Diabetes

More than 10 years after the withdrawal of the weight-loss drug Mediator (benfluorex) from the market in France, the Paris Court issued its judgment on March 29, 2021, against Servier Laboratories and the French National Agency for the Safety of Medicines and Health Products (ANSM).

Servier Laboratories was convicted of “aggravated deception” and fined 2.7 million euros (approximately $3.2 million) but were found not guilty of fraud. ANSM will also have to pay a fine.

Mediator was brought to the market in 1976 for the treatment of hyperlipidemia and for overweight patients with type 2 diabetes but was used off label as an appetite suppressant. It was taken by 5 million people and was only removed from the market in France in 2009 because of its toxic effects.

Mediator was taken off the market in Spain 6 years earlier, and in Switzerland 12 years earlier, and more than 30 years before in Belgium. It was never marketed in the United States.

The number of deaths because of heart valve damage related to the drug in France has been estimated at 220-300 in the short term (2.5 years) and 1,300-1,800 in the long term. In addition, the drug has been responsible for 3,100-4,200 hospital admissions for valvular insufficiency and pulmonary arterial hypertension.

“Despite knowing the risks for very many years ... [Servier Laboratories] never took the necessary measures and thus deceived” consumers of Mediator, declared the president of the criminal court, Sylvie Daunois.

Servier has “weakened confidence in the health system,” she added.

“I am very happy that ‘aggravated deception,’ the heart of the case, has been recognized and condemned,” Irène Frachon, MD, a pulmonologist at Brest (France) University Hospital and whistleblower on the Mediator scandal, said in an interview.

However, Dr. Frachon continued: “The major problem, putting a toxic agent on the market for years, is a given. But the weakness of the sentences gives a mixed message.

“The judgment is too cautious in its punishments,” she added, pointing out that, “in the case of contaminated blood, there were prison sentences.”
 

Servier deceived doctors and patients

The French trial in September 2019 was extraordinary, with about 100 witnesses, nearly 400 lawyers, and 5,000 victims.

On June 23, 2020, the prosecutor, Aude Le Guilcher, requested at the end of her indictment that the six companies of the Servier group be fined, notably for “deception, homicide, involuntary injuries, and fraud,” to the tune of 20.3 million euros (approximately $23.8 million).

Against the former No. 2 of Servier, Jean-Philippe Seta, Ms. Le Guilcher requested 5 years in prison, with 2 years suspended, and a 200,000 euro (approximately $235,000) fine.

The same sum was requested against ANSM for homicide and unintentional injuries.

In the end, Mr. Seta, the former right hand of Jacques Servier, who died in 2004, was sentenced to 4 years in prison, suspended. For their part, ANSM was fined 303,000 euros(approximately $350,000).

It is now clearly established that Servier Laboratories knowingly concealed the similarity of Mediator to the fenfluramine family of compounds, which was banned in 1990 because of adverse effects.

The group also deceived doctors who prescribed the drug and patients who took it by hiding its toxicity.
 

Mediator should never have been authorized for use

In terms of the fraud charges, the prosecutor estimated that the losses incurred by the primary health insurance industry were in the region of several hundred million euros.

She argued that Mediator should never have been reimbursed, as “it should never have benefited from market authorization, which it received solely due to the fraudulent actions of the company.”

But because of the statute of limitations, this argument was not heard, explained Dr. Frachon, “and the same is true of conflicts of interest, where limitations led to them being discharged.

“We understand the legal difficulties, but it’s a shame in terms of the signal sent.”

“I hope the medical world will learn the lesson and not continue with ‘business as usual’ with people who are delinquents. I think it will be essential to restore public confidence,” concluded Dr. Frachon.

No conflicts of interest or funding were declared.

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

More than 10 years after the withdrawal of the weight-loss drug Mediator (benfluorex) from the market in France, the Paris Court issued its judgment on March 29, 2021, against Servier Laboratories and the French National Agency for the Safety of Medicines and Health Products (ANSM).

Servier Laboratories was convicted of “aggravated deception” and fined 2.7 million euros (approximately $3.2 million) but were found not guilty of fraud. ANSM will also have to pay a fine.

Mediator was brought to the market in 1976 for the treatment of hyperlipidemia and for overweight patients with type 2 diabetes but was used off label as an appetite suppressant. It was taken by 5 million people and was only removed from the market in France in 2009 because of its toxic effects.

Mediator was taken off the market in Spain 6 years earlier, and in Switzerland 12 years earlier, and more than 30 years before in Belgium. It was never marketed in the United States.

The number of deaths because of heart valve damage related to the drug in France has been estimated at 220-300 in the short term (2.5 years) and 1,300-1,800 in the long term. In addition, the drug has been responsible for 3,100-4,200 hospital admissions for valvular insufficiency and pulmonary arterial hypertension.

“Despite knowing the risks for very many years ... [Servier Laboratories] never took the necessary measures and thus deceived” consumers of Mediator, declared the president of the criminal court, Sylvie Daunois.

Servier has “weakened confidence in the health system,” she added.

“I am very happy that ‘aggravated deception,’ the heart of the case, has been recognized and condemned,” Irène Frachon, MD, a pulmonologist at Brest (France) University Hospital and whistleblower on the Mediator scandal, said in an interview.

However, Dr. Frachon continued: “The major problem, putting a toxic agent on the market for years, is a given. But the weakness of the sentences gives a mixed message.

“The judgment is too cautious in its punishments,” she added, pointing out that, “in the case of contaminated blood, there were prison sentences.”
 

Servier deceived doctors and patients

The French trial in September 2019 was extraordinary, with about 100 witnesses, nearly 400 lawyers, and 5,000 victims.

On June 23, 2020, the prosecutor, Aude Le Guilcher, requested at the end of her indictment that the six companies of the Servier group be fined, notably for “deception, homicide, involuntary injuries, and fraud,” to the tune of 20.3 million euros (approximately $23.8 million).

Against the former No. 2 of Servier, Jean-Philippe Seta, Ms. Le Guilcher requested 5 years in prison, with 2 years suspended, and a 200,000 euro (approximately $235,000) fine.

The same sum was requested against ANSM for homicide and unintentional injuries.

In the end, Mr. Seta, the former right hand of Jacques Servier, who died in 2004, was sentenced to 4 years in prison, suspended. For their part, ANSM was fined 303,000 euros(approximately $350,000).

It is now clearly established that Servier Laboratories knowingly concealed the similarity of Mediator to the fenfluramine family of compounds, which was banned in 1990 because of adverse effects.

The group also deceived doctors who prescribed the drug and patients who took it by hiding its toxicity.
 

Mediator should never have been authorized for use

In terms of the fraud charges, the prosecutor estimated that the losses incurred by the primary health insurance industry were in the region of several hundred million euros.

She argued that Mediator should never have been reimbursed, as “it should never have benefited from market authorization, which it received solely due to the fraudulent actions of the company.”

But because of the statute of limitations, this argument was not heard, explained Dr. Frachon, “and the same is true of conflicts of interest, where limitations led to them being discharged.

“We understand the legal difficulties, but it’s a shame in terms of the signal sent.”

“I hope the medical world will learn the lesson and not continue with ‘business as usual’ with people who are delinquents. I think it will be essential to restore public confidence,” concluded Dr. Frachon.

No conflicts of interest or funding were declared.

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

More than 10 years after the withdrawal of the weight-loss drug Mediator (benfluorex) from the market in France, the Paris Court issued its judgment on March 29, 2021, against Servier Laboratories and the French National Agency for the Safety of Medicines and Health Products (ANSM).

Servier Laboratories was convicted of “aggravated deception” and fined 2.7 million euros (approximately $3.2 million) but were found not guilty of fraud. ANSM will also have to pay a fine.

Mediator was brought to the market in 1976 for the treatment of hyperlipidemia and for overweight patients with type 2 diabetes but was used off label as an appetite suppressant. It was taken by 5 million people and was only removed from the market in France in 2009 because of its toxic effects.

Mediator was taken off the market in Spain 6 years earlier, and in Switzerland 12 years earlier, and more than 30 years before in Belgium. It was never marketed in the United States.

The number of deaths because of heart valve damage related to the drug in France has been estimated at 220-300 in the short term (2.5 years) and 1,300-1,800 in the long term. In addition, the drug has been responsible for 3,100-4,200 hospital admissions for valvular insufficiency and pulmonary arterial hypertension.

“Despite knowing the risks for very many years ... [Servier Laboratories] never took the necessary measures and thus deceived” consumers of Mediator, declared the president of the criminal court, Sylvie Daunois.

Servier has “weakened confidence in the health system,” she added.

“I am very happy that ‘aggravated deception,’ the heart of the case, has been recognized and condemned,” Irène Frachon, MD, a pulmonologist at Brest (France) University Hospital and whistleblower on the Mediator scandal, said in an interview.

However, Dr. Frachon continued: “The major problem, putting a toxic agent on the market for years, is a given. But the weakness of the sentences gives a mixed message.

“The judgment is too cautious in its punishments,” she added, pointing out that, “in the case of contaminated blood, there were prison sentences.”
 

Servier deceived doctors and patients

The French trial in September 2019 was extraordinary, with about 100 witnesses, nearly 400 lawyers, and 5,000 victims.

On June 23, 2020, the prosecutor, Aude Le Guilcher, requested at the end of her indictment that the six companies of the Servier group be fined, notably for “deception, homicide, involuntary injuries, and fraud,” to the tune of 20.3 million euros (approximately $23.8 million).

Against the former No. 2 of Servier, Jean-Philippe Seta, Ms. Le Guilcher requested 5 years in prison, with 2 years suspended, and a 200,000 euro (approximately $235,000) fine.

The same sum was requested against ANSM for homicide and unintentional injuries.

In the end, Mr. Seta, the former right hand of Jacques Servier, who died in 2004, was sentenced to 4 years in prison, suspended. For their part, ANSM was fined 303,000 euros(approximately $350,000).

It is now clearly established that Servier Laboratories knowingly concealed the similarity of Mediator to the fenfluramine family of compounds, which was banned in 1990 because of adverse effects.

The group also deceived doctors who prescribed the drug and patients who took it by hiding its toxicity.
 

Mediator should never have been authorized for use

In terms of the fraud charges, the prosecutor estimated that the losses incurred by the primary health insurance industry were in the region of several hundred million euros.

She argued that Mediator should never have been reimbursed, as “it should never have benefited from market authorization, which it received solely due to the fraudulent actions of the company.”

But because of the statute of limitations, this argument was not heard, explained Dr. Frachon, “and the same is true of conflicts of interest, where limitations led to them being discharged.

“We understand the legal difficulties, but it’s a shame in terms of the signal sent.”

“I hope the medical world will learn the lesson and not continue with ‘business as usual’ with people who are delinquents. I think it will be essential to restore public confidence,” concluded Dr. Frachon.

No conflicts of interest or funding were declared.

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

An updated worldwide estimate of complementary and alternative medicine (CAM) use among individuals with diabetes found widespread use, though it varied greatly by region and is sometimes hard to define.

The report is the first literature review of the subject since 2007. The researchers looked at CAM use by region, as well as by patient categories such as those with advanced diabetes and by length of time since diagnosis. The most commonly reported CAMs in use were herbal medicine, acupuncture, homeopathy, and spiritual healing.

Only about one-third of patients disclosed their CAM use to their physician or health care provider. “We suggest that health care professionals should carefully anticipate the likelihood of their [patients’] diabetic CAM use in order to enhance treatment optimization and promote medication adherence, as well as to provide a fully informed consultation,” said first author Abdulaziz S. Alzahrani, a PhD student at the University of Birmingham (England). The study was published March 8, 2021, in the European Journal of Clinical Pharmacology.

Patients also have a responsibility, said Gregory Rhee, PhD, assistant professor of public health sciences at the University of Connecticut, Farmington. He was the lead author of a 2018 survey of CAM use in adults aged 65 years and older with diabetes in the United States using data from the 2012 National Health Interview Survey, and found that 25% had used CAM in some form in the prior year. “They need to be more up front, more proactive talking about CAM use with their doctors, and the second part is the physician. They also should be better educated in terms of CAM use. Traditionally, the physician in Western societies have pretty much ignored CAM use. But they are getting aware of CAM use and also we know that people are coming from multiple cultural backgrounds. The physicians and other health care providers should be better informed about CAM, and they should be better educated about it to provide patients better practice,” said Dr. Rhee.

He also distinguished between approaches like yoga or Tai Chi, which are physically oriented and not particularly controversial, and herbal medicines or dietary supplements. “Those can be controversial because we do not have strong scientific evidence to support those modalities for effectiveness on diabetes management,” Dr. Rhee added.

Mr. Alzahrani and colleagues conducted a meta-analysis of 38 studies, which included data from 25 countries. The included studies varied in their approach. For example, 16 studies focused exclusively on herbal and nutritional supplements. The most commonly mentioned CAMs were acupuncture and mind-body therapies (each named in six studies), religious and spiritual healing (five studies), and homeopathy (four studies). Among 31 studies focusing on herbal and nutritional supplements, the most common herbs mentioned were cinnamon and fenugreek (mentioned in 18 studies), garlic (17 studies), aloe vera (14 studies), and black seed (12 studies).

Prevalence of CAM use varied widely, ranging from 17% in Jordan to 89% in India and in a separate study in Jordan. The pooled prevalence of CAM use was 51% (95% confidence interval, 43%-59%). Subgroup analyses found the highest rate of CAM use in Europe (76%) and Africa (55%), and the lowest in North America (45%).

When the researchers examined patient characteristics, they found no significant relationship between CAM use and established ethnicity groups, or between type 1 and type 2 diabetes. The prevalence ratio was lower among men (PR, 0.86; 95% CI, 0.81-0.91). PRs for CAM use were lower among those with diabetic complications (PR, 0.81; 95% CI, 0.66-0.99). Individuals with diabetes of at least 5 years’ duration were more likely to use CAM than those with shorter duration of illness (PR, 1.71; 95% CI, 1.04-1.32).

Most (78%) CAM users employed it as an addition to their treatment regimen (95% CI, 56-94%), while 21% used it as an alternative to prescribed medicine (95% CI, 12-31%). More than two-thirds (67%) of individuals did not disclose CAM use to health care professionals (95% CI, 58-76%).

Although CAM use can be a source of friction between patients and physicians, Dr. Rhee also sees it as an opportunity. Patients from diverse backgrounds may be using CAM, often as a result of different cultural backgrounds. He cited the belief in some Asian countries that the balance of Yin and Yang is key to health, which many patients believe can be addressed through CAM. “If we want to promote cultural diversity, if we really care about patient diversity, I think CAM is one of the potential sources where the doctors should know [more about] the issue,” said Dr. Rhee.

The study was funded by the University of Birmingham. Dr. Rhee and Mr. Alzahrani have no relevant financial disclosures.

An updated worldwide estimate of complementary and alternative medicine (CAM) use among individuals with diabetes found widespread use, though it varied greatly by region and is sometimes hard to define.

The report is the first literature review of the subject since 2007. The researchers looked at CAM use by region, as well as by patient categories such as those with advanced diabetes and by length of time since diagnosis. The most commonly reported CAMs in use were herbal medicine, acupuncture, homeopathy, and spiritual healing.

Only about one-third of patients disclosed their CAM use to their physician or health care provider. “We suggest that health care professionals should carefully anticipate the likelihood of their [patients’] diabetic CAM use in order to enhance treatment optimization and promote medication adherence, as well as to provide a fully informed consultation,” said first author Abdulaziz S. Alzahrani, a PhD student at the University of Birmingham (England). The study was published March 8, 2021, in the European Journal of Clinical Pharmacology.

Patients also have a responsibility, said Gregory Rhee, PhD, assistant professor of public health sciences at the University of Connecticut, Farmington. He was the lead author of a 2018 survey of CAM use in adults aged 65 years and older with diabetes in the United States using data from the 2012 National Health Interview Survey, and found that 25% had used CAM in some form in the prior year. “They need to be more up front, more proactive talking about CAM use with their doctors, and the second part is the physician. They also should be better educated in terms of CAM use. Traditionally, the physician in Western societies have pretty much ignored CAM use. But they are getting aware of CAM use and also we know that people are coming from multiple cultural backgrounds. The physicians and other health care providers should be better informed about CAM, and they should be better educated about it to provide patients better practice,” said Dr. Rhee.

He also distinguished between approaches like yoga or Tai Chi, which are physically oriented and not particularly controversial, and herbal medicines or dietary supplements. “Those can be controversial because we do not have strong scientific evidence to support those modalities for effectiveness on diabetes management,” Dr. Rhee added.

Mr. Alzahrani and colleagues conducted a meta-analysis of 38 studies, which included data from 25 countries. The included studies varied in their approach. For example, 16 studies focused exclusively on herbal and nutritional supplements. The most commonly mentioned CAMs were acupuncture and mind-body therapies (each named in six studies), religious and spiritual healing (five studies), and homeopathy (four studies). Among 31 studies focusing on herbal and nutritional supplements, the most common herbs mentioned were cinnamon and fenugreek (mentioned in 18 studies), garlic (17 studies), aloe vera (14 studies), and black seed (12 studies).

Prevalence of CAM use varied widely, ranging from 17% in Jordan to 89% in India and in a separate study in Jordan. The pooled prevalence of CAM use was 51% (95% confidence interval, 43%-59%). Subgroup analyses found the highest rate of CAM use in Europe (76%) and Africa (55%), and the lowest in North America (45%).

When the researchers examined patient characteristics, they found no significant relationship between CAM use and established ethnicity groups, or between type 1 and type 2 diabetes. The prevalence ratio was lower among men (PR, 0.86; 95% CI, 0.81-0.91). PRs for CAM use were lower among those with diabetic complications (PR, 0.81; 95% CI, 0.66-0.99). Individuals with diabetes of at least 5 years’ duration were more likely to use CAM than those with shorter duration of illness (PR, 1.71; 95% CI, 1.04-1.32).

Most (78%) CAM users employed it as an addition to their treatment regimen (95% CI, 56-94%), while 21% used it as an alternative to prescribed medicine (95% CI, 12-31%). More than two-thirds (67%) of individuals did not disclose CAM use to health care professionals (95% CI, 58-76%).

Although CAM use can be a source of friction between patients and physicians, Dr. Rhee also sees it as an opportunity. Patients from diverse backgrounds may be using CAM, often as a result of different cultural backgrounds. He cited the belief in some Asian countries that the balance of Yin and Yang is key to health, which many patients believe can be addressed through CAM. “If we want to promote cultural diversity, if we really care about patient diversity, I think CAM is one of the potential sources where the doctors should know [more about] the issue,” said Dr. Rhee.

The study was funded by the University of Birmingham. Dr. Rhee and Mr. Alzahrani have no relevant financial disclosures.

An updated worldwide estimate of complementary and alternative medicine (CAM) use among individuals with diabetes found widespread use, though it varied greatly by region and is sometimes hard to define.

The report is the first literature review of the subject since 2007. The researchers looked at CAM use by region, as well as by patient categories such as those with advanced diabetes and by length of time since diagnosis. The most commonly reported CAMs in use were herbal medicine, acupuncture, homeopathy, and spiritual healing.

Only about one-third of patients disclosed their CAM use to their physician or health care provider. “We suggest that health care professionals should carefully anticipate the likelihood of their [patients’] diabetic CAM use in order to enhance treatment optimization and promote medication adherence, as well as to provide a fully informed consultation,” said first author Abdulaziz S. Alzahrani, a PhD student at the University of Birmingham (England). The study was published March 8, 2021, in the European Journal of Clinical Pharmacology.

Patients also have a responsibility, said Gregory Rhee, PhD, assistant professor of public health sciences at the University of Connecticut, Farmington. He was the lead author of a 2018 survey of CAM use in adults aged 65 years and older with diabetes in the United States using data from the 2012 National Health Interview Survey, and found that 25% had used CAM in some form in the prior year. “They need to be more up front, more proactive talking about CAM use with their doctors, and the second part is the physician. They also should be better educated in terms of CAM use. Traditionally, the physician in Western societies have pretty much ignored CAM use. But they are getting aware of CAM use and also we know that people are coming from multiple cultural backgrounds. The physicians and other health care providers should be better informed about CAM, and they should be better educated about it to provide patients better practice,” said Dr. Rhee.

He also distinguished between approaches like yoga or Tai Chi, which are physically oriented and not particularly controversial, and herbal medicines or dietary supplements. “Those can be controversial because we do not have strong scientific evidence to support those modalities for effectiveness on diabetes management,” Dr. Rhee added.

Mr. Alzahrani and colleagues conducted a meta-analysis of 38 studies, which included data from 25 countries. The included studies varied in their approach. For example, 16 studies focused exclusively on herbal and nutritional supplements. The most commonly mentioned CAMs were acupuncture and mind-body therapies (each named in six studies), religious and spiritual healing (five studies), and homeopathy (four studies). Among 31 studies focusing on herbal and nutritional supplements, the most common herbs mentioned were cinnamon and fenugreek (mentioned in 18 studies), garlic (17 studies), aloe vera (14 studies), and black seed (12 studies).

Prevalence of CAM use varied widely, ranging from 17% in Jordan to 89% in India and in a separate study in Jordan. The pooled prevalence of CAM use was 51% (95% confidence interval, 43%-59%). Subgroup analyses found the highest rate of CAM use in Europe (76%) and Africa (55%), and the lowest in North America (45%).

When the researchers examined patient characteristics, they found no significant relationship between CAM use and established ethnicity groups, or between type 1 and type 2 diabetes. The prevalence ratio was lower among men (PR, 0.86; 95% CI, 0.81-0.91). PRs for CAM use were lower among those with diabetic complications (PR, 0.81; 95% CI, 0.66-0.99). Individuals with diabetes of at least 5 years’ duration were more likely to use CAM than those with shorter duration of illness (PR, 1.71; 95% CI, 1.04-1.32).

Most (78%) CAM users employed it as an addition to their treatment regimen (95% CI, 56-94%), while 21% used it as an alternative to prescribed medicine (95% CI, 12-31%). More than two-thirds (67%) of individuals did not disclose CAM use to health care professionals (95% CI, 58-76%).

Although CAM use can be a source of friction between patients and physicians, Dr. Rhee also sees it as an opportunity. Patients from diverse backgrounds may be using CAM, often as a result of different cultural backgrounds. He cited the belief in some Asian countries that the balance of Yin and Yang is key to health, which many patients believe can be addressed through CAM. “If we want to promote cultural diversity, if we really care about patient diversity, I think CAM is one of the potential sources where the doctors should know [more about] the issue,” said Dr. Rhee.

The study was funded by the University of Birmingham. Dr. Rhee and Mr. Alzahrani have no relevant financial disclosures.

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Weekly injections with the GLP-1 receptor agonist semaglutide helped people maintain, and even increase, their initial weight loss on the agent when they continued treatment beyond 20 weeks in results from an international, multicenter trial with 803 randomized subjects.

The study “reflects what we always see in practice, that when people lose weight their body then fights to regain it. The results underscore this” by showing what happens when people stop the drug, Domenica M. Rubino, MD, reported at the annual meeting of the Endocrine Society.

The STEP 4 study began with 902 obese or higher-risk people with an average body mass index of about 38 kg/m² who underwent a 20-week, open-label, run-in phase of weekly subcutaneous injections of semaglutide (Ozempic), during which all subjects gradually up-titrated to the study’s maintenance dosage of 2.4 mg/week and allowing investigators to weed out intolerant, noncompliant, or nonresponsive people. After this phase excluded 99 subjects from continuing, and documented that the remaining 803 patients had already lost an average of 11% of their starting weight, the core of the study kicked in by randomizing them 2:1 to either maintain their weekly semaglutide injections for another 48 weeks or change to placebo injections.

After 48 more weeks, the 535 people who continued active semaglutide treatment lost on average an additional 8% of their weight. Meanwhile, the 268 who switched to placebo gained 7% of the weight they had reached at the 20-week point, for a significant between-group weight-loss difference of about 15% for the study’s primary endpoint. Those maintained on semaglutide for the full 68 weeks had a cumulative average weight loss of about 17%, compared with when they first began treatment, Dr. Rubino said. Concurrently with her report, the results also appeared in an article published online in JAMA.

“It’s reassuring that people who remain on this treatment can sustain weight losses of 15%, and in some cases 20% or more. That’s huge,” Dr. Rubino said in an interview. . After 68 weeks, 40% of the people who maintained their semaglutide treatment had lost at least 20% of their weight, compared with when they first started treatment.

“Preventing weight regain following initial weight loss is a well-known major challenge for people who lose weight,” commented John Clark III, MD, PhD, a weight management specialist at the University of Texas Southwestern Medical Center in Dallas who was not involved with the study. The findings from STEP 4 will be “helpful to have a discussion [with weight-loss patients] about the risks and benefits of continuing to take this medication longer than just a few months and if they want to continue taking the medication after they reach their goal weight,” Dr. Clark noted in an interview. “This new information reinforces that treatment continues to be effective after the short term.”

“This is obesity 101. If a treatment is provided that targets mechanisms of obesity, and then the treatment stops, we should not be surprised that weight regain occurs,” commented Ania M. Jastreboff, MD, PhD, codirector of the Yale Center for Weight Management in New Haven, Conn. “It’s tragic to see patients who, after successful weight loss, suffer regain because the treatment by which they lost weight stopped,” she said in an interview.

The STEP 4 study ran at 73 centers in 10 countries during 2018-2020. It enrolled adults without diabetes and with a BMI of at least 30, or at least 27 if they also had at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. Participants averaged about 47 years of age, almost 80% were women, and about 84% were White, including 8% of Hispanic or Latinx ethnicity.

The adverse-event profile was consistent with findings from trials where semaglutide treated hyperglycemia in patients with type 2 diabetes (semaglutide at a maximum once-weekly dosage of 1 mg has Food and Drug Administration approval for controlling hyperglycemia in patients with type 2 diabetes), as well results from other semaglutide studies and from studies of other agents in the GLP-1 receptor agonist class.

In STEP 4 9% of patients who received semaglutide during the randomized phase and 7% of those randomized to placebo had a serious adverse reaction, and about 2% of those in both treatment arms stopped treatment because of an adverse event. The most common adverse events on semaglutide were gastrointestinal, with diarrhea in 14%, nausea in 14%, constipation in 12%, and vomiting in 10%.

These GI effects are often mitigated by slower dose escalation, eating smaller amounts of food at a time, and not eating beyond the point of feeling full, noted Dr. Jastreboff.

The STEP 4 results follow prior reports from three other large trials – STEP 1, STEP 2, and STEP 3 – that studied the weight-loss effects of weekly semaglutide treatment in adults using varying enrollment criteria and treatment designs. “We’ve seen very consistent results [across all four studies] for efficacy and safety,” said Dr. Rubino, who owns and directs the Washington Center for Weight Management & Research in Arlington, Va.

NovoNordisk, the company that markets semaglutide, submitted data from all four studies to the FDA late last year in an application for a new label for a weight loss indication at the 2.4-mg/week dosage. The company has said it expects an agency decision by June 2021.

Dr. Rubino has been an adviser and consultant to and a speaker on behalf of Novo Nordisk, and she has also been an investigator for studies sponsored by AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr. Clark had no disclosures. Dr. Jastreboff is consultant for and has received research funding from NovoNordisk, and she has also been a consultant to and/or received research from Eli Lilly and Boehringer Ingelheim.

[email protected]

Overcoming the challenges in managing type 1 diabetes can sometimes feel like an unappreciated “superpower.” That was part of the thinking behind the creation of a comic book trilogy that aims to educate people of all ages – including health care providers – about the realities of living with this condition.

The series was initially launched by a team from Portsmouth (England) Hospitals University National Health Service Trust and University Hospital Southampton NHS Foundation Trust. It is now officially backed by the NHS. The first book in the trilogy, published in 2016, visually illustrates the challenges faced by a teenage boy who had recently been diagnosed with type 1 diabetes. The second volume, released in 2018, follows a young girl who is hospitalized with diabetic ketoacidosis. The third, published in December 2020, explores the stigma associated with diabetes and delves into hypoglycemia.

Available for free online, the three comic books are meant for adults, children, health care professionals, and laypeople. This news organization spoke with series cocreator Partha Kar, MBBS, MD, national specialty adviser, Diabetes for NHS England, about the series. This interview has been edited for length and clarity.
 

How did the idea for a comic book series about type 1 diabetes come about?Dr. Kar: My Southampton colleague Mayank Patel, BM, DM, FRCP, and I were discussing ways of reaching different audiences to raise awareness about type 1 diabetes, and we had the idea of comic books. After all, comic book movies are among the biggest blockbusters if one looks at popular culture, because it’s not just kids watching them.

One of our patients made an interesting observation that really resonated. He said having type 1 diabetes was like the Marvel Comics superhero Hulk.

Several scenes in the first publication, Type 1: Origins, were based on the Hulk, a scientist who gets a radioactive dose by accident. He doesn’t like turning green when he’s angry, even though he also becomes very strong. He basically spends the rest of his life trying to find the cure for himself, but he eventually makes the best of his two worlds – Professor and Hulk – rather than constantly fighting his situation.

The story line was primarily written by a group of patients with type 1 diabetes based on their own experiences. Mayank and I were mostly just supervising and financing the project. The graphics and layout were done by Revolve Comics, a publisher specializing in health education via the comic book medium.

Our aim was to bring awareness of type 1 diabetes to people who don’t have diabetes, including teachers, family members, and friends. At the end of Origins, we provide a list of online resources for more information and for social connection.

Since it launched in October 2016, Origins has been downloaded nearly 10,000 times. Lots of local charities and schools have picked it up. Parents and kids have come to us asking for more and giving us ideas. That’s what prompted the next one.

 

The second volume, Type 1: Attack of the Ketones, is more technical and somewhat surprising in that it portrays some hospital staff members as not well-informed about type 1 diabetes. Are they part of the intended audience?

Yes, this one was directed a little bit more towards professionals, hospitals, and staff. It’s also informed by patient feedback, and dovetails with my efforts to improve hospital care for people with type 1 diabetes. But of course, patients and interested laypeople can also learn from it.

A theme in volume 2 comes from another Marvel Comics superhero, Iron Man. In the movie, when Tony Stark’s heart is severely damaged with shrapnel, he acquires an arc reactor that keeps him alive and also powers the suit that gives him superpowers. After the reactor is taken away, he devises a way to replace the missing part and reassemble the suit.

Similarly, in type 1 diabetes, the ability to produce insulin has been taken away without permission. But what is missing can thankfully be replaced, albeit imperfectly. As we illustrate, things don’t always go to plan despite best efforts to administer insulin in the right dose at the right time.

At the end of Attack of the Ketones, we provide two pages of text about recognizing and managing hyperglycemia and preventing diabetic ketoacidosis. This volume was funded by NHS England and then backed by JDRF and Diabetes UK, and many hospitals picked it up. It has had about 8,000 downloads.

 

In Volume 3, you explore stigma and the issue of language regarding type 1 diabetes. How did those topics come about?

Kar: Type 1 Mission 3: S.T.I.G.M.A. was also based on patient feedback, with input from some Indian diabetes groups I’ve worked with. Here, the protagonist is a young man with type 1 diabetes who goes on holiday to India, where diabetes stigma is widespread. The characters address language problems such as use of the word “diabetic” to label a person, and they counter misconceptions such as that diabetes is contagious. There’s an Indian comic book version of this volume out now.

The main character of this volume experiences severe hypoglycemia and is saved by a glucagon injection from a colleague, one of several presented as superheroes who help in the fight to end diabetes stigma. They are referred to as Guardians of the Glucose, a take on yet another Marvel franchise, Guardians of the Galaxy.

At the end of this volume, we provide two pages of text about recognizing, managing, and preventing hypoglycemia. Again, we hope to educate as wide an audience as possible.
 

At the end of volume 3, you also briefly mention the COVID-19 pandemic. Will there be a fourth volume dealing with that, or other topics, such as diabetes technology?

We’ve left it open. We want to see how volume 3 lands. Depending on that, we might take it forward. There are certainly plenty of topics to tackle. We’ve also discussed moving into gaming or virtual reality. Overall, we hope to educate people by engaging them in different ways.

Dr. Kar has been a consultant diabetologist/endocrinologist within the NHS since 2008. He disclosed no relevant financial relationships.

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

Overcoming the challenges in managing type 1 diabetes can sometimes feel like an unappreciated “superpower.” That was part of the thinking behind the creation of a comic book trilogy that aims to educate people of all ages – including health care providers – about the realities of living with this condition.

The series was initially launched by a team from Portsmouth (England) Hospitals University National Health Service Trust and University Hospital Southampton NHS Foundation Trust. It is now officially backed by the NHS. The first book in the trilogy, published in 2016, visually illustrates the challenges faced by a teenage boy who had recently been diagnosed with type 1 diabetes. The second volume, released in 2018, follows a young girl who is hospitalized with diabetic ketoacidosis. The third, published in December 2020, explores the stigma associated with diabetes and delves into hypoglycemia.

Available for free online, the three comic books are meant for adults, children, health care professionals, and laypeople. This news organization spoke with series cocreator Partha Kar, MBBS, MD, national specialty adviser, Diabetes for NHS England, about the series. This interview has been edited for length and clarity.
 

How did the idea for a comic book series about type 1 diabetes come about?Dr. Kar: My Southampton colleague Mayank Patel, BM, DM, FRCP, and I were discussing ways of reaching different audiences to raise awareness about type 1 diabetes, and we had the idea of comic books. After all, comic book movies are among the biggest blockbusters if one looks at popular culture, because it’s not just kids watching them.

One of our patients made an interesting observation that really resonated. He said having type 1 diabetes was like the Marvel Comics superhero Hulk.

Several scenes in the first publication, Type 1: Origins, were based on the Hulk, a scientist who gets a radioactive dose by accident. He doesn’t like turning green when he’s angry, even though he also becomes very strong. He basically spends the rest of his life trying to find the cure for himself, but he eventually makes the best of his two worlds – Professor and Hulk – rather than constantly fighting his situation.

The story line was primarily written by a group of patients with type 1 diabetes based on their own experiences. Mayank and I were mostly just supervising and financing the project. The graphics and layout were done by Revolve Comics, a publisher specializing in health education via the comic book medium.

Our aim was to bring awareness of type 1 diabetes to people who don’t have diabetes, including teachers, family members, and friends. At the end of Origins, we provide a list of online resources for more information and for social connection.

Since it launched in October 2016, Origins has been downloaded nearly 10,000 times. Lots of local charities and schools have picked it up. Parents and kids have come to us asking for more and giving us ideas. That’s what prompted the next one.

 

The second volume, Type 1: Attack of the Ketones, is more technical and somewhat surprising in that it portrays some hospital staff members as not well-informed about type 1 diabetes. Are they part of the intended audience?

Yes, this one was directed a little bit more towards professionals, hospitals, and staff. It’s also informed by patient feedback, and dovetails with my efforts to improve hospital care for people with type 1 diabetes. But of course, patients and interested laypeople can also learn from it.

A theme in volume 2 comes from another Marvel Comics superhero, Iron Man. In the movie, when Tony Stark’s heart is severely damaged with shrapnel, he acquires an arc reactor that keeps him alive and also powers the suit that gives him superpowers. After the reactor is taken away, he devises a way to replace the missing part and reassemble the suit.

Similarly, in type 1 diabetes, the ability to produce insulin has been taken away without permission. But what is missing can thankfully be replaced, albeit imperfectly. As we illustrate, things don’t always go to plan despite best efforts to administer insulin in the right dose at the right time.

At the end of Attack of the Ketones, we provide two pages of text about recognizing and managing hyperglycemia and preventing diabetic ketoacidosis. This volume was funded by NHS England and then backed by JDRF and Diabetes UK, and many hospitals picked it up. It has had about 8,000 downloads.

 

In Volume 3, you explore stigma and the issue of language regarding type 1 diabetes. How did those topics come about?

Kar: Type 1 Mission 3: S.T.I.G.M.A. was also based on patient feedback, with input from some Indian diabetes groups I’ve worked with. Here, the protagonist is a young man with type 1 diabetes who goes on holiday to India, where diabetes stigma is widespread. The characters address language problems such as use of the word “diabetic” to label a person, and they counter misconceptions such as that diabetes is contagious. There’s an Indian comic book version of this volume out now.

The main character of this volume experiences severe hypoglycemia and is saved by a glucagon injection from a colleague, one of several presented as superheroes who help in the fight to end diabetes stigma. They are referred to as Guardians of the Glucose, a take on yet another Marvel franchise, Guardians of the Galaxy.

At the end of this volume, we provide two pages of text about recognizing, managing, and preventing hypoglycemia. Again, we hope to educate as wide an audience as possible.
 

At the end of volume 3, you also briefly mention the COVID-19 pandemic. Will there be a fourth volume dealing with that, or other topics, such as diabetes technology?

We’ve left it open. We want to see how volume 3 lands. Depending on that, we might take it forward. There are certainly plenty of topics to tackle. We’ve also discussed moving into gaming or virtual reality. Overall, we hope to educate people by engaging them in different ways.

Dr. Kar has been a consultant diabetologist/endocrinologist within the NHS since 2008. He disclosed no relevant financial relationships.

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

Overcoming the challenges in managing type 1 diabetes can sometimes feel like an unappreciated “superpower.” That was part of the thinking behind the creation of a comic book trilogy that aims to educate people of all ages – including health care providers – about the realities of living with this condition.

The series was initially launched by a team from Portsmouth (England) Hospitals University National Health Service Trust and University Hospital Southampton NHS Foundation Trust. It is now officially backed by the NHS. The first book in the trilogy, published in 2016, visually illustrates the challenges faced by a teenage boy who had recently been diagnosed with type 1 diabetes. The second volume, released in 2018, follows a young girl who is hospitalized with diabetic ketoacidosis. The third, published in December 2020, explores the stigma associated with diabetes and delves into hypoglycemia.

Available for free online, the three comic books are meant for adults, children, health care professionals, and laypeople. This news organization spoke with series cocreator Partha Kar, MBBS, MD, national specialty adviser, Diabetes for NHS England, about the series. This interview has been edited for length and clarity.
 

How did the idea for a comic book series about type 1 diabetes come about?Dr. Kar: My Southampton colleague Mayank Patel, BM, DM, FRCP, and I were discussing ways of reaching different audiences to raise awareness about type 1 diabetes, and we had the idea of comic books. After all, comic book movies are among the biggest blockbusters if one looks at popular culture, because it’s not just kids watching them.

One of our patients made an interesting observation that really resonated. He said having type 1 diabetes was like the Marvel Comics superhero Hulk.

Several scenes in the first publication, Type 1: Origins, were based on the Hulk, a scientist who gets a radioactive dose by accident. He doesn’t like turning green when he’s angry, even though he also becomes very strong. He basically spends the rest of his life trying to find the cure for himself, but he eventually makes the best of his two worlds – Professor and Hulk – rather than constantly fighting his situation.

The story line was primarily written by a group of patients with type 1 diabetes based on their own experiences. Mayank and I were mostly just supervising and financing the project. The graphics and layout were done by Revolve Comics, a publisher specializing in health education via the comic book medium.

Our aim was to bring awareness of type 1 diabetes to people who don’t have diabetes, including teachers, family members, and friends. At the end of Origins, we provide a list of online resources for more information and for social connection.

Since it launched in October 2016, Origins has been downloaded nearly 10,000 times. Lots of local charities and schools have picked it up. Parents and kids have come to us asking for more and giving us ideas. That’s what prompted the next one.

 

The second volume, Type 1: Attack of the Ketones, is more technical and somewhat surprising in that it portrays some hospital staff members as not well-informed about type 1 diabetes. Are they part of the intended audience?

Yes, this one was directed a little bit more towards professionals, hospitals, and staff. It’s also informed by patient feedback, and dovetails with my efforts to improve hospital care for people with type 1 diabetes. But of course, patients and interested laypeople can also learn from it.

A theme in volume 2 comes from another Marvel Comics superhero, Iron Man. In the movie, when Tony Stark’s heart is severely damaged with shrapnel, he acquires an arc reactor that keeps him alive and also powers the suit that gives him superpowers. After the reactor is taken away, he devises a way to replace the missing part and reassemble the suit.

Similarly, in type 1 diabetes, the ability to produce insulin has been taken away without permission. But what is missing can thankfully be replaced, albeit imperfectly. As we illustrate, things don’t always go to plan despite best efforts to administer insulin in the right dose at the right time.

At the end of Attack of the Ketones, we provide two pages of text about recognizing and managing hyperglycemia and preventing diabetic ketoacidosis. This volume was funded by NHS England and then backed by JDRF and Diabetes UK, and many hospitals picked it up. It has had about 8,000 downloads.

 

In Volume 3, you explore stigma and the issue of language regarding type 1 diabetes. How did those topics come about?

Kar: Type 1 Mission 3: S.T.I.G.M.A. was also based on patient feedback, with input from some Indian diabetes groups I’ve worked with. Here, the protagonist is a young man with type 1 diabetes who goes on holiday to India, where diabetes stigma is widespread. The characters address language problems such as use of the word “diabetic” to label a person, and they counter misconceptions such as that diabetes is contagious. There’s an Indian comic book version of this volume out now.

The main character of this volume experiences severe hypoglycemia and is saved by a glucagon injection from a colleague, one of several presented as superheroes who help in the fight to end diabetes stigma. They are referred to as Guardians of the Glucose, a take on yet another Marvel franchise, Guardians of the Galaxy.

At the end of this volume, we provide two pages of text about recognizing, managing, and preventing hypoglycemia. Again, we hope to educate as wide an audience as possible.
 

At the end of volume 3, you also briefly mention the COVID-19 pandemic. Will there be a fourth volume dealing with that, or other topics, such as diabetes technology?

We’ve left it open. We want to see how volume 3 lands. Depending on that, we might take it forward. There are certainly plenty of topics to tackle. We’ve also discussed moving into gaming or virtual reality. Overall, we hope to educate people by engaging them in different ways.

Dr. Kar has been a consultant diabetologist/endocrinologist within the NHS since 2008. He disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Women with polycystic ovary syndrome (PCOS) face an almost 30% increased risk for COVID-19 compared with unaffected women, even after adjusting for cardiometabolic and other related factors, suggests an analysis of United Kingdom primary care data.

“Our research has highlighted that women with PCOS are an often overlooked and potentially high-risk population for contracting COVID-19,” said joint senior author Wiebke Arlt, MD, PhD, director of the Institute of Metabolism and Systems Research at the University of Birmingham (England), in a press release.

“Before the onset of the COVID-19 pandemic, women with PCOS consistently report fragmented care, delayed diagnosis and a perception of poor clinician understanding of their condition,” added co-author Michael W. O’Reilly, MD, PhD, University of Medicine and Health Sciences, Dublin.

“Women suffering from this condition may fear, with some degree of justification, that an enhanced risk of COVID-19 infection will further compromise timely access to health care and serve to increase the sense of disenfranchisement currently experienced by many patients,” he added.

Consequently, “these findings need to be considered when designing public health policy and advice as our understanding of COVID-19 evolves,” noted first author Anuradhaa Subramanian, PhD Student, Institute of Applied Health Research, University of Birmingham.

The research was published by the European Journal of Endocrinology on March 9.
 

Women with PCOS: A distinct subgroup?

PCOS, which is thought to affect up to 16% of women, is associated with a significantly increased risk for type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease, all which have been linked to more severe COVID-19.

The condition is more prevalent in Black and South Asian women, who also appear to have an increased risk for severe COVID-19 vs. their White counterparts.

However, women and younger people in general have a lower overall risk for severe COVID-19 and mortality compared with older people and men.

Women with PCOS may therefore “represent a distinct subgroup of women at higher than average [on the basis of their sex and age] risk of adverse COVID-19–related outcomes,” the researchers note.

To investigate further, they collated data from The Health Improvement Network primary care database, which includes information from 365 active general practices in the U.K. for the period Jan. 31, 2020, to July 22, 2020.

They identified women with PCOS or a coded diagnosis of polycystic ovaries (PCO), and then for each woman randomly selected four unaffected controls matched for age and general practice location.

They included 21,292 women with PCOS/PCO and 78,310 controls, who had a mean age at study entry of 39.3 years and 39.5 years, respectively. The mean age at diagnosis of PCOS was 27 years, and the mean duration of the condition was 12.4 years.

The crude incidence of COVID-19 was 18.1 per 1000 person-years among women with PCOS vs. 11.9 per 1000 person-years in those without.

Cox regression analysis adjusted for age indicated that women with PCOS faced a significantly increased risk for COVID-19 than those without, at a hazard ratio of 1.51 (P < .001).

Further adjustment for body mass index (BMI) and age reduced the hazard ratio to 1.36 (P = .001).

In the fully adjusted model, which also took into account impaired glucose regulation, androgen excess, anovulation, hypertension, and other PCOS-related factors, the hazard ratio remained significant, at 1.28 (P = .015).
 

For shielding, balance benefits with impact on mental health

Joint senior author Krishnarajah Nirantharakumar, MD, PhD, also of the University of Birmingham, commented that, despite the increased risks, shielding strategies for COVID-19 need to take into account the impact of PCOS on women’s mental health.

“The risk of mental health problems, including low self-esteem, anxiety, and depression, is significantly higher in women with PCOS,” he said, “and advice on strict adherence to social distancing needs to be tempered by the associated risk of exacerbating these underlying problems.”

Arlt also pointed out that the study only looked at the incidence of COVID-19 infection, rather than outcomes.

“Our study does not provide information on the risk of a severe course of the COVID-19 infection or on the risk of COVID-19–related long-term complications [in women with PCOS], and further research is required,” she concluded.

The study was funded by Health Data Research UK and supported by the Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre based at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust. The study authors have disclosed no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

Two newly published studies highlight recent success toward delaying the onset of type 1 diabetes in people at high risk and slowing progression in those with recent onset of the condition.

Both studies were initially presented in June 2020 at the annual scientific sessions of the American Diabetes Association and reported by this news organization at the time.  

As yet, neither of the two strategies – preserving insulin-producing pancreatic beta-cell function soon after diagnosis or delaying type 1 diabetes onset in those at high risk – represent a cure or certain disease prevention.

However, both can potentially lead to better long-term glycemic control with less hypoglycemia and a lower risk for diabetes-related complications.
 

Combination treatment prolongs beta-cell function in new-onset disease

The first study, entitled, “Anti–interleukin-21 antibody and liraglutide for the preservation of beta-cell function in adults with recent-onset type 1 diabetes,” was published online March 1, 2021, in The Lancet Diabetes & Endocrinology by Matthias von Herrath, MD, of Novo Nordisk, Søborg, Denmark, and colleagues.

The randomized, placebo-controlled, double-blind, phase 2 combination treatment trial involved 308 individuals aged 18-45 years who had been diagnosed with type 1 diabetes in the previous 20 weeks and still had residual beta-cell function.

Patients were randomized with 77 per group to receive monoclonal anti-IL-21 plus liraglutide, anti-IL-21 alone, liraglutide alone, or placebo. The antibody was given intravenously every 6 weeks and liraglutide or matching placebo were self-administered by daily injections.

Compared with placebo (ratio to baseline, 0.61; 39% decrease), the decrease in mixed meal tolerance test stimulated C-peptide concentration from baseline to week 54 – the primary outcome – was significantly smaller with combination treatment (0.90, 10% decrease; estimated treatment ratio, 1.48; P = .0017), but not with anti-IL-21 alone (1.23; P = .093) or liraglutide alone (1.12; P = .38).

Despite greater insulin use in the placebo group, the decrease in hemoglobin A1c (a key secondary outcome) at week 54 was greater with all active treatments (–0.50 percentage points) than with placebo (–0.10 percentage points), although the differences versus placebo were not significant.

“The combination of anti-IL-21 and liraglutide could preserve beta-cell function in recently diagnosed type 1 diabetes,” the researchers said.

“These results suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes. However, the efficacy and safety need to be further investigated in a phase 3 program,” Dr. von Herrath and colleagues concluded.
 

Teplizumab: 3-year data continue to show benefit

The other study looked at delaying the onset of type 1 diabetes. Entitled, “Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals,” the article was published online March 3, 2021, in Science Translational Medicine by Emily K. Sims, MD, of the department of pediatrics, Indiana University, Indianapolis, and colleagues.

This trial of the anti-CD3 monoclonal antibody adds an additional year of follow-up to the “game-changer” 2-year data reported in 2019.

Among the 76 individuals aged 8-49 years who were positive for two or more type 1 diabetes–related autoantibodies, 50% of those randomized to a single 14-day infusion course of teplizumab remained diabetes free at a median follow-up of 923 days, compared with only 22% of those who received placebo infusions (hazard ratio, 0.457; P = .01).

The teplizumab group had a greater average C-peptide area under the curve, compared with placebo, reflecting improved beta-cell function (1.96 vs 1.68 pmol/mL; P = .006).

C-peptide levels declined over time in the placebo group but stabilized in those receiving teplizumab (P = .0015).

“It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high-risk population for approximately 3 years versus placebo,” said Frank Martin, PhD, JDRF director of research at Provention Bio, which is developing teplizumab.

“These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care,” he concluded.

The teplizumab study was funded by TrialNet. Dr. von Herrath is an employee of Novo Nordisk, which funded the study involving its drug liraglutide. Dr. Sims reported no relevant financial relationships.

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

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In January, as Mississippi health officials planned for their incoming shipments of COVID-19 vaccine, they assessed the state’s most vulnerable: health care workers, of course, and elderly people in nursing homes. But among those who needed urgent protection from the virus ripping across the Magnolia State were 1 million Mississippians with obesity.

Obesity and weight-related illnesses have been deadly liabilities in the COVID era. A report released this month by the World Obesity Federation found that increased body weight is the second-greatest predictor of COVID-related hospitalization and death across the globe, trailing only old age as a risk factor.

As a fixture of life in the American South – home to 9 of the nation’s 12 heaviest states – obesity is playing a role not only in COVID outcomes, but in the calculus of the vaccination rollout. Mississippi was one of the first states to add a body mass index of 30 or more (a rough gauge of obesity tied to height and weight) to the list of qualifying medical conditions for a shot. About 40% of the state’s adults meet that definition, according to federal health survey data, and combined with the risk group already eligible for vaccination – residents 65 and older – that means fully half of Mississippi’s adults are entitled to vie for a restricted allotment of shots.

At least 29 states have green-lighted obesity for inclusion in the first phases of the vaccine rollout, according to KFF – a vast widening of eligibility that has the potential to overwhelm government efforts and heighten competition for scarce doses.

“We have a lifesaving intervention, and we don’t have enough of it,” said Jen Kates, PhD, director of global health and HIV policy for Kaiser Family Foundation. “Hard choices are being made about who should go first, and there is no right answer.”

The sheer prevalence of obesity in the nation – two in three Americans exceed what is considered a healthy weight – was a public health concern well before the pandemic. But COVID-19 dramatically fast-tracked the discussion from warnings about the long-term damage excess fat tissue can pose to heart, lung and metabolic functions to far more immediate threats.

In the United Kingdom, for example, overweight COVID patients were 67% more likely to require intensive care, and obese patients three times likelier, according to the World Obesity Federation report. A Centers for Disease Control and Prevention study released Monday found a similar trend among U.S. patients and noted that the risk of COVID-related hospitalization, ventilation and death increased with patients’ obesity level.

The counties that hug the southern Mississippi River are home to some of the most concentrated pockets of extreme obesity in the United States. Coronavirus infections began surging in Southern states early last summer, and hospitalizations rose in step.

Deaths in rural stretches of Arkansas, Louisiana, Mississippi, and Tennessee have been overshadowed by the sheer number of deaths in metropolitan areas like New York, Los Angeles, and Essex County, N.J. But as a share of the population, the coronavirus has been similarly unsparing in many Southern communities. In sparsely populated Claiborne County, Miss., on the floodplains of the Mississippi River, 30 residents – about 1 in 300 – had died as of early March. In East Feliciana Parish, La., north of Baton Rouge, with 106 deaths, about 1 in 180 had died by then.

“It’s just math. If the population is more obese and obesity clearly contributes to worse outcomes, then neighborhoods, cities, states and countries that are more obese will have a greater toll from COVID,” said Dr. James de Lemos, MD, a professor of internal medicine at UT Southwestern Medical Center in Dallas who led a study of hospitalized COVID patients published in the medical journal Circulation.

And, because in the U.S. obesity rates tend to be relatively high among African Americans and Latinos who are poor, with diminished access to health care, “it’s a triple whammy,” Dr. de Lemos said. “All these things intersect.”

Poverty and limited access to medical care are common features in the South, where residents like Michelle Antonyshyn, a former registered nurse and mother of seven in Salem, Ark., say they are afraid of the virus. Ms. Antonyshyn, 49, has obesity and debilitating pain in her knees and back, though she does not have high blood pressure or diabetes, two underlying conditions that federal health officials have determined are added risk factors for severe cases of COVID-19.

Still, she said, she “was very concerned just knowing that being obese puts you more at risk for bad outcomes such as being on a ventilator and death.” As a precaution, Ms. Antonyshyn said, she and her large brood locked down early and stopped attending church services in person, watching online instead.

“It’s not the same as having fellowship, but the risk for me was enough,” said Ms. Antonyshyn.

Governors throughout the South seem to recognize that weight can contribute to COVID-19 complications and have pushed for vaccine eligibility rules that prioritize obesity. But on the ground, local health officials are girding for having to tell newly eligible people who qualify as obese that there aren’t enough shots to go around.

In Port Gibson, Miss., Mheja Williams, MD, medical director of the Claiborne County Family Health Center, has been receiving barely enough doses to inoculate the health workers and oldest seniors in her county of 9,600. One week in early February, she received 100 doses.

Obesity and extreme obesity are endemic in Claiborne County, and health officials say the “normalization” of obesity means people often don’t register their weight as a risk factor, whether for COVID or other health issues. The risks are exacerbated by a general flouting of pandemic etiquette: Dr. Williams said that middle-aged and younger residents are not especially vigilant about physical distancing and that mask use is rare.

The rise of obesity in the United States is well documented over the past half-century, as the nation turned from a diet of fruits, vegetables and limited meats to one laden with ultra-processed foods and rich with salt, fat, sugar, and flavorings, along with copious amounts of meat, fast food, and soda. The U.S. has generally led the global obesity race, setting records as even toddlers and young children grew implausibly, dangerously overweight.

Well before COVID, obesity was a leading cause of preventable death in the United States. The National Institutes of Health declared it a disease in 1998, one that fosters heart disease, stroke, type 2 diabetes, and breast, colon, and other cancers.

Researchers say it is no coincidence that nations like the United States, the United Kingdom, and Italy, with relatively high obesity rates, have proved particularly vulnerable to the novel coronavirus.

They believe the virus may exploit underlying metabolic and physiological impairments that often exist in concert with obesity. Extra fat can lead to a cascade of metabolic disruptions, chronic systemic inflammation, and hormonal dysregulation that may thwart the body’s response to infection.

Other respiratory viruses, like influenza and SARS, which appeared in China in 2002, rely on cholesterol to spread enveloped RNA virus to neighboring cells, and researchers have proposed that a similar mechanism may play a role in the spread of the novel coronavirus.

There are also practical problems for coronavirus patients with obesity admitted to the hospital. They can be more difficult to intubate because of excess central weight pressing down on the diaphragm, making breathing with infected lungs even more difficult.

Physicians who specialize in treating patients with obesity say public health officials need to be more forthright and urgent in their messaging, telegraphing the risks of this COVID era.

“It should be explicit and direct,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General Hospital, Boston, and a Harvard Medical School instructor.

Dr. Stanford denounces the fat-shaming and bullying that people with obesity often experience. But telling patients – and the public – that obesity increases the risk of hospitalization and death is crucial, she said.

“I don’t think it’s stigmatizing,” she said. “If you tell them in that way, it’s not to scare you, it’s just giving information. Sometimes people are just unaware.”



KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.

“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.

The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.

Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.

“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.

The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.

They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.

“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.

“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added.  “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”

For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.

The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).

The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51). 

Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.  

For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.

Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.

On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.

In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.

Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.  

Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.  

Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.

“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.

This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.

Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.