Diabetes

TOPLINE:

Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).

METHODOLOGY:

• Understanding the relative timing and association between chronic diabetic complications and mental health disorders may aid in improving diabetes screening and care.
• Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication.
• The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association.
• Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years.

TAKEAWAY:

• Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women).
• The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9).
• Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5).
• Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years.
• The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions).

IN PRACTICE:

“Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes,” the authors wrote.

SOURCE:

The study, led by Maya Watanabe, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, was published online in Diabetes Care.

LIMITATIONS:

The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States.

DISCLOSURES:

The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies.

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

TOPLINE:

Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).

METHODOLOGY:

• Understanding the relative timing and association between chronic diabetic complications and mental health disorders may aid in improving diabetes screening and care.
• Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication.
• The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association.
• Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years.

TAKEAWAY:

• Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women).
• The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9).
• Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5).
• Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years.
• The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions).

IN PRACTICE:

“Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes,” the authors wrote.

SOURCE:

The study, led by Maya Watanabe, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, was published online in Diabetes Care.

LIMITATIONS:

The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States.

DISCLOSURES:

The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies.

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

TOPLINE:

Mental health disorders increase the likelihood of developing chronic diabetic complications and vice versa across all age groups in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).

METHODOLOGY:

• Understanding the relative timing and association between chronic diabetic complications and mental health disorders may aid in improving diabetes screening and care.
• Researchers used a US national healthcare claims database (data obtained from 2001 to 2018) to analyze individuals with and without T1D and T2D, who had no prior mental health disorder or chronic diabetic complication.
• The onset and presence of chronic diabetic complications and mental health disorders were identified to determine their possible association.
• Individuals were stratified by age: 0-19, 20-39, 40-59, and ≥ 60 years.

TAKEAWAY:

• Researchers analyzed 44,735 patients with T1D (47.5% women) and 152,187 with T2D (46.0% women), who were matched with 356,630 individuals without diabetes (51.8% women).
• The presence of chronic diabetic complications increased the risk for a mental health disorder across all age groups, with the highest risk seen in patients aged ≥ 60 years (hazard ratio [HR], 2.9).
• Similarly, diagnosis of a mental health disorder increased the risk for chronic diabetic complications across all age groups, with the highest risk seen in patients aged 0-19 years (HR, 2.5).
• Patients with T2D had a significantly higher risk for a mental health disorder and a lower risk for chronic diabetic complications than those with T1D across all age groups, except those aged ≥ 60 years.
• The bidirectional association between mental health disorders and chronic diabetic complications was not affected by the diabetes type (P > .05 for all interactions).

IN PRACTICE:

“Clinicians and healthcare systems likely need to increase their focus on MHDs [mental health disorders], and innovative models of care are required to optimize care for both individuals with type 1 diabetes and those with type 2 diabetes,” the authors wrote.

SOURCE:

The study, led by Maya Watanabe, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, was published online in Diabetes Care.

LIMITATIONS:

The study relied on International Classification of Diseases 9th and 10th revision codes, which might have led to misclassification of mental health conditions, chronic diabetes complications, and diabetes type. The data did not capture the symptom onset and severity. The findings may not be generalizable to populations outside the United States.

DISCLOSURES:

The study was supported by the Juvenile Diabetes Research Foundation (now Breakthrough T1D). Some authors reported receiving speaker or expert testimony honoraria and research support, and some declared serving on medical or digital advisory boards or as consultants for various pharmaceutical and medical device companies.

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

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.

Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.

He’s far from alone. Mr. Mikhael and other industry officials estimate that several large compounding pharmacies like his are provisioning up to 2 million American patients with regular doses of semaglutide, the scientific name for Novo Nordisk’s Wegovy, Ozempic, and Rybelsus formulations, or tirzepatide, the active ingredient in Eli Lilly’s Zepbound and Mounjaro.

The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.

But this isn’t an illegal black market, though it has shades of gray.

The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.

In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.

Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.

While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”

Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)

The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.

Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.

However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.

To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.

“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
 

Warnings From the Past

The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.

In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.

The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.

The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.

Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.

The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.

“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”

Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.

The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
 

Compounding for Dummies

At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.

Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.

While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.

Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.

She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.

He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.

There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.

“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”

Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.

It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
 

Corporate Battles

Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.

When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.

The evaporation of the compounded drug supply could come as a shock to patients.

“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.

Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.

He’s far from alone. Mr. Mikhael and other industry officials estimate that several large compounding pharmacies like his are provisioning up to 2 million American patients with regular doses of semaglutide, the scientific name for Novo Nordisk’s Wegovy, Ozempic, and Rybelsus formulations, or tirzepatide, the active ingredient in Eli Lilly’s Zepbound and Mounjaro.

The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.

But this isn’t an illegal black market, though it has shades of gray.

The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.

In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.

Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.

While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”

Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)

The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.

Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.

However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.

To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.

“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
 

Warnings From the Past

The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.

In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.

The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.

The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.

Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.

The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.

“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”

Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.

The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
 

Compounding for Dummies

At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.

Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.

While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.

Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.

She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.

He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.

There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.

“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”

Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.

It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
 

Corporate Battles

Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.

When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.

The evaporation of the compounded drug supply could come as a shock to patients.

“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Pharmacist Mark Mikhael has lost 50 pounds over the past 12 months. He no longer has diabetes and finds himself “at my ideal body weight,” with his cholesterol below 200 for the first time in 20 years. “I feel fantastic,” he said.

Like millions of others, Mr. Mikhael credits the new class of weight loss drugs. But he isn’t using brand-name Wegovy or Zepbound. Mr. Mikhael, CEO of Orlando, Florida–based Olympia Pharmaceuticals, has been getting by with his own supply: injecting himself with copies of the drugs formulated by his company.

He’s far from alone. Mr. Mikhael and other industry officials estimate that several large compounding pharmacies like his are provisioning up to 2 million American patients with regular doses of semaglutide, the scientific name for Novo Nordisk’s Wegovy, Ozempic, and Rybelsus formulations, or tirzepatide, the active ingredient in Eli Lilly’s Zepbound and Mounjaro.

The drug-making behemoths fiercely oppose that compounding business. Novo Nordisk and Lilly lump the compounders together with Internet cowboys and unregulated medical spas peddling bogus semaglutide, and have high-powered legal teams trying to stop them. Novo Nordisk has filed at least 21 lawsuits nationwide against companies making purported copies of its drugs, said Brianna Kelley, a spokesperson for the company, and urges doctors to avoid them. The Food and Drug Administration (FDA), too, has cautioned about the potential danger of the compounds, and leading obesity medicine groups starkly warn patients against their use.

But this isn’t an illegal black market, though it has shades of gray.

The FDA allows and even encourages compounding pharmacies to produce and sell copycats when a drug is in short supply, and the wildly popular glucagon-like peptide 1 (GLP-1) drugs have enduring shortages — first reported in March 2022 for semaglutide and in December 2022 for tirzepatide. The drugs have registered unprecedented success in weight loss. They are also showing promise against heart, kidney, and liver diseases and are being tested against conditions as diverse as Alzheimer’s disease and drug addiction.

In recent years, the US health care system has come to depend on compounding pharmacies, many of which are run as nonprofits, to plug supply holes of crucial drugs like cancer medicines cisplatin, methotrexate, and 5-fluorouracil.

Most compounded drugs are old, cheap generics. Semaglutide and tirzepatide, on the other hand, are under patent and earn Novo Nordisk and Lilly billions of dollars a year. Sales of the diabetes and weight loss drugs in 2024 made Novo Nordisk Europe’s most valuable company and Lilly the world’s biggest pharmaceutical company.

While the companies can’t keep up with demand, they heatedly dispute the right of compounders to make and sell copies. Lilly spokesperson Kristiane Silva Bello said her company was “deeply concerned” about “serious health risks” from compounded drugs that “should not be on the market.”

Yet marketed they are. Even Hims & Hers Health — the telemedicine prescriber that got its start with erectile dysfunction drugs — is now peddling compounded semaglutide. It ran ads for the drugs during NBA playoff games. (According to a Hunterbrook Media report, Hims & Hers’ semaglutide supplier has faced legal scrutiny.)

The compounded forms are significantly cheaper than the branded drugs. Patients pay about $100-$450 a month, compared with list prices of roughly $1,000-$1,400 for Lilly and Novo Nordisk products.

Five compounders and distributors interviewed for this article said they conduct due diligence on every lot of semaglutide or tirzepatide they buy or produce, upholding standards of purity, sterility, and consistency similar to those practiced in the commercial drug industry. Compounders operate under strict federal and state standards, they noted.

However, the raw materials used in the compounded forms may differ from those produced for Novo Nordisk and Lilly, said GLP-1 coinventor Jens Juul Holst, of the University of Copenhagen, adding that care must be taken in drug production lest it cause potentially harmful immune reactions.

To date, according to FDA spokespeople, reports of side effects from taking compounded versions haven’t raised major alarms. But everyone with knowledge of the industry, including the compounders themselves, worry that a single batch of a poorly made drug could kill or maim people and destroy confidence in their business.

“I liken the compounding industry to the airline industry,” Mr. Mikhael said. “When you have an airline crash, it hurts everybody.”
 

Warnings From the Past

The industry endured just such a catastrophe in 2012, when the New England Compounding Center released a contaminated injectable steroid that killed at least 64 people and harmed hundreds more.

In response, Congress and the FDA had strengthened oversight. Mr. Mikhael’s company is an outsourcing facility, or 503B compounding pharmacy — so-named for a section of the 2013 law that set new requirements for drug compounders. The companies are licensed to make slightly different versions of FDA-approved drugs in response to shortages or a patient’s special needs.

The law created two classes of compounding pharmacies: The FDA regulates the larger 503B compounders with standards like commercial drug companies, while 503A pharmacies make smaller lots of drugs and are largely overseen by state boards of pharmacy.

The 503A facilities also are producing compounded semaglutide and tirzepatide for hundreds of thousands of patients. Like the 503Bs, these operations take the active ingredient, produced as a powder in FDA-registered factories, mostly in China, then reconstitute it with sterile water and an antimicrobial in small glass vials.

Together, the compounding pharmacies may account for up to 30% of the semaglutide sold in the United States, Mr. Mikhael said, although he cautions that is a “wild ballpark figure” since no one, including the FDA, is tracking sales in the industry.

The compounders say the companies should increase production if they’re worried about competition. Like the dozens of other drugs they produce for hospitals and medical practices, the compounders say, the two diet drugs are essential products.

“If you don’t want a 503B facility to make a copy, it’s pretty simple: Don’t go short,” said Lee Rosebush, chair of a trade association for 503B pharmacies. “FDA created this system because these are necessary drugs.”

Novo Nordisk hasn’t specified why it can’t keep up with demand, but the bottleneck apparently lies in the company’s inability to fill and sterilize enough of its special drug auto-injectors, said Evan Seigerman, a managing director at BMO Capital Markets.

The company announced June 24 that it was investing $4.1 billion in new production lines at its Clayton, North Carolina, site. In 2023, the FDA issued a warning over procedural violations at the site and separate cautions at an Indiana facility that Novo Nordisk took over recently.
 

Compounding for Dummies

At least 28 companies, mostly in China, are registered with the FDA to produce or distribute semaglutide. At least half the companies have entered the market in the past 12 months, driving the raw material’s price down by 35%, according to Scott Welch, who runs a 503A pharmacy in Arlington, Virginia.

Compounders can buy powdered semaglutide from some US distributors for less than $4,000 a gram, said Matthew Johnson, president and CEO of distributor Pharma Source Direct. That comes out to as little as $10 per weekly 2.5-microgram dose – not including overhead and other costs.

While Ozempic or Wegovy patients use a Novo Nordisk device to inject the drug, patients using compounded products draw them from a vial with a small needle, like the device diabetics use for insulin.

Some medical practices provide the compounded drug to patients as part of a weight loss package, with markups. In July 2023, Tabitha Ries, a single mother of six who works as a home health care aide in Garfield, Washington, found an online clinic that charged her $1,000 for 3 months of semaglutide along with counseling. She has lost 35 pounds.

She gets the drug from Mindful Weight Loss, a mostly telehealth-based operation led by physician Vivek Gupta, MD, of Manhattan Beach, California. Dr. Gupta said he’s prescribed the weight loss drugs to 1,500 patients, with about 60% using compounded versions from a 503A pharmacy.

He hasn’t seen any essential difference in patients using the branded and compounded forms, although “some people say the compounding is a little less effective,” Dr. Gupta said.

There’s some risk in using the non–FDA-approved product, he acknowledged, and he requires patients to sign an informed consent waiver.

“Nothing in life is without risk, but I would also argue that the status quo is not safe for people who need the medicine and can’t get it,” he said. “They’re constantly triggered by all this food that’s causing their weight to go up and their sugar to go high, increasing their insulin resistance and affecting their limbs and eyes.”

Compounding semaglutide is a helpful sideline for pharmacists like him, Mr. Welch said, especially given the pinch on drug sale revenue that has led many independents to close in recent years. He figures he earns 95% of his revenue from compounding drugs, rather than traditional prescriptions.

It’s important to distinguish compounded semaglutide from unregulated powders sold as “generic Ozempic” and the like, which may be contaminated or counterfeit, said FDA spokesperson Amanda Hils. But since compounded forms of the drug are not FDA approved, those who make, prescribe, or use them also should have “an increased level of responsibility or awareness,” she said.
 

Corporate Battles

Novo Nordisk and Lilly, in lawsuits each company has filed against competitors, say their own testing has found bacteria and other impurities in products made by compounding pharmacies. The companies also report patent infringement, but compounders, pointing to the FDA loophole for drugs in shortage, appear to have defeated that argument for now.

When the FDA removes the drugs from the shortage list, 503B compounders must immediately stop selling them. Smaller compounders may be able to produce their products for a reduced number of patients, said Scott Brunner, CEO of the Alliance for Pharmacy Compounding, which represents 503A compounders.

The evaporation of the compounded drug supply could come as a shock to patients.

“I dread it,” said David Wertheimer, an internist in Franklin Lakes, New Jersey, who prescribes compounded semaglutide to some patients. “People are not going to be able to plunk down a grand every month. A lot of people will go off the drug, and that’s a shame.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Irregular sleep duration was associated with a higher risk for diabetes in middle-aged to older adults in a new UK Biobank study.

The analysis of more than 84,000 participants with 7-day accelerometry data suggested that individuals with the most irregular sleep duration patterns had a 34% higher risk for diabetes compared with their peers who had more consistent sleep patterns.

“It’s recommended to have 7-9 hours of nightly sleep, but what is not considered much in policy guidelines or at the clinical level is how regularly that’s needed,” Sina Kianersi, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in an interview. “What our study added is that it’s not just the duration but keeping it consistent. Patients can reduce their risk of diabetes by maintaining their 7-9 hours of sleep, not just for 1 night but throughout life.”

The study was published online in Diabetes Care.
 

Modifiable Lifestyle Factor

Researchers analyzed data from 84,421 UK Biobank participants who were free of diabetes when they provided accelerometer data in 2013-2015 and who were followed for a median of 7.5 years (622,080 person-years).

Participants had an average age of 62 years, 57% were women, 97% were White individuals, and 50% were employed in non–shift work jobs.

Sleep duration variability was quantified by the within-person standard deviation (SD) of 7-night accelerometer-measured sleep duration.

Participants with higher sleep duration SD were younger and more likely to be women, shift workers, or current smokers; those who reported definite “evening” chronotype (natural preference of the body to sleep at a certain time); those having lower socioeconomic status, higher body mass index, and shorter mean sleep duration; and were less likely to be White individuals.

In addition, a family history of diabetes and of depression was more prevalent among these participants.

A total of 2058 incident diabetes cases occurred during follow-up.

After adjustment for age, sex, and race, compared with a sleep duration SD ≤ 30 minutes, the hazard ratio (HR) was 1.15 for 31-45 minutes, 1.28 for 46-60 minutes, 1.54 for 61-90 minutes, and 1.59 for ≥ 91 minutes.

After the initial adjustment, individuals with a sleep duration SD of > 60 vs ≤ 60 minutes had a 34% higher diabetes risk. However, further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association — ie, the HR comparing sleep duration SD of > 60 vs ≤ 60 minutes was 1.11.

Furthermore, researchers found that the association between sleep duration and diabetes was stronger among individuals with lower diabetes polygenic risk score. 

“One possible explanation for this finding is that the impact of sleep irregularity on diabetes risk may be less noticeable in individuals with a high genetic predisposition, where genetic factors dominate,” Dr. Kianersi said. “However, it is important to note that these sleep-gene interaction effects were not consistently observed across different measures and gene-related variables. This is something that remains to be further studied.”

Nevertheless, he added, “I want to emphasize that the association between irregular sleep duration and increased diabetes risk was evident across all levels of diabetes polygenic risk scores.”

The association also was stronger with longer sleep duration. The authors suggested that longer sleep duration “might reduce daylight exposure, which could, in turn, give rise to circadian disruption.”

Overall, Dr. Kianersi said, “Our study identified a modifiable lifestyle factor that can help lower the risk of developing type 2 diabetes.”

The study had several limitations. There was a time lag of a median of 5 years between sleep duration measurements and covariate assessments, which might bias lifestyle behaviors that may vary over time. In addition, a single 7-day sleep duration measurement may not capture long-term sleep patterns. A constrained random sampling approach was used to select participants, raising the potential of selection bias.
 

Regular Sleep Routine Best

Ana Krieger, MD, MPH, director of the Center for Sleep Medicine at Weill Cornell Medicine in New York City, commented on the study for this news organization. “This is a very interesting study, as it adds to the literature,” she said. “Previous research studies have shown metabolic abnormalities with variations in sleep time and duration.”

“This particular study evaluated a large sample of patients in the UK which were mostly White middle-aged and may not be representative of the general population,” she noted. “A similar study in a Hispanic/Latino group failed to demonstrate any significant association between sleep timing variability and incidence of diabetes. It would be desirable to see if prospective studies are able to demonstrate a reduction in diabetes risk by implementing a more regular sleep routine.”

The importance of the body’s natural circadian rhythm in regulating and anchoring many physiological processes was highlighted by the 2017 Nobel Prize of Medicine, which was awarded to three researchers in circadian biology, she pointed out.

“Alterations in the circadian rhythm are known to affect mood regulation, gastrointestinal function, and alertness, among other factors,” she said. “Keeping a regular sleep routine will help to improve our circadian rhythm and better regulate many processes, including our metabolism and appetite-controlling hormones.”

Notably, a study published online in Diabetologia in a racially and economically diverse US population also found that adults with persistent suboptimal sleep durations (< 7 or > 9 hours nightly over a mean of 5 years) were more likely to develop incident diabetes. The strongest association was found among participants reporting extreme changes and higher variability in their sleep durations.

This study was supported by the National Institutes of Health (grant number R01HL155395) and the UKB project 85501. Dr. Kianersi was supported by the American Heart Association Postdoctoral Fellowship. Dr. Kianersi and Dr. Krieger reported no conflicts of interest.

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

Irregular sleep duration was associated with a higher risk for diabetes in middle-aged to older adults in a new UK Biobank study.

The analysis of more than 84,000 participants with 7-day accelerometry data suggested that individuals with the most irregular sleep duration patterns had a 34% higher risk for diabetes compared with their peers who had more consistent sleep patterns.

“It’s recommended to have 7-9 hours of nightly sleep, but what is not considered much in policy guidelines or at the clinical level is how regularly that’s needed,” Sina Kianersi, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in an interview. “What our study added is that it’s not just the duration but keeping it consistent. Patients can reduce their risk of diabetes by maintaining their 7-9 hours of sleep, not just for 1 night but throughout life.”

The study was published online in Diabetes Care.
 

Modifiable Lifestyle Factor

Researchers analyzed data from 84,421 UK Biobank participants who were free of diabetes when they provided accelerometer data in 2013-2015 and who were followed for a median of 7.5 years (622,080 person-years).

Participants had an average age of 62 years, 57% were women, 97% were White individuals, and 50% were employed in non–shift work jobs.

Sleep duration variability was quantified by the within-person standard deviation (SD) of 7-night accelerometer-measured sleep duration.

Participants with higher sleep duration SD were younger and more likely to be women, shift workers, or current smokers; those who reported definite “evening” chronotype (natural preference of the body to sleep at a certain time); those having lower socioeconomic status, higher body mass index, and shorter mean sleep duration; and were less likely to be White individuals.

In addition, a family history of diabetes and of depression was more prevalent among these participants.

A total of 2058 incident diabetes cases occurred during follow-up.

After adjustment for age, sex, and race, compared with a sleep duration SD ≤ 30 minutes, the hazard ratio (HR) was 1.15 for 31-45 minutes, 1.28 for 46-60 minutes, 1.54 for 61-90 minutes, and 1.59 for ≥ 91 minutes.

After the initial adjustment, individuals with a sleep duration SD of > 60 vs ≤ 60 minutes had a 34% higher diabetes risk. However, further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association — ie, the HR comparing sleep duration SD of > 60 vs ≤ 60 minutes was 1.11.

Furthermore, researchers found that the association between sleep duration and diabetes was stronger among individuals with lower diabetes polygenic risk score. 

“One possible explanation for this finding is that the impact of sleep irregularity on diabetes risk may be less noticeable in individuals with a high genetic predisposition, where genetic factors dominate,” Dr. Kianersi said. “However, it is important to note that these sleep-gene interaction effects were not consistently observed across different measures and gene-related variables. This is something that remains to be further studied.”

Nevertheless, he added, “I want to emphasize that the association between irregular sleep duration and increased diabetes risk was evident across all levels of diabetes polygenic risk scores.”

The association also was stronger with longer sleep duration. The authors suggested that longer sleep duration “might reduce daylight exposure, which could, in turn, give rise to circadian disruption.”

Overall, Dr. Kianersi said, “Our study identified a modifiable lifestyle factor that can help lower the risk of developing type 2 diabetes.”

The study had several limitations. There was a time lag of a median of 5 years between sleep duration measurements and covariate assessments, which might bias lifestyle behaviors that may vary over time. In addition, a single 7-day sleep duration measurement may not capture long-term sleep patterns. A constrained random sampling approach was used to select participants, raising the potential of selection bias.
 

Regular Sleep Routine Best

Ana Krieger, MD, MPH, director of the Center for Sleep Medicine at Weill Cornell Medicine in New York City, commented on the study for this news organization. “This is a very interesting study, as it adds to the literature,” she said. “Previous research studies have shown metabolic abnormalities with variations in sleep time and duration.”

“This particular study evaluated a large sample of patients in the UK which were mostly White middle-aged and may not be representative of the general population,” she noted. “A similar study in a Hispanic/Latino group failed to demonstrate any significant association between sleep timing variability and incidence of diabetes. It would be desirable to see if prospective studies are able to demonstrate a reduction in diabetes risk by implementing a more regular sleep routine.”

The importance of the body’s natural circadian rhythm in regulating and anchoring many physiological processes was highlighted by the 2017 Nobel Prize of Medicine, which was awarded to three researchers in circadian biology, she pointed out.

“Alterations in the circadian rhythm are known to affect mood regulation, gastrointestinal function, and alertness, among other factors,” she said. “Keeping a regular sleep routine will help to improve our circadian rhythm and better regulate many processes, including our metabolism and appetite-controlling hormones.”

Notably, a study published online in Diabetologia in a racially and economically diverse US population also found that adults with persistent suboptimal sleep durations (< 7 or > 9 hours nightly over a mean of 5 years) were more likely to develop incident diabetes. The strongest association was found among participants reporting extreme changes and higher variability in their sleep durations.

This study was supported by the National Institutes of Health (grant number R01HL155395) and the UKB project 85501. Dr. Kianersi was supported by the American Heart Association Postdoctoral Fellowship. Dr. Kianersi and Dr. Krieger reported no conflicts of interest.

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

Irregular sleep duration was associated with a higher risk for diabetes in middle-aged to older adults in a new UK Biobank study.

The analysis of more than 84,000 participants with 7-day accelerometry data suggested that individuals with the most irregular sleep duration patterns had a 34% higher risk for diabetes compared with their peers who had more consistent sleep patterns.

“It’s recommended to have 7-9 hours of nightly sleep, but what is not considered much in policy guidelines or at the clinical level is how regularly that’s needed,” Sina Kianersi, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in an interview. “What our study added is that it’s not just the duration but keeping it consistent. Patients can reduce their risk of diabetes by maintaining their 7-9 hours of sleep, not just for 1 night but throughout life.”

The study was published online in Diabetes Care.
 

Modifiable Lifestyle Factor

Researchers analyzed data from 84,421 UK Biobank participants who were free of diabetes when they provided accelerometer data in 2013-2015 and who were followed for a median of 7.5 years (622,080 person-years).

Participants had an average age of 62 years, 57% were women, 97% were White individuals, and 50% were employed in non–shift work jobs.

Sleep duration variability was quantified by the within-person standard deviation (SD) of 7-night accelerometer-measured sleep duration.

Participants with higher sleep duration SD were younger and more likely to be women, shift workers, or current smokers; those who reported definite “evening” chronotype (natural preference of the body to sleep at a certain time); those having lower socioeconomic status, higher body mass index, and shorter mean sleep duration; and were less likely to be White individuals.

In addition, a family history of diabetes and of depression was more prevalent among these participants.

A total of 2058 incident diabetes cases occurred during follow-up.

After adjustment for age, sex, and race, compared with a sleep duration SD ≤ 30 minutes, the hazard ratio (HR) was 1.15 for 31-45 minutes, 1.28 for 46-60 minutes, 1.54 for 61-90 minutes, and 1.59 for ≥ 91 minutes.

After the initial adjustment, individuals with a sleep duration SD of > 60 vs ≤ 60 minutes had a 34% higher diabetes risk. However, further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association — ie, the HR comparing sleep duration SD of > 60 vs ≤ 60 minutes was 1.11.

Furthermore, researchers found that the association between sleep duration and diabetes was stronger among individuals with lower diabetes polygenic risk score. 

“One possible explanation for this finding is that the impact of sleep irregularity on diabetes risk may be less noticeable in individuals with a high genetic predisposition, where genetic factors dominate,” Dr. Kianersi said. “However, it is important to note that these sleep-gene interaction effects were not consistently observed across different measures and gene-related variables. This is something that remains to be further studied.”

Nevertheless, he added, “I want to emphasize that the association between irregular sleep duration and increased diabetes risk was evident across all levels of diabetes polygenic risk scores.”

The association also was stronger with longer sleep duration. The authors suggested that longer sleep duration “might reduce daylight exposure, which could, in turn, give rise to circadian disruption.”

Overall, Dr. Kianersi said, “Our study identified a modifiable lifestyle factor that can help lower the risk of developing type 2 diabetes.”

The study had several limitations. There was a time lag of a median of 5 years between sleep duration measurements and covariate assessments, which might bias lifestyle behaviors that may vary over time. In addition, a single 7-day sleep duration measurement may not capture long-term sleep patterns. A constrained random sampling approach was used to select participants, raising the potential of selection bias.
 

Regular Sleep Routine Best

Ana Krieger, MD, MPH, director of the Center for Sleep Medicine at Weill Cornell Medicine in New York City, commented on the study for this news organization. “This is a very interesting study, as it adds to the literature,” she said. “Previous research studies have shown metabolic abnormalities with variations in sleep time and duration.”

“This particular study evaluated a large sample of patients in the UK which were mostly White middle-aged and may not be representative of the general population,” she noted. “A similar study in a Hispanic/Latino group failed to demonstrate any significant association between sleep timing variability and incidence of diabetes. It would be desirable to see if prospective studies are able to demonstrate a reduction in diabetes risk by implementing a more regular sleep routine.”

The importance of the body’s natural circadian rhythm in regulating and anchoring many physiological processes was highlighted by the 2017 Nobel Prize of Medicine, which was awarded to three researchers in circadian biology, she pointed out.

“Alterations in the circadian rhythm are known to affect mood regulation, gastrointestinal function, and alertness, among other factors,” she said. “Keeping a regular sleep routine will help to improve our circadian rhythm and better regulate many processes, including our metabolism and appetite-controlling hormones.”

Notably, a study published online in Diabetologia in a racially and economically diverse US population also found that adults with persistent suboptimal sleep durations (< 7 or > 9 hours nightly over a mean of 5 years) were more likely to develop incident diabetes. The strongest association was found among participants reporting extreme changes and higher variability in their sleep durations.

This study was supported by the National Institutes of Health (grant number R01HL155395) and the UKB project 85501. Dr. Kianersi was supported by the American Heart Association Postdoctoral Fellowship. Dr. Kianersi and Dr. Krieger reported no conflicts of interest.

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

The role of body mass index (BMI) in defining obesity and the definition of obesity as a disease merit reevaluation to avoid unintended consequences, experts said in three new opinion papers.

The three statements were published on July 22, 2024, in Annals of Internal Medicine. In one, the authors expressed caution about the recent movement away from using BMI alone to define obesity, noting that the measure remains a useful population-level and clinical tool for addressing adiposity, particularly within racial and ethnic groups. But the authors of a second paper pointed out that the use of lower BMI cutoffs to define obesity in Asian populations, in place since 2004, is inadequate in part because it doesn’t account for heterogeneity among different Asian groups.

And in the third paper, an editorial, an Annals editor cautioned that the recent framing of obesity exclusively as a “disease” rather than a “broader, more inclusive construct” may inadvertently reinforce the bias it was meant to combat.

Asked to comment on the issues raised in the papers, Professor Gijs Goossens of Maastricht University Medical Center, Maastricht, the Netherlands, said, “It is important to emphasize that the management and treatment of obesity have wider objectives than weight loss alone and include the prevention, resolution, or improvement of obesity-related complications; achieving better quality of life and mental well-being; and improvement of physical and social functioning.”

Added Dr. Goossens, who was an author of a recent European Association for the Study of Obesity (EASO) framework calling for moving beyond BMI in defining obesity, “Personalized therapeutic goals should be set at the beginning of the treatment, according to the stage of obesity, taking into account available therapeutic options, possible side effects or risks, and patient preferences. The drivers of obesity and possible barriers to treatment should also be discussed with the patient.” Dr. Goossens emphasized that he was providing his personal views and not speaking for the EASO or his coauthors.
 

BMI: ‘Not a Perfect Measure of Adiposity but Remains Useful’

In their “Ideas and Opinions” paper, Adolfo G. Cuevas, PhD, of New York University School of Global Public Health, New York City, and Walter C. Willett, MD, DrPH, of Harvard T.H. Chan School of Public Health, Boston, argued that “BMI, although not a perfect measure of adiposity, remains a useful population-level and clinical tool for addressing adiposity, including within groups defined by race and ethnicity.”

They added that despite the criticism that BMI doesn’t distinguish between fat and lean body mass, the measure still strongly correlates with fat mass as well as cardiovascular risk and mortality, and it does so similarly across racial and ethnic groups.

Clinically, Dr. Cuevas and Dr. Willett pointed out that BMI correlates fat mass as assessed with the gold standard measure dual x-ray absorptiometry but is far simpler and less expensive. Measuring waist circumference can provide additional information about visceral fat and disease risk but is “more difficult to standardize and suffers from the same limitations as BMI when cut points are used.”

They suggest the addition of change in weight since early adulthood and over time as a “simple and sensitive variable” for assessing adiposity.

Luca Busetto, MD, associate professor of medicine at the University of Padua, Italy, and the first author of the EASO framework, said, “The paper from Cuevas and Willett sounds like a strong defense of BMI, and I can substantially agree with this defense ... We remain anchored on BMI, but we tried to move beyond it adding an estimate of high risk abdominal fat — waist to height ratio — and coupling the anthropometric assessment with a complete clinical evaluation and staging.”

Dr. Goossens said, “I agree with the authors that despite the limitations of BMI as a measure of body fatness, it remains a useful clinical screening tool. Yet the diagnosis of obesity should not be based solely on BMI” due to the stronger association of abdominal fat with cardiometabolic complications.

That link, he noted, “also applies to individuals with a BMI level below the current cutoff values for obesity, who may already have medical, functional, or psychological impairments. We should be aware of the risk of undertreatment in this particular group of patients.”
 

Does Calling Obesity a ‘Disease’ Have Unintended Consequences?

In her editorial, Christina C. Wee, MD, senior deputy editor, Annals of Internal Medicine, wrote, “Beyond diagnostic challenges, framing obesity exclusively as a disease rather than a broader, more inclusive construct may have unintended consequences — including reinforcing the weight bias this framing was in part intended to combat.”

Focusing solely on biological causes of obesity while ignoring psychosocial, cultural, environmental, and behavioral contexts could undermine public health and policy efforts to address those factors, Dr. Wee argued.

Moreover, she wrote, “Ironically, framing obesity as a disease to justify coverage for treatment reinforces weight bias. It conflates the need to label a condition a disease with healthcare reimbursement and raises the stakes for developing accurate diagnostic criteria ... By exclusively linking obesity as a disease to reimbursement, it sends the message that only those who manifest disease from excess adiposity warrant treatment — and, by inference, those on the continuum who have not yet manifested disease do not warrant treatment.”

Likening obesity to other risk factors such as hypertension or dyslipidemia for which treatment is typically reimbursed, Dr. Wee pointed out that Medicare still prohibits coverage of medications for obesity.

Regarding the high costs of newer obesity medications and the need for payers and clinicians to ration their use, Dr. Wee argued, “Rather than focusing on whether one’s adiposity conforms to an expert panel’s definition of ‘disease,’ we should address how to best stage obesity risk with sufficient accuracy and fairness and reach a consensus on how to prioritize and match treatments to individual patients.”

Dr. Busetto said that EASO stands by its definition of obesity as a disease, adding “we can adhere to the suggestion of a holistic approach deciding treatment modalities according to the risk and the presence of mental, functional, and medical complications of impairments. Of course, we cannot agree on any proposal that is oriented at leaving patients with obesity still in the asymptomatic phase of the disease without treatment. This would be like treating diabetes only after the occurrence of nephropathy or managing hypertension only after a stroke. Prevention of the symptomatic stage is a part of obesity management, even beyond weight loss.”

Dr. Goossens said, “indeed, it is of utmost importance to develop accurate risk stratification tools for adequately clinical staging of obesity, according to the severity of its medical, psychological and functional impairments.”
 

Do the Current Lower BMI Cutoffs for Defining Obesity in Asian People Make Sense?

Simar S. Bajaj, AB, of Harvard University, Cambridge, Massachusetts, and colleagues, all of Harvard Medical School, Boston, raised several concerns regarding the 2004 World Health Organization’s suggestion to use lower BMI categories for defining overweight and obesity in Asian populations, that is, 23-27.5 kg/m² and 27.5 kg/m² or higher for obesity, respectively, as opposed to 25-29.9 and ≥ 30, respectively, for other populations.

Different Asian countries have created their own obesity BMI cutoffs, ranging from 25 kg/m² in India to 28 kg/m² in China. But “Asian Americans continue to be treated as a monolith without official disaggregated cutoffs,” Mr. Bajaj and colleagues noted.

The heterogeneity translates to different risk levels across Asian subgroups. For example, in one study, age- and sex-adjusted BMI cutoffs for increased risk of developing type 2 diabetes were 23.9 kg/m² in South Asian populations, 26.6 kg/m² in Arab populations, 26.9 kg/m² in Chinese populations, and 28.1 kg/m² in Black populations.

These findings raise important questions, the researchers said. “Does it make sense for people of Chinese descent to use the same BMI threshold as the South Asian group when their ‘equivalent risk cutoff’ is closer to that of Arab and Black groups who share the standard BMI threshold?” Most data in this area are cross-sectional rather than the longitudinal data needed to answer those questions, they noted.

They suggest that professional diabetes and obesity organizations consider BMI thresholds to be “placeholders” until more sensitive and specific thresholds can be defined for Asian American populations.

Mr. Bajaj and colleagues also noted the need for disaggregated data is not unique to Asian groups but that they focused on Asian Americans for two main reasons. “First, success would create a precedent for complete disaggregation and help ensure that other groups do not stall at an intermediary level. Second, substantial research into Asian ethnic groups — and the WHO’s precedent 20 years ago — creates a solid foundation to build upon.”

Ultimately, they said, “advancing equity will require funding research that engages diverse Asian communities and developing tailored interventions for all ethnicities.”

Dr. Cuevas, Dr. Willett, Mr. Bajaj, and Dr. Wee had no disclosures. Dr. Goossens received research funding from the European Foundation for the Study of Diabetes, the Dutch Diabetes Research Foundation, and the Dutch Research Council. Dr. Busetto received personal funding from Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Pfizer, and Bruno Farmaceutici as a member of advisory boards and from Rhythm Pharmaceuticals and Pronokal as a speaker.
 

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

The role of body mass index (BMI) in defining obesity and the definition of obesity as a disease merit reevaluation to avoid unintended consequences, experts said in three new opinion papers.

The three statements were published on July 22, 2024, in Annals of Internal Medicine. In one, the authors expressed caution about the recent movement away from using BMI alone to define obesity, noting that the measure remains a useful population-level and clinical tool for addressing adiposity, particularly within racial and ethnic groups. But the authors of a second paper pointed out that the use of lower BMI cutoffs to define obesity in Asian populations, in place since 2004, is inadequate in part because it doesn’t account for heterogeneity among different Asian groups.

And in the third paper, an editorial, an Annals editor cautioned that the recent framing of obesity exclusively as a “disease” rather than a “broader, more inclusive construct” may inadvertently reinforce the bias it was meant to combat.

Asked to comment on the issues raised in the papers, Professor Gijs Goossens of Maastricht University Medical Center, Maastricht, the Netherlands, said, “It is important to emphasize that the management and treatment of obesity have wider objectives than weight loss alone and include the prevention, resolution, or improvement of obesity-related complications; achieving better quality of life and mental well-being; and improvement of physical and social functioning.”

Added Dr. Goossens, who was an author of a recent European Association for the Study of Obesity (EASO) framework calling for moving beyond BMI in defining obesity, “Personalized therapeutic goals should be set at the beginning of the treatment, according to the stage of obesity, taking into account available therapeutic options, possible side effects or risks, and patient preferences. The drivers of obesity and possible barriers to treatment should also be discussed with the patient.” Dr. Goossens emphasized that he was providing his personal views and not speaking for the EASO or his coauthors.
 

BMI: ‘Not a Perfect Measure of Adiposity but Remains Useful’

In their “Ideas and Opinions” paper, Adolfo G. Cuevas, PhD, of New York University School of Global Public Health, New York City, and Walter C. Willett, MD, DrPH, of Harvard T.H. Chan School of Public Health, Boston, argued that “BMI, although not a perfect measure of adiposity, remains a useful population-level and clinical tool for addressing adiposity, including within groups defined by race and ethnicity.”

They added that despite the criticism that BMI doesn’t distinguish between fat and lean body mass, the measure still strongly correlates with fat mass as well as cardiovascular risk and mortality, and it does so similarly across racial and ethnic groups.

Clinically, Dr. Cuevas and Dr. Willett pointed out that BMI correlates fat mass as assessed with the gold standard measure dual x-ray absorptiometry but is far simpler and less expensive. Measuring waist circumference can provide additional information about visceral fat and disease risk but is “more difficult to standardize and suffers from the same limitations as BMI when cut points are used.”

They suggest the addition of change in weight since early adulthood and over time as a “simple and sensitive variable” for assessing adiposity.

Luca Busetto, MD, associate professor of medicine at the University of Padua, Italy, and the first author of the EASO framework, said, “The paper from Cuevas and Willett sounds like a strong defense of BMI, and I can substantially agree with this defense ... We remain anchored on BMI, but we tried to move beyond it adding an estimate of high risk abdominal fat — waist to height ratio — and coupling the anthropometric assessment with a complete clinical evaluation and staging.”

Dr. Goossens said, “I agree with the authors that despite the limitations of BMI as a measure of body fatness, it remains a useful clinical screening tool. Yet the diagnosis of obesity should not be based solely on BMI” due to the stronger association of abdominal fat with cardiometabolic complications.

That link, he noted, “also applies to individuals with a BMI level below the current cutoff values for obesity, who may already have medical, functional, or psychological impairments. We should be aware of the risk of undertreatment in this particular group of patients.”
 

Does Calling Obesity a ‘Disease’ Have Unintended Consequences?

In her editorial, Christina C. Wee, MD, senior deputy editor, Annals of Internal Medicine, wrote, “Beyond diagnostic challenges, framing obesity exclusively as a disease rather than a broader, more inclusive construct may have unintended consequences — including reinforcing the weight bias this framing was in part intended to combat.”

Focusing solely on biological causes of obesity while ignoring psychosocial, cultural, environmental, and behavioral contexts could undermine public health and policy efforts to address those factors, Dr. Wee argued.

Moreover, she wrote, “Ironically, framing obesity as a disease to justify coverage for treatment reinforces weight bias. It conflates the need to label a condition a disease with healthcare reimbursement and raises the stakes for developing accurate diagnostic criteria ... By exclusively linking obesity as a disease to reimbursement, it sends the message that only those who manifest disease from excess adiposity warrant treatment — and, by inference, those on the continuum who have not yet manifested disease do not warrant treatment.”

Likening obesity to other risk factors such as hypertension or dyslipidemia for which treatment is typically reimbursed, Dr. Wee pointed out that Medicare still prohibits coverage of medications for obesity.

Regarding the high costs of newer obesity medications and the need for payers and clinicians to ration their use, Dr. Wee argued, “Rather than focusing on whether one’s adiposity conforms to an expert panel’s definition of ‘disease,’ we should address how to best stage obesity risk with sufficient accuracy and fairness and reach a consensus on how to prioritize and match treatments to individual patients.”

Dr. Busetto said that EASO stands by its definition of obesity as a disease, adding “we can adhere to the suggestion of a holistic approach deciding treatment modalities according to the risk and the presence of mental, functional, and medical complications of impairments. Of course, we cannot agree on any proposal that is oriented at leaving patients with obesity still in the asymptomatic phase of the disease without treatment. This would be like treating diabetes only after the occurrence of nephropathy or managing hypertension only after a stroke. Prevention of the symptomatic stage is a part of obesity management, even beyond weight loss.”

Dr. Goossens said, “indeed, it is of utmost importance to develop accurate risk stratification tools for adequately clinical staging of obesity, according to the severity of its medical, psychological and functional impairments.”
 

Do the Current Lower BMI Cutoffs for Defining Obesity in Asian People Make Sense?

Simar S. Bajaj, AB, of Harvard University, Cambridge, Massachusetts, and colleagues, all of Harvard Medical School, Boston, raised several concerns regarding the 2004 World Health Organization’s suggestion to use lower BMI categories for defining overweight and obesity in Asian populations, that is, 23-27.5 kg/m² and 27.5 kg/m² or higher for obesity, respectively, as opposed to 25-29.9 and ≥ 30, respectively, for other populations.

Different Asian countries have created their own obesity BMI cutoffs, ranging from 25 kg/m² in India to 28 kg/m² in China. But “Asian Americans continue to be treated as a monolith without official disaggregated cutoffs,” Mr. Bajaj and colleagues noted.

The heterogeneity translates to different risk levels across Asian subgroups. For example, in one study, age- and sex-adjusted BMI cutoffs for increased risk of developing type 2 diabetes were 23.9 kg/m² in South Asian populations, 26.6 kg/m² in Arab populations, 26.9 kg/m² in Chinese populations, and 28.1 kg/m² in Black populations.

These findings raise important questions, the researchers said. “Does it make sense for people of Chinese descent to use the same BMI threshold as the South Asian group when their ‘equivalent risk cutoff’ is closer to that of Arab and Black groups who share the standard BMI threshold?” Most data in this area are cross-sectional rather than the longitudinal data needed to answer those questions, they noted.

They suggest that professional diabetes and obesity organizations consider BMI thresholds to be “placeholders” until more sensitive and specific thresholds can be defined for Asian American populations.

Mr. Bajaj and colleagues also noted the need for disaggregated data is not unique to Asian groups but that they focused on Asian Americans for two main reasons. “First, success would create a precedent for complete disaggregation and help ensure that other groups do not stall at an intermediary level. Second, substantial research into Asian ethnic groups — and the WHO’s precedent 20 years ago — creates a solid foundation to build upon.”

Ultimately, they said, “advancing equity will require funding research that engages diverse Asian communities and developing tailored interventions for all ethnicities.”

Dr. Cuevas, Dr. Willett, Mr. Bajaj, and Dr. Wee had no disclosures. Dr. Goossens received research funding from the European Foundation for the Study of Diabetes, the Dutch Diabetes Research Foundation, and the Dutch Research Council. Dr. Busetto received personal funding from Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Pfizer, and Bruno Farmaceutici as a member of advisory boards and from Rhythm Pharmaceuticals and Pronokal as a speaker.
 

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

The role of body mass index (BMI) in defining obesity and the definition of obesity as a disease merit reevaluation to avoid unintended consequences, experts said in three new opinion papers.

The three statements were published on July 22, 2024, in Annals of Internal Medicine. In one, the authors expressed caution about the recent movement away from using BMI alone to define obesity, noting that the measure remains a useful population-level and clinical tool for addressing adiposity, particularly within racial and ethnic groups. But the authors of a second paper pointed out that the use of lower BMI cutoffs to define obesity in Asian populations, in place since 2004, is inadequate in part because it doesn’t account for heterogeneity among different Asian groups.

And in the third paper, an editorial, an Annals editor cautioned that the recent framing of obesity exclusively as a “disease” rather than a “broader, more inclusive construct” may inadvertently reinforce the bias it was meant to combat.

Asked to comment on the issues raised in the papers, Professor Gijs Goossens of Maastricht University Medical Center, Maastricht, the Netherlands, said, “It is important to emphasize that the management and treatment of obesity have wider objectives than weight loss alone and include the prevention, resolution, or improvement of obesity-related complications; achieving better quality of life and mental well-being; and improvement of physical and social functioning.”

Added Dr. Goossens, who was an author of a recent European Association for the Study of Obesity (EASO) framework calling for moving beyond BMI in defining obesity, “Personalized therapeutic goals should be set at the beginning of the treatment, according to the stage of obesity, taking into account available therapeutic options, possible side effects or risks, and patient preferences. The drivers of obesity and possible barriers to treatment should also be discussed with the patient.” Dr. Goossens emphasized that he was providing his personal views and not speaking for the EASO or his coauthors.
 

BMI: ‘Not a Perfect Measure of Adiposity but Remains Useful’

In their “Ideas and Opinions” paper, Adolfo G. Cuevas, PhD, of New York University School of Global Public Health, New York City, and Walter C. Willett, MD, DrPH, of Harvard T.H. Chan School of Public Health, Boston, argued that “BMI, although not a perfect measure of adiposity, remains a useful population-level and clinical tool for addressing adiposity, including within groups defined by race and ethnicity.”

They added that despite the criticism that BMI doesn’t distinguish between fat and lean body mass, the measure still strongly correlates with fat mass as well as cardiovascular risk and mortality, and it does so similarly across racial and ethnic groups.

Clinically, Dr. Cuevas and Dr. Willett pointed out that BMI correlates fat mass as assessed with the gold standard measure dual x-ray absorptiometry but is far simpler and less expensive. Measuring waist circumference can provide additional information about visceral fat and disease risk but is “more difficult to standardize and suffers from the same limitations as BMI when cut points are used.”

They suggest the addition of change in weight since early adulthood and over time as a “simple and sensitive variable” for assessing adiposity.

Luca Busetto, MD, associate professor of medicine at the University of Padua, Italy, and the first author of the EASO framework, said, “The paper from Cuevas and Willett sounds like a strong defense of BMI, and I can substantially agree with this defense ... We remain anchored on BMI, but we tried to move beyond it adding an estimate of high risk abdominal fat — waist to height ratio — and coupling the anthropometric assessment with a complete clinical evaluation and staging.”

Dr. Goossens said, “I agree with the authors that despite the limitations of BMI as a measure of body fatness, it remains a useful clinical screening tool. Yet the diagnosis of obesity should not be based solely on BMI” due to the stronger association of abdominal fat with cardiometabolic complications.

That link, he noted, “also applies to individuals with a BMI level below the current cutoff values for obesity, who may already have medical, functional, or psychological impairments. We should be aware of the risk of undertreatment in this particular group of patients.”
 

Does Calling Obesity a ‘Disease’ Have Unintended Consequences?

In her editorial, Christina C. Wee, MD, senior deputy editor, Annals of Internal Medicine, wrote, “Beyond diagnostic challenges, framing obesity exclusively as a disease rather than a broader, more inclusive construct may have unintended consequences — including reinforcing the weight bias this framing was in part intended to combat.”

Focusing solely on biological causes of obesity while ignoring psychosocial, cultural, environmental, and behavioral contexts could undermine public health and policy efforts to address those factors, Dr. Wee argued.

Moreover, she wrote, “Ironically, framing obesity as a disease to justify coverage for treatment reinforces weight bias. It conflates the need to label a condition a disease with healthcare reimbursement and raises the stakes for developing accurate diagnostic criteria ... By exclusively linking obesity as a disease to reimbursement, it sends the message that only those who manifest disease from excess adiposity warrant treatment — and, by inference, those on the continuum who have not yet manifested disease do not warrant treatment.”

Likening obesity to other risk factors such as hypertension or dyslipidemia for which treatment is typically reimbursed, Dr. Wee pointed out that Medicare still prohibits coverage of medications for obesity.

Regarding the high costs of newer obesity medications and the need for payers and clinicians to ration their use, Dr. Wee argued, “Rather than focusing on whether one’s adiposity conforms to an expert panel’s definition of ‘disease,’ we should address how to best stage obesity risk with sufficient accuracy and fairness and reach a consensus on how to prioritize and match treatments to individual patients.”

Dr. Busetto said that EASO stands by its definition of obesity as a disease, adding “we can adhere to the suggestion of a holistic approach deciding treatment modalities according to the risk and the presence of mental, functional, and medical complications of impairments. Of course, we cannot agree on any proposal that is oriented at leaving patients with obesity still in the asymptomatic phase of the disease without treatment. This would be like treating diabetes only after the occurrence of nephropathy or managing hypertension only after a stroke. Prevention of the symptomatic stage is a part of obesity management, even beyond weight loss.”

Dr. Goossens said, “indeed, it is of utmost importance to develop accurate risk stratification tools for adequately clinical staging of obesity, according to the severity of its medical, psychological and functional impairments.”
 

Do the Current Lower BMI Cutoffs for Defining Obesity in Asian People Make Sense?

Simar S. Bajaj, AB, of Harvard University, Cambridge, Massachusetts, and colleagues, all of Harvard Medical School, Boston, raised several concerns regarding the 2004 World Health Organization’s suggestion to use lower BMI categories for defining overweight and obesity in Asian populations, that is, 23-27.5 kg/m² and 27.5 kg/m² or higher for obesity, respectively, as opposed to 25-29.9 and ≥ 30, respectively, for other populations.

Different Asian countries have created their own obesity BMI cutoffs, ranging from 25 kg/m² in India to 28 kg/m² in China. But “Asian Americans continue to be treated as a monolith without official disaggregated cutoffs,” Mr. Bajaj and colleagues noted.

The heterogeneity translates to different risk levels across Asian subgroups. For example, in one study, age- and sex-adjusted BMI cutoffs for increased risk of developing type 2 diabetes were 23.9 kg/m² in South Asian populations, 26.6 kg/m² in Arab populations, 26.9 kg/m² in Chinese populations, and 28.1 kg/m² in Black populations.

These findings raise important questions, the researchers said. “Does it make sense for people of Chinese descent to use the same BMI threshold as the South Asian group when their ‘equivalent risk cutoff’ is closer to that of Arab and Black groups who share the standard BMI threshold?” Most data in this area are cross-sectional rather than the longitudinal data needed to answer those questions, they noted.

They suggest that professional diabetes and obesity organizations consider BMI thresholds to be “placeholders” until more sensitive and specific thresholds can be defined for Asian American populations.

Mr. Bajaj and colleagues also noted the need for disaggregated data is not unique to Asian groups but that they focused on Asian Americans for two main reasons. “First, success would create a precedent for complete disaggregation and help ensure that other groups do not stall at an intermediary level. Second, substantial research into Asian ethnic groups — and the WHO’s precedent 20 years ago — creates a solid foundation to build upon.”

Ultimately, they said, “advancing equity will require funding research that engages diverse Asian communities and developing tailored interventions for all ethnicities.”

Dr. Cuevas, Dr. Willett, Mr. Bajaj, and Dr. Wee had no disclosures. Dr. Goossens received research funding from the European Foundation for the Study of Diabetes, the Dutch Diabetes Research Foundation, and the Dutch Research Council. Dr. Busetto received personal funding from Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Pfizer, and Bruno Farmaceutici as a member of advisory boards and from Rhythm Pharmaceuticals and Pronokal as a speaker.
 

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

TOPLINE:

Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes. 

METHODOLOGY:

• Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
• Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
• Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
• Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.

TAKEAWAY:

• Overall, 10.8% of participants were identified as having constipation.
• Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
• Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.

IN PRACTICE:

“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.

SOURCE:

The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.

DISCLOSURES:

The study had no specific funding source. The authors declared no competing interests. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes. 

METHODOLOGY:

• Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
• Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
• Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
• Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.

TAKEAWAY:

• Overall, 10.8% of participants were identified as having constipation.
• Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
• Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.

IN PRACTICE:

“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.

SOURCE:

The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.

DISCLOSURES:

The study had no specific funding source. The authors declared no competing interests. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Increased dietary intake of vitamin B1 is associated with a lower prevalence of constipation, particularly among men and individuals without hypertension or diabetes. 

METHODOLOGY:

• Researchers conducted a cross-sectional study using National Health and Nutrition Examination Survey data from 2005-2010 involving 10,371 adults aged ≥ 20 years.
• Participants provided information on fecal characteristics and bowel movement frequency, which was documented for 30 days prior to data collection.
• Constipation was established by either frequency of bowel movements (fewer than three per week) or stool consistency (Bristol Stool Scale type 1 or 2).
• Data on vitamin B1 intake were collected through 24-hour total nutritional intake recall interviews. Patients were divided into three groups based on their level of B1 intake: 0.064-1.21 mg, 1.21-1.76 mg, and 1.76-12.61 mg.

TAKEAWAY:

• Overall, 10.8% of participants were identified as having constipation.
• Greater dietary vitamin B1 intake was associated with a 23% reduction in constipation risk (P = .034).
• Additionally, a subgroup analysis found that higher B1 intake was associated with a reduction in constipation risk of 20% in men, 16% in people without hypertension, and 14% in those without diabetes.

IN PRACTICE:

“This association suggests that enhanced intake of vitamin B1 through diet may facilitate softer stools and heightened intestinal motility, thereby potentially alleviating constipation symptoms. Consequently, healthcare professionals are advised to prioritize the promotion of a well-balanced diet as an initial therapeutic approach, preceding medical interventions,” the authors wrote.

SOURCE:

The study, led by Wenyi Du, the Affiliated Stomatological Hospital of Soochow University, Suzhou Stomatological Hospital, Suzhou, China, and Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center, Wuxi, China, was published online in BMC Gastroenterology.

LIMITATIONS:

A causal relationship could not be established between vitamin B1 intake and constipation owing to the cross-sectional nature of the study. The study relied on patient interviews and patient self-reported data. Additionally, 24-hour dietary recalls may not have accurately reflected the long-term eating habits of the participants.

DISCLOSURES:

The study had no specific funding source. The authors declared no competing interests. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

For 3 years, Ajala Efem’s type 2 diabetes was so poorly controlled that her blood sugar often soared northward of 500 mg/dL despite insulin shots three to five times a day. She would experience dizziness, vomiting, severe headaches, and the neuropathy in her feet made walking painful. She was also — literally — frothing at the mouth. The 47-year-old single mother of two adult children with mental disabilities feared that she would die.

Ms. Efem lives in the South Bronx, which is among the poorest areas of New York City, where the combined rate of prediabetes and diabetes is close to 30%, the highest rate of any borough in the city.

She had to wait 8 months for an appointment with an endocrinologist, but that visit proved to be life-changing. She lost 28 pounds and got off 15 medications in a single month. She did not join a gym or count calories; she simply changed the food she ate and adopted a low-carb diet.

“I went from being sick to feeling so great,” she told her endocrinologist recently: “My feet aren’t hurting; I’m not in pain; I’m eating as much as I want, and I really enjoy my food so much.” 

Ms. Efem’s life-changing visit was with Mariela Glandt, MD, at the offices of Essen Health Care. One month earlier, Dr. Glandt’s company, OwnaHealth, was contracted by Essen to conduct a 100-person pilot program for endocrinology patients. Essen is the largest Medicaid provider in New York City, and “they were desperate for an endocrinologist,” said Dr. Glandt, who trained at Columbia University in New York. So she came — all the way from Madrid, Spain. She commutes monthly, staying for a week each visit.

Dr. Glandt keeps up this punishing schedule because, as she explains, “it’s such a high for me to see these incredible transformations.” Her mostly Black and Hispanic patients are poor and lack resources, yet they lose significant amounts of weight, and their health issues resolve.

“Food is medicine” is an idea very much in vogue. The concept was central to the landmark White House Conference on Hunger, Nutrition, and Health in 2022 and is now the focus of a number of a wide range of government programs. Recently, the Senate held a hearing aimed at further expanding food as medicine programs.

Still, only a single randomized controlled clinical trial has been conducted on this nutritional approach, with unexpectedly disappointing results. In the mid-Atlantic region, 456 food-insecure adults with type 2 diabetes were randomly assigned to usual care or the provision of weekly groceries for their entire families for about 1 year. Provisions for a Mediterranean-style diet included whole grains, fruits and vegetables, lean protein, low-fat dairy products, cereal, brown rice, and bread. In addition, participants received dietary consultations. Yet, those who got free food and coaching did not see improvements in their average blood sugar (the study’s primary outcome), and their low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels appeared to have worsened. 

“To be honest, I was surprised,” the study’s lead author, Joseph Doyle, PhD, professor at the Sloan School of Management at MIT in Cambridge, Massachusetts, told me. “I was hoping we would show improved outcomes, but the way to make progress is to do well-randomized trials to find out what works.”

I was not surprised by these results because a recent rigorous systematic review and meta-analysis in The BMJ did not show a Mediterranean-style diet to be the most effective for glycemic control. And Ms. Efem was not in fact following a Mediterranean-style diet.

Ms. Efem’s low-carb success story is anecdotal, but Dr. Glandt has an established track record from her 9 years’ experience as the medical director of the eponymous diabetes center she founded in Tel Aviv. A recent audit of 344 patients from the center found that after 6 months of following a very low–carbohydrate diet, 96.3% of those with diabetes saw their A1c fall from a median 7.6% to 6.3%. Weight loss was significant, with a median drop of 6.5 kg (14 pounds) for patients with diabetes and 5.7 kg for those with prediabetes. The diet comprises 5%-10% of calories from carbs, but Dr. Glandt does not use numeric targets with her patients.

Blood pressure, triglycerides, and liver enzymes also improved. And though LDL cholesterol went up by 8%, this result may have been offset by an accompanying 13% rise in HDL cholesterol. Of the 78 patients initially on insulin, 62 were able to stop this medication entirely.

Although these results aren’t from a clinical trial, they’re still highly meaningful because the current dietary standard of care for type 2 diabetes can only slow the progression of the disease, not cause remission. Indeed, the idea that type 2 diabetes could be put into remission was not seriously considered by the American Diabetes Association (ADA) until 2009. By 2019, an ADA report concluded that “[r]educing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia.” In other words, the best way to improve the key factor in diabetes is to reduce total carbohydrates. Yet, the ADA still advocates filling one quarter of one’s plate with carbohydrate-based foods, an amount that will prevent remission. Given that the ADA’s vision statement is “a life free of diabetes,” it seems negligent not to tell people with a deadly condition that they can reverse this diagnosis. 

A 2023 meta-analysis of 42 controlled clinical trials on 4809 patients showed that a very low–carbohydrate ketogenic diet (keto) was “superior” to alternatives for glycemic control. A more recent review of 11 clinical trials found that this diet was equal but not superior to other nutritional approaches in terms of blood sugar control, but this review also concluded that keto led to greater increases in HDL cholesterol and lower triglycerides. 

Dr. Glandt’s patients in the Bronx might not seem like obvious low-carb candidates. The diet is considered expensive and difficult to sustain. My interviews with a half dozen patients revealed some of these difficulties, but even for a woman living in a homeless shelter, the obstacles are not insurmountable.

Jerrilyn, who preferred that I use only her first name, lives in a shelter in Queens. While we strolled through a nearby park, she told me about her desire to lose weight and recover from polycystic ovary syndrome, which terrified her because it had caused dramatic hair loss. When she landed in Dr. Glandt’s office at age 28, she weighed 180 pounds. 

Less than 5 months later, Jerrilyn had lost 25 pounds, and her period had returned with some regularity. She said she used “food stamps,” known as the Supplemental Nutrition Assistance Program (SNAP), to buy most of her food at local delis because the meals served at the shelter were too heavy in starches. She starts her day with eggs, turkey bacon, and avocado. 

“It was hard to give up carbohydrates because in my culture [Latina], we have nothing but carbs: rice, potatoes, yuca,” Jerrilyn shared. She noticed that carbs make her hungrier, but after 3 days of going low-carb, her cravings diminished. “It was like getting over an addiction,” she said.

Jerrilyn told me she’d seen many doctors but none as involved as Dr. Glandt. “It feels awesome to know that I have a lot of really useful information coming from her all the time.” The OwnaHealth app tracks weight, blood pressure, blood sugar, ketones, meals, mood, and cravings. Patients wear continuous glucose monitors and enter other information manually. Ketone bodies are used to measure dietary adherence and are obtained through finger pricks and test strips provided by OwnaHealth. Dr. Glandt gives patients her own food plan, along with free visual guides to low-carbohydrate foods by dietdoctor.com. 

Dr. Glandt also sends her patients for regular blood work. She says she does not frequently see a rise in LDL cholesterol, which can sometimes occur on a low-carbohydrate diet. This effect is most common among people who are lean and fit. She says she doesn’t discontinue statins unless cholesterol levels improve significantly.

Samuel Gonzalez, age 56, weighed 275 pounds when he walked into Dr. Glandt’s office this past November. His A1c was 9.2%, but none of his previous doctors had diagnosed him with diabetes. “I was like a walking bag of sugar!” he joked. 

A low-carbohydrate diet seemed absurd to a Puerto Rican like himself: “Having coffee without sugar? That’s like sacrilegious in my culture!” exclaimed Mr. Gonzalez. Still, he managed, with SNAP, to cook eggs and bacon for breakfast and some kind of protein for dinner. He keeps lunch light, “like tuna fish,” and finds checking in with the OwnaHealth app to be very helpful. “Every day, I’m on it,” he said. In the past 7 months, he’s lost 50 pounds, normalized his cholesterol and blood pressure levels, and lowered his A1c to 5.5%.

Mr. Gonzalez gets disability payments due to a back injury, and Ms. Efem receives government payments because her husband died serving in the military. Ms. Efem says her new diet challenges her budget, but Mr. Gonzalez says he manages easily.

Mélissa Cruz, a 28-year-old studying to be a nail technician while also doing back office work at a physical therapy practice, says she’s stretched thin. “I end up sad because I can’t put energy into looking up recipes and cooking for me and my boyfriend,” she told me. She’ll often cook rice and plantains for him and meat for herself, but “it’s frustrating when I’m low on funds and can’t figure out what to eat.” 

Low-carbohydrate diets have a reputation for being expensive because people often start eating pricier foods, like meat and cheese, to replace cheaper starchy foods such as pasta and rice. Eggs and ground beef are less expensive low-carb meal options, and meat, unlike fruits and vegetables, is easy to freeze and doesn’t spoil quickly. These advantages can add up.

A 2019 cost analysis published in Nutrition & Dietetics compared a low-carbohydrate dietary pattern with the New Zealand government’s recommended guidelines (which are almost identical to those in the United States) and found that it cost only an extra $1.27 in US dollars per person per day. One explanation is that protein and fat are more satiating than carbohydrates, so people who mostly consume these macronutrients often cut back on snacks like packaged chips, crackers, and even fruits. Also, those on a ketogenic diet usually cut down on medications, so the additional $1.27 daily is likely offset by reduced spending at the pharmacy.

It’s not just Bronx residents with low socioeconomic status (SES) who adapt well to low-carbohydrate diets. Among Alabama state employees with diabetes enrolled in a low-carbohydrate dietary program provided by a company called Virta, the low SES population had the best outcomes. Virta also published survey data in 2023 showing that participants in a program with the Veteran’s Administration did not find additional costs to be an obstacle to dietary adherence. In fact, some participants saw cost reductions due to decreased spending on processed snacks and fast foods.

Ms. Cruz told me she struggles financially, yet she’s still lost nearly 30 pounds in 5 months, and her A1c went from 7.1% down to 5.9%, putting her diabetes into remission. Equally motivating for her are the improvements she’s seen in other hormonal issues. Since childhood, she’s had acanthosis, a condition that causes the skin to darken in velvety patches, and more recently, she developed severe hirsutism to the point of growing sideburns. “I had tried going vegan and fasting, but these just weren’t sustainable for me, and I was so overwhelmed with counting calories all the time.” Now, on a low-carbohydrate diet, which doesn’t require calorie counting, she’s finally seeing both these conditions improve significantly.

When I last checked in with Ms. Cruz, she said she had “kind of ghosted” Dr. Glandt due to her work and school constraints, but she hadn’t abandoned the diet. She appreciated, too, that Dr. Glandt had not given up on her and kept calling and messaging. “She’s not at all like a typical doctor who would just tell me to lose weight and shake their head at me,” Ms. Cruz said. 

Because Dr. Glandt’s approach is time-intensive and high-touch, it might seem impractical to scale up, but Dr. Glandt’s app uses artificial intelligence to help with communications thus allowing her, with help from part-time health coaches, to care for patients. 

This early success in one of the United States’ poorest and sickest neighborhoods should give us hope that type 2 diabetes need not to be a progressive irreversible disease, even among the disadvantaged. 

OwnaHealth’s track record, along with that of Virta and other similar low-carbohydrate medical practices also give hope to the food-is-medicine idea. Diabetes can go into remission, and people can be healed, provided that health practitioners prescribe the right foods. And in truth, it’s not a diet. It’s a way of eating that must be maintained. The sustainability of low-carbohydrate diets has been a point of contention, but the Virta trial, with 38% of patients sustaining remission at 2 years, showed that it’s possible. (OwnaHealth, for its part, offers long-term maintenance plans to help patients stay very low-carb permanently.) 

Given the tremendous costs and health burden of diabetes, this approach should no doubt be the first line of treatment for doctors and the ADA. The past two decades of clinical trial research have demonstrated that remission of type 2 diabetes is possible through diet alone. It turns out that for metabolic diseases, only certain foods are truly medicine. 
 

Tools and Tips for Clinicians: 

• Free two-page keto starter’s guide by OwnaHealth; Dr. Glandt uses this guide with her patients.
• Illustrated low-carb guides by dietdoctor.com
• Free low-carbohydrate starter guide by the Michigan Collaborative for Type 2 Diabetes
• Low-Carb for Any Budget, a free digital booklet by Mark Cucuzzella, MD, and Kristie Sullivan, PhD
• Recipe and meal ideas from Ruled.me, Keto-Mojo.com, and 

Dr. Teicholz is the founder of Nutrition Coalition, an independent nonprofit dedicated to ensuring that US dietary guidelines align with current science. She disclosed receiving book royalties from The Big Fat Surprise, and received honorarium not exceeding $2000 for speeches from various sources.

A version of this article appeared on Medscape.com.

For 3 years, Ajala Efem’s type 2 diabetes was so poorly controlled that her blood sugar often soared northward of 500 mg/dL despite insulin shots three to five times a day. She would experience dizziness, vomiting, severe headaches, and the neuropathy in her feet made walking painful. She was also — literally — frothing at the mouth. The 47-year-old single mother of two adult children with mental disabilities feared that she would die.

Ms. Efem lives in the South Bronx, which is among the poorest areas of New York City, where the combined rate of prediabetes and diabetes is close to 30%, the highest rate of any borough in the city.

She had to wait 8 months for an appointment with an endocrinologist, but that visit proved to be life-changing. She lost 28 pounds and got off 15 medications in a single month. She did not join a gym or count calories; she simply changed the food she ate and adopted a low-carb diet.

“I went from being sick to feeling so great,” she told her endocrinologist recently: “My feet aren’t hurting; I’m not in pain; I’m eating as much as I want, and I really enjoy my food so much.” 

Ms. Efem’s life-changing visit was with Mariela Glandt, MD, at the offices of Essen Health Care. One month earlier, Dr. Glandt’s company, OwnaHealth, was contracted by Essen to conduct a 100-person pilot program for endocrinology patients. Essen is the largest Medicaid provider in New York City, and “they were desperate for an endocrinologist,” said Dr. Glandt, who trained at Columbia University in New York. So she came — all the way from Madrid, Spain. She commutes monthly, staying for a week each visit.

Dr. Glandt keeps up this punishing schedule because, as she explains, “it’s such a high for me to see these incredible transformations.” Her mostly Black and Hispanic patients are poor and lack resources, yet they lose significant amounts of weight, and their health issues resolve.

“Food is medicine” is an idea very much in vogue. The concept was central to the landmark White House Conference on Hunger, Nutrition, and Health in 2022 and is now the focus of a number of a wide range of government programs. Recently, the Senate held a hearing aimed at further expanding food as medicine programs.

Still, only a single randomized controlled clinical trial has been conducted on this nutritional approach, with unexpectedly disappointing results. In the mid-Atlantic region, 456 food-insecure adults with type 2 diabetes were randomly assigned to usual care or the provision of weekly groceries for their entire families for about 1 year. Provisions for a Mediterranean-style diet included whole grains, fruits and vegetables, lean protein, low-fat dairy products, cereal, brown rice, and bread. In addition, participants received dietary consultations. Yet, those who got free food and coaching did not see improvements in their average blood sugar (the study’s primary outcome), and their low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels appeared to have worsened. 

“To be honest, I was surprised,” the study’s lead author, Joseph Doyle, PhD, professor at the Sloan School of Management at MIT in Cambridge, Massachusetts, told me. “I was hoping we would show improved outcomes, but the way to make progress is to do well-randomized trials to find out what works.”

I was not surprised by these results because a recent rigorous systematic review and meta-analysis in The BMJ did not show a Mediterranean-style diet to be the most effective for glycemic control. And Ms. Efem was not in fact following a Mediterranean-style diet.

Ms. Efem’s low-carb success story is anecdotal, but Dr. Glandt has an established track record from her 9 years’ experience as the medical director of the eponymous diabetes center she founded in Tel Aviv. A recent audit of 344 patients from the center found that after 6 months of following a very low–carbohydrate diet, 96.3% of those with diabetes saw their A1c fall from a median 7.6% to 6.3%. Weight loss was significant, with a median drop of 6.5 kg (14 pounds) for patients with diabetes and 5.7 kg for those with prediabetes. The diet comprises 5%-10% of calories from carbs, but Dr. Glandt does not use numeric targets with her patients.

Blood pressure, triglycerides, and liver enzymes also improved. And though LDL cholesterol went up by 8%, this result may have been offset by an accompanying 13% rise in HDL cholesterol. Of the 78 patients initially on insulin, 62 were able to stop this medication entirely.

Although these results aren’t from a clinical trial, they’re still highly meaningful because the current dietary standard of care for type 2 diabetes can only slow the progression of the disease, not cause remission. Indeed, the idea that type 2 diabetes could be put into remission was not seriously considered by the American Diabetes Association (ADA) until 2009. By 2019, an ADA report concluded that “[r]educing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia.” In other words, the best way to improve the key factor in diabetes is to reduce total carbohydrates. Yet, the ADA still advocates filling one quarter of one’s plate with carbohydrate-based foods, an amount that will prevent remission. Given that the ADA’s vision statement is “a life free of diabetes,” it seems negligent not to tell people with a deadly condition that they can reverse this diagnosis. 

A 2023 meta-analysis of 42 controlled clinical trials on 4809 patients showed that a very low–carbohydrate ketogenic diet (keto) was “superior” to alternatives for glycemic control. A more recent review of 11 clinical trials found that this diet was equal but not superior to other nutritional approaches in terms of blood sugar control, but this review also concluded that keto led to greater increases in HDL cholesterol and lower triglycerides. 

Dr. Glandt’s patients in the Bronx might not seem like obvious low-carb candidates. The diet is considered expensive and difficult to sustain. My interviews with a half dozen patients revealed some of these difficulties, but even for a woman living in a homeless shelter, the obstacles are not insurmountable.

Jerrilyn, who preferred that I use only her first name, lives in a shelter in Queens. While we strolled through a nearby park, she told me about her desire to lose weight and recover from polycystic ovary syndrome, which terrified her because it had caused dramatic hair loss. When she landed in Dr. Glandt’s office at age 28, she weighed 180 pounds. 

Less than 5 months later, Jerrilyn had lost 25 pounds, and her period had returned with some regularity. She said she used “food stamps,” known as the Supplemental Nutrition Assistance Program (SNAP), to buy most of her food at local delis because the meals served at the shelter were too heavy in starches. She starts her day with eggs, turkey bacon, and avocado. 

“It was hard to give up carbohydrates because in my culture [Latina], we have nothing but carbs: rice, potatoes, yuca,” Jerrilyn shared. She noticed that carbs make her hungrier, but after 3 days of going low-carb, her cravings diminished. “It was like getting over an addiction,” she said.

Jerrilyn told me she’d seen many doctors but none as involved as Dr. Glandt. “It feels awesome to know that I have a lot of really useful information coming from her all the time.” The OwnaHealth app tracks weight, blood pressure, blood sugar, ketones, meals, mood, and cravings. Patients wear continuous glucose monitors and enter other information manually. Ketone bodies are used to measure dietary adherence and are obtained through finger pricks and test strips provided by OwnaHealth. Dr. Glandt gives patients her own food plan, along with free visual guides to low-carbohydrate foods by dietdoctor.com. 

Dr. Glandt also sends her patients for regular blood work. She says she does not frequently see a rise in LDL cholesterol, which can sometimes occur on a low-carbohydrate diet. This effect is most common among people who are lean and fit. She says she doesn’t discontinue statins unless cholesterol levels improve significantly.

Samuel Gonzalez, age 56, weighed 275 pounds when he walked into Dr. Glandt’s office this past November. His A1c was 9.2%, but none of his previous doctors had diagnosed him with diabetes. “I was like a walking bag of sugar!” he joked. 

A low-carbohydrate diet seemed absurd to a Puerto Rican like himself: “Having coffee without sugar? That’s like sacrilegious in my culture!” exclaimed Mr. Gonzalez. Still, he managed, with SNAP, to cook eggs and bacon for breakfast and some kind of protein for dinner. He keeps lunch light, “like tuna fish,” and finds checking in with the OwnaHealth app to be very helpful. “Every day, I’m on it,” he said. In the past 7 months, he’s lost 50 pounds, normalized his cholesterol and blood pressure levels, and lowered his A1c to 5.5%.

Mr. Gonzalez gets disability payments due to a back injury, and Ms. Efem receives government payments because her husband died serving in the military. Ms. Efem says her new diet challenges her budget, but Mr. Gonzalez says he manages easily.

Mélissa Cruz, a 28-year-old studying to be a nail technician while also doing back office work at a physical therapy practice, says she’s stretched thin. “I end up sad because I can’t put energy into looking up recipes and cooking for me and my boyfriend,” she told me. She’ll often cook rice and plantains for him and meat for herself, but “it’s frustrating when I’m low on funds and can’t figure out what to eat.” 

Low-carbohydrate diets have a reputation for being expensive because people often start eating pricier foods, like meat and cheese, to replace cheaper starchy foods such as pasta and rice. Eggs and ground beef are less expensive low-carb meal options, and meat, unlike fruits and vegetables, is easy to freeze and doesn’t spoil quickly. These advantages can add up.

A 2019 cost analysis published in Nutrition & Dietetics compared a low-carbohydrate dietary pattern with the New Zealand government’s recommended guidelines (which are almost identical to those in the United States) and found that it cost only an extra $1.27 in US dollars per person per day. One explanation is that protein and fat are more satiating than carbohydrates, so people who mostly consume these macronutrients often cut back on snacks like packaged chips, crackers, and even fruits. Also, those on a ketogenic diet usually cut down on medications, so the additional $1.27 daily is likely offset by reduced spending at the pharmacy.

It’s not just Bronx residents with low socioeconomic status (SES) who adapt well to low-carbohydrate diets. Among Alabama state employees with diabetes enrolled in a low-carbohydrate dietary program provided by a company called Virta, the low SES population had the best outcomes. Virta also published survey data in 2023 showing that participants in a program with the Veteran’s Administration did not find additional costs to be an obstacle to dietary adherence. In fact, some participants saw cost reductions due to decreased spending on processed snacks and fast foods.

Ms. Cruz told me she struggles financially, yet she’s still lost nearly 30 pounds in 5 months, and her A1c went from 7.1% down to 5.9%, putting her diabetes into remission. Equally motivating for her are the improvements she’s seen in other hormonal issues. Since childhood, she’s had acanthosis, a condition that causes the skin to darken in velvety patches, and more recently, she developed severe hirsutism to the point of growing sideburns. “I had tried going vegan and fasting, but these just weren’t sustainable for me, and I was so overwhelmed with counting calories all the time.” Now, on a low-carbohydrate diet, which doesn’t require calorie counting, she’s finally seeing both these conditions improve significantly.

When I last checked in with Ms. Cruz, she said she had “kind of ghosted” Dr. Glandt due to her work and school constraints, but she hadn’t abandoned the diet. She appreciated, too, that Dr. Glandt had not given up on her and kept calling and messaging. “She’s not at all like a typical doctor who would just tell me to lose weight and shake their head at me,” Ms. Cruz said. 

Because Dr. Glandt’s approach is time-intensive and high-touch, it might seem impractical to scale up, but Dr. Glandt’s app uses artificial intelligence to help with communications thus allowing her, with help from part-time health coaches, to care for patients. 

This early success in one of the United States’ poorest and sickest neighborhoods should give us hope that type 2 diabetes need not to be a progressive irreversible disease, even among the disadvantaged. 

OwnaHealth’s track record, along with that of Virta and other similar low-carbohydrate medical practices also give hope to the food-is-medicine idea. Diabetes can go into remission, and people can be healed, provided that health practitioners prescribe the right foods. And in truth, it’s not a diet. It’s a way of eating that must be maintained. The sustainability of low-carbohydrate diets has been a point of contention, but the Virta trial, with 38% of patients sustaining remission at 2 years, showed that it’s possible. (OwnaHealth, for its part, offers long-term maintenance plans to help patients stay very low-carb permanently.) 

Given the tremendous costs and health burden of diabetes, this approach should no doubt be the first line of treatment for doctors and the ADA. The past two decades of clinical trial research have demonstrated that remission of type 2 diabetes is possible through diet alone. It turns out that for metabolic diseases, only certain foods are truly medicine. 
 

Tools and Tips for Clinicians: 

• Free two-page keto starter’s guide by OwnaHealth; Dr. Glandt uses this guide with her patients.
• Illustrated low-carb guides by dietdoctor.com
• Free low-carbohydrate starter guide by the Michigan Collaborative for Type 2 Diabetes
• Low-Carb for Any Budget, a free digital booklet by Mark Cucuzzella, MD, and Kristie Sullivan, PhD
• Recipe and meal ideas from Ruled.me, Keto-Mojo.com, and 

Dr. Teicholz is the founder of Nutrition Coalition, an independent nonprofit dedicated to ensuring that US dietary guidelines align with current science. She disclosed receiving book royalties from The Big Fat Surprise, and received honorarium not exceeding $2000 for speeches from various sources.

A version of this article appeared on Medscape.com.

For 3 years, Ajala Efem’s type 2 diabetes was so poorly controlled that her blood sugar often soared northward of 500 mg/dL despite insulin shots three to five times a day. She would experience dizziness, vomiting, severe headaches, and the neuropathy in her feet made walking painful. She was also — literally — frothing at the mouth. The 47-year-old single mother of two adult children with mental disabilities feared that she would die.

Ms. Efem lives in the South Bronx, which is among the poorest areas of New York City, where the combined rate of prediabetes and diabetes is close to 30%, the highest rate of any borough in the city.

She had to wait 8 months for an appointment with an endocrinologist, but that visit proved to be life-changing. She lost 28 pounds and got off 15 medications in a single month. She did not join a gym or count calories; she simply changed the food she ate and adopted a low-carb diet.

“I went from being sick to feeling so great,” she told her endocrinologist recently: “My feet aren’t hurting; I’m not in pain; I’m eating as much as I want, and I really enjoy my food so much.” 

Ms. Efem’s life-changing visit was with Mariela Glandt, MD, at the offices of Essen Health Care. One month earlier, Dr. Glandt’s company, OwnaHealth, was contracted by Essen to conduct a 100-person pilot program for endocrinology patients. Essen is the largest Medicaid provider in New York City, and “they were desperate for an endocrinologist,” said Dr. Glandt, who trained at Columbia University in New York. So she came — all the way from Madrid, Spain. She commutes monthly, staying for a week each visit.

Dr. Glandt keeps up this punishing schedule because, as she explains, “it’s such a high for me to see these incredible transformations.” Her mostly Black and Hispanic patients are poor and lack resources, yet they lose significant amounts of weight, and their health issues resolve.

“Food is medicine” is an idea very much in vogue. The concept was central to the landmark White House Conference on Hunger, Nutrition, and Health in 2022 and is now the focus of a number of a wide range of government programs. Recently, the Senate held a hearing aimed at further expanding food as medicine programs.

Still, only a single randomized controlled clinical trial has been conducted on this nutritional approach, with unexpectedly disappointing results. In the mid-Atlantic region, 456 food-insecure adults with type 2 diabetes were randomly assigned to usual care or the provision of weekly groceries for their entire families for about 1 year. Provisions for a Mediterranean-style diet included whole grains, fruits and vegetables, lean protein, low-fat dairy products, cereal, brown rice, and bread. In addition, participants received dietary consultations. Yet, those who got free food and coaching did not see improvements in their average blood sugar (the study’s primary outcome), and their low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels appeared to have worsened. 

“To be honest, I was surprised,” the study’s lead author, Joseph Doyle, PhD, professor at the Sloan School of Management at MIT in Cambridge, Massachusetts, told me. “I was hoping we would show improved outcomes, but the way to make progress is to do well-randomized trials to find out what works.”

I was not surprised by these results because a recent rigorous systematic review and meta-analysis in The BMJ did not show a Mediterranean-style diet to be the most effective for glycemic control. And Ms. Efem was not in fact following a Mediterranean-style diet.

Ms. Efem’s low-carb success story is anecdotal, but Dr. Glandt has an established track record from her 9 years’ experience as the medical director of the eponymous diabetes center she founded in Tel Aviv. A recent audit of 344 patients from the center found that after 6 months of following a very low–carbohydrate diet, 96.3% of those with diabetes saw their A1c fall from a median 7.6% to 6.3%. Weight loss was significant, with a median drop of 6.5 kg (14 pounds) for patients with diabetes and 5.7 kg for those with prediabetes. The diet comprises 5%-10% of calories from carbs, but Dr. Glandt does not use numeric targets with her patients.

Blood pressure, triglycerides, and liver enzymes also improved. And though LDL cholesterol went up by 8%, this result may have been offset by an accompanying 13% rise in HDL cholesterol. Of the 78 patients initially on insulin, 62 were able to stop this medication entirely.

Although these results aren’t from a clinical trial, they’re still highly meaningful because the current dietary standard of care for type 2 diabetes can only slow the progression of the disease, not cause remission. Indeed, the idea that type 2 diabetes could be put into remission was not seriously considered by the American Diabetes Association (ADA) until 2009. By 2019, an ADA report concluded that “[r]educing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia.” In other words, the best way to improve the key factor in diabetes is to reduce total carbohydrates. Yet, the ADA still advocates filling one quarter of one’s plate with carbohydrate-based foods, an amount that will prevent remission. Given that the ADA’s vision statement is “a life free of diabetes,” it seems negligent not to tell people with a deadly condition that they can reverse this diagnosis. 

A 2023 meta-analysis of 42 controlled clinical trials on 4809 patients showed that a very low–carbohydrate ketogenic diet (keto) was “superior” to alternatives for glycemic control. A more recent review of 11 clinical trials found that this diet was equal but not superior to other nutritional approaches in terms of blood sugar control, but this review also concluded that keto led to greater increases in HDL cholesterol and lower triglycerides. 

Dr. Glandt’s patients in the Bronx might not seem like obvious low-carb candidates. The diet is considered expensive and difficult to sustain. My interviews with a half dozen patients revealed some of these difficulties, but even for a woman living in a homeless shelter, the obstacles are not insurmountable.

Jerrilyn, who preferred that I use only her first name, lives in a shelter in Queens. While we strolled through a nearby park, she told me about her desire to lose weight and recover from polycystic ovary syndrome, which terrified her because it had caused dramatic hair loss. When she landed in Dr. Glandt’s office at age 28, she weighed 180 pounds. 

Less than 5 months later, Jerrilyn had lost 25 pounds, and her period had returned with some regularity. She said she used “food stamps,” known as the Supplemental Nutrition Assistance Program (SNAP), to buy most of her food at local delis because the meals served at the shelter were too heavy in starches. She starts her day with eggs, turkey bacon, and avocado. 

“It was hard to give up carbohydrates because in my culture [Latina], we have nothing but carbs: rice, potatoes, yuca,” Jerrilyn shared. She noticed that carbs make her hungrier, but after 3 days of going low-carb, her cravings diminished. “It was like getting over an addiction,” she said.

Jerrilyn told me she’d seen many doctors but none as involved as Dr. Glandt. “It feels awesome to know that I have a lot of really useful information coming from her all the time.” The OwnaHealth app tracks weight, blood pressure, blood sugar, ketones, meals, mood, and cravings. Patients wear continuous glucose monitors and enter other information manually. Ketone bodies are used to measure dietary adherence and are obtained through finger pricks and test strips provided by OwnaHealth. Dr. Glandt gives patients her own food plan, along with free visual guides to low-carbohydrate foods by dietdoctor.com. 

Dr. Glandt also sends her patients for regular blood work. She says she does not frequently see a rise in LDL cholesterol, which can sometimes occur on a low-carbohydrate diet. This effect is most common among people who are lean and fit. She says she doesn’t discontinue statins unless cholesterol levels improve significantly.

Samuel Gonzalez, age 56, weighed 275 pounds when he walked into Dr. Glandt’s office this past November. His A1c was 9.2%, but none of his previous doctors had diagnosed him with diabetes. “I was like a walking bag of sugar!” he joked. 

A low-carbohydrate diet seemed absurd to a Puerto Rican like himself: “Having coffee without sugar? That’s like sacrilegious in my culture!” exclaimed Mr. Gonzalez. Still, he managed, with SNAP, to cook eggs and bacon for breakfast and some kind of protein for dinner. He keeps lunch light, “like tuna fish,” and finds checking in with the OwnaHealth app to be very helpful. “Every day, I’m on it,” he said. In the past 7 months, he’s lost 50 pounds, normalized his cholesterol and blood pressure levels, and lowered his A1c to 5.5%.

Mr. Gonzalez gets disability payments due to a back injury, and Ms. Efem receives government payments because her husband died serving in the military. Ms. Efem says her new diet challenges her budget, but Mr. Gonzalez says he manages easily.

Mélissa Cruz, a 28-year-old studying to be a nail technician while also doing back office work at a physical therapy practice, says she’s stretched thin. “I end up sad because I can’t put energy into looking up recipes and cooking for me and my boyfriend,” she told me. She’ll often cook rice and plantains for him and meat for herself, but “it’s frustrating when I’m low on funds and can’t figure out what to eat.” 

Low-carbohydrate diets have a reputation for being expensive because people often start eating pricier foods, like meat and cheese, to replace cheaper starchy foods such as pasta and rice. Eggs and ground beef are less expensive low-carb meal options, and meat, unlike fruits and vegetables, is easy to freeze and doesn’t spoil quickly. These advantages can add up.

A 2019 cost analysis published in Nutrition & Dietetics compared a low-carbohydrate dietary pattern with the New Zealand government’s recommended guidelines (which are almost identical to those in the United States) and found that it cost only an extra $1.27 in US dollars per person per day. One explanation is that protein and fat are more satiating than carbohydrates, so people who mostly consume these macronutrients often cut back on snacks like packaged chips, crackers, and even fruits. Also, those on a ketogenic diet usually cut down on medications, so the additional $1.27 daily is likely offset by reduced spending at the pharmacy.

It’s not just Bronx residents with low socioeconomic status (SES) who adapt well to low-carbohydrate diets. Among Alabama state employees with diabetes enrolled in a low-carbohydrate dietary program provided by a company called Virta, the low SES population had the best outcomes. Virta also published survey data in 2023 showing that participants in a program with the Veteran’s Administration did not find additional costs to be an obstacle to dietary adherence. In fact, some participants saw cost reductions due to decreased spending on processed snacks and fast foods.

Ms. Cruz told me she struggles financially, yet she’s still lost nearly 30 pounds in 5 months, and her A1c went from 7.1% down to 5.9%, putting her diabetes into remission. Equally motivating for her are the improvements she’s seen in other hormonal issues. Since childhood, she’s had acanthosis, a condition that causes the skin to darken in velvety patches, and more recently, she developed severe hirsutism to the point of growing sideburns. “I had tried going vegan and fasting, but these just weren’t sustainable for me, and I was so overwhelmed with counting calories all the time.” Now, on a low-carbohydrate diet, which doesn’t require calorie counting, she’s finally seeing both these conditions improve significantly.

When I last checked in with Ms. Cruz, she said she had “kind of ghosted” Dr. Glandt due to her work and school constraints, but she hadn’t abandoned the diet. She appreciated, too, that Dr. Glandt had not given up on her and kept calling and messaging. “She’s not at all like a typical doctor who would just tell me to lose weight and shake their head at me,” Ms. Cruz said. 

Because Dr. Glandt’s approach is time-intensive and high-touch, it might seem impractical to scale up, but Dr. Glandt’s app uses artificial intelligence to help with communications thus allowing her, with help from part-time health coaches, to care for patients. 

This early success in one of the United States’ poorest and sickest neighborhoods should give us hope that type 2 diabetes need not to be a progressive irreversible disease, even among the disadvantaged. 

OwnaHealth’s track record, along with that of Virta and other similar low-carbohydrate medical practices also give hope to the food-is-medicine idea. Diabetes can go into remission, and people can be healed, provided that health practitioners prescribe the right foods. And in truth, it’s not a diet. It’s a way of eating that must be maintained. The sustainability of low-carbohydrate diets has been a point of contention, but the Virta trial, with 38% of patients sustaining remission at 2 years, showed that it’s possible. (OwnaHealth, for its part, offers long-term maintenance plans to help patients stay very low-carb permanently.) 

Given the tremendous costs and health burden of diabetes, this approach should no doubt be the first line of treatment for doctors and the ADA. The past two decades of clinical trial research have demonstrated that remission of type 2 diabetes is possible through diet alone. It turns out that for metabolic diseases, only certain foods are truly medicine. 
 

Tools and Tips for Clinicians: 

• Free two-page keto starter’s guide by OwnaHealth; Dr. Glandt uses this guide with her patients.
• Illustrated low-carb guides by dietdoctor.com
• Free low-carbohydrate starter guide by the Michigan Collaborative for Type 2 Diabetes
• Low-Carb for Any Budget, a free digital booklet by Mark Cucuzzella, MD, and Kristie Sullivan, PhD
• Recipe and meal ideas from Ruled.me, Keto-Mojo.com, and 

Dr. Teicholz is the founder of Nutrition Coalition, an independent nonprofit dedicated to ensuring that US dietary guidelines align with current science. She disclosed receiving book royalties from The Big Fat Surprise, and received honorarium not exceeding $2000 for speeches from various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Long-term gender-affirming hormone treatment with testosterone increases the risk for metabolic syndromes in transmasculine individuals, whereas transfeminine individuals receiving estradiol have a lower risk.

METHODOLOGY:

• Many transgender individuals receive exogenous sex hormone therapy to reduce gender dysphoria and improve quality of life. These treatments, however, may influence the development of metabolic syndrome.
• This retrospective, longitudinal cohort study investigated the association between gender-affirming hormone treatment and metabolic syndrome scores in transfeminine and transmasculine individuals compared with cisgender men and women not receiving the treatment.
• Overall, 645 transgender participants (mean age at index date, 41.3 years; 494 transfeminine and 151 transmasculine) were matched with 645 cisgender participants (280 women and 365 men) from the Veterans Health Administration.
• Metabolic syndrome scores were calculated based on blood pressure; body mass index (BMI); and levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and blood glucose.
• Changes in metabolic syndrome scores before and after hormonal transition were compared among transgender and cisgender individuals for the corresponding dates.

TAKEAWAY:

• After hormonal transition, all measured metabolic syndrome components significantly worsened in the transmasculine group (P < .05 for all).
• In contrast, the systolic blood pressure and triglyceride levels decreased, HDL cholesterol levels increased, and BMI showed no significant change in the transfeminine group after hormonal transition.
• The increase in metabolic syndrome scores after vs before the date of hormonal transition was the highest for transmasculine individuals (298.0%; P < .001), followed by cisgender women (108.3%; P < .001), cisgender men (49.3%; P = .02), and transfeminine individuals (3.0%; P = .77).

IN PRACTICE:

“This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease,” the authors wrote.

SOURCE:

Leila Hashemi, MD, MS, of the Department of General Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

Causal inferences could not be drawn because of the study’s observational nature. The transmasculine and cisgender female groups were limited in size, and military veterans have special circumstances not representative of the general population. Minority stress among the transgender veterans was also not considered, which may have affected the health and well-being outcomes.

DISCLOSURES:

This study was supported by the National Institutes of Health and Office of Research on Women’s Health grants. One author received grants from the National Institutes of Health.

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

TOPLINE:

Long-term gender-affirming hormone treatment with testosterone increases the risk for metabolic syndromes in transmasculine individuals, whereas transfeminine individuals receiving estradiol have a lower risk.

METHODOLOGY:

• Many transgender individuals receive exogenous sex hormone therapy to reduce gender dysphoria and improve quality of life. These treatments, however, may influence the development of metabolic syndrome.
• This retrospective, longitudinal cohort study investigated the association between gender-affirming hormone treatment and metabolic syndrome scores in transfeminine and transmasculine individuals compared with cisgender men and women not receiving the treatment.
• Overall, 645 transgender participants (mean age at index date, 41.3 years; 494 transfeminine and 151 transmasculine) were matched with 645 cisgender participants (280 women and 365 men) from the Veterans Health Administration.
• Metabolic syndrome scores were calculated based on blood pressure; body mass index (BMI); and levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and blood glucose.
• Changes in metabolic syndrome scores before and after hormonal transition were compared among transgender and cisgender individuals for the corresponding dates.

TAKEAWAY:

• After hormonal transition, all measured metabolic syndrome components significantly worsened in the transmasculine group (P < .05 for all).
• In contrast, the systolic blood pressure and triglyceride levels decreased, HDL cholesterol levels increased, and BMI showed no significant change in the transfeminine group after hormonal transition.
• The increase in metabolic syndrome scores after vs before the date of hormonal transition was the highest for transmasculine individuals (298.0%; P < .001), followed by cisgender women (108.3%; P < .001), cisgender men (49.3%; P = .02), and transfeminine individuals (3.0%; P = .77).

IN PRACTICE:

“This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease,” the authors wrote.

SOURCE:

Leila Hashemi, MD, MS, of the Department of General Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

Causal inferences could not be drawn because of the study’s observational nature. The transmasculine and cisgender female groups were limited in size, and military veterans have special circumstances not representative of the general population. Minority stress among the transgender veterans was also not considered, which may have affected the health and well-being outcomes.

DISCLOSURES:

This study was supported by the National Institutes of Health and Office of Research on Women’s Health grants. One author received grants from the National Institutes of Health.

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

TOPLINE:

Long-term gender-affirming hormone treatment with testosterone increases the risk for metabolic syndromes in transmasculine individuals, whereas transfeminine individuals receiving estradiol have a lower risk.

METHODOLOGY:

• Many transgender individuals receive exogenous sex hormone therapy to reduce gender dysphoria and improve quality of life. These treatments, however, may influence the development of metabolic syndrome.
• This retrospective, longitudinal cohort study investigated the association between gender-affirming hormone treatment and metabolic syndrome scores in transfeminine and transmasculine individuals compared with cisgender men and women not receiving the treatment.
• Overall, 645 transgender participants (mean age at index date, 41.3 years; 494 transfeminine and 151 transmasculine) were matched with 645 cisgender participants (280 women and 365 men) from the Veterans Health Administration.
• Metabolic syndrome scores were calculated based on blood pressure; body mass index (BMI); and levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and blood glucose.
• Changes in metabolic syndrome scores before and after hormonal transition were compared among transgender and cisgender individuals for the corresponding dates.

TAKEAWAY:

• After hormonal transition, all measured metabolic syndrome components significantly worsened in the transmasculine group (P < .05 for all).
• In contrast, the systolic blood pressure and triglyceride levels decreased, HDL cholesterol levels increased, and BMI showed no significant change in the transfeminine group after hormonal transition.
• The increase in metabolic syndrome scores after vs before the date of hormonal transition was the highest for transmasculine individuals (298.0%; P < .001), followed by cisgender women (108.3%; P < .001), cisgender men (49.3%; P = .02), and transfeminine individuals (3.0%; P = .77).

IN PRACTICE:

“This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease,” the authors wrote.

SOURCE:

Leila Hashemi, MD, MS, of the Department of General Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, led this study, which was published online in JAMA Network Open.

LIMITATIONS:

Causal inferences could not be drawn because of the study’s observational nature. The transmasculine and cisgender female groups were limited in size, and military veterans have special circumstances not representative of the general population. Minority stress among the transgender veterans was also not considered, which may have affected the health and well-being outcomes.

DISCLOSURES:

This study was supported by the National Institutes of Health and Office of Research on Women’s Health grants. One author received grants from the National Institutes of Health.

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

This transcript has been edited for clarity. 
 

I’m going to tell you the story of two patients with diabetes who had false-positive alcohol tests. 

The first patient is a patient of mine with type 1 diabetes. He was in a car accident. He hit the car in front of him that hit the car in front of them. Because the cars were quite damaged, the police were summoned. 

At the scene, he had a breathalyzer test. He flunked the breathalyzer test, and he was charged with a DUI. The woman in the middle car got out of her car and said her neck hurt. This then rose this to the level of a DUI with injury to one of the other people, and my patient was charged with a felony. He was taken to jail. 

He told them at the scene and at the jail that he had type 1 diabetes. The reason this is so important is because type 1 diabetes can cause a false-positive breathalyzer test. In particular, this patient of mine had not been eating all day long. He’d been getting his basal insulin through the pump, but he had not given any bolus doses of insulin. He was actually quite ketotic.

When he was put in jail, they took away his cell phone so he could no longer see his glucose levels, and they took away the controller for his Omnipod system. He basically had no way to give bolus doses of insulin. Fortunately, the Omnipod system lasted for a day and a half just by giving him basal. The jail physicians did not give him insulin until he’d been in jail for 3 days. 

This is someone with type 1 diabetes, and their protocol for insulin has something to do with high glucose levels and giving something like a sliding scale of insulin. They were not really prepared for managing somebody with type 1 diabetes who was on an automated insulin delivery system. 

I, along with my patient’s parents, worked very hard to get the jail doctors to finally give him Lantus. Inherent in all of this, it made me aware of a number of different issues. The first is that breathalyzer tests can be falsely positive in people with type 1 diabetes if they are ketotic; therefore, people with type 1 diabetes should ask for a blood test to test their alcohol levels if they think it could be a false positive. 

Second, we need to actually figure out a way to help people with type 1 diabetes who happen to be in jail or in prison because if they don’t have access to a smartphone, they’re not going to be able to run their devices. We need to make sure that devices have receivers that can be used, particularly continuous glucose monitors (CGMs), because CGM is the standard of care for patients and should be so for people who are incarcerated. 

The second case is much shorter and isn’t mine, but it was a letter in The New England Journal of Medicine about a man who was on probation, who was having urine tests to show that he had not been consuming alcohol. He was started on empagliflozin, which, interestingly, made his urine test become falsely positive. 

Why? Well, it’s thought it’s because it caused fermentation of the sugar with the bacteria that was in his urine because the people who were processing the sample hadn’t done it correctly, and they kept it out at room temperature for a prolonged period of time before testing it. The urine samples should be kept refrigerated to prevent this from happening. 

These are two people who had false-positive tests because they had diabetes. I think it’s important that we realize that this can happen, and we need to help our patients deal with these situations.

Dr. Peters is professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles. She reported conflicts of interest with Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, Zafgen, Dexcom, MannKind, and AstraZeneca.

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

This transcript has been edited for clarity. 
 

I’m going to tell you the story of two patients with diabetes who had false-positive alcohol tests. 

The first patient is a patient of mine with type 1 diabetes. He was in a car accident. He hit the car in front of him that hit the car in front of them. Because the cars were quite damaged, the police were summoned. 

At the scene, he had a breathalyzer test. He flunked the breathalyzer test, and he was charged with a DUI. The woman in the middle car got out of her car and said her neck hurt. This then rose this to the level of a DUI with injury to one of the other people, and my patient was charged with a felony. He was taken to jail. 

He told them at the scene and at the jail that he had type 1 diabetes. The reason this is so important is because type 1 diabetes can cause a false-positive breathalyzer test. In particular, this patient of mine had not been eating all day long. He’d been getting his basal insulin through the pump, but he had not given any bolus doses of insulin. He was actually quite ketotic.

When he was put in jail, they took away his cell phone so he could no longer see his glucose levels, and they took away the controller for his Omnipod system. He basically had no way to give bolus doses of insulin. Fortunately, the Omnipod system lasted for a day and a half just by giving him basal. The jail physicians did not give him insulin until he’d been in jail for 3 days. 

This is someone with type 1 diabetes, and their protocol for insulin has something to do with high glucose levels and giving something like a sliding scale of insulin. They were not really prepared for managing somebody with type 1 diabetes who was on an automated insulin delivery system. 

I, along with my patient’s parents, worked very hard to get the jail doctors to finally give him Lantus. Inherent in all of this, it made me aware of a number of different issues. The first is that breathalyzer tests can be falsely positive in people with type 1 diabetes if they are ketotic; therefore, people with type 1 diabetes should ask for a blood test to test their alcohol levels if they think it could be a false positive. 

Second, we need to actually figure out a way to help people with type 1 diabetes who happen to be in jail or in prison because if they don’t have access to a smartphone, they’re not going to be able to run their devices. We need to make sure that devices have receivers that can be used, particularly continuous glucose monitors (CGMs), because CGM is the standard of care for patients and should be so for people who are incarcerated. 

The second case is much shorter and isn’t mine, but it was a letter in The New England Journal of Medicine about a man who was on probation, who was having urine tests to show that he had not been consuming alcohol. He was started on empagliflozin, which, interestingly, made his urine test become falsely positive. 

Why? Well, it’s thought it’s because it caused fermentation of the sugar with the bacteria that was in his urine because the people who were processing the sample hadn’t done it correctly, and they kept it out at room temperature for a prolonged period of time before testing it. The urine samples should be kept refrigerated to prevent this from happening. 

These are two people who had false-positive tests because they had diabetes. I think it’s important that we realize that this can happen, and we need to help our patients deal with these situations.

Dr. Peters is professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles. She reported conflicts of interest with Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, Zafgen, Dexcom, MannKind, and AstraZeneca.

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

This transcript has been edited for clarity. 
 

I’m going to tell you the story of two patients with diabetes who had false-positive alcohol tests. 

The first patient is a patient of mine with type 1 diabetes. He was in a car accident. He hit the car in front of him that hit the car in front of them. Because the cars were quite damaged, the police were summoned. 

At the scene, he had a breathalyzer test. He flunked the breathalyzer test, and he was charged with a DUI. The woman in the middle car got out of her car and said her neck hurt. This then rose this to the level of a DUI with injury to one of the other people, and my patient was charged with a felony. He was taken to jail. 

He told them at the scene and at the jail that he had type 1 diabetes. The reason this is so important is because type 1 diabetes can cause a false-positive breathalyzer test. In particular, this patient of mine had not been eating all day long. He’d been getting his basal insulin through the pump, but he had not given any bolus doses of insulin. He was actually quite ketotic.

When he was put in jail, they took away his cell phone so he could no longer see his glucose levels, and they took away the controller for his Omnipod system. He basically had no way to give bolus doses of insulin. Fortunately, the Omnipod system lasted for a day and a half just by giving him basal. The jail physicians did not give him insulin until he’d been in jail for 3 days. 

This is someone with type 1 diabetes, and their protocol for insulin has something to do with high glucose levels and giving something like a sliding scale of insulin. They were not really prepared for managing somebody with type 1 diabetes who was on an automated insulin delivery system. 

I, along with my patient’s parents, worked very hard to get the jail doctors to finally give him Lantus. Inherent in all of this, it made me aware of a number of different issues. The first is that breathalyzer tests can be falsely positive in people with type 1 diabetes if they are ketotic; therefore, people with type 1 diabetes should ask for a blood test to test their alcohol levels if they think it could be a false positive. 

Second, we need to actually figure out a way to help people with type 1 diabetes who happen to be in jail or in prison because if they don’t have access to a smartphone, they’re not going to be able to run their devices. We need to make sure that devices have receivers that can be used, particularly continuous glucose monitors (CGMs), because CGM is the standard of care for patients and should be so for people who are incarcerated. 

The second case is much shorter and isn’t mine, but it was a letter in The New England Journal of Medicine about a man who was on probation, who was having urine tests to show that he had not been consuming alcohol. He was started on empagliflozin, which, interestingly, made his urine test become falsely positive. 

Why? Well, it’s thought it’s because it caused fermentation of the sugar with the bacteria that was in his urine because the people who were processing the sample hadn’t done it correctly, and they kept it out at room temperature for a prolonged period of time before testing it. The urine samples should be kept refrigerated to prevent this from happening. 

These are two people who had false-positive tests because they had diabetes. I think it’s important that we realize that this can happen, and we need to help our patients deal with these situations.

Dr. Peters is professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles. She reported conflicts of interest with Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, Zafgen, Dexcom, MannKind, and AstraZeneca.

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