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Baricitinib found effective for moderate to severe AD out to 52 weeks
“With long-term therapy, the baricitinib 2 mg response remains stable or slightly improved, compared with week 16 for skin inflammation, itch, sleep, and quality of life,” presenting study author Eric L. Simpson, MD, said during the Revolutionizing Atopic Dermatitis symposium.
Baricitinib is an oral selective Janus kinase 1/JAK2 inhibitor being developed for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. The drug is already approved for AD in Europe at the 2-mg and 4-mg doses. A 16-week placebo-controlled study conducted in North America known as BREEZE-AD5 found that 2 mg of baricitinib improved disease in adults with moderate to severe AD.
For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland, and colleagues integrated data from BREEZE-AD5 and BREEZE-AD6, an ongoing, open-label study of BREEZE-AD5, to evaluate the long-term efficacy and safety of baricitinib 2 mg in patients with moderate to severe AD.
At week 16, patients from BREEZE-AD5 who were on baricitinib 2 mg could either continue the trial out to week 52, or they could transition to BREEZE-AD6 if they were nonresponders. The use of low-potency corticosteroids was permitted after week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Endpoints of interest at week 52 in both trials were the proportions of patients with 75% or greater improvement from baseline in the Eczema and Severity Index (EASI75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, a Dermatology Life Quality Index (DLQI) score of 5 or less, as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores, and the mean percent change from baseline in EASI score.
Dr. Simpson presented data on 146 patients from both trials who were randomized to baricitinib 2 mg. Their mean age was 40 years, 53% were female, 58% were White, 21% were Black, 15% were Asian, and the remainder were from other backgrounds. Their mean duration of AD was 16 years and their average EASI score was 26.6. At weeks 16, 32, and 52, the proportion of patients who achieved an EASI75 response was 40%, 51%, and 49%, respectively, while the mean percent change from baseline in EASI score was –50%, –59%, and –57%.
At weeks 16, 32, and 52, the vIGA-AD responses of 0 or 1 were observed in 27%, 38%, and 31% of patients. The mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at week 16 and was maintained at weeks 32 (3.8) and 52 (4.3). The mean SCORAD sleeplessness score also improved from 6.5 at baseline to 3.9 at week 16 and remained stable through weeks 32 (3.4) and 52 (3.7).
Finally, among 129 patients who had a baseline DLQI of greater than 5, 39% had DLQI scores of 5 or lower at week 16, compared with 49% at week 32 and 45% at week 52, indicating a small or no effect of AD on quality of life.
The study was sponsored by Eli Lilly, which is developing baricitinib. Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Eli Lilly.
“With long-term therapy, the baricitinib 2 mg response remains stable or slightly improved, compared with week 16 for skin inflammation, itch, sleep, and quality of life,” presenting study author Eric L. Simpson, MD, said during the Revolutionizing Atopic Dermatitis symposium.
Baricitinib is an oral selective Janus kinase 1/JAK2 inhibitor being developed for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. The drug is already approved for AD in Europe at the 2-mg and 4-mg doses. A 16-week placebo-controlled study conducted in North America known as BREEZE-AD5 found that 2 mg of baricitinib improved disease in adults with moderate to severe AD.
For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland, and colleagues integrated data from BREEZE-AD5 and BREEZE-AD6, an ongoing, open-label study of BREEZE-AD5, to evaluate the long-term efficacy and safety of baricitinib 2 mg in patients with moderate to severe AD.
At week 16, patients from BREEZE-AD5 who were on baricitinib 2 mg could either continue the trial out to week 52, or they could transition to BREEZE-AD6 if they were nonresponders. The use of low-potency corticosteroids was permitted after week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Endpoints of interest at week 52 in both trials were the proportions of patients with 75% or greater improvement from baseline in the Eczema and Severity Index (EASI75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, a Dermatology Life Quality Index (DLQI) score of 5 or less, as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores, and the mean percent change from baseline in EASI score.
Dr. Simpson presented data on 146 patients from both trials who were randomized to baricitinib 2 mg. Their mean age was 40 years, 53% were female, 58% were White, 21% were Black, 15% were Asian, and the remainder were from other backgrounds. Their mean duration of AD was 16 years and their average EASI score was 26.6. At weeks 16, 32, and 52, the proportion of patients who achieved an EASI75 response was 40%, 51%, and 49%, respectively, while the mean percent change from baseline in EASI score was –50%, –59%, and –57%.
At weeks 16, 32, and 52, the vIGA-AD responses of 0 or 1 were observed in 27%, 38%, and 31% of patients. The mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at week 16 and was maintained at weeks 32 (3.8) and 52 (4.3). The mean SCORAD sleeplessness score also improved from 6.5 at baseline to 3.9 at week 16 and remained stable through weeks 32 (3.4) and 52 (3.7).
Finally, among 129 patients who had a baseline DLQI of greater than 5, 39% had DLQI scores of 5 or lower at week 16, compared with 49% at week 32 and 45% at week 52, indicating a small or no effect of AD on quality of life.
The study was sponsored by Eli Lilly, which is developing baricitinib. Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Eli Lilly.
“With long-term therapy, the baricitinib 2 mg response remains stable or slightly improved, compared with week 16 for skin inflammation, itch, sleep, and quality of life,” presenting study author Eric L. Simpson, MD, said during the Revolutionizing Atopic Dermatitis symposium.
Baricitinib is an oral selective Janus kinase 1/JAK2 inhibitor being developed for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. The drug is already approved for AD in Europe at the 2-mg and 4-mg doses. A 16-week placebo-controlled study conducted in North America known as BREEZE-AD5 found that 2 mg of baricitinib improved disease in adults with moderate to severe AD.
For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health and Science University, Portland, and colleagues integrated data from BREEZE-AD5 and BREEZE-AD6, an ongoing, open-label study of BREEZE-AD5, to evaluate the long-term efficacy and safety of baricitinib 2 mg in patients with moderate to severe AD.
At week 16, patients from BREEZE-AD5 who were on baricitinib 2 mg could either continue the trial out to week 52, or they could transition to BREEZE-AD6 if they were nonresponders. The use of low-potency corticosteroids was permitted after week 16 in BREEZE-AD5 and throughout BREEZE-AD6. Endpoints of interest at week 52 in both trials were the proportions of patients with 75% or greater improvement from baseline in the Eczema and Severity Index (EASI75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1, a Dermatology Life Quality Index (DLQI) score of 5 or less, as well as mean SCORing AD (SCORAD) visual analog scales of itch and sleeplessness scores, and the mean percent change from baseline in EASI score.
Dr. Simpson presented data on 146 patients from both trials who were randomized to baricitinib 2 mg. Their mean age was 40 years, 53% were female, 58% were White, 21% were Black, 15% were Asian, and the remainder were from other backgrounds. Their mean duration of AD was 16 years and their average EASI score was 26.6. At weeks 16, 32, and 52, the proportion of patients who achieved an EASI75 response was 40%, 51%, and 49%, respectively, while the mean percent change from baseline in EASI score was –50%, –59%, and –57%.
At weeks 16, 32, and 52, the vIGA-AD responses of 0 or 1 were observed in 27%, 38%, and 31% of patients. The mean SCORAD pruritus score improved from 7.7 at baseline to 4.8 at week 16 and was maintained at weeks 32 (3.8) and 52 (4.3). The mean SCORAD sleeplessness score also improved from 6.5 at baseline to 3.9 at week 16 and remained stable through weeks 32 (3.4) and 52 (3.7).
Finally, among 129 patients who had a baseline DLQI of greater than 5, 39% had DLQI scores of 5 or lower at week 16, compared with 49% at week 32 and 45% at week 52, indicating a small or no effect of AD on quality of life.
The study was sponsored by Eli Lilly, which is developing baricitinib. Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Eli Lilly.
FROM REVOLUTIONIZING AD 2021
'Full throttle': 'Diabetes Garage' workshops boost Mexican American men's self-management
Automotive-themed workshops that refer to doctor visits as “tune-ups” and nutritious food as “high-performance fuel” are showing promise as a strategy to better explain diabetes self-management to Mexican American men, an investigator has reported.
The workshops, which started out in person and transitioned online because of the COVID-19 pandemic, have improved self-care behaviors among Mexican American men with diabetes, said Jeannie Belinda Concha, PhD, MPH, of the University of Texas, El Paso.
After participating in the workshops, known as The Diabetes Garage, men more often measured food portions and counted carbohydrates, and had improved confidence in their ability to self-manage their diabetes, Dr. Concha said in a virtual presentation on the study.
Although those improvements in self-care behaviors didn’t translate into significant improvements in blood pressure or hemoglobin A1c, she said, they could be predecessors to improved physical health outcomes with longer follow-up.
”We know it takes some time to move those numbers, but they are going in the right direction,” Dr. Concha said in her presentation, which took place during the annual scientific sessions of the American Diabetes Association.
Meeting Mexican American men where they’re at
Robert Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said The Diabetes Garage is an “innovative” approach to tailoring diabetes self-care message for a specific of individuals.
“It’s such a wonderful example of something that we believe so strongly, which is that you’ve got to meet people where they’re at,” Dr. Gabbay said in an interview.
“We know that people learn in different ways, and people and with different backgrounds have different things that resonate with them,” he continued. “For better or worse, one size doesn’t fit all, and that in a sense is one of the challenges around diabetes, because we’re really trying to help everybody.”
Unmet needs for diabetes education
The prevalence of diabetes in the United States is high among Hispanics, higher among Mexican Americans, and even higher still among Mexican-American men, according to Dr. Concha.
The age-adjusted prevalence of diabetes is 16.2% among Mexican-American men, as compared with 12.8% for Mexican American women, and 8.6% for White non-Hispanic men, according to 2018 data from the Centers for Disease Control and Prevention that Dr. Concha highlighted in her presentation.
Moreover, only 25% of participants in diabetes education are men, highlighting another disparity that needs to be addressed, she said.
Infusing diabetes self-management with car culture
The Diabetes Garage leverages a positive “car culture” that is prevalent in Mexican American communities in general, and cities like El Paso in particular, Dr. Concha said.
This culture brings Mexican American people together at numerous car shows, and is viewed as a form of family identification for enthusiasts, who will illustrate their own pride by customizing their cars with cultural symbols, according to Dr. Concha.
The diabetes education intervention consists of four workshops delivered as 2-hour weekly sessions that include a diabetes educator and an automotive instructor:
In the first session, men learn about “starting and operating” their body with diabetes, and checking their “gauges” when it comes to blood pressure, cholesterol, and other measures, according to Dr. Concha.
The second session stresses the importance of physical activity (“using all your gears”) and of managing stress (“full throttle”).
The third session highlights medication as a tool (“to keep your battery charged”) and the importance of diabetes complications (“catastrophic failure”) as well as visiting the doctor (“tune ups and inspections”).
Finally, men learn about nutrition (high-performance fuel) in a workshop on eating well with diabetes. “We ask them to invite their family and friends, and they do,” said Dr. Concha.
Rubber hits the road
Since 2018, 16 workshops have been completed in El Paso, San Antonio, and Harlingen, Tex., of which 9 were in English, 5 were in Spanish, and 2 were bilingual. Due to the COVID-19 pandemic, 10 of the workshops were completed online, Dr. Concha said.
In total, 97 men engaged in the workshops, of whom 91% were Hispanic/Latino; 71% were employed, 71% were married, and 84% had health insurance. Eighty-six percent completed all four workshops, while 89% completed at least three workshops.
The number of days men measured food portions increased significantly from pre- to postworkshop assessment, from a mean of 2.1 days to 2.74 days, Dr. Concha reported. Similarly, the mean number of days counting carbohydrate portions increased significantly, from 1.92 to 2.64 days.
The proportion of men agreeing or strongly agreeing they were confident they could manage diabetes increased from 74% before the intervention to 93% afterward, according to Dr. Concha’s presentation.
By contrast, there were no statistically significant increases in physical outcomes including physical activity, weight, waist circumference, A1c, or blood pressure from before the workshop to after, though outcomes trended in an improved direction, according to Dr. Concha.
Postactivity satisfaction survey results showed that 86%of men said the automotive analogies in the program helped them understand the importance of diabetes management. “I am looking forward to better managing my human-mobile for a long, long time with a good quality of life,” one of the men wrote in survey feedback.
Dr. Concha and coauthors reported no conflicts of interest related to the study.
Automotive-themed workshops that refer to doctor visits as “tune-ups” and nutritious food as “high-performance fuel” are showing promise as a strategy to better explain diabetes self-management to Mexican American men, an investigator has reported.
The workshops, which started out in person and transitioned online because of the COVID-19 pandemic, have improved self-care behaviors among Mexican American men with diabetes, said Jeannie Belinda Concha, PhD, MPH, of the University of Texas, El Paso.
After participating in the workshops, known as The Diabetes Garage, men more often measured food portions and counted carbohydrates, and had improved confidence in their ability to self-manage their diabetes, Dr. Concha said in a virtual presentation on the study.
Although those improvements in self-care behaviors didn’t translate into significant improvements in blood pressure or hemoglobin A1c, she said, they could be predecessors to improved physical health outcomes with longer follow-up.
”We know it takes some time to move those numbers, but they are going in the right direction,” Dr. Concha said in her presentation, which took place during the annual scientific sessions of the American Diabetes Association.
Meeting Mexican American men where they’re at
Robert Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said The Diabetes Garage is an “innovative” approach to tailoring diabetes self-care message for a specific of individuals.
“It’s such a wonderful example of something that we believe so strongly, which is that you’ve got to meet people where they’re at,” Dr. Gabbay said in an interview.
“We know that people learn in different ways, and people and with different backgrounds have different things that resonate with them,” he continued. “For better or worse, one size doesn’t fit all, and that in a sense is one of the challenges around diabetes, because we’re really trying to help everybody.”
Unmet needs for diabetes education
The prevalence of diabetes in the United States is high among Hispanics, higher among Mexican Americans, and even higher still among Mexican-American men, according to Dr. Concha.
The age-adjusted prevalence of diabetes is 16.2% among Mexican-American men, as compared with 12.8% for Mexican American women, and 8.6% for White non-Hispanic men, according to 2018 data from the Centers for Disease Control and Prevention that Dr. Concha highlighted in her presentation.
Moreover, only 25% of participants in diabetes education are men, highlighting another disparity that needs to be addressed, she said.
Infusing diabetes self-management with car culture
The Diabetes Garage leverages a positive “car culture” that is prevalent in Mexican American communities in general, and cities like El Paso in particular, Dr. Concha said.
This culture brings Mexican American people together at numerous car shows, and is viewed as a form of family identification for enthusiasts, who will illustrate their own pride by customizing their cars with cultural symbols, according to Dr. Concha.
The diabetes education intervention consists of four workshops delivered as 2-hour weekly sessions that include a diabetes educator and an automotive instructor:
In the first session, men learn about “starting and operating” their body with diabetes, and checking their “gauges” when it comes to blood pressure, cholesterol, and other measures, according to Dr. Concha.
The second session stresses the importance of physical activity (“using all your gears”) and of managing stress (“full throttle”).
The third session highlights medication as a tool (“to keep your battery charged”) and the importance of diabetes complications (“catastrophic failure”) as well as visiting the doctor (“tune ups and inspections”).
Finally, men learn about nutrition (high-performance fuel) in a workshop on eating well with diabetes. “We ask them to invite their family and friends, and they do,” said Dr. Concha.
Rubber hits the road
Since 2018, 16 workshops have been completed in El Paso, San Antonio, and Harlingen, Tex., of which 9 were in English, 5 were in Spanish, and 2 were bilingual. Due to the COVID-19 pandemic, 10 of the workshops were completed online, Dr. Concha said.
In total, 97 men engaged in the workshops, of whom 91% were Hispanic/Latino; 71% were employed, 71% were married, and 84% had health insurance. Eighty-six percent completed all four workshops, while 89% completed at least three workshops.
The number of days men measured food portions increased significantly from pre- to postworkshop assessment, from a mean of 2.1 days to 2.74 days, Dr. Concha reported. Similarly, the mean number of days counting carbohydrate portions increased significantly, from 1.92 to 2.64 days.
The proportion of men agreeing or strongly agreeing they were confident they could manage diabetes increased from 74% before the intervention to 93% afterward, according to Dr. Concha’s presentation.
By contrast, there were no statistically significant increases in physical outcomes including physical activity, weight, waist circumference, A1c, or blood pressure from before the workshop to after, though outcomes trended in an improved direction, according to Dr. Concha.
Postactivity satisfaction survey results showed that 86%of men said the automotive analogies in the program helped them understand the importance of diabetes management. “I am looking forward to better managing my human-mobile for a long, long time with a good quality of life,” one of the men wrote in survey feedback.
Dr. Concha and coauthors reported no conflicts of interest related to the study.
Automotive-themed workshops that refer to doctor visits as “tune-ups” and nutritious food as “high-performance fuel” are showing promise as a strategy to better explain diabetes self-management to Mexican American men, an investigator has reported.
The workshops, which started out in person and transitioned online because of the COVID-19 pandemic, have improved self-care behaviors among Mexican American men with diabetes, said Jeannie Belinda Concha, PhD, MPH, of the University of Texas, El Paso.
After participating in the workshops, known as The Diabetes Garage, men more often measured food portions and counted carbohydrates, and had improved confidence in their ability to self-manage their diabetes, Dr. Concha said in a virtual presentation on the study.
Although those improvements in self-care behaviors didn’t translate into significant improvements in blood pressure or hemoglobin A1c, she said, they could be predecessors to improved physical health outcomes with longer follow-up.
”We know it takes some time to move those numbers, but they are going in the right direction,” Dr. Concha said in her presentation, which took place during the annual scientific sessions of the American Diabetes Association.
Meeting Mexican American men where they’re at
Robert Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said The Diabetes Garage is an “innovative” approach to tailoring diabetes self-care message for a specific of individuals.
“It’s such a wonderful example of something that we believe so strongly, which is that you’ve got to meet people where they’re at,” Dr. Gabbay said in an interview.
“We know that people learn in different ways, and people and with different backgrounds have different things that resonate with them,” he continued. “For better or worse, one size doesn’t fit all, and that in a sense is one of the challenges around diabetes, because we’re really trying to help everybody.”
Unmet needs for diabetes education
The prevalence of diabetes in the United States is high among Hispanics, higher among Mexican Americans, and even higher still among Mexican-American men, according to Dr. Concha.
The age-adjusted prevalence of diabetes is 16.2% among Mexican-American men, as compared with 12.8% for Mexican American women, and 8.6% for White non-Hispanic men, according to 2018 data from the Centers for Disease Control and Prevention that Dr. Concha highlighted in her presentation.
Moreover, only 25% of participants in diabetes education are men, highlighting another disparity that needs to be addressed, she said.
Infusing diabetes self-management with car culture
The Diabetes Garage leverages a positive “car culture” that is prevalent in Mexican American communities in general, and cities like El Paso in particular, Dr. Concha said.
This culture brings Mexican American people together at numerous car shows, and is viewed as a form of family identification for enthusiasts, who will illustrate their own pride by customizing their cars with cultural symbols, according to Dr. Concha.
The diabetes education intervention consists of four workshops delivered as 2-hour weekly sessions that include a diabetes educator and an automotive instructor:
In the first session, men learn about “starting and operating” their body with diabetes, and checking their “gauges” when it comes to blood pressure, cholesterol, and other measures, according to Dr. Concha.
The second session stresses the importance of physical activity (“using all your gears”) and of managing stress (“full throttle”).
The third session highlights medication as a tool (“to keep your battery charged”) and the importance of diabetes complications (“catastrophic failure”) as well as visiting the doctor (“tune ups and inspections”).
Finally, men learn about nutrition (high-performance fuel) in a workshop on eating well with diabetes. “We ask them to invite their family and friends, and they do,” said Dr. Concha.
Rubber hits the road
Since 2018, 16 workshops have been completed in El Paso, San Antonio, and Harlingen, Tex., of which 9 were in English, 5 were in Spanish, and 2 were bilingual. Due to the COVID-19 pandemic, 10 of the workshops were completed online, Dr. Concha said.
In total, 97 men engaged in the workshops, of whom 91% were Hispanic/Latino; 71% were employed, 71% were married, and 84% had health insurance. Eighty-six percent completed all four workshops, while 89% completed at least three workshops.
The number of days men measured food portions increased significantly from pre- to postworkshop assessment, from a mean of 2.1 days to 2.74 days, Dr. Concha reported. Similarly, the mean number of days counting carbohydrate portions increased significantly, from 1.92 to 2.64 days.
The proportion of men agreeing or strongly agreeing they were confident they could manage diabetes increased from 74% before the intervention to 93% afterward, according to Dr. Concha’s presentation.
By contrast, there were no statistically significant increases in physical outcomes including physical activity, weight, waist circumference, A1c, or blood pressure from before the workshop to after, though outcomes trended in an improved direction, according to Dr. Concha.
Postactivity satisfaction survey results showed that 86%of men said the automotive analogies in the program helped them understand the importance of diabetes management. “I am looking forward to better managing my human-mobile for a long, long time with a good quality of life,” one of the men wrote in survey feedback.
Dr. Concha and coauthors reported no conflicts of interest related to the study.
FROM ADA 2021
Real-world CAR T outcomes for DLBCL mimic clinical trials
Data from a large French registry on a multicenter experience with chimeric antigen receptor T-cell (CAR T) therapy for aggressive lymphoma suggests that the favorable outcomes seen in clinical trials can be replicated in the real world.
Among 481 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with either of two commercially available CAR T products – tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) – the duration of responses, progression-free survival (PFS), and overall survival (OS) rates at 6 months mirror those seen in clinical trials, reported Steven LeGouill, MD, PhD, from the University of Nantes (France), on behalf of colleagues in the DESCAR-T (Dispositive d’Evaluation et de Suivi des CAR-T) registry.
“CAR T has now become a standard of care in a lot of French centers, with more than 640 patients treated with CAR T in less than 2 years. The DESCAR-T real-life experience mimics the experience that had been previously by other real-life registries but also in clinical trials. We didn’t see new emerging toxicity signals in real life,” he said in an oral abstract session during the European Hematology Association annual congress (Abstract S216).
“I am convinced that a population registry about CAR T–treated patients is needed,” commented Pieter Sonneveld, MD, from Erasmus Medical Center in Rotterdam, the Netherlands, who was not involved in the study.
“Selection criteria for CAR T trials have been incredibly restrictive, and academic trials have not gained ground yet. It is important to collect and analyze more data, include non-trial patients and analyze long-term follow-up in order to determine the real effects of this innovative treatment in lymphoma and other diseases,” he said.
Dr. Sonneveld, EHA past president, was the moderator a briefing where Dr. LeGouill presented the DESCAR-T study findings.
Natalie Sophia Grover, MD, a leukemia and lymphoma specialist at the University of North Carolina at Chapel Hill, noted in an interview that “there have been several publications recently that have shown that these promising outcomes for these really refractory, high-risk patients with diffuse large B-cell lymphoma seem to be similar with what we’ve seen in trials, which is definitely exciting.”
She noted that the median time from CAR T order to treatment in the study, 50 days, was longer than in her experience.
“Generally, from collection to treatment is less than a month. Looking at that, I would have expected more patients not to make it CAR T, but nearly 90% of patients who had collections got treatment, which is pretty good. Those patients that didn’t make it to treatment had really poor outcomes,” she said.
Dr. Grover was not involved in the study.
More data, s’il vous plait
The DESCAR-T registry was created in response to a request from French health authorities for data beyond that provided in the EBMT patient registry. The health authorities asked for characterization of the CAR T–eligible population in an intention to treat, 15-year follow-up of both CAR T recipients and candidates who were not treated for whatever reasons, and a full accounting of previous lines of therapy.
Dr. LeGouill presented the first analysis of data from the registry involving 19 enrolling site and 647 patients with DLBCL for whom CAR T cells were ordered from January 2018 to March 2021.
Of the 647 candidates, 10 did not have CAR T ordered for reasons that included patient deaths or disease progression, infection, and patient refusal. An additional 30 patients either had leukapheresis performed or pending, and 607 had CAR T ordered.
Of the 607 patients, 53 did not receive CAR T infusions because of disease progression, death before product administration, manufacturing or leukapheresis failures, uncontrolled infections, patient choice, or progression of other malignancies.
That left 550 patients (85%) who received a CAR T product, either tisagenlecleucel (200 patients) or axicabtagene ciloleucel (350 patients).
Among all patients, the median age at CAR T order was 63 for patients who received tisagenlecleucel, and 65 for patients receiving axicabtagene ciloleucel. Patients 65 and older comprised 44% and 51% of the population, respectively.
Patients treated with each CAR T product had a median of three prior lines of therapy.
Manageable toxicities
Toxicities within 10 days of CAR T infusion included 418 cases among 515 patients (81.2%) of cytokine release syndrome, with most being grade 1 or 2 in severity; 44 patients had grade 3 or 4 CRS.
Any-grade neurotoxicity was seen in 184 patients (35.7%), primarily grade 1 or 2 in severity; 50 patients had grade 3 or greater neurotoxicity.
Of 427 patients with at least one CAR T–specific toxicity within 10 days, 139 (32.8%) required ICU admission, 325 (76,1%) were treated for CAR T–specific toxicities, 278 (65.1%) received tocilizumab, 13 (3%) received siltuximab, and 176 (41.2%) received corticosteroids.
Favorable outcomes
Overall response rates, at 1, 3, and 6 months post infusions were 70.6%, 56.3%, and 60%, respectively, with the majority of response at each time point being complete responses (CR).
The 6-month overall survival (OS) rate among all patients who were treated was 83.7%, compared with 5.5% for patients who did not receive CAR T infusions.
Progression-free survival (PFS) at 6 months was 44.5%, and 57.7% of patients had an ongoing response at the same time point.
Among patients who received bridging therapy between leukapheresis and CAR T infusion, the 6-month PFS was 58.4% for patients with either a CR, partial response, or stable disease, compared with 63.3% for patients who did not receive bridging therapy, and 29.8% for those with disease progression.
The respective 6 months OS rates were 87.4%, 82.3%, and 65.5%.
The results showed that patients who do not have at least stable disease at the time of CAR T infusion are at risk for early relapse, but approximately 30% of these patients still had long-term disease control, Dr. LeGouill said.
He acknowledged that longer follow-up will be need to see whether the plateaus in the PFS and OS curves the investigators observed can be maintained over time. Questions that still need to be answered include the impact of bridging therapy or disease status at the start of treatment on outcomes, and how to improve CAR T efficacy based on individual patient characteristics.
The registry will be extended to include data on patients treated with CAR T for mantle cell lymphoma and multiple myeloma, investigators announced.
The study is supported by participating centers and Gilead/Kite and Novartis. Dr. LeGouill disclosed advisory board activity and honoraria from the companies and others. Dr. Grover disclosed advisory board participating for Kite and others. Dr. Sonneveld has disclosed research grants and honoraria from several companies, not including Kite or Novartis.
Data from a large French registry on a multicenter experience with chimeric antigen receptor T-cell (CAR T) therapy for aggressive lymphoma suggests that the favorable outcomes seen in clinical trials can be replicated in the real world.
Among 481 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with either of two commercially available CAR T products – tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) – the duration of responses, progression-free survival (PFS), and overall survival (OS) rates at 6 months mirror those seen in clinical trials, reported Steven LeGouill, MD, PhD, from the University of Nantes (France), on behalf of colleagues in the DESCAR-T (Dispositive d’Evaluation et de Suivi des CAR-T) registry.
“CAR T has now become a standard of care in a lot of French centers, with more than 640 patients treated with CAR T in less than 2 years. The DESCAR-T real-life experience mimics the experience that had been previously by other real-life registries but also in clinical trials. We didn’t see new emerging toxicity signals in real life,” he said in an oral abstract session during the European Hematology Association annual congress (Abstract S216).
“I am convinced that a population registry about CAR T–treated patients is needed,” commented Pieter Sonneveld, MD, from Erasmus Medical Center in Rotterdam, the Netherlands, who was not involved in the study.
“Selection criteria for CAR T trials have been incredibly restrictive, and academic trials have not gained ground yet. It is important to collect and analyze more data, include non-trial patients and analyze long-term follow-up in order to determine the real effects of this innovative treatment in lymphoma and other diseases,” he said.
Dr. Sonneveld, EHA past president, was the moderator a briefing where Dr. LeGouill presented the DESCAR-T study findings.
Natalie Sophia Grover, MD, a leukemia and lymphoma specialist at the University of North Carolina at Chapel Hill, noted in an interview that “there have been several publications recently that have shown that these promising outcomes for these really refractory, high-risk patients with diffuse large B-cell lymphoma seem to be similar with what we’ve seen in trials, which is definitely exciting.”
She noted that the median time from CAR T order to treatment in the study, 50 days, was longer than in her experience.
“Generally, from collection to treatment is less than a month. Looking at that, I would have expected more patients not to make it CAR T, but nearly 90% of patients who had collections got treatment, which is pretty good. Those patients that didn’t make it to treatment had really poor outcomes,” she said.
Dr. Grover was not involved in the study.
More data, s’il vous plait
The DESCAR-T registry was created in response to a request from French health authorities for data beyond that provided in the EBMT patient registry. The health authorities asked for characterization of the CAR T–eligible population in an intention to treat, 15-year follow-up of both CAR T recipients and candidates who were not treated for whatever reasons, and a full accounting of previous lines of therapy.
Dr. LeGouill presented the first analysis of data from the registry involving 19 enrolling site and 647 patients with DLBCL for whom CAR T cells were ordered from January 2018 to March 2021.
Of the 647 candidates, 10 did not have CAR T ordered for reasons that included patient deaths or disease progression, infection, and patient refusal. An additional 30 patients either had leukapheresis performed or pending, and 607 had CAR T ordered.
Of the 607 patients, 53 did not receive CAR T infusions because of disease progression, death before product administration, manufacturing or leukapheresis failures, uncontrolled infections, patient choice, or progression of other malignancies.
That left 550 patients (85%) who received a CAR T product, either tisagenlecleucel (200 patients) or axicabtagene ciloleucel (350 patients).
Among all patients, the median age at CAR T order was 63 for patients who received tisagenlecleucel, and 65 for patients receiving axicabtagene ciloleucel. Patients 65 and older comprised 44% and 51% of the population, respectively.
Patients treated with each CAR T product had a median of three prior lines of therapy.
Manageable toxicities
Toxicities within 10 days of CAR T infusion included 418 cases among 515 patients (81.2%) of cytokine release syndrome, with most being grade 1 or 2 in severity; 44 patients had grade 3 or 4 CRS.
Any-grade neurotoxicity was seen in 184 patients (35.7%), primarily grade 1 or 2 in severity; 50 patients had grade 3 or greater neurotoxicity.
Of 427 patients with at least one CAR T–specific toxicity within 10 days, 139 (32.8%) required ICU admission, 325 (76,1%) were treated for CAR T–specific toxicities, 278 (65.1%) received tocilizumab, 13 (3%) received siltuximab, and 176 (41.2%) received corticosteroids.
Favorable outcomes
Overall response rates, at 1, 3, and 6 months post infusions were 70.6%, 56.3%, and 60%, respectively, with the majority of response at each time point being complete responses (CR).
The 6-month overall survival (OS) rate among all patients who were treated was 83.7%, compared with 5.5% for patients who did not receive CAR T infusions.
Progression-free survival (PFS) at 6 months was 44.5%, and 57.7% of patients had an ongoing response at the same time point.
Among patients who received bridging therapy between leukapheresis and CAR T infusion, the 6-month PFS was 58.4% for patients with either a CR, partial response, or stable disease, compared with 63.3% for patients who did not receive bridging therapy, and 29.8% for those with disease progression.
The respective 6 months OS rates were 87.4%, 82.3%, and 65.5%.
The results showed that patients who do not have at least stable disease at the time of CAR T infusion are at risk for early relapse, but approximately 30% of these patients still had long-term disease control, Dr. LeGouill said.
He acknowledged that longer follow-up will be need to see whether the plateaus in the PFS and OS curves the investigators observed can be maintained over time. Questions that still need to be answered include the impact of bridging therapy or disease status at the start of treatment on outcomes, and how to improve CAR T efficacy based on individual patient characteristics.
The registry will be extended to include data on patients treated with CAR T for mantle cell lymphoma and multiple myeloma, investigators announced.
The study is supported by participating centers and Gilead/Kite and Novartis. Dr. LeGouill disclosed advisory board activity and honoraria from the companies and others. Dr. Grover disclosed advisory board participating for Kite and others. Dr. Sonneveld has disclosed research grants and honoraria from several companies, not including Kite or Novartis.
Data from a large French registry on a multicenter experience with chimeric antigen receptor T-cell (CAR T) therapy for aggressive lymphoma suggests that the favorable outcomes seen in clinical trials can be replicated in the real world.
Among 481 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with either of two commercially available CAR T products – tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) – the duration of responses, progression-free survival (PFS), and overall survival (OS) rates at 6 months mirror those seen in clinical trials, reported Steven LeGouill, MD, PhD, from the University of Nantes (France), on behalf of colleagues in the DESCAR-T (Dispositive d’Evaluation et de Suivi des CAR-T) registry.
“CAR T has now become a standard of care in a lot of French centers, with more than 640 patients treated with CAR T in less than 2 years. The DESCAR-T real-life experience mimics the experience that had been previously by other real-life registries but also in clinical trials. We didn’t see new emerging toxicity signals in real life,” he said in an oral abstract session during the European Hematology Association annual congress (Abstract S216).
“I am convinced that a population registry about CAR T–treated patients is needed,” commented Pieter Sonneveld, MD, from Erasmus Medical Center in Rotterdam, the Netherlands, who was not involved in the study.
“Selection criteria for CAR T trials have been incredibly restrictive, and academic trials have not gained ground yet. It is important to collect and analyze more data, include non-trial patients and analyze long-term follow-up in order to determine the real effects of this innovative treatment in lymphoma and other diseases,” he said.
Dr. Sonneveld, EHA past president, was the moderator a briefing where Dr. LeGouill presented the DESCAR-T study findings.
Natalie Sophia Grover, MD, a leukemia and lymphoma specialist at the University of North Carolina at Chapel Hill, noted in an interview that “there have been several publications recently that have shown that these promising outcomes for these really refractory, high-risk patients with diffuse large B-cell lymphoma seem to be similar with what we’ve seen in trials, which is definitely exciting.”
She noted that the median time from CAR T order to treatment in the study, 50 days, was longer than in her experience.
“Generally, from collection to treatment is less than a month. Looking at that, I would have expected more patients not to make it CAR T, but nearly 90% of patients who had collections got treatment, which is pretty good. Those patients that didn’t make it to treatment had really poor outcomes,” she said.
Dr. Grover was not involved in the study.
More data, s’il vous plait
The DESCAR-T registry was created in response to a request from French health authorities for data beyond that provided in the EBMT patient registry. The health authorities asked for characterization of the CAR T–eligible population in an intention to treat, 15-year follow-up of both CAR T recipients and candidates who were not treated for whatever reasons, and a full accounting of previous lines of therapy.
Dr. LeGouill presented the first analysis of data from the registry involving 19 enrolling site and 647 patients with DLBCL for whom CAR T cells were ordered from January 2018 to March 2021.
Of the 647 candidates, 10 did not have CAR T ordered for reasons that included patient deaths or disease progression, infection, and patient refusal. An additional 30 patients either had leukapheresis performed or pending, and 607 had CAR T ordered.
Of the 607 patients, 53 did not receive CAR T infusions because of disease progression, death before product administration, manufacturing or leukapheresis failures, uncontrolled infections, patient choice, or progression of other malignancies.
That left 550 patients (85%) who received a CAR T product, either tisagenlecleucel (200 patients) or axicabtagene ciloleucel (350 patients).
Among all patients, the median age at CAR T order was 63 for patients who received tisagenlecleucel, and 65 for patients receiving axicabtagene ciloleucel. Patients 65 and older comprised 44% and 51% of the population, respectively.
Patients treated with each CAR T product had a median of three prior lines of therapy.
Manageable toxicities
Toxicities within 10 days of CAR T infusion included 418 cases among 515 patients (81.2%) of cytokine release syndrome, with most being grade 1 or 2 in severity; 44 patients had grade 3 or 4 CRS.
Any-grade neurotoxicity was seen in 184 patients (35.7%), primarily grade 1 or 2 in severity; 50 patients had grade 3 or greater neurotoxicity.
Of 427 patients with at least one CAR T–specific toxicity within 10 days, 139 (32.8%) required ICU admission, 325 (76,1%) were treated for CAR T–specific toxicities, 278 (65.1%) received tocilizumab, 13 (3%) received siltuximab, and 176 (41.2%) received corticosteroids.
Favorable outcomes
Overall response rates, at 1, 3, and 6 months post infusions were 70.6%, 56.3%, and 60%, respectively, with the majority of response at each time point being complete responses (CR).
The 6-month overall survival (OS) rate among all patients who were treated was 83.7%, compared with 5.5% for patients who did not receive CAR T infusions.
Progression-free survival (PFS) at 6 months was 44.5%, and 57.7% of patients had an ongoing response at the same time point.
Among patients who received bridging therapy between leukapheresis and CAR T infusion, the 6-month PFS was 58.4% for patients with either a CR, partial response, or stable disease, compared with 63.3% for patients who did not receive bridging therapy, and 29.8% for those with disease progression.
The respective 6 months OS rates were 87.4%, 82.3%, and 65.5%.
The results showed that patients who do not have at least stable disease at the time of CAR T infusion are at risk for early relapse, but approximately 30% of these patients still had long-term disease control, Dr. LeGouill said.
He acknowledged that longer follow-up will be need to see whether the plateaus in the PFS and OS curves the investigators observed can be maintained over time. Questions that still need to be answered include the impact of bridging therapy or disease status at the start of treatment on outcomes, and how to improve CAR T efficacy based on individual patient characteristics.
The registry will be extended to include data on patients treated with CAR T for mantle cell lymphoma and multiple myeloma, investigators announced.
The study is supported by participating centers and Gilead/Kite and Novartis. Dr. LeGouill disclosed advisory board activity and honoraria from the companies and others. Dr. Grover disclosed advisory board participating for Kite and others. Dr. Sonneveld has disclosed research grants and honoraria from several companies, not including Kite or Novartis.
FROM EHA 2021
Nocturnal hypoglycemia halved with insulin degludec vs. glargine
Patients with type 1 diabetes who used insulin degludec as their basal insulin had fewer than half the number of nocturnal hypoglycemia events, compared with patients who used insulin glargine U100, in a head-to-head crossover study with 51 patients who had a history of nighttime hypoglycemia episodes.
Patients with type 1 diabetes who are “struggling with nocturnal hypoglycemia would benefit from insulin degludec treatment,” said Julie M. Brøsen, MD, at the annual scientific sessions of the American Diabetes Association.
Accumulating evidence for less hypoglycemia with insulin degludec
Results from several studies comparing insulin degludec (Tresiba), a second-generation, longer-acting insulin with more stable steady-state performance, with the first-generation basal insulin analogue glargine (Lantus), have built the case that degludec produces fewer hypoglycemia events.
The landmark SWITCH 1 crossover study published in 2017 showed in about 500 patients with type 1 diabetes and a risk factor for hypoglycemia that treatment with insulin degludec led to significantly few total hypoglycemia episodes and significantly fewer nocturnal episodes, compared with insulin glargine.
Next came similar findings from ReFLeCT, a multicenter observational study that followed 556 unselected patients with type 1 diabetes in routine practice settings who switched to insulin degludec following treatment with a different basal insulin. The results again showed a significant drop-off in total, nonsevere, severe, and nocturnal hypoglycemia events.
Homing in on higher-risk patients
The current study, HypoDeg (Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia), ran at 10 Danish centers and enrolled 149 adults with type 1 diabetes who had at least one episode of severe nocturnal hypoglycemia within the prior 2 years, focusing on patients most at risk for future nocturnal hypoglycemia events. In an unusual study design, researchers identified nocturnal hypoglycemic episodes with hourly venous blood samples drawn from a subcutaneous line.
They randomized the patients to basal insulin treatment with either insulin degludec or to insulin glargine U100, allowed their treatment to stabilize for 3 months, and then tallied nocturnal hypoglycemia events for 9 months. They then crossed patients to the alternative basal insulin and repeated the process.
Results from the full study have not yet appeared in published form but were in a pair of reports at the 2020 scientific sessions of the ADA.
One report included findings based on 136 episodes of severe hypoglycemia identified clinically and showed these events occurred 35% less often during treatment with insulin degludec, a significant difference. The overall finding was primarily driven by 48% fewer episodes of severe nocturnal hypoglycemia, but this difference was not significant.
The second report identified hypoglycemia events with continuous glucose monitoring in 74 of the study participants, which identified 193 episodes of nonsevere nocturnal hypoglycemia and found that treatment with insulin degludec cut the rate by 47%, primarily by reducing asymptomatic episodes.
Hourly blood draws track overnight hypoglycemia
The current study included 51 of the 149 HypoDeg patients who agreed to undergo overnight blood sampling and had this done at least once while treated with each of the two study insulins. (The study design called for two blood sampling nights for each willing patient during each of the two treatment periods.) The 51 patients had type 1 diabetes for an average of 28 years and an average age of 58 years. Two-thirds were men, their baseline A1c was 7.8%, and on average had 2.6 episodes of severe nocturnal hypoglycemia during the prior 2 years.
The researchers drew hourly blood specimens on a total of 196 nights from the 51 participating patients and identified 57 nights when blood glucose levels reached hypoglycemia thresholds in 33 patients. One-third of the events occurred when patients were on insulin degludec treatment, and two-thirds when they were on insulin glargine, reported Dr. Brøsen.
She presented three separate analyses of the data. One analysis focused on level 1 hypoglycemia events, when blood glucose dips to 70 mg/dL or less, which occurred 54% less often when patients were on insulin degludec. A second analysis looked at level 2 events, when blood glucose falls below 54 mg/dL, and treatment with insulin degludec cut this by 64% compared with insulin glargine. The third analysis focused on symptomatic events when blood glucose was 70 mg/dL or less, and treatment with insulin degludec linked with a 62% cut in this metric. All three between-group differences were significant.
Evidence supports already-changed practice
This new evidence “supports recommending” insulin degludec over insulin glargine, commented Bastiaan E. de Galan, MD, PhD, an endocrinologist and professor at Maastrict (the Netherlands) University Medical Center. The new results “extend those from previous trials in populations with type 1 diabetes that were unselected for the risk of hypoglycemia. In clinical practice, insulin degludec is already considered for patients who reported nocturnal hypoglycemia while on insulin glargine U100, but it’s great this study provides the scientific evidence,” said Dr. de Galan in an interview.
“The lower rate of nocturnal hypoglycemia with degludec, compared with glargine U100 is well established. Inpatient assessment of hypoglycemia with measurement of hourly plasma glucose allowed HypoDeg to provide stronger evidence than prior studies. The benefit of delgudec versus glargine U100 was significant and clinically meaningful, in hypo-prone patients who would benefit the most” by using insulin degludec, commented Gian Paolo Fadini, MD, an endocrinologist at the University of Padova (Italy), and a lead investigator on the ReFLeCT study.
But insulin degludec is not a completely silver bullet. Its prolonged duration of action and stability that may in part explain why it limits hypoglycemia events can also be a drawback: “It probably offers fewer options for flexibility. Any change in dose takes at least a day or 2 to settle, which may be unfavorable in certain circumstances,” noted Dr. de Galan.
“I wouldn’t recommend insulin degludec for all patients with type 1 diabetes. It’s an individual evaluation in each patient,” said Dr. Brøsen. “We will be looking into whether some patients are better off on insulin glargine.”
Cost makes a difference
Another, potentially more consequential flaw is insulin degludec’s relative expense.
“To date, use of degludec in routine practice has been limited by its cost, compared with older basal insulins,” observed Dr. Fadini in an interview. “In several countries, including the United States, degludec is substantially more expensive than glargine.”
The ADA’s Standards of Medical Care in Diabetes–2021 includes table 9.3 that lists the costs of various insulins and shows the median average wholesale price of insulin glargine U100 follow-on products as $190/vial, compared with a $407 price for a similar vial of insulin degludec.
Insulin degludec “is clearly superior from a hypoglycemia standpoint. Patients with type 1 diabetes like the reduction because hypoglycemia is scary, and dangerous. The main issue is cost, and the extent to which it may be covered by insurance,” commented Lisa Chow, MD, an endocrinologist at the University of Minnesota, Minneapolis. “We generally won’t prescribe degludec unless it is at a price affordable to the patient. We try to use patient assistance programs sponsored by the company [that markets insulin degludec: Novo Nordisk] to try to make it more affordable.”
Dr. Chow also highlighted that a new wrinkle has been introduction of a more concentrated formulation of insulin glargine, U300, which appears to cause less hypoglycemia than insulin glargine U100. Recent study results indicated that no significant difference exists in the incidence of hypoglycemia among patients treated with insulin glargine U300 and those treated with insulin degludec, such as findings from the BRIGHT trial, which included just over 900 patients, and in the CONCLUDE trial, which randomized more than 1,600 patients.
The HypoDeg study was sponsored by Novo Nordisk, the company that markets insulin degludec. Dr. Brøsen had no personal disclosures, but several of her coauthors were either Novo Nordisk employees or had financial relationships with the company. Dr. de Galan has received research funding from Novo Nordisk. Dr. Fadini has received lecture fees and research funding from Novo Nordisk, from Sanofi, the company that markets insulin glargine, and from several other companies. Dr. Chow has received research funding from Dexcom.
Patients with type 1 diabetes who used insulin degludec as their basal insulin had fewer than half the number of nocturnal hypoglycemia events, compared with patients who used insulin glargine U100, in a head-to-head crossover study with 51 patients who had a history of nighttime hypoglycemia episodes.
Patients with type 1 diabetes who are “struggling with nocturnal hypoglycemia would benefit from insulin degludec treatment,” said Julie M. Brøsen, MD, at the annual scientific sessions of the American Diabetes Association.
Accumulating evidence for less hypoglycemia with insulin degludec
Results from several studies comparing insulin degludec (Tresiba), a second-generation, longer-acting insulin with more stable steady-state performance, with the first-generation basal insulin analogue glargine (Lantus), have built the case that degludec produces fewer hypoglycemia events.
The landmark SWITCH 1 crossover study published in 2017 showed in about 500 patients with type 1 diabetes and a risk factor for hypoglycemia that treatment with insulin degludec led to significantly few total hypoglycemia episodes and significantly fewer nocturnal episodes, compared with insulin glargine.
Next came similar findings from ReFLeCT, a multicenter observational study that followed 556 unselected patients with type 1 diabetes in routine practice settings who switched to insulin degludec following treatment with a different basal insulin. The results again showed a significant drop-off in total, nonsevere, severe, and nocturnal hypoglycemia events.
Homing in on higher-risk patients
The current study, HypoDeg (Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia), ran at 10 Danish centers and enrolled 149 adults with type 1 diabetes who had at least one episode of severe nocturnal hypoglycemia within the prior 2 years, focusing on patients most at risk for future nocturnal hypoglycemia events. In an unusual study design, researchers identified nocturnal hypoglycemic episodes with hourly venous blood samples drawn from a subcutaneous line.
They randomized the patients to basal insulin treatment with either insulin degludec or to insulin glargine U100, allowed their treatment to stabilize for 3 months, and then tallied nocturnal hypoglycemia events for 9 months. They then crossed patients to the alternative basal insulin and repeated the process.
Results from the full study have not yet appeared in published form but were in a pair of reports at the 2020 scientific sessions of the ADA.
One report included findings based on 136 episodes of severe hypoglycemia identified clinically and showed these events occurred 35% less often during treatment with insulin degludec, a significant difference. The overall finding was primarily driven by 48% fewer episodes of severe nocturnal hypoglycemia, but this difference was not significant.
The second report identified hypoglycemia events with continuous glucose monitoring in 74 of the study participants, which identified 193 episodes of nonsevere nocturnal hypoglycemia and found that treatment with insulin degludec cut the rate by 47%, primarily by reducing asymptomatic episodes.
Hourly blood draws track overnight hypoglycemia
The current study included 51 of the 149 HypoDeg patients who agreed to undergo overnight blood sampling and had this done at least once while treated with each of the two study insulins. (The study design called for two blood sampling nights for each willing patient during each of the two treatment periods.) The 51 patients had type 1 diabetes for an average of 28 years and an average age of 58 years. Two-thirds were men, their baseline A1c was 7.8%, and on average had 2.6 episodes of severe nocturnal hypoglycemia during the prior 2 years.
The researchers drew hourly blood specimens on a total of 196 nights from the 51 participating patients and identified 57 nights when blood glucose levels reached hypoglycemia thresholds in 33 patients. One-third of the events occurred when patients were on insulin degludec treatment, and two-thirds when they were on insulin glargine, reported Dr. Brøsen.
She presented three separate analyses of the data. One analysis focused on level 1 hypoglycemia events, when blood glucose dips to 70 mg/dL or less, which occurred 54% less often when patients were on insulin degludec. A second analysis looked at level 2 events, when blood glucose falls below 54 mg/dL, and treatment with insulin degludec cut this by 64% compared with insulin glargine. The third analysis focused on symptomatic events when blood glucose was 70 mg/dL or less, and treatment with insulin degludec linked with a 62% cut in this metric. All three between-group differences were significant.
Evidence supports already-changed practice
This new evidence “supports recommending” insulin degludec over insulin glargine, commented Bastiaan E. de Galan, MD, PhD, an endocrinologist and professor at Maastrict (the Netherlands) University Medical Center. The new results “extend those from previous trials in populations with type 1 diabetes that were unselected for the risk of hypoglycemia. In clinical practice, insulin degludec is already considered for patients who reported nocturnal hypoglycemia while on insulin glargine U100, but it’s great this study provides the scientific evidence,” said Dr. de Galan in an interview.
“The lower rate of nocturnal hypoglycemia with degludec, compared with glargine U100 is well established. Inpatient assessment of hypoglycemia with measurement of hourly plasma glucose allowed HypoDeg to provide stronger evidence than prior studies. The benefit of delgudec versus glargine U100 was significant and clinically meaningful, in hypo-prone patients who would benefit the most” by using insulin degludec, commented Gian Paolo Fadini, MD, an endocrinologist at the University of Padova (Italy), and a lead investigator on the ReFLeCT study.
But insulin degludec is not a completely silver bullet. Its prolonged duration of action and stability that may in part explain why it limits hypoglycemia events can also be a drawback: “It probably offers fewer options for flexibility. Any change in dose takes at least a day or 2 to settle, which may be unfavorable in certain circumstances,” noted Dr. de Galan.
“I wouldn’t recommend insulin degludec for all patients with type 1 diabetes. It’s an individual evaluation in each patient,” said Dr. Brøsen. “We will be looking into whether some patients are better off on insulin glargine.”
Cost makes a difference
Another, potentially more consequential flaw is insulin degludec’s relative expense.
“To date, use of degludec in routine practice has been limited by its cost, compared with older basal insulins,” observed Dr. Fadini in an interview. “In several countries, including the United States, degludec is substantially more expensive than glargine.”
The ADA’s Standards of Medical Care in Diabetes–2021 includes table 9.3 that lists the costs of various insulins and shows the median average wholesale price of insulin glargine U100 follow-on products as $190/vial, compared with a $407 price for a similar vial of insulin degludec.
Insulin degludec “is clearly superior from a hypoglycemia standpoint. Patients with type 1 diabetes like the reduction because hypoglycemia is scary, and dangerous. The main issue is cost, and the extent to which it may be covered by insurance,” commented Lisa Chow, MD, an endocrinologist at the University of Minnesota, Minneapolis. “We generally won’t prescribe degludec unless it is at a price affordable to the patient. We try to use patient assistance programs sponsored by the company [that markets insulin degludec: Novo Nordisk] to try to make it more affordable.”
Dr. Chow also highlighted that a new wrinkle has been introduction of a more concentrated formulation of insulin glargine, U300, which appears to cause less hypoglycemia than insulin glargine U100. Recent study results indicated that no significant difference exists in the incidence of hypoglycemia among patients treated with insulin glargine U300 and those treated with insulin degludec, such as findings from the BRIGHT trial, which included just over 900 patients, and in the CONCLUDE trial, which randomized more than 1,600 patients.
The HypoDeg study was sponsored by Novo Nordisk, the company that markets insulin degludec. Dr. Brøsen had no personal disclosures, but several of her coauthors were either Novo Nordisk employees or had financial relationships with the company. Dr. de Galan has received research funding from Novo Nordisk. Dr. Fadini has received lecture fees and research funding from Novo Nordisk, from Sanofi, the company that markets insulin glargine, and from several other companies. Dr. Chow has received research funding from Dexcom.
Patients with type 1 diabetes who used insulin degludec as their basal insulin had fewer than half the number of nocturnal hypoglycemia events, compared with patients who used insulin glargine U100, in a head-to-head crossover study with 51 patients who had a history of nighttime hypoglycemia episodes.
Patients with type 1 diabetes who are “struggling with nocturnal hypoglycemia would benefit from insulin degludec treatment,” said Julie M. Brøsen, MD, at the annual scientific sessions of the American Diabetes Association.
Accumulating evidence for less hypoglycemia with insulin degludec
Results from several studies comparing insulin degludec (Tresiba), a second-generation, longer-acting insulin with more stable steady-state performance, with the first-generation basal insulin analogue glargine (Lantus), have built the case that degludec produces fewer hypoglycemia events.
The landmark SWITCH 1 crossover study published in 2017 showed in about 500 patients with type 1 diabetes and a risk factor for hypoglycemia that treatment with insulin degludec led to significantly few total hypoglycemia episodes and significantly fewer nocturnal episodes, compared with insulin glargine.
Next came similar findings from ReFLeCT, a multicenter observational study that followed 556 unselected patients with type 1 diabetes in routine practice settings who switched to insulin degludec following treatment with a different basal insulin. The results again showed a significant drop-off in total, nonsevere, severe, and nocturnal hypoglycemia events.
Homing in on higher-risk patients
The current study, HypoDeg (Insulin Degludec and Symptomatic Nocturnal Hypoglycaemia), ran at 10 Danish centers and enrolled 149 adults with type 1 diabetes who had at least one episode of severe nocturnal hypoglycemia within the prior 2 years, focusing on patients most at risk for future nocturnal hypoglycemia events. In an unusual study design, researchers identified nocturnal hypoglycemic episodes with hourly venous blood samples drawn from a subcutaneous line.
They randomized the patients to basal insulin treatment with either insulin degludec or to insulin glargine U100, allowed their treatment to stabilize for 3 months, and then tallied nocturnal hypoglycemia events for 9 months. They then crossed patients to the alternative basal insulin and repeated the process.
Results from the full study have not yet appeared in published form but were in a pair of reports at the 2020 scientific sessions of the ADA.
One report included findings based on 136 episodes of severe hypoglycemia identified clinically and showed these events occurred 35% less often during treatment with insulin degludec, a significant difference. The overall finding was primarily driven by 48% fewer episodes of severe nocturnal hypoglycemia, but this difference was not significant.
The second report identified hypoglycemia events with continuous glucose monitoring in 74 of the study participants, which identified 193 episodes of nonsevere nocturnal hypoglycemia and found that treatment with insulin degludec cut the rate by 47%, primarily by reducing asymptomatic episodes.
Hourly blood draws track overnight hypoglycemia
The current study included 51 of the 149 HypoDeg patients who agreed to undergo overnight blood sampling and had this done at least once while treated with each of the two study insulins. (The study design called for two blood sampling nights for each willing patient during each of the two treatment periods.) The 51 patients had type 1 diabetes for an average of 28 years and an average age of 58 years. Two-thirds were men, their baseline A1c was 7.8%, and on average had 2.6 episodes of severe nocturnal hypoglycemia during the prior 2 years.
The researchers drew hourly blood specimens on a total of 196 nights from the 51 participating patients and identified 57 nights when blood glucose levels reached hypoglycemia thresholds in 33 patients. One-third of the events occurred when patients were on insulin degludec treatment, and two-thirds when they were on insulin glargine, reported Dr. Brøsen.
She presented three separate analyses of the data. One analysis focused on level 1 hypoglycemia events, when blood glucose dips to 70 mg/dL or less, which occurred 54% less often when patients were on insulin degludec. A second analysis looked at level 2 events, when blood glucose falls below 54 mg/dL, and treatment with insulin degludec cut this by 64% compared with insulin glargine. The third analysis focused on symptomatic events when blood glucose was 70 mg/dL or less, and treatment with insulin degludec linked with a 62% cut in this metric. All three between-group differences were significant.
Evidence supports already-changed practice
This new evidence “supports recommending” insulin degludec over insulin glargine, commented Bastiaan E. de Galan, MD, PhD, an endocrinologist and professor at Maastrict (the Netherlands) University Medical Center. The new results “extend those from previous trials in populations with type 1 diabetes that were unselected for the risk of hypoglycemia. In clinical practice, insulin degludec is already considered for patients who reported nocturnal hypoglycemia while on insulin glargine U100, but it’s great this study provides the scientific evidence,” said Dr. de Galan in an interview.
“The lower rate of nocturnal hypoglycemia with degludec, compared with glargine U100 is well established. Inpatient assessment of hypoglycemia with measurement of hourly plasma glucose allowed HypoDeg to provide stronger evidence than prior studies. The benefit of delgudec versus glargine U100 was significant and clinically meaningful, in hypo-prone patients who would benefit the most” by using insulin degludec, commented Gian Paolo Fadini, MD, an endocrinologist at the University of Padova (Italy), and a lead investigator on the ReFLeCT study.
But insulin degludec is not a completely silver bullet. Its prolonged duration of action and stability that may in part explain why it limits hypoglycemia events can also be a drawback: “It probably offers fewer options for flexibility. Any change in dose takes at least a day or 2 to settle, which may be unfavorable in certain circumstances,” noted Dr. de Galan.
“I wouldn’t recommend insulin degludec for all patients with type 1 diabetes. It’s an individual evaluation in each patient,” said Dr. Brøsen. “We will be looking into whether some patients are better off on insulin glargine.”
Cost makes a difference
Another, potentially more consequential flaw is insulin degludec’s relative expense.
“To date, use of degludec in routine practice has been limited by its cost, compared with older basal insulins,” observed Dr. Fadini in an interview. “In several countries, including the United States, degludec is substantially more expensive than glargine.”
The ADA’s Standards of Medical Care in Diabetes–2021 includes table 9.3 that lists the costs of various insulins and shows the median average wholesale price of insulin glargine U100 follow-on products as $190/vial, compared with a $407 price for a similar vial of insulin degludec.
Insulin degludec “is clearly superior from a hypoglycemia standpoint. Patients with type 1 diabetes like the reduction because hypoglycemia is scary, and dangerous. The main issue is cost, and the extent to which it may be covered by insurance,” commented Lisa Chow, MD, an endocrinologist at the University of Minnesota, Minneapolis. “We generally won’t prescribe degludec unless it is at a price affordable to the patient. We try to use patient assistance programs sponsored by the company [that markets insulin degludec: Novo Nordisk] to try to make it more affordable.”
Dr. Chow also highlighted that a new wrinkle has been introduction of a more concentrated formulation of insulin glargine, U300, which appears to cause less hypoglycemia than insulin glargine U100. Recent study results indicated that no significant difference exists in the incidence of hypoglycemia among patients treated with insulin glargine U300 and those treated with insulin degludec, such as findings from the BRIGHT trial, which included just over 900 patients, and in the CONCLUDE trial, which randomized more than 1,600 patients.
The HypoDeg study was sponsored by Novo Nordisk, the company that markets insulin degludec. Dr. Brøsen had no personal disclosures, but several of her coauthors were either Novo Nordisk employees or had financial relationships with the company. Dr. de Galan has received research funding from Novo Nordisk. Dr. Fadini has received lecture fees and research funding from Novo Nordisk, from Sanofi, the company that markets insulin glargine, and from several other companies. Dr. Chow has received research funding from Dexcom.
FROM ADA 2021
Calories may outweigh nutrients in diets for fatty liver
Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat (LCHF) diet for treating nonalcoholic fatty liver disease (NAFLD), researchers say.
The intermittent diet offers more benefit for liver stiffness and LDL cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the hepatology unit at the Karolinska Institute in Stockholm.
But the intermittent diet also has drawbacks and the differences between the two were slight, he said in an interview.
“They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight,” he said. “And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat.”
Dr. Holmer and colleagues presented their findings at the meeting sponsored by the European Association for the Study of the Liver and published them in JHEP Reports
While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular LCHF diets might cause more harm than good.
At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.
How do the two diets compare?
To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) greater than 280 dB/m and obesity, or a CAP greater than 280 dB/m, elevated ALT, and overweight. Sixteen of the patients were being treated with statins.
The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index, liver stiffness, and most other criteria at baseline, although there were more women in the standard-care group.
At the start of the study, the participants in the standard-care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.
The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2,000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2,400 kcal/day the other 5 days.
They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.
The researchers asked women in the LCHF diet to eat an average of 1,600 kcal/day and men to eat an average of 1,900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.
All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.
In addition, the researchers measured the participants’ linoleic acid and alpha-linolenic acid intake to verify that the participants’ diets were different among the groups.
After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.
The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.
In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL cholesterol, HDL cholesterol, and total cholesterol all increased.
The long-term implications of the cholesterol findings are unclear, Dr. Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease.
Diet adherence
Only one person dropped out of the 5:2 group, compared with five in the LCHF group and four in the standard-care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.
“With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons.
The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.
LCHF and 5:2 diets can work
But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said.
“I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interested in some sort of specific diet, then I can, based on these findings, encourage that.”
Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, England, said that longer-term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation.
Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.
Still, Dr. Harrison greeted the findings enthusiastically, saying: “This is an important study.”
It’s useful to compare two popular diets head to head, and it’s also encouraging to get confirmation that either one can work, he added.
The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Dr. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat (LCHF) diet for treating nonalcoholic fatty liver disease (NAFLD), researchers say.
The intermittent diet offers more benefit for liver stiffness and LDL cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the hepatology unit at the Karolinska Institute in Stockholm.
But the intermittent diet also has drawbacks and the differences between the two were slight, he said in an interview.
“They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight,” he said. “And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat.”
Dr. Holmer and colleagues presented their findings at the meeting sponsored by the European Association for the Study of the Liver and published them in JHEP Reports
While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular LCHF diets might cause more harm than good.
At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.
How do the two diets compare?
To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) greater than 280 dB/m and obesity, or a CAP greater than 280 dB/m, elevated ALT, and overweight. Sixteen of the patients were being treated with statins.
The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index, liver stiffness, and most other criteria at baseline, although there were more women in the standard-care group.
At the start of the study, the participants in the standard-care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.
The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2,000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2,400 kcal/day the other 5 days.
They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.
The researchers asked women in the LCHF diet to eat an average of 1,600 kcal/day and men to eat an average of 1,900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.
All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.
In addition, the researchers measured the participants’ linoleic acid and alpha-linolenic acid intake to verify that the participants’ diets were different among the groups.
After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.
The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.
In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL cholesterol, HDL cholesterol, and total cholesterol all increased.
The long-term implications of the cholesterol findings are unclear, Dr. Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease.
Diet adherence
Only one person dropped out of the 5:2 group, compared with five in the LCHF group and four in the standard-care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.
“With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons.
The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.
LCHF and 5:2 diets can work
But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said.
“I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interested in some sort of specific diet, then I can, based on these findings, encourage that.”
Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, England, said that longer-term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation.
Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.
Still, Dr. Harrison greeted the findings enthusiastically, saying: “This is an important study.”
It’s useful to compare two popular diets head to head, and it’s also encouraging to get confirmation that either one can work, he added.
The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Dr. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Intermittent calorie restriction offers only modest advantages over a low-carbohydrate, high-fat (LCHF) diet for treating nonalcoholic fatty liver disease (NAFLD), researchers say.
The intermittent diet offers more benefit for liver stiffness and LDL cholesterol, and might be easier to maintain, said Magnus Holmer, MD, head of the hepatology unit at the Karolinska Institute in Stockholm.
But the intermittent diet also has drawbacks and the differences between the two were slight, he said in an interview.
“They were more or less identically effective in reducing liver steatosis in NAFLD and also reducing body weight,” he said. “And from this, we can say that the composition of macronutrients such as fat or sugar seems to be less important than how many calories you eat.”
Dr. Holmer and colleagues presented their findings at the meeting sponsored by the European Association for the Study of the Liver and published them in JHEP Reports
While previous studies have shown that dieting can effectively treat NAFLD, researchers have debated whether popular LCHF diets might cause more harm than good.
At the same time, intermittent-calorie restriction diets have also been gaining in popularity, particularly the 5:2 diet in which participants eat normally for 5 days a week and restrict their calories the other 2 days.
How do the two diets compare?
To see if one was more effective than the other, the researchers recruited 74 people with NAFLD. They diagnosed the patients either by radiologic assessment or a combination of controlled attenuation parameter (CAP) greater than 280 dB/m and obesity, or a CAP greater than 280 dB/m, elevated ALT, and overweight. Sixteen of the patients were being treated with statins.
The researchers randomly assigned 25 people to an LCHF diet, 25 to a 5:2 diet, and 24 to standard care. The groups were similar in diet, age, body mass index, liver stiffness, and most other criteria at baseline, although there were more women in the standard-care group.
At the start of the study, the participants in the standard-care group consulted with a hepatologist who advised them to avoid sweets and saturated fats, eat three meals a day, and avoid large portions.
The researchers asked women in the 5:2 diet to eat up to 500 kcal/day each of 2 days per week and up to 2,000 kcal/day each of the other 5 days. They asked men in the group to eat up to 600 kcal/day each of 2 days per week and up to 2,400 kcal/day the other 5 days.
They provided all the 5:2 participants with recipes that followed the Nordic Nutrition Recommendations, an adaptation of the Mediterranean diet that emphasizes foods traditional in Nordic countries, particularly grains such as whole-grain rye, oats, and barley; fruits such as apples, pears, berries, and plums; root vegetables, cabbages, onions, peas, beans, fish, boiled potatoes, and dairy products; and the use of rapeseed (canola) oil. The calories provided in the recipes were composed of 45%-60% carbohydrates, 25% fat, and 10%-20% protein.
The researchers asked women in the LCHF diet to eat an average of 1,600 kcal/day and men to eat an average of 1,900 kcal/day. All the participants used recipes based on meat, fish, eggs, low-carbohydrate vegetables, and dairy fat. Participants avoided sugar, bread, pasta, rice, pies, potatoes, and fruit. The calories in the recipes were composed of 5%-10% carbohydrates, 50%-80% fat, and 15%-40% protein.
All the participants reported what they ate over the previous 3 days, both at the start of the study and after 12 weeks. Participants in the 5:2 and LCHF groups also received follow-up calls to report their past 24 hours of eating at 2, 4, 8, and 12 weeks, and also at week 6, when they visited a dietitian.
In addition, the researchers measured the participants’ linoleic acid and alpha-linolenic acid intake to verify that the participants’ diets were different among the groups.
After 12 weeks, all three groups lost a significant amount of liver fat, but the LCHF and 5:2 groups lost more than the standard care group. Liver stiffness decreased significantly in the 5:2 and standard care groups, but not in the LCHF group.
The differences in steatosis change between the standard care and LCHF groups was statistically significant (P = .001), as it was between the standard care and 5:2 groups (P = .029). The differences between the LCHF and 5:2 groups were not statistically significant for weight or steatosis, but they were statistically significant for liver stiffness.
In addition, the 5:2 group significantly reduced total and LDL cholesterol, while the standard care group did not. In the LCHF group, levels of LDL cholesterol, HDL cholesterol, and total cholesterol all increased.
The long-term implications of the cholesterol findings are unclear, Dr. Holmer said. He hopes to follow up on these patients after 18-24 months. But the initial cholesterol findings are perhaps enough to constitute a red flag for anyone with a history of cardiovascular disease.
Diet adherence
Only one person dropped out of the 5:2 group, compared with five in the LCHF group and four in the standard-care group. More people in the LCHF group reported adverse events, such as gastrointestinal upset.
“With LCHF, it’s a drastic change for most people,” Dr. Holmer said. “Many patients are a bit shocked when they realize how much fat they are supposed to eat for breakfast, for lunch, and for dinner. They might eat bacon and eggs for breakfast every day.” The diet could be challenging for people who want to reduce their consumption of meat for environmental reasons.
The 5:2 group offers the advantage that people can choose what they want to eat as long as they adhere to the calorie restrictions, he pointed out. Still, he cautioned that the diet would not work well for people with insulin-dependent diabetes because of the difficulty of adjusting insulin levels on fasting days. He also recommended against this diet for people with cirrhosis because they need to eat frequent meals.
LCHF and 5:2 diets can work
But for most people the good news is that a variety of diets will work to treat NAFLD, Dr. Holmer said.
“I begin with saying to my patients that this can be completely cured, as long as you’re able to lose weight,” he said. “Then the next question is, how are they going to go ahead with that task? And if they’re already interested in some sort of specific diet, then I can, based on these findings, encourage that.”
Stephen Harrison, MD, a visiting professor of hepatology at Radcliffe Department of Medicine, University of Oxford, England, said that longer-term results will be important. For example, it will be interesting to see if the diets had effects on ballooning or inflammation.
Another limitation of the study is that it is relatively small in size, he said. He pointed out that people with NAFLD should increase their physical activity as well as eating less.
Still, Dr. Harrison greeted the findings enthusiastically, saying: “This is an important study.”
It’s useful to compare two popular diets head to head, and it’s also encouraging to get confirmation that either one can work, he added.
The study was supported by grants from the Stockholm County Council, the Dietary Science Foundation (Kostfonden), the Skandia Research Foundation, and the Åke Wiberg Foundation. Dr. Holmer has disclosed no relevant financial relationships. Harrison is a consultant to Madrigal Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Omnipod 5 ‘artificial pancreas’ shows benefit in type 1 diabetes
Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.
The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021.
Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.
Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers.
If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
‘No-tubing’ feature will be a draw for parents of young children
Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”
“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”
Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.
But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”
Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
Pivotal data show benefit in ‘difficult-to-manage’ preschool children
Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.
“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.
A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.
At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05).
Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).
“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.
Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.
In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.
The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.
There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.
Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.
All 80 patients completed the study and elected to continue in a 12-month extension phase.
Ongoing benefit seen in older children and adults
In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.
A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).
There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
Reduced diabetes distress, don’t forget parents’ quality of life
Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.
Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.
“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.
There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.
“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.
Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.
A version of this article first appeared on Medscape.com.
Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.
The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021.
Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.
Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers.
If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
‘No-tubing’ feature will be a draw for parents of young children
Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”
“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”
Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.
But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”
Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
Pivotal data show benefit in ‘difficult-to-manage’ preschool children
Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.
“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.
A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.
At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05).
Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).
“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.
Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.
In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.
The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.
There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.
Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.
All 80 patients completed the study and elected to continue in a 12-month extension phase.
Ongoing benefit seen in older children and adults
In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.
A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).
There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
Reduced diabetes distress, don’t forget parents’ quality of life
Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.
Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.
“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.
There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.
“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.
Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.
A version of this article first appeared on Medscape.com.
Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.
The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021.
Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.
Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers.
If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
‘No-tubing’ feature will be a draw for parents of young children
Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”
“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”
Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.
But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”
Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
Pivotal data show benefit in ‘difficult-to-manage’ preschool children
Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.
“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.
A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.
At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05).
Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).
“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.
Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.
In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.
The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.
There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.
Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.
All 80 patients completed the study and elected to continue in a 12-month extension phase.
Ongoing benefit seen in older children and adults
In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.
A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).
There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
Reduced diabetes distress, don’t forget parents’ quality of life
Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.
Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.
“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.
There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.
“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.
Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.
A version of this article first appeared on Medscape.com.
Intervention opens access to care for minority youths with type 1 diabetes
For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.
Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.
By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.
The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.
The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.
“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
A NICH for youths with chronic health conditions
The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.
“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”
NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.
While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.
Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.
In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.
Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
Intervention linked to increased BIPOC care access
The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.
While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.
Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.
A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.
Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
Systemic changes needed
This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.
“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.
In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.
Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.
For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.
Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.
By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.
The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.
The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.
“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
A NICH for youths with chronic health conditions
The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.
“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”
NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.
While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.
Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.
In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.
Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
Intervention linked to increased BIPOC care access
The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.
While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.
Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.
A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.
Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
Systemic changes needed
This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.
“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.
In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.
Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.
For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.
Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.
By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.
The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.
The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.
“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
A NICH for youths with chronic health conditions
The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.
“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”
NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.
While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.
Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.
In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.
Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
Intervention linked to increased BIPOC care access
The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.
While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.
Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.
A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.
Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
Systemic changes needed
This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.
“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.
In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.
Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.
FROM ADA 2021
Type 1 diabetes amputation rates fall in Sweden, rise in U.S.
according to a national registry analysis.
The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.
Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.
“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
Drilling down on amputation risk in type 1 diabetes
Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).
“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.
Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.
Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
Trends over time
In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.
The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.
The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.
Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.
Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.
Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
U.S. amputations on the rise overall
While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.
“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”
Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.
To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.
In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.
Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.
according to a national registry analysis.
The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.
Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.
“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
Drilling down on amputation risk in type 1 diabetes
Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).
“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.
Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.
Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
Trends over time
In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.
The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.
The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.
Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.
Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.
Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
U.S. amputations on the rise overall
While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.
“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”
Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.
To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.
In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.
Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.
according to a national registry analysis.
The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.
Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.
“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
Drilling down on amputation risk in type 1 diabetes
Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).
“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.
Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.
Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
Trends over time
In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.
The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.
The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.
Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.
Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.
Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
U.S. amputations on the rise overall
While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.
“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”
Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.
To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.
In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.
Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.
FROM ADA 2020
SUSTAIN FORTE: Higher-dose semaglutide safely boosts glycemic control, weight loss
Accumulating evidence shows that
Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.
“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.
Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).
In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.
Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.
A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
Gradual up-titration aids tolerance
“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”
A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.
The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.
Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).
“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
Several doses to choose from
SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.
The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).
Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.
In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.
SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.
Accumulating evidence shows that
Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.
“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.
Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).
In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.
Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.
A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
Gradual up-titration aids tolerance
“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”
A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.
The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.
Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).
“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
Several doses to choose from
SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.
The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).
Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.
In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.
SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.
Accumulating evidence shows that
Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.
“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.
Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).
In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.
Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.
A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
Gradual up-titration aids tolerance
“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”
A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.
The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.
Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).
“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
Several doses to choose from
SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.
The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).
Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.
In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.
SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.
FROM ADA 2021
‘Staggering’ doubling of type 2 diabetes in children during pandemic
The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.
Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.
And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.
“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
More hospitalizations, racial disparities aggravated by COVID-19
Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”
Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”
Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.
During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.
In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.
The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).
However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.
Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
Shift in diagnoses to type 2 diabetes
The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.
“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.
Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.
Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.
While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.
“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
‘A microcosm’: Similar findings in a smaller population
Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.
Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).
“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.
In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.
Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”
“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.
Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.
Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.
And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.
“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
More hospitalizations, racial disparities aggravated by COVID-19
Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”
Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”
Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.
During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.
In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.
The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).
However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.
Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
Shift in diagnoses to type 2 diabetes
The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.
“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.
Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.
Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.
While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.
“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
‘A microcosm’: Similar findings in a smaller population
Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.
Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).
“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.
In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.
Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”
“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.
Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.
Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.
And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.
“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
More hospitalizations, racial disparities aggravated by COVID-19
Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”
Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”
Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.
During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.
In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.
The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).
However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.
Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
Shift in diagnoses to type 2 diabetes
The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.
“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.
Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.
Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.
While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.
“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
‘A microcosm’: Similar findings in a smaller population
Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.
Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).
“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.
In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.
Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”
“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.
Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.