings in other populations and identify underlying mechanisms.

This study was supported by the USDA Agricultural Research Service and the National Institutes of Health. The authors reported no conflicts of interest. The commentators disclosed no relevant competing interests.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

FAIRFAX, VIRGINIA — The lack of data on optimal timing of delivery for pregnancies complicated by diabetes remains a major challenge in obstetrics — one with considerable implications given the high and rising prevalence of pregestational and gestational diabetes, Katherine Laughon Grantz, MD, MS, of the National Institute of Child Health and Human Development, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“While 39-40 weeks might be ideal for low-risk pregnancies, the optimal timing for pregnancies with complications [like diabetes] is unknown,” said Dr. Grantz, a senior investigator in the NICHD’s epidemiology branch.

The percentage of mothers with gestational diabetes mellitus (GDM) increased from 6% in 2016 to 8% in 2021, according to the most recent data from the National Vital Statistics System of the Centers for Disease Control and Prevention (MMWR Morb Mortal Wkly Rep. 2023;72:16). Meanwhile, the prevalence of prepregnancy obesity, which raises the risk of gestational and type 2 diabetes, was 29% in 2019; this represents an 11% increase from 2015 (NCHS Data Brief. 2020;392:1-8) and has occurred across all maternal ages, races, ethnic groups, and educational levels, she said.

“The reason clinicians deliver pregnancies with diabetes earlier is because there’s a decreased risk of macrosomia, shoulder dystocia, and stillbirth. And these risks need to be balanced with the increased risk of neonatal morbidity and mortality associated with earlier delivery,” said Dr. Grantz, who noted during her talk that delivery timing also appears to influence long-term neurodevelopmental outcomes. “Yet despite [diabetes in pregnancy] being so common, there is complete uncertainty about when to deliver.”
 

ACOG Recommendations, Randomized Trials (New And Old)

The American College of Obstetricians and Gynecologists, in a Committee Opinion on Medically Indicated Late-Preterm and Early-Term Deliveries, published in collaboration with the Society of Maternal-Fetal Medicine, offers recommendations based on the type of diabetes and the level of control. For instance, the suggested delivery timing for well-controlled GDM is full term (39 0/7 to 40 6/7 weeks of gestation), while the recommendation for poorly controlled diabetes is individualized late preterm/early term management (Obstet Gynecol. 2021;138:e35-9).

In defining and evaluating control, she noted, “the clinical focus is on glucose, but there are likely other important parameters that are not taken into account ... which [could be] important when considering the timing of delivery.” Potentially important factors include estimated fetal weight, fetal growth velocity, lipids, and amino acids, she said.

ACOG’s recommendations are based mainly on retrospective data, Dr. Grantz said. Only two randomized controlled trials have investigated the timing of delivery in the context of diabetes, and both focused on cesarean section and were “generally underpowered to study neonatal outcomes,” she said.

The first RCT, published in 1993, enrolled 200 women with uncomplicated insulin-requiring diabetes (187 with GDM and 13 with pregestational diabetes) at 38 weeks of gestation, and compared active induction of labor within 5 days to expectant management. There was no significant difference in the cesarean delivery rate (the primary outcome), but rates of macrosomia and large for gestational age were higher in the expectant management group (27% vs. 15%, P = .05, and 23% vs. 10%, P = .02, respectively). Shoulder dystocia occurred in three deliveries, each of which was expectantly managed (Am J Obstet Gynecol. 1993;169[3]:611-5). Notably, the study included “only women with excellent glucose control,” Dr. Grantz said.

The second RCT, published in 2017 by a group in Italy, enrolled 425 patients with GDM (diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria) between week 38 and week 39 of gestation and similarly randomized them to induction of labor or expectant management. No difference in cesarean delivery was found (BJOG. 2017;124[4]:669-77). Induction of labor was associated with a higher risk of hyperbilirubinemia, and there was a trend toward a decreased risk of macrosomia, but again, the study was underpowered to detect differences in most outcomes, she said. (The study also was stopped early because of an inability to recruit, she noted.)

Dr. Grantz is currently recruiting for a randomized trial aimed at determining the optimal time between 37 and 39 weeks to initiate delivery — the time when neonatal morbidity and perinatal mortality risk is the lowest – for uncontrolled GDM-complicated pregnancies. The trial is designed to recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery (NCT05515744).

Those who are eligible for the study but do not consent to participate in randomization for delivery will be asked about chart review only (an estimated additional 3,000). The SPAN TIME study will also assess newborn development and behavior outcomes, as well as anthropometric measures, as secondary outcomes. An exploratory analysis will look for clinical, nonclinical or biochemical factors that could be helpful in optimizing delivery timing.

What Retrospective Studies Reveal

Factors that may influence the timing of delivery include the duration of neonatal exposure to hyperglycemia/hyperinsulinemia (pregestational vs. gestational diabetes), the level of diabetes control, and comorbidities (e.g. maternal renal disease or chronic hypertension). However, research “investigating how these factors influence morbidity and the timing of delivery is limited,” said Dr. Grantz.

Overall, it has been difficult through retrospective studies, she said, to investigate neonatal morbidity in diabetic pregnancies and tease apart the relative effects of diabetes as a precursor for early delivery and prematurity itself. Among the studies suggesting an independent risk of diabetes is a retrospective study focusing on neonatal respiratory morbidity — “one of the most common adverse outcomes associated with diabetes.”

The study, an analysis of the Consortium on Safe Labor study (an electronic medical record study of more than 220,000 singleton pregnancies), stratified morbidity by the probability of delivering at term (≥ 37 weeks). GDM and pregestational diabetes complicated 5.1% and 1.5% of the pregnancies, respectively, and were found to be associated with increased risks of neonatal respiratory morbidity compared to women without diabetes — regardless of the probability of delivering at term.

However, these associations were stronger with a higher probability of delivering at term, which suggests that the neonatal respiratory morbidity associated with diabetes is not fully explained by a greater propensity for prematurity (Am J Perinatol. 2017;34[11]:1160-8).

In addition, the rates of all neonatal respiratory morbidities and mortality were higher for pregestational diabetes compared with gestational diabetes, said Dr. Grantz, a senior author of the study. (Morbidities included neonatal intensive care unit admission, transient tachypnea of newborn, apnea, respiratory distress syndrome, mechanical ventilation, and stillbirth.)

The pathophysiology of diabetes and neonatal respiratory morbidity is “not fully known,” she said. It is believed that fetal hyperinsulinemia may cause delayed pulmonary maturation and there is evidence from animal studies that insulin decreases the incorporation of glucose and fatty acids into phospholipid phosphatidylglycerol. Indirect effects stem from the physiologic immaturity of earlier delivery and a higher cesarean delivery rate in pregnancies complicated by diabetes, Dr. Grantz said.

Among other retrospective studies was a population-based study from Canada (2004-2014), published in 2020, of large numbers of women with all types of diabetes and a comparison group of over 2.5 million without diabetes. For maternal morbidity/mortality, there were no significant differences by gestational age between iatrogenic delivery and expectant management among any form of diabetes. But for neonatal morbidity and mortality, the study found differences.

In women with gestational diabetes, iatrogenic delivery was associated with increased risk of neonatal morbidity/mortality at 36 and 37 weeks’ gestation and with decreased risk at weeks 38-40. Increased risk with iatrogenic delivery was also found for women with type 1 and type 2 diabetes at weeks 36 and 37 (Acta Obstet Gynecol Scand. 2020;99[3]:341-9).

Another retrospective study using California vital statistics (1997-2006) examined rates of stillbirth and infant death in women with GDM by gestational age at delivery (Am J Obstet Gynecol. 2012;206[4]:309.e1-e7). The 190,000-plus women with GDM had elevated risk of stillbirth at each gestational age compared to those without GDM, but “the [excess] risk for GDM was lowest at 38 weeks and again at 40 weeks,” Dr. Grantz said. The investigators concluded, she said, “that the risk of expectant management exceeded that of delivery at 38 weeks and beyond.”

Dr. Grantz reported no disclosures.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .

The FDA is formally looking into reports that some people who took popular diabetes and weight loss drugs had suicidal thoughts or two other health problems.

A new FDA report listed potential links between the medications and alopecia, aspiration, or suicidal ideation, CBS News reported. The investigation centers on reports of the health problems among people taking GLP-1 receptor agonists, some of which are Ozempic, Wegovy, Mounjaro, and Zepbound. The drugs are used to treat diabetes and overweight or obesity.

An investigation by the FDA doesn’t mean that the FDA has concluded a risk exists, the FDA’s webpage for risk evaluation cautions.

“It means that FDA has identified a potential safety issue, but it does not mean that FDA has identified a causal relationship between the drug and the listed risk,” the FDA site states.

Possible next steps after an investigation could include updating drug labels with new information, putting a risk management plan in place to prevent or manage the health risks, or gathering more information.

“The FDA monitors the safety of drugs throughout their life cycle,” even after the drugs are approved. In addition, the FDA uses “surveillance and risk assessment programs to identify and evaluate adverse events that did not appear during the drug development process,” FDA spokesperson Chanapa Tantibanchachai said in an email published by multiple news outlets.

Although an investigation may lead to no changes in how a drug is regulated by the FDA, this isn’t the first time that the popular medicines have landed on the FDA’s radar for safety reevaluation. Last year, the label for the drug Ozempic was updated to acknowledge reports of intestinal obstructions, CBS News reported.

European regulators are also looking into reports of suicidal thoughts among people taking GLP-1 receptor agonists, although no link has been established.

Concerns about aspiration during surgery resulted in the American Society of Anesthesiologists advising in June that people should stop taking GLP-1 receptor agonists before they have elective surgeries.

“While there is currently a lack of scientific data on how GLP-1 receptor agonists affect patients having surgery and interact with anesthesia, we’ve received anecdotal reports that the delay in stomach emptying could be associated with an increased risk of regurgitation and aspiration of food into the airways and lungs during general anesthesia and deep sedation,” the society’s president, Michael W. Champeau, MD, said in a statement at the time.

According to CBS News, the FDA’s drug reporting system links the medications to 201 reports of suicide or suicidal ideation, 18 reports that mention aspiration, and 422 reports that mention alopecia.

Novo Nordisk, whose portfolio includes Wegovy and Ozempic, told CNN that it works with the FDA to monitor safety and is aware of the reports of side effects.

“Novo Nordisk stands behind the safety and efficacy of all of our GLP-1RA medicines when they are used as indicated and when they are taken under the care of a licensed healthcare professional,” the company said in a statement to CNN.

A spokesperson for Eli Lilly, which makes Mounjaro and Zepbound, told CBS News in a statement, “Currently, the FDA is reviewing data on certain potential risks for GLP-1 receptor agonist medicines. Patient safety is our priority, and we are collaborating with the FDA on these potential signals.”
 

A version of this article appeared on WebMD.com .