Endocrinology

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article first appeared on Medscape.com.

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article first appeared on Medscape.com.

The optimal first step to address mild to moderately elevated blood pressure and cholesterol in otherwise healthy adults is a “prescription” to sit less and move more, the American Heart Association says in a new scientific statement.

“The current American Heart Association guidelines for diagnosing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks,” Bethany Barone Gibbs, PhD, chair of the statement writing group, said in an AHA news release.

“The first treatment strategy for many of these patients should be healthy lifestyle changes beginning with increasing physical activity,” said Dr. Gibbs, from the University of Pittsburgh.

The 12-page AHA scientific statement – Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? – was published online June 2 in Hypertension.
 

Every little bit helps

According to the AHA, about 21% of American adults have systolic blood pressure between 120 and 139 mm Hg, or diastolic blood pressure between 80 and 89 mm Hg, which meets the criteria for lifestyle-only treatment for elevated BP outlined in the American College of Cardiology (ACC)/AHA high blood pressure guideline.

In addition, about 28% of American adults have LDL cholesterol above 70 mg/dL and otherwise meet the low-risk criteria for heart disease or stroke. These individuals would meet the criteria for lifestyle-only treatment outlined in the 2018 ACC/AHA cholesterol treatment guidelines, which include increased physical activity, weight loss, better diet, smoking cessation, and moderating alcohol intake.

“Of the recommended lifestyle changes, increasing physical activity has extensive benefits, including improving both blood pressure and blood cholesterol, that are comparable, superior, or complementary to other healthy lifestyle changes,” the writing group says.

“Physical activity assessment and prescription are an excellent lifestyle behavior treatment option for all patients, including for the large population of mild-moderate-risk patients with elevated blood pressure and blood cholesterol,” they note.

Research has shown that increasing physical activity can lead to clinically meaningful 3 or 4 mm Hg reductions in systolic and diastolic blood pressure, and 3 to 6 mg/dL decreases in LDL cholesterol, the authors point out.

Previous evidence also shows that physically active people have a 21% lower risk of developing cardiovascular disease and a 36% lower risk for death from cardiovascular diseases than those who are not physically active.

Physical activity also has benefits beyond heart health, including a lower risk for some cancers; improved bone, brain, and mental health; and better sleep, they note.

The U.S. Department of Health and Human Services 2018 physical activity guidelines advise Americans to log 150 minutes of moderate-intensity aerobic exercise or 75 minutes of vigorous aerobic activity each week and to participate in two or more weekly strength training sessions.

However, there is no minimum amount of time to receive benefits from physical activity.

“Every little bit of activity is better than none. Even small initial increases of 5 to 10 minutes a day can yield health benefits,” Dr. Gibbs said.
 

Translational advice for clinicians

The AHA statement encourages clinicians to ask patients about their physical activity at every interaction; provide ideas and resources to help patients improve and sustain regular life-long physical activity; and encourage and celebrate small increases in activity, such as walking more or taking the stairs, to help with motivation.

“In our world where physical activity is increasingly engineered out of our lives and the overwhelming default is to sit – and even more so now as the nation and the world is practicing quarantine and isolation to reduce the spread of coronavirus – the message that we must be relentless in our pursuit to ‘sit less and move more’ throughout the day is more important than ever,” said Dr. Gibbs.

The statement was prepared by a volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology.

This research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article first appeared on Medscape.com.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

It follows that, as the prevalence of obesity among people with type 1 diabetes mellitus (T1DM) increases, so would the incidence of nonalcoholic fatty liver (NAFL), as it does in type 2 diabetes.

However, researchers in Finland report that the incidence of NAFL in T1DM is much lower, and that the use of the waist-to-height ratio to calculate midsection girth could be a low-cost alternative to MRI and computed tomography to more precisely diagnose NAFL in T1DM.

In a cross-sectional analysis of 121 adults with T1DM in the Finnish Diabetic Nephropathy study, known as FinnDiane, researchers from the University of Helsinki report in Diabetes Care that a waist-to-height ratio of 0.5 showed a relatively high rate of accuracy for identifying NAFL that was statistically significant (P = .04).

Lead author Erika B. Parente, MD, PhD, a researcher at the Folkhälsän Research Center in Helsinki, noted that the findings do not identify any causality between what the researchers called visceral adiposity and NAFL. “As long as they have accumulation of fat in the center of body and they can develop this low-grade inflammation that also goes to insulin-load sensitivity, people with T1DM can accumulate fat in the liver as do people with T2DM and the general population,” she said in an interview.

These findings build on her group’s previous work published in Scientific Reports showing a strong relationship between waist-to-height ratio and visceral fat percentage in adults with T1DM. The most recent FinnDiane analysis found no similar relationship between NAFL and fat tissue in the hips, arms and legs, and total adipose tissue.
 

Better than BMI as a measure

“We also found that waist-to-height ratio is better than body mass index to identify those individuals at higher risk of having NAFL,” Dr. Parente said. However, it’s not possible to predict which patients referred to imaging evaluation after being screened by waist-to-height ratio of 0.5 will surely have NAFL, she added.

That answer, she said, would require a longitudinal and cost-effectiveness study with larger population.

The waist-to-height ratio cutoff of 0.5 showed an 86% sensitivity and 55% specificity for NAFL, whereas BMI of 26.6 kg/m² showed an 79% sensitivity and 57% specificity.

“The most important message from our research is that health care professionals should be aware that individuals with T1DM can have NAFL, and waist-to-height ratio may help to identify those at higher risk,” she said.

The prevalence of NAFL among the adults with T1DM in the study was 11.6%, which is lower than the prevalence other studies reported in T2DM – 76% in a U.S. study – and in the general population – ranging from 19% to 46%. This underscores, Dr. Parente noted, the importance of using waist-to-height ratio in T1DM patients to determine the status of NAFL.

She said that few studies have investigated the consequences of NAFL in T1DM, pointing to two that linked NAFL with chronic kidney disease and cardiovascular disease in T1DM (Diabetes Care. 2014;37:1729-36; J Hepatol. 2010;53:713-8). “Most of the studies about the consequences of NAFL included people with T2DM,” she said. “From our research, we cannot conclude about the impact of NAFL in cardiovascular or kidney complications in our population because this is a cross-sectional study.”

That question may be answered by a future follow-up study of the ongoing FinnDiane study, she said.

The study is a “good reminder” that people with central adiposity and metabolic syndrome can develop NAFL disease, said Jeanne Marie Clark, MD, MPH, of Johns Hopkins University, Baltimore. “Even patients we may not think of having insulin resistance, such as those with T1DM.”

However, Dr. Clark added, “I do not think we can really determine which measure of central adiposity is best.” She noted that the study was “pretty small” with only 14 patients who had NAFL disease. “Waist-to-height ratio is certainly a reasonable option,” she added. “Waist circumference alone is known to be a strong predictor. I would say some measure is better than none, and it should be more routine in clinical practice.”

Dr. Parente disclosed financial relationships with Eli Lilly, Abbott, AstraZeneca, Sanofi, and Boehringer Ingelheim. Two of eight coauthors disclosed financial relationships with AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Fresenius, GE Healthcare, Medscape, Merck Sharpe and Dohme, Mundipharma, Novo Nordisk, Peer-Voice, Sanofi, and Sciarc. The remaining coauthors had no disclosures.

Dr. Clark had no disclosures.

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

A version of this article first appeared on Medscape.com.

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

A version of this article first appeared on Medscape.com.

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

A version of this article first appeared on Medscape.com.

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

Hemoglobin A1c above 5% but below the prediabetes cutoff of 5.5% is an additional potential biomarker of subclinical atherosclerosis in people with low cardiovascular disease risk, according to an analysis of data on almost 4,000 middle-aged individuals.

Mount Sinai Heart/CCA 3.0

“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.

“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”

The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.

Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).

Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
 

A call for earlier intervention

Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.

“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”

Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.

“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”

Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.

Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.

“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”

These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.

Hemoglobin A1c above 5% but below the prediabetes cutoff of 5.5% is an additional potential biomarker of subclinical atherosclerosis in people with low cardiovascular disease risk, according to an analysis of data on almost 4,000 middle-aged individuals.

Mount Sinai Heart/CCA 3.0

“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.

“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”

The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.

Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).

Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
 

A call for earlier intervention

Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.

“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”

Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.

“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”

Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.

Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.

“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”

These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.

Hemoglobin A1c above 5% but below the prediabetes cutoff of 5.5% is an additional potential biomarker of subclinical atherosclerosis in people with low cardiovascular disease risk, according to an analysis of data on almost 4,000 middle-aged individuals.

Mount Sinai Heart/CCA 3.0

“If one looks at the incidence of generalized subclinical atherosclerosis, we are not talking small numbers,” senior study author Valentin Fuster, MD, PhD, said in an interview. “We are talking about between 45% and 82% of this middle-age population that already has atherosclerotic disease subclinically.

“Actually,” he added, “the disease was extensive in 5%-30% of these individuals of middle age.”

The study included 3,973 participants from the Progression of Early Subclinical Atherosclerosis study who did not have diabetes. A1c showed an association with the prevalence and multiterritorial extent of subclinical atherosclerosis as measured by two-dimensional ultrasound and coronary artery calcium score (CACS; P < .001). For example, those with A1c above 6.1% (133 participants) had a 33.1% rate of generalized subclinical atherosclerosis, compared with 4.9% for those with A1c below 4.8% (243), the lowest-score group in the study.

Patients in the subprediabetes band, between 5.0% and 5.5%, had significantly higher rates of generalized subclinical atherosclerosis than did the lowest-score group: 8% in the 4.9%-5.0% group (375 participants); 9.9% in the 5.1%-5.2% range (687); 10.3% in the 5.3%-5.4% group (928); and 11.5% in the 5.5%-5.6% group (842).

Those in the 5.1%-5.2% and 5/3%-5.4% A1c groups had a 27% greater chance of having subclinical atherosclerosis, while those in the 5.5%-5.6% group had a 36% greater risk, according to an odds ratio analysis adjusted for established cardiovascular risk factors. The risks were even higher for patients with prediabetes, the researchers reported in the Journal of the American College of Cardiology.
 

A call for earlier intervention

Notably, the study found that fasting plasma glucose testing did not yield a similar association between A1c and atherosclerosis.

“The message is that we all talk about people when they are close to the development of cardiovascular events, and here we are talking about people who we should pay attention to much earlier,” said Dr. Fuster, physician-in-chief at Icahn School of Medicine at Mount Sinai in New York and director of the National Center for Cardiovascular Investigation in Madrid, where the observational study originated said. “People should be sensitized to HbA1c much more than they would’ve been in the past, and I think this study actually validates that.”

Christie Ballantyne, MD, noted in an interview that these findings support the utility of A1c for predicting CVD risk.

“I think more and more we should be ordering a HbA1c” during routine physical exams, Dr. Ballantyne said. “You don’t have to be obese to get it; there are lots of people, maybe they’re slightly overweight. It’s a reasonable test to be getting when you get to middle age and older to get an idea for assessing for both developing diabetes and also the presence of atherosclerosis and the risk for having cardiovascular events.”

Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center in Houston, coauthored an editorial comment on the study.

Clinicians typically start to manage CVD and diabetes risk “late in the process,” Dr. Ballantyne said. This study suggested that earlier use of antidiabetes therapies, namely peptide-1 agonists and semisynthetic glucagon-like peptide-2 inhibitors, may be warranted in patients with intermediate risk of CVD.

“It’s just more data for the rationale that, perhaps we could end up doing trials to show we can take high-risk people and prevent them from getting both heart disease and diabetes,” Dr. Ballantyne added. “Could we start a little earlier with better precision?”

These finding don’t yet call for a change in how cardiologists and endocrinologists manage patients on the cusp of prediabetes, said Paul S. Jellinger, MD, of Hollywood, Fla., and a professor at the University of Miami. “The endpoint of subclinical atherosclerosis does not necessarily translate into the harder endpoint of CVD events, although there is certainly reason to believe it does,” he said in an interview, noting that he’s often used CACS to stratify atherosclerotic CVD risk in patients.

Taking more steps each day, in short spurts or longer bouts, was associated with a longer life in women older than 60 years, according to data from more than 16,000 participants in the ongoing Women’s Health Study.

The American Heart Association recommends at least 150 minutes per week of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of both as fitness guidelines for adults. Walking is a safe and easy way for many adults to follow these guidelines, according to Christopher C. Moore, MS, a PhD candidate at the University of North Carolina at Chapel Hill.

The popularity of step counts reflect that they are simple and objective, and “focusing on steps can help promote an active lifestyle,” he said. Data on the impact of sporadic steps accumulated outside of longer bouts of activity on health outcomes are limited; however, technology advances in the form of fitness apps and wearable devices make it possible for researchers to track and measure the benefits of short periods of activity as well as longer periods.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the AHA, Mr. Moore and colleagues assessed data from women older than 60 years who used wearable step-counting devices to measure their daily steps and walking patterns.

The study population included 16,732 women enrolled in the Women’s Health Study, a longstanding study of heart disease, cancer, and disease prevention among women in the United States. The participants wore waist step counters 4-7 days a week during 2011-2015. The average of the women was 72 years; 96% were non-Hispanic White, and the average BMI was 26 kg/m².

The researchers divided the total number of steps for each study participant into two groups: “bouted” steps, defined as 10 minutes or longer bouts of walking with few interruptions; and “sporadic” steps, defined as short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car.

A total of 804 deaths occurred during an average of 6 years of follow-up. Each initial increase of 1,000 steps including sporadic or bouted steps was associated with a 28% decrease in death, compared with no daily steps (hazard ratio, 0.72).

Each increasing quartile of sporadic steps was linked with higher total steps per day, Mr. Moore said. “Initial increase in sporadic steps corresponded to the greatest reductions in mortality,” with a HR of 0.69 per additional sporadic steps below 3,200 per day, and the impact on reduced mortality plateaued at about 4,500 sporadic steps per day.

In further analysis, the researchers also found a roughly 32% decrease in death in participants who took more than 2,000 steps daily in uninterrupted bouts (HR, 0.69).

The study findings were limited by several factors, including the relatively short follow-up period and number of events, the assessment of steps at a single time point, and the mostly homogeneous population, Mr. Moore noted. Additional research is needed to assess whether the results are generalizable to men, younger women, and diverse racial and ethnic groups.

However, the results may have implications for public health messaging, he emphasized. The message is that, to impact longevity, the total volume of steps is more important than the type of activity through which they are accumulated.

“You can accumulate your steps through longer bouts of purposeful activity or through everyday behaviors such as walking to your car, taking the stairs, and doing housework,” Mr. Moore concluded.

Find a friend, both of you benefit

On the basis of this study and other available evidence, more steps daily are recommended for everyone, Nieca Goldberg, MD, a cardiologist at New York University Langone Health, said in an interview.

“You can increase minutes of walking and frequency of walking,” she said.

Dr. Goldberg emphasized that you don’t need a fancy app or wearable device to up your steps. She offered some tips to help overcome barriers to putting one foot in front of the other. “Take the steps instead of the elevator. Park your car farther from your destination so you can walk.” Also, you can help yourself and help a friend to better health. “Get a walking buddy so you can encourage each other to walk,” Dr. Goldberg added.

Mr. Moore and Dr. Goldberg had no financial conflicts to disclose. The Women’s Health Study is funded by Brigham and Women’s Hospital; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Mr. Moore was funded by a grant from the NHLBI but had no other financial conflicts to disclose.

Taking more steps each day, in short spurts or longer bouts, was associated with a longer life in women older than 60 years, according to data from more than 16,000 participants in the ongoing Women’s Health Study.

The American Heart Association recommends at least 150 minutes per week of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of both as fitness guidelines for adults. Walking is a safe and easy way for many adults to follow these guidelines, according to Christopher C. Moore, MS, a PhD candidate at the University of North Carolina at Chapel Hill.

The popularity of step counts reflect that they are simple and objective, and “focusing on steps can help promote an active lifestyle,” he said. Data on the impact of sporadic steps accumulated outside of longer bouts of activity on health outcomes are limited; however, technology advances in the form of fitness apps and wearable devices make it possible for researchers to track and measure the benefits of short periods of activity as well as longer periods.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the AHA, Mr. Moore and colleagues assessed data from women older than 60 years who used wearable step-counting devices to measure their daily steps and walking patterns.

The study population included 16,732 women enrolled in the Women’s Health Study, a longstanding study of heart disease, cancer, and disease prevention among women in the United States. The participants wore waist step counters 4-7 days a week during 2011-2015. The average of the women was 72 years; 96% were non-Hispanic White, and the average BMI was 26 kg/m².

The researchers divided the total number of steps for each study participant into two groups: “bouted” steps, defined as 10 minutes or longer bouts of walking with few interruptions; and “sporadic” steps, defined as short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car.

A total of 804 deaths occurred during an average of 6 years of follow-up. Each initial increase of 1,000 steps including sporadic or bouted steps was associated with a 28% decrease in death, compared with no daily steps (hazard ratio, 0.72).

Each increasing quartile of sporadic steps was linked with higher total steps per day, Mr. Moore said. “Initial increase in sporadic steps corresponded to the greatest reductions in mortality,” with a HR of 0.69 per additional sporadic steps below 3,200 per day, and the impact on reduced mortality plateaued at about 4,500 sporadic steps per day.

In further analysis, the researchers also found a roughly 32% decrease in death in participants who took more than 2,000 steps daily in uninterrupted bouts (HR, 0.69).

The study findings were limited by several factors, including the relatively short follow-up period and number of events, the assessment of steps at a single time point, and the mostly homogeneous population, Mr. Moore noted. Additional research is needed to assess whether the results are generalizable to men, younger women, and diverse racial and ethnic groups.

However, the results may have implications for public health messaging, he emphasized. The message is that, to impact longevity, the total volume of steps is more important than the type of activity through which they are accumulated.

“You can accumulate your steps through longer bouts of purposeful activity or through everyday behaviors such as walking to your car, taking the stairs, and doing housework,” Mr. Moore concluded.

Find a friend, both of you benefit

On the basis of this study and other available evidence, more steps daily are recommended for everyone, Nieca Goldberg, MD, a cardiologist at New York University Langone Health, said in an interview.

“You can increase minutes of walking and frequency of walking,” she said.

Dr. Goldberg emphasized that you don’t need a fancy app or wearable device to up your steps. She offered some tips to help overcome barriers to putting one foot in front of the other. “Take the steps instead of the elevator. Park your car farther from your destination so you can walk.” Also, you can help yourself and help a friend to better health. “Get a walking buddy so you can encourage each other to walk,” Dr. Goldberg added.

Mr. Moore and Dr. Goldberg had no financial conflicts to disclose. The Women’s Health Study is funded by Brigham and Women’s Hospital; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Mr. Moore was funded by a grant from the NHLBI but had no other financial conflicts to disclose.

Taking more steps each day, in short spurts or longer bouts, was associated with a longer life in women older than 60 years, according to data from more than 16,000 participants in the ongoing Women’s Health Study.

The American Heart Association recommends at least 150 minutes per week of moderate physical activity, 75 minutes of vigorous physical activity, or a combination of both as fitness guidelines for adults. Walking is a safe and easy way for many adults to follow these guidelines, according to Christopher C. Moore, MS, a PhD candidate at the University of North Carolina at Chapel Hill.

The popularity of step counts reflect that they are simple and objective, and “focusing on steps can help promote an active lifestyle,” he said. Data on the impact of sporadic steps accumulated outside of longer bouts of activity on health outcomes are limited; however, technology advances in the form of fitness apps and wearable devices make it possible for researchers to track and measure the benefits of short periods of activity as well as longer periods.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the AHA, Mr. Moore and colleagues assessed data from women older than 60 years who used wearable step-counting devices to measure their daily steps and walking patterns.

The study population included 16,732 women enrolled in the Women’s Health Study, a longstanding study of heart disease, cancer, and disease prevention among women in the United States. The participants wore waist step counters 4-7 days a week during 2011-2015. The average of the women was 72 years; 96% were non-Hispanic White, and the average BMI was 26 kg/m².

The researchers divided the total number of steps for each study participant into two groups: “bouted” steps, defined as 10 minutes or longer bouts of walking with few interruptions; and “sporadic” steps, defined as short spurts of walking during regular daily activities such as housework, taking the stairs, or walking to or from a car.

A total of 804 deaths occurred during an average of 6 years of follow-up. Each initial increase of 1,000 steps including sporadic or bouted steps was associated with a 28% decrease in death, compared with no daily steps (hazard ratio, 0.72).

Each increasing quartile of sporadic steps was linked with higher total steps per day, Mr. Moore said. “Initial increase in sporadic steps corresponded to the greatest reductions in mortality,” with a HR of 0.69 per additional sporadic steps below 3,200 per day, and the impact on reduced mortality plateaued at about 4,500 sporadic steps per day.

In further analysis, the researchers also found a roughly 32% decrease in death in participants who took more than 2,000 steps daily in uninterrupted bouts (HR, 0.69).

The study findings were limited by several factors, including the relatively short follow-up period and number of events, the assessment of steps at a single time point, and the mostly homogeneous population, Mr. Moore noted. Additional research is needed to assess whether the results are generalizable to men, younger women, and diverse racial and ethnic groups.

However, the results may have implications for public health messaging, he emphasized. The message is that, to impact longevity, the total volume of steps is more important than the type of activity through which they are accumulated.

“You can accumulate your steps through longer bouts of purposeful activity or through everyday behaviors such as walking to your car, taking the stairs, and doing housework,” Mr. Moore concluded.

Find a friend, both of you benefit

On the basis of this study and other available evidence, more steps daily are recommended for everyone, Nieca Goldberg, MD, a cardiologist at New York University Langone Health, said in an interview.

“You can increase minutes of walking and frequency of walking,” she said.

Dr. Goldberg emphasized that you don’t need a fancy app or wearable device to up your steps. She offered some tips to help overcome barriers to putting one foot in front of the other. “Take the steps instead of the elevator. Park your car farther from your destination so you can walk.” Also, you can help yourself and help a friend to better health. “Get a walking buddy so you can encourage each other to walk,” Dr. Goldberg added.

Mr. Moore and Dr. Goldberg had no financial conflicts to disclose. The Women’s Health Study is funded by Brigham and Women’s Hospital; the National Heart, Lung, and Blood Institute; and the National Cancer Institute. Mr. Moore was funded by a grant from the NHLBI but had no other financial conflicts to disclose.

People with prediabetes, defined by having a hemoglobin A1c of 5.7%-6.4%, had a significantly increased rate of atherosclerotic cardiovascular disease events and incident chronic kidney disease in a study of nearly 337,000 people included in the UK Biobank database.

The findings suggest that people with prediabetes have “heightened risk even without progression to type 2 diabetes,” Michael C. Honigberg, MD, said at the annual scientific sessions of the American College of Cardiology.

“Hemoglobin A1c may be better considered as a continuous measure of risk rather than dichotomized” as either less than 6.5%, or 6.5% or higher, the usual threshold defining people with type 2 diabetes, said Dr. Honigberg, a cardiologist at Massachusetts General Hospital in Boston.
 

‘Prediabetes is not a benign entity’

“Our findings reinforce the notion that A1c represents a continuum of risk, with elevated risks observed, especially for atherosclerotic cardiovascular disease [ASCVD], at levels where some clinicians wouldn’t think twice about them. Prediabetes is not a benign entity in the middle-aged population we studied,” Dr. Honigberg said in an interview. “Risks are higher in individuals with type 2 diabetes,” he stressed, “however, prediabetes is so much more common that it appears to confer similar cardio, renal, and metabolic risks at a population level.”

Results from prior observational studies also showed elevated incidence rate of cardiovascular disease events in people with prediabetes, including a 2010 report based on data from about 11,000 U.S. residents, and in a more recent meta-analysis of 129 studies involving more than 10 million people. The new report by Dr. Honigberg “is the first to comprehensively evaluate diverse cardio-renal-metabolic outcomes across a range of A1c levels using a very large, contemporary database,” he noted. In addition, most prior reports did not include chronic kidney disease as an examined outcome.

The primary endpoint examined in the new analysis was the combined incidence during a median follow-up of just over 11 years of ASCVD events (coronary artery disease, ischemic stroke, or peripheral artery disease), CKD, or heart failure among 336,709 adults in the UK Biobank who at baseline had none of these conditions nor type 1 diabetes.

The vast majority, 82%, were normoglycemic at baseline, based on having an A1c of less than 5.7%; 14% had prediabetes, with an A1c of 5.7%-6.4%; and 4% had type 2 diabetes based on an A1c of at least 6.5% or on insulin treatment. Patients averaged about 57 years of age, slightly more than half were women, and average body mass index was in the overweight category except for those with type 2 diabetes.

The primary endpoint, the combined incidence of ASCVD, CKD, and heart failure, was 24% among those with type 2 diabetes, 14% in those with prediabetes, and 8% in those who were normoglycemic at entry. Concurrently with the report, the results appeared online. Most of these events involved ASCVD, which occurred in 11% of those in the prediabetes subgroup (roughly four-fifths of the events in this subgroup), and in 17% of those with type 2 diabetes (nearly three-quarters of the events in this subgroup).

In an analysis that adjusted for more than a dozen demographic and clinical factors, the presence of prediabetes linked with significant increases in the incidence rate of all three outcomes compared with people who were normoglycemic at baseline. The analysis also identified an A1c level of 5.0% as linked with the lowest incidence of each of the three adverse outcomes. And a very granular analysis suggested that a significantly elevated risk for ASCVD first appeared when A1c levels were in the range of 5.4%-5.7%; a significantly increased incidence of CKD became apparent once A1c was in the range of 6.2%-6.5%; and a significantly increased incidence of heart failure began to manifest once A1c levels reached at least 7.0%.

Need for comprehensive cardiometabolic risk management

The findings “highlight the importance of identifying and comprehensively managing cardiometabolic risk in people with prediabetes, including dietary modification, exercise, weight loss and obesity management, smoking cessation, and attention to hypertension and hypercholesterolemia,” Dr. Honigberg said. While these data cannot address the appropriateness of using novel drug interventions in people with prediabetes, they suggest that people with prediabetes should be the focus of future prevention trials testing agents such as sodium-glucose cotransporter 2 inhibitors.

“These data help us discuss risk with patients [with prediabetes], and reemphasize the importance of guideline-directed preventive care,” said Vijay Nambi, MD, PhD, a preventive cardiologist and lipid specialist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, who was not involved with the study.

An additional analysis reported by Dr. Honigberg examined the risk among people with prediabetes who also were current or former smokers and in the top tertile of the prediabetes study population for systolic blood pressure, high non-HDL cholesterol, and C-reactive protein (a marker of inflammation). This very high-risk subgroup of people with prediabetes had incidence rates for ASCVD events and for heart failure that tracked identically to those with type 2 diabetes. However. the incidence rate for CKD in these high-risk people with prediabetes remained below that of patients with type 2 diabetes.

Dr. Honigberg had no disclosures. Dr. Nambi has received research funding from Amgen, Merck, and Roche.

[email protected]

People with prediabetes, defined by having a hemoglobin A1c of 5.7%-6.4%, had a significantly increased rate of atherosclerotic cardiovascular disease events and incident chronic kidney disease in a study of nearly 337,000 people included in the UK Biobank database.

The findings suggest that people with prediabetes have “heightened risk even without progression to type 2 diabetes,” Michael C. Honigberg, MD, said at the annual scientific sessions of the American College of Cardiology.

“Hemoglobin A1c may be better considered as a continuous measure of risk rather than dichotomized” as either less than 6.5%, or 6.5% or higher, the usual threshold defining people with type 2 diabetes, said Dr. Honigberg, a cardiologist at Massachusetts General Hospital in Boston.
 

‘Prediabetes is not a benign entity’

“Our findings reinforce the notion that A1c represents a continuum of risk, with elevated risks observed, especially for atherosclerotic cardiovascular disease [ASCVD], at levels where some clinicians wouldn’t think twice about them. Prediabetes is not a benign entity in the middle-aged population we studied,” Dr. Honigberg said in an interview. “Risks are higher in individuals with type 2 diabetes,” he stressed, “however, prediabetes is so much more common that it appears to confer similar cardio, renal, and metabolic risks at a population level.”

Results from prior observational studies also showed elevated incidence rate of cardiovascular disease events in people with prediabetes, including a 2010 report based on data from about 11,000 U.S. residents, and in a more recent meta-analysis of 129 studies involving more than 10 million people. The new report by Dr. Honigberg “is the first to comprehensively evaluate diverse cardio-renal-metabolic outcomes across a range of A1c levels using a very large, contemporary database,” he noted. In addition, most prior reports did not include chronic kidney disease as an examined outcome.

The primary endpoint examined in the new analysis was the combined incidence during a median follow-up of just over 11 years of ASCVD events (coronary artery disease, ischemic stroke, or peripheral artery disease), CKD, or heart failure among 336,709 adults in the UK Biobank who at baseline had none of these conditions nor type 1 diabetes.

The vast majority, 82%, were normoglycemic at baseline, based on having an A1c of less than 5.7%; 14% had prediabetes, with an A1c of 5.7%-6.4%; and 4% had type 2 diabetes based on an A1c of at least 6.5% or on insulin treatment. Patients averaged about 57 years of age, slightly more than half were women, and average body mass index was in the overweight category except for those with type 2 diabetes.

The primary endpoint, the combined incidence of ASCVD, CKD, and heart failure, was 24% among those with type 2 diabetes, 14% in those with prediabetes, and 8% in those who were normoglycemic at entry. Concurrently with the report, the results appeared online. Most of these events involved ASCVD, which occurred in 11% of those in the prediabetes subgroup (roughly four-fifths of the events in this subgroup), and in 17% of those with type 2 diabetes (nearly three-quarters of the events in this subgroup).

In an analysis that adjusted for more than a dozen demographic and clinical factors, the presence of prediabetes linked with significant increases in the incidence rate of all three outcomes compared with people who were normoglycemic at baseline. The analysis also identified an A1c level of 5.0% as linked with the lowest incidence of each of the three adverse outcomes. And a very granular analysis suggested that a significantly elevated risk for ASCVD first appeared when A1c levels were in the range of 5.4%-5.7%; a significantly increased incidence of CKD became apparent once A1c was in the range of 6.2%-6.5%; and a significantly increased incidence of heart failure began to manifest once A1c levels reached at least 7.0%.

Need for comprehensive cardiometabolic risk management

The findings “highlight the importance of identifying and comprehensively managing cardiometabolic risk in people with prediabetes, including dietary modification, exercise, weight loss and obesity management, smoking cessation, and attention to hypertension and hypercholesterolemia,” Dr. Honigberg said. While these data cannot address the appropriateness of using novel drug interventions in people with prediabetes, they suggest that people with prediabetes should be the focus of future prevention trials testing agents such as sodium-glucose cotransporter 2 inhibitors.

“These data help us discuss risk with patients [with prediabetes], and reemphasize the importance of guideline-directed preventive care,” said Vijay Nambi, MD, PhD, a preventive cardiologist and lipid specialist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, who was not involved with the study.

An additional analysis reported by Dr. Honigberg examined the risk among people with prediabetes who also were current or former smokers and in the top tertile of the prediabetes study population for systolic blood pressure, high non-HDL cholesterol, and C-reactive protein (a marker of inflammation). This very high-risk subgroup of people with prediabetes had incidence rates for ASCVD events and for heart failure that tracked identically to those with type 2 diabetes. However. the incidence rate for CKD in these high-risk people with prediabetes remained below that of patients with type 2 diabetes.

Dr. Honigberg had no disclosures. Dr. Nambi has received research funding from Amgen, Merck, and Roche.

[email protected]

People with prediabetes, defined by having a hemoglobin A1c of 5.7%-6.4%, had a significantly increased rate of atherosclerotic cardiovascular disease events and incident chronic kidney disease in a study of nearly 337,000 people included in the UK Biobank database.

The findings suggest that people with prediabetes have “heightened risk even without progression to type 2 diabetes,” Michael C. Honigberg, MD, said at the annual scientific sessions of the American College of Cardiology.

“Hemoglobin A1c may be better considered as a continuous measure of risk rather than dichotomized” as either less than 6.5%, or 6.5% or higher, the usual threshold defining people with type 2 diabetes, said Dr. Honigberg, a cardiologist at Massachusetts General Hospital in Boston.
 

‘Prediabetes is not a benign entity’

“Our findings reinforce the notion that A1c represents a continuum of risk, with elevated risks observed, especially for atherosclerotic cardiovascular disease [ASCVD], at levels where some clinicians wouldn’t think twice about them. Prediabetes is not a benign entity in the middle-aged population we studied,” Dr. Honigberg said in an interview. “Risks are higher in individuals with type 2 diabetes,” he stressed, “however, prediabetes is so much more common that it appears to confer similar cardio, renal, and metabolic risks at a population level.”

Results from prior observational studies also showed elevated incidence rate of cardiovascular disease events in people with prediabetes, including a 2010 report based on data from about 11,000 U.S. residents, and in a more recent meta-analysis of 129 studies involving more than 10 million people. The new report by Dr. Honigberg “is the first to comprehensively evaluate diverse cardio-renal-metabolic outcomes across a range of A1c levels using a very large, contemporary database,” he noted. In addition, most prior reports did not include chronic kidney disease as an examined outcome.

The primary endpoint examined in the new analysis was the combined incidence during a median follow-up of just over 11 years of ASCVD events (coronary artery disease, ischemic stroke, or peripheral artery disease), CKD, or heart failure among 336,709 adults in the UK Biobank who at baseline had none of these conditions nor type 1 diabetes.

The vast majority, 82%, were normoglycemic at baseline, based on having an A1c of less than 5.7%; 14% had prediabetes, with an A1c of 5.7%-6.4%; and 4% had type 2 diabetes based on an A1c of at least 6.5% or on insulin treatment. Patients averaged about 57 years of age, slightly more than half were women, and average body mass index was in the overweight category except for those with type 2 diabetes.

The primary endpoint, the combined incidence of ASCVD, CKD, and heart failure, was 24% among those with type 2 diabetes, 14% in those with prediabetes, and 8% in those who were normoglycemic at entry. Concurrently with the report, the results appeared online. Most of these events involved ASCVD, which occurred in 11% of those in the prediabetes subgroup (roughly four-fifths of the events in this subgroup), and in 17% of those with type 2 diabetes (nearly three-quarters of the events in this subgroup).

In an analysis that adjusted for more than a dozen demographic and clinical factors, the presence of prediabetes linked with significant increases in the incidence rate of all three outcomes compared with people who were normoglycemic at baseline. The analysis also identified an A1c level of 5.0% as linked with the lowest incidence of each of the three adverse outcomes. And a very granular analysis suggested that a significantly elevated risk for ASCVD first appeared when A1c levels were in the range of 5.4%-5.7%; a significantly increased incidence of CKD became apparent once A1c was in the range of 6.2%-6.5%; and a significantly increased incidence of heart failure began to manifest once A1c levels reached at least 7.0%.

Need for comprehensive cardiometabolic risk management

The findings “highlight the importance of identifying and comprehensively managing cardiometabolic risk in people with prediabetes, including dietary modification, exercise, weight loss and obesity management, smoking cessation, and attention to hypertension and hypercholesterolemia,” Dr. Honigberg said. While these data cannot address the appropriateness of using novel drug interventions in people with prediabetes, they suggest that people with prediabetes should be the focus of future prevention trials testing agents such as sodium-glucose cotransporter 2 inhibitors.

“These data help us discuss risk with patients [with prediabetes], and reemphasize the importance of guideline-directed preventive care,” said Vijay Nambi, MD, PhD, a preventive cardiologist and lipid specialist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, who was not involved with the study.

An additional analysis reported by Dr. Honigberg examined the risk among people with prediabetes who also were current or former smokers and in the top tertile of the prediabetes study population for systolic blood pressure, high non-HDL cholesterol, and C-reactive protein (a marker of inflammation). This very high-risk subgroup of people with prediabetes had incidence rates for ASCVD events and for heart failure that tracked identically to those with type 2 diabetes. However. the incidence rate for CKD in these high-risk people with prediabetes remained below that of patients with type 2 diabetes.

Dr. Honigberg had no disclosures. Dr. Nambi has received research funding from Amgen, Merck, and Roche.

[email protected]

The American Association of Clinical Endocrinology (AACE) has issued its first-ever official guidelines addressing the use of advanced technologies in the management of people with diabetes.

They were presented on May 28 at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists and simultaneously published in Endocrine Practice.

Previous AACE guidance on the clinical use of insulin pumps and CGM over the past decade has been published in the form of consensus or position statements rather than official evidence-based guidelines, task force cochair George Grunberger, MD, of the Grunberger Diabetes Institute, Bloomfield Hills, Mich., explained.

“There’s never really been, until now, hardcore evidence, [with] peer-reviewed, quality trials published in the literature to go after the evidence that is required for guidelines. ... This is not an opinion piece or position statement.”

The problem with that strict approach to “guidelines” is how quickly the diabetes technology field is evolving, he acknowledged. “It’s frustrating because we know what’s [coming up], but we can’t put it in a guideline because it hasn’t been published yet.”

In an AACE podcast, Dr. Grunberger said the guidelines will likely become a “living” document, along the lines of the American Diabetes Association’s annual Standards of Care, as “any cutoff date is arbitrary. More and more papers will be published on these technologies. ... This is certainly not a static field.”

In the meantime, task force cochair and author Jennifer Sherr, MD, PhD, a pediatric endocrinologist, said she hopes the guidelines will help to reduce insurance company barriers to use of the currently available technologies.

“I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so they can appropriately change their coverage practices,” added Dr. Sherr, of Yale University, New Haven, Conn.
 

Recommendations address CGM, pumps, and connected systems

In the guidelines, CGM is “strongly recommended for all persons with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or the use of an insulin pump.” For those with diabetes who use CGM, “priority metrics” include a “time in range” of greater than 70% from 14 days of active use. Targets for mean glucose should be individualized, with glycemic variability 36% or lower.

Further specific CGM target metrics are given for people with type 1 diabetes, older/high risk individuals, and for pregnant women. The recommendations align with those issued in a 2019 joint consensus statement on CGM time-in-range endorsed by several organizations, including AACE.    

In response to an audience question about whether AACE is advising that time-in-range replace A1c for glycemia assessment, Dr. Sherr responded: “I think currently we’re not in a position where we can completely replace A1c with time in range. However, I’m hopeful that in future years we’ll see further data gathered ... to allow for that recommendation to occur.”

For now, she said, “What we really want to hone in on in the guidelines is that time-in-range and use of CGM truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It’s not just a number of whether we’re hitting target. It tells us whether we need to attack time above range or time below range. So we really think it’s critical for clinical care.”

The document also provides specifics about real-time versus intermittently scanned CGM and use of diagnostic/professional CGM.

The “insulin delivery technologies” section covers use of connected pens, insulin pumps without CGM, insulin pumps with separate CGM, and the more advanced combined insulin pump-CGM systems including those with low-glucose suspend, predictive low-glucose suspend, and hybrid closed-loops (sometimes called the artificial pancreas).

In general, these automated insulin delivery systems (artificial pancreas), “are strongly recommended for all persons with [type 1 diabetes], since their use has been shown to increase time in range, especially in the overnight period, without causing an increased risk of hypoglycemia,” Dr. Sherr observed.
 

Other tech topics: Apps, telemedicine, and safety

The new guidelines say that “clinically validated” smartphone apps should be recommended to help teach or reinforce diabetes self-management skills and provide support and encouragement for healthy behaviors around food and exercise.

Dr. Grunberger pointed out: “As we know, there are tons of apps out there, and patients are using them. The problem is that very few of them have actually been validated in clinical trials in published peer-reviewed [journals].”

He recommended a joint statement on diabetes apps from the American Diabetes Association and the European Association for the Study of Diabetes that was initially discussed at the 2019 EASD meeting, as reported by this news organization, and subsequently published in January 2020 in Diabetes Care and Diabetologia.

“Telemedicine, including periodic phone calls, smartphone-web interactions ... by health care professionals ... is strongly recommended to treat persons with diabetes, provide diabetes education, remotely monitor glucose and/or insulin data to indicate the need for therapy adjustments, and improve diabetes-related outcomes/control with better engagement,” the document says.

Safety concerns addressed include the issue of certain medications interfering with CGM [readings] ... including acetaminophen, high-dose vitamin C, and hydroxyurea, as well as cautions about what to do in the event of device malfunction and assessing that the patient is sufficiently trained in proper device use. Criteria for insulin pump discontinuation are also given.
 

Implementation: Who will be prescribing? ‘This is not for amateurs’

A final section on implementation recommends that “initiation and use of diabetes technology should be implemented by health care professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technology.”

Dr. Grunberger commented: “I think the key is going to be who should be doing this? What is the role of a clinical endocrinologist in the future? What is our responsibility, [since] we don’t have the manpower and womanpower to take care of all these people as these technologies advance? It’s our responsibility to provide these hopefully valued recommendations as a resource for those who want to know more about it.”

However, he noted, “This is not for amateurs. If you want to actually use this in your practice, you need the infrastructure, the expertise, the training, the dedication, and the energy to be there for the patients all the time ... This clinical practice guideline is a foundation.”

Dr. Sherr added: “To me, it’s really thinking about ... changing our mindset from who is an appropriate candidate to who can benefit and how vast a group that entails ... I’m hopeful that we will see more technology use through continued conversations with our patients with diabetes, and hopefully through more clinicians being excited to be part of this revolution.”

Dr. Grunberger has reported being on speakers bureaus for Eli Lilly, Novo Nordisk, and Abbott. Dr. Sherr has reported being a consultant and speaker for Lilly and Medtronic Diabetes, a consultant for Insulet and Sanofi, and on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, JDRF T1D fund, and Medtronic.

A version of this article first appeared on Medscape.com.

The American Association of Clinical Endocrinology (AACE) has issued its first-ever official guidelines addressing the use of advanced technologies in the management of people with diabetes.

They were presented on May 28 at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists and simultaneously published in Endocrine Practice.

Previous AACE guidance on the clinical use of insulin pumps and CGM over the past decade has been published in the form of consensus or position statements rather than official evidence-based guidelines, task force cochair George Grunberger, MD, of the Grunberger Diabetes Institute, Bloomfield Hills, Mich., explained.

“There’s never really been, until now, hardcore evidence, [with] peer-reviewed, quality trials published in the literature to go after the evidence that is required for guidelines. ... This is not an opinion piece or position statement.”

The problem with that strict approach to “guidelines” is how quickly the diabetes technology field is evolving, he acknowledged. “It’s frustrating because we know what’s [coming up], but we can’t put it in a guideline because it hasn’t been published yet.”

In an AACE podcast, Dr. Grunberger said the guidelines will likely become a “living” document, along the lines of the American Diabetes Association’s annual Standards of Care, as “any cutoff date is arbitrary. More and more papers will be published on these technologies. ... This is certainly not a static field.”

In the meantime, task force cochair and author Jennifer Sherr, MD, PhD, a pediatric endocrinologist, said she hopes the guidelines will help to reduce insurance company barriers to use of the currently available technologies.

“I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so they can appropriately change their coverage practices,” added Dr. Sherr, of Yale University, New Haven, Conn.
 

Recommendations address CGM, pumps, and connected systems

In the guidelines, CGM is “strongly recommended for all persons with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or the use of an insulin pump.” For those with diabetes who use CGM, “priority metrics” include a “time in range” of greater than 70% from 14 days of active use. Targets for mean glucose should be individualized, with glycemic variability 36% or lower.

Further specific CGM target metrics are given for people with type 1 diabetes, older/high risk individuals, and for pregnant women. The recommendations align with those issued in a 2019 joint consensus statement on CGM time-in-range endorsed by several organizations, including AACE.    

In response to an audience question about whether AACE is advising that time-in-range replace A1c for glycemia assessment, Dr. Sherr responded: “I think currently we’re not in a position where we can completely replace A1c with time in range. However, I’m hopeful that in future years we’ll see further data gathered ... to allow for that recommendation to occur.”

For now, she said, “What we really want to hone in on in the guidelines is that time-in-range and use of CGM truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It’s not just a number of whether we’re hitting target. It tells us whether we need to attack time above range or time below range. So we really think it’s critical for clinical care.”

The document also provides specifics about real-time versus intermittently scanned CGM and use of diagnostic/professional CGM.

The “insulin delivery technologies” section covers use of connected pens, insulin pumps without CGM, insulin pumps with separate CGM, and the more advanced combined insulin pump-CGM systems including those with low-glucose suspend, predictive low-glucose suspend, and hybrid closed-loops (sometimes called the artificial pancreas).

In general, these automated insulin delivery systems (artificial pancreas), “are strongly recommended for all persons with [type 1 diabetes], since their use has been shown to increase time in range, especially in the overnight period, without causing an increased risk of hypoglycemia,” Dr. Sherr observed.
 

Other tech topics: Apps, telemedicine, and safety

The new guidelines say that “clinically validated” smartphone apps should be recommended to help teach or reinforce diabetes self-management skills and provide support and encouragement for healthy behaviors around food and exercise.

Dr. Grunberger pointed out: “As we know, there are tons of apps out there, and patients are using them. The problem is that very few of them have actually been validated in clinical trials in published peer-reviewed [journals].”

He recommended a joint statement on diabetes apps from the American Diabetes Association and the European Association for the Study of Diabetes that was initially discussed at the 2019 EASD meeting, as reported by this news organization, and subsequently published in January 2020 in Diabetes Care and Diabetologia.

“Telemedicine, including periodic phone calls, smartphone-web interactions ... by health care professionals ... is strongly recommended to treat persons with diabetes, provide diabetes education, remotely monitor glucose and/or insulin data to indicate the need for therapy adjustments, and improve diabetes-related outcomes/control with better engagement,” the document says.

Safety concerns addressed include the issue of certain medications interfering with CGM [readings] ... including acetaminophen, high-dose vitamin C, and hydroxyurea, as well as cautions about what to do in the event of device malfunction and assessing that the patient is sufficiently trained in proper device use. Criteria for insulin pump discontinuation are also given.
 

Implementation: Who will be prescribing? ‘This is not for amateurs’

A final section on implementation recommends that “initiation and use of diabetes technology should be implemented by health care professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technology.”

Dr. Grunberger commented: “I think the key is going to be who should be doing this? What is the role of a clinical endocrinologist in the future? What is our responsibility, [since] we don’t have the manpower and womanpower to take care of all these people as these technologies advance? It’s our responsibility to provide these hopefully valued recommendations as a resource for those who want to know more about it.”

However, he noted, “This is not for amateurs. If you want to actually use this in your practice, you need the infrastructure, the expertise, the training, the dedication, and the energy to be there for the patients all the time ... This clinical practice guideline is a foundation.”

Dr. Sherr added: “To me, it’s really thinking about ... changing our mindset from who is an appropriate candidate to who can benefit and how vast a group that entails ... I’m hopeful that we will see more technology use through continued conversations with our patients with diabetes, and hopefully through more clinicians being excited to be part of this revolution.”

Dr. Grunberger has reported being on speakers bureaus for Eli Lilly, Novo Nordisk, and Abbott. Dr. Sherr has reported being a consultant and speaker for Lilly and Medtronic Diabetes, a consultant for Insulet and Sanofi, and on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, JDRF T1D fund, and Medtronic.

A version of this article first appeared on Medscape.com.

The American Association of Clinical Endocrinology (AACE) has issued its first-ever official guidelines addressing the use of advanced technologies in the management of people with diabetes.

They were presented on May 28 at the annual scientific & clinical congress of the American Association of Clinical Endocrinologists and simultaneously published in Endocrine Practice.

Previous AACE guidance on the clinical use of insulin pumps and CGM over the past decade has been published in the form of consensus or position statements rather than official evidence-based guidelines, task force cochair George Grunberger, MD, of the Grunberger Diabetes Institute, Bloomfield Hills, Mich., explained.

“There’s never really been, until now, hardcore evidence, [with] peer-reviewed, quality trials published in the literature to go after the evidence that is required for guidelines. ... This is not an opinion piece or position statement.”

The problem with that strict approach to “guidelines” is how quickly the diabetes technology field is evolving, he acknowledged. “It’s frustrating because we know what’s [coming up], but we can’t put it in a guideline because it hasn’t been published yet.”

In an AACE podcast, Dr. Grunberger said the guidelines will likely become a “living” document, along the lines of the American Diabetes Association’s annual Standards of Care, as “any cutoff date is arbitrary. More and more papers will be published on these technologies. ... This is certainly not a static field.”

In the meantime, task force cochair and author Jennifer Sherr, MD, PhD, a pediatric endocrinologist, said she hopes the guidelines will help to reduce insurance company barriers to use of the currently available technologies.

“I am very hopeful that these guidelines will also encourage payers to change their stance. And I think that we as a community can continue to advocate and inform them of these guidelines so they can appropriately change their coverage practices,” added Dr. Sherr, of Yale University, New Haven, Conn.
 

Recommendations address CGM, pumps, and connected systems

In the guidelines, CGM is “strongly recommended for all persons with diabetes treated with intensive insulin therapy, defined as three or more injections of insulin per day or the use of an insulin pump.” For those with diabetes who use CGM, “priority metrics” include a “time in range” of greater than 70% from 14 days of active use. Targets for mean glucose should be individualized, with glycemic variability 36% or lower.

Further specific CGM target metrics are given for people with type 1 diabetes, older/high risk individuals, and for pregnant women. The recommendations align with those issued in a 2019 joint consensus statement on CGM time-in-range endorsed by several organizations, including AACE.    

In response to an audience question about whether AACE is advising that time-in-range replace A1c for glycemia assessment, Dr. Sherr responded: “I think currently we’re not in a position where we can completely replace A1c with time in range. However, I’m hopeful that in future years we’ll see further data gathered ... to allow for that recommendation to occur.”

For now, she said, “What we really want to hone in on in the guidelines is that time-in-range and use of CGM truly allow clinicians to better understand how to optimize care for their persons with diabetes. It gives us a better picture. It’s not just a number of whether we’re hitting target. It tells us whether we need to attack time above range or time below range. So we really think it’s critical for clinical care.”

The document also provides specifics about real-time versus intermittently scanned CGM and use of diagnostic/professional CGM.

The “insulin delivery technologies” section covers use of connected pens, insulin pumps without CGM, insulin pumps with separate CGM, and the more advanced combined insulin pump-CGM systems including those with low-glucose suspend, predictive low-glucose suspend, and hybrid closed-loops (sometimes called the artificial pancreas).

In general, these automated insulin delivery systems (artificial pancreas), “are strongly recommended for all persons with [type 1 diabetes], since their use has been shown to increase time in range, especially in the overnight period, without causing an increased risk of hypoglycemia,” Dr. Sherr observed.
 

Other tech topics: Apps, telemedicine, and safety

The new guidelines say that “clinically validated” smartphone apps should be recommended to help teach or reinforce diabetes self-management skills and provide support and encouragement for healthy behaviors around food and exercise.

Dr. Grunberger pointed out: “As we know, there are tons of apps out there, and patients are using them. The problem is that very few of them have actually been validated in clinical trials in published peer-reviewed [journals].”

He recommended a joint statement on diabetes apps from the American Diabetes Association and the European Association for the Study of Diabetes that was initially discussed at the 2019 EASD meeting, as reported by this news organization, and subsequently published in January 2020 in Diabetes Care and Diabetologia.

“Telemedicine, including periodic phone calls, smartphone-web interactions ... by health care professionals ... is strongly recommended to treat persons with diabetes, provide diabetes education, remotely monitor glucose and/or insulin data to indicate the need for therapy adjustments, and improve diabetes-related outcomes/control with better engagement,” the document says.

Safety concerns addressed include the issue of certain medications interfering with CGM [readings] ... including acetaminophen, high-dose vitamin C, and hydroxyurea, as well as cautions about what to do in the event of device malfunction and assessing that the patient is sufficiently trained in proper device use. Criteria for insulin pump discontinuation are also given.
 

Implementation: Who will be prescribing? ‘This is not for amateurs’

A final section on implementation recommends that “initiation and use of diabetes technology should be implemented by health care professionals who are trained, committed, and experienced to prescribe and direct the use of these tools. Clinicians should have the infrastructure to support the needs of persons with diabetes using the technology.”

Dr. Grunberger commented: “I think the key is going to be who should be doing this? What is the role of a clinical endocrinologist in the future? What is our responsibility, [since] we don’t have the manpower and womanpower to take care of all these people as these technologies advance? It’s our responsibility to provide these hopefully valued recommendations as a resource for those who want to know more about it.”

However, he noted, “This is not for amateurs. If you want to actually use this in your practice, you need the infrastructure, the expertise, the training, the dedication, and the energy to be there for the patients all the time ... This clinical practice guideline is a foundation.”

Dr. Sherr added: “To me, it’s really thinking about ... changing our mindset from who is an appropriate candidate to who can benefit and how vast a group that entails ... I’m hopeful that we will see more technology use through continued conversations with our patients with diabetes, and hopefully through more clinicians being excited to be part of this revolution.”

Dr. Grunberger has reported being on speakers bureaus for Eli Lilly, Novo Nordisk, and Abbott. Dr. Sherr has reported being a consultant and speaker for Lilly and Medtronic Diabetes, a consultant for Insulet and Sanofi, and on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, JDRF T1D fund, and Medtronic.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.