Miriam E. Tucker

STOCKHOLM – The investigational once-weekly insulin icodec (Novo Nordisk) significantly reduces A1c without increasing hypoglycemia in people with type 2 diabetes, the first phase 3 data of such an insulin formulation suggest. The data are from one of six trials in the company’s ONWARDS program.

“Once-weekly insulin may redefine diabetes management,” enthused Athena Philis-Tsimikas, MD, who presented the findings at a session during the European Association for the Study of Diabetes (EASD) 2022 Annual Meeting, which also included a summary of previously reported top-line data from other ONWARDS trials as well as phase 2 data for Lilly›s investigational once-weekly Basal Insulin Fc (BIF).

Phase 2 data for icodec were published in 2020 in the New England Journal of Medicine and in 2021 in Diabetes Care, as reported by this news organization.

The capacity for reducing the number of basal insulin injections from at least 365 to just 52 per year means that once-weekly insulin “has the potential to facilitate insulin initiation and improve treatment adherence and persistence in diabetes,” noted Dr. Philis-Tsimikas, corporate vice president of Scripps Whittier Diabetes Institute, San Diego.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, told this news organization that the new data from ONWARDS 2 of patients switching from daily to once-weekly basal insulin were reassuring with regard to hypoglycemia, at least for people with type 2 diabetes.

“For type 2, I think there’s enough data now to feel comfortable that it’s going to be good, especially for people who are on once-weekly [glucagon-like peptide-1 (GLP-1) agonists].”

However, for type 1 diabetes, the company reported top-line ONWARDS 6 data earlier this year, in which icodec was associated with significantly increased rates of hypoglycemia compared with daily degludec. “In type 1, even the basal needs are [often] changing. That kind of person would want to stay away from once-weekly insulin,” Dr. Alexander said.

And he noted, for any patient who adjusts their insulin dose frequently, “obviously, you’re not going to be able to do that with a once-weekly.”
 

Similar A1c reduction as daily basal without increased hypoglycemia

In ONWARDS 2, 526 adults with type 2 diabetes were randomized to switch from their current once- or twice-daily basal insulin to either once-weekly icodec or once-daily insulin degludec (Tresiba) for 26 weeks. The study was open-label, with a treat-to-glucose target of 80-130 mg/dL design.

Participants had A1c levels of 7.0%-10.0% and were also taking stable doses of other noninsulin glucose-lowering medications. Over 80% were taking metformin, a third were taking an SGLT2 inhibitor, and about a quarter each were taking a GLP-1 agonist or DPP-4 inhibitor. Those medications were continued, but sulfonylureas were discontinued in the 22% taking those at baseline.

The basal insulin used at baseline was glargine U100 for 42%, degludec for 28%, and glargine U300 for 16%, “so, a very typical presentation of patients we see in our practices today,” Dr. Philis-Tsimikas noted.

The primary endpoint, change in A1c from baseline to week 26, dropped from 8.17% to 7.20% with icodec and from 8.10% to 7.42% with degludec. The estimated treatment difference of –0.22 percentage points met the margins for both noninferiority (P < .0001) and superiority (P = .0028). Those taking icodec were significantly more likely to achieve an A1c under 7% compared with degludec, at 40.3% versus 26.5% (P = .0019).

Continuous glucose monitoring parameters during weeks 22-26 showed time in glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) was 63.1% for icodec and 59.5% for degludec, which was not significantly different, Dr. Philis-Tsimikas reported.

Body weight increased by 1.4 kg (3 lb) with icodec but dropped slightly by 0.30 kg with degludec, which was significantly different (P < .001).

When asked about the body weight results, Dr. Alexander said: “It’s really hard to say. We know that insulin generally causes weight gain. A 1.4-kg weight gain over 6 months isn’t really surprising. Why there wasn’t with degludec, I don’t know.”

There was just one episode of severe hypoglycemia (requiring assistance) in the trial in the degludec group. Rates of combined severe or clinically significant hypoglycemic events (glucose < 54 mg/dL / < 3.0 mmol/L) per patient-year exposed were 0.73 for icodec versus 0.27 for degludec, which was not significantly different (P = .0782). Similar findings were seen for nocturnal hypoglycemia.

Significantly more patients achieved an A1c under 7% without significant hypoglycemia with icodec than degludec, at 36.7% versus 26.8% (P = .0223). Other adverse events were equivalent between the two groups, Dr. Philis-Tsimikas reported.

Scores on the diabetes treatment satisfaction questionnaire, which addresses convenience, flexibility, satisfaction, and willingness to recommend treatment to others, were significantly higher for icodec than degludec, at 4.22 versus 2.96 (P = .0036).

“For me, this is one of the most important outcomes,” she commented.  
 

Benefit in type 2 diabetes, potential concern in type 1 diabetes

Top-line results from ONWARDS 1, a phase 3a 78-week trial in 984 drug-naive people with type 2 diabetes and ONWARDS 6, a 52-week trial in 583 people with type 1 diabetes, were presented earlier this year at the American Diabetes Association 81st Scientific Sessions.

In ONWARDS 1, icodec achieved noninferiority to daily insulin glargine, reducing A1c by 1.55 versus 1.35 percentage points, with superior time in range and no significant differences in hypoglycemia rates.

However, in ONWARDS 6, while noninferiority in A1c lowering compared with daily degludec was achieved, with reductions of 0.47 versus 0.51 percentage points from a baseline A1c of 7.6%, there was a significantly greater rate of severe or clinically significant hypoglycemia with icodec, at 19.93 versus 10.37 events per patient-year with degludec.

Dr. Philis-Tsimikas has reported performing research and serving as an advisor on behalf of her employer for Abbott, Bayer, Dexcom, Eli Lilly, Medtronic, Merck, Novo Nordisk, and Sanofi. All reimbursements go to her employer. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum.

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

STOCKHOLM – The investigational once-weekly insulin icodec (Novo Nordisk) significantly reduces A1c without increasing hypoglycemia in people with type 2 diabetes, the first phase 3 data of such an insulin formulation suggest. The data are from one of six trials in the company’s ONWARDS program.

“Once-weekly insulin may redefine diabetes management,” enthused Athena Philis-Tsimikas, MD, who presented the findings at a session during the European Association for the Study of Diabetes (EASD) 2022 Annual Meeting, which also included a summary of previously reported top-line data from other ONWARDS trials as well as phase 2 data for Lilly›s investigational once-weekly Basal Insulin Fc (BIF).

Phase 2 data for icodec were published in 2020 in the New England Journal of Medicine and in 2021 in Diabetes Care, as reported by this news organization.

The capacity for reducing the number of basal insulin injections from at least 365 to just 52 per year means that once-weekly insulin “has the potential to facilitate insulin initiation and improve treatment adherence and persistence in diabetes,” noted Dr. Philis-Tsimikas, corporate vice president of Scripps Whittier Diabetes Institute, San Diego.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, told this news organization that the new data from ONWARDS 2 of patients switching from daily to once-weekly basal insulin were reassuring with regard to hypoglycemia, at least for people with type 2 diabetes.

“For type 2, I think there’s enough data now to feel comfortable that it’s going to be good, especially for people who are on once-weekly [glucagon-like peptide-1 (GLP-1) agonists].”

However, for type 1 diabetes, the company reported top-line ONWARDS 6 data earlier this year, in which icodec was associated with significantly increased rates of hypoglycemia compared with daily degludec. “In type 1, even the basal needs are [often] changing. That kind of person would want to stay away from once-weekly insulin,” Dr. Alexander said.

And he noted, for any patient who adjusts their insulin dose frequently, “obviously, you’re not going to be able to do that with a once-weekly.”
 

Similar A1c reduction as daily basal without increased hypoglycemia

In ONWARDS 2, 526 adults with type 2 diabetes were randomized to switch from their current once- or twice-daily basal insulin to either once-weekly icodec or once-daily insulin degludec (Tresiba) for 26 weeks. The study was open-label, with a treat-to-glucose target of 80-130 mg/dL design.

Participants had A1c levels of 7.0%-10.0% and were also taking stable doses of other noninsulin glucose-lowering medications. Over 80% were taking metformin, a third were taking an SGLT2 inhibitor, and about a quarter each were taking a GLP-1 agonist or DPP-4 inhibitor. Those medications were continued, but sulfonylureas were discontinued in the 22% taking those at baseline.

The basal insulin used at baseline was glargine U100 for 42%, degludec for 28%, and glargine U300 for 16%, “so, a very typical presentation of patients we see in our practices today,” Dr. Philis-Tsimikas noted.

The primary endpoint, change in A1c from baseline to week 26, dropped from 8.17% to 7.20% with icodec and from 8.10% to 7.42% with degludec. The estimated treatment difference of –0.22 percentage points met the margins for both noninferiority (P < .0001) and superiority (P = .0028). Those taking icodec were significantly more likely to achieve an A1c under 7% compared with degludec, at 40.3% versus 26.5% (P = .0019).

Continuous glucose monitoring parameters during weeks 22-26 showed time in glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) was 63.1% for icodec and 59.5% for degludec, which was not significantly different, Dr. Philis-Tsimikas reported.

Body weight increased by 1.4 kg (3 lb) with icodec but dropped slightly by 0.30 kg with degludec, which was significantly different (P < .001).

When asked about the body weight results, Dr. Alexander said: “It’s really hard to say. We know that insulin generally causes weight gain. A 1.4-kg weight gain over 6 months isn’t really surprising. Why there wasn’t with degludec, I don’t know.”

There was just one episode of severe hypoglycemia (requiring assistance) in the trial in the degludec group. Rates of combined severe or clinically significant hypoglycemic events (glucose < 54 mg/dL / < 3.0 mmol/L) per patient-year exposed were 0.73 for icodec versus 0.27 for degludec, which was not significantly different (P = .0782). Similar findings were seen for nocturnal hypoglycemia.

Significantly more patients achieved an A1c under 7% without significant hypoglycemia with icodec than degludec, at 36.7% versus 26.8% (P = .0223). Other adverse events were equivalent between the two groups, Dr. Philis-Tsimikas reported.

Scores on the diabetes treatment satisfaction questionnaire, which addresses convenience, flexibility, satisfaction, and willingness to recommend treatment to others, were significantly higher for icodec than degludec, at 4.22 versus 2.96 (P = .0036).

“For me, this is one of the most important outcomes,” she commented.  
 

Benefit in type 2 diabetes, potential concern in type 1 diabetes

Top-line results from ONWARDS 1, a phase 3a 78-week trial in 984 drug-naive people with type 2 diabetes and ONWARDS 6, a 52-week trial in 583 people with type 1 diabetes, were presented earlier this year at the American Diabetes Association 81st Scientific Sessions.

In ONWARDS 1, icodec achieved noninferiority to daily insulin glargine, reducing A1c by 1.55 versus 1.35 percentage points, with superior time in range and no significant differences in hypoglycemia rates.

However, in ONWARDS 6, while noninferiority in A1c lowering compared with daily degludec was achieved, with reductions of 0.47 versus 0.51 percentage points from a baseline A1c of 7.6%, there was a significantly greater rate of severe or clinically significant hypoglycemia with icodec, at 19.93 versus 10.37 events per patient-year with degludec.

Dr. Philis-Tsimikas has reported performing research and serving as an advisor on behalf of her employer for Abbott, Bayer, Dexcom, Eli Lilly, Medtronic, Merck, Novo Nordisk, and Sanofi. All reimbursements go to her employer. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum.

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

STOCKHOLM – The investigational once-weekly insulin icodec (Novo Nordisk) significantly reduces A1c without increasing hypoglycemia in people with type 2 diabetes, the first phase 3 data of such an insulin formulation suggest. The data are from one of six trials in the company’s ONWARDS program.

“Once-weekly insulin may redefine diabetes management,” enthused Athena Philis-Tsimikas, MD, who presented the findings at a session during the European Association for the Study of Diabetes (EASD) 2022 Annual Meeting, which also included a summary of previously reported top-line data from other ONWARDS trials as well as phase 2 data for Lilly›s investigational once-weekly Basal Insulin Fc (BIF).

Phase 2 data for icodec were published in 2020 in the New England Journal of Medicine and in 2021 in Diabetes Care, as reported by this news organization.

The capacity for reducing the number of basal insulin injections from at least 365 to just 52 per year means that once-weekly insulin “has the potential to facilitate insulin initiation and improve treatment adherence and persistence in diabetes,” noted Dr. Philis-Tsimikas, corporate vice president of Scripps Whittier Diabetes Institute, San Diego.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, told this news organization that the new data from ONWARDS 2 of patients switching from daily to once-weekly basal insulin were reassuring with regard to hypoglycemia, at least for people with type 2 diabetes.

“For type 2, I think there’s enough data now to feel comfortable that it’s going to be good, especially for people who are on once-weekly [glucagon-like peptide-1 (GLP-1) agonists].”

However, for type 1 diabetes, the company reported top-line ONWARDS 6 data earlier this year, in which icodec was associated with significantly increased rates of hypoglycemia compared with daily degludec. “In type 1, even the basal needs are [often] changing. That kind of person would want to stay away from once-weekly insulin,” Dr. Alexander said.

And he noted, for any patient who adjusts their insulin dose frequently, “obviously, you’re not going to be able to do that with a once-weekly.”
 

Similar A1c reduction as daily basal without increased hypoglycemia

In ONWARDS 2, 526 adults with type 2 diabetes were randomized to switch from their current once- or twice-daily basal insulin to either once-weekly icodec or once-daily insulin degludec (Tresiba) for 26 weeks. The study was open-label, with a treat-to-glucose target of 80-130 mg/dL design.

Participants had A1c levels of 7.0%-10.0% and were also taking stable doses of other noninsulin glucose-lowering medications. Over 80% were taking metformin, a third were taking an SGLT2 inhibitor, and about a quarter each were taking a GLP-1 agonist or DPP-4 inhibitor. Those medications were continued, but sulfonylureas were discontinued in the 22% taking those at baseline.

The basal insulin used at baseline was glargine U100 for 42%, degludec for 28%, and glargine U300 for 16%, “so, a very typical presentation of patients we see in our practices today,” Dr. Philis-Tsimikas noted.

The primary endpoint, change in A1c from baseline to week 26, dropped from 8.17% to 7.20% with icodec and from 8.10% to 7.42% with degludec. The estimated treatment difference of –0.22 percentage points met the margins for both noninferiority (P < .0001) and superiority (P = .0028). Those taking icodec were significantly more likely to achieve an A1c under 7% compared with degludec, at 40.3% versus 26.5% (P = .0019).

Continuous glucose monitoring parameters during weeks 22-26 showed time in glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) was 63.1% for icodec and 59.5% for degludec, which was not significantly different, Dr. Philis-Tsimikas reported.

Body weight increased by 1.4 kg (3 lb) with icodec but dropped slightly by 0.30 kg with degludec, which was significantly different (P < .001).

When asked about the body weight results, Dr. Alexander said: “It’s really hard to say. We know that insulin generally causes weight gain. A 1.4-kg weight gain over 6 months isn’t really surprising. Why there wasn’t with degludec, I don’t know.”

There was just one episode of severe hypoglycemia (requiring assistance) in the trial in the degludec group. Rates of combined severe or clinically significant hypoglycemic events (glucose < 54 mg/dL / < 3.0 mmol/L) per patient-year exposed were 0.73 for icodec versus 0.27 for degludec, which was not significantly different (P = .0782). Similar findings were seen for nocturnal hypoglycemia.

Significantly more patients achieved an A1c under 7% without significant hypoglycemia with icodec than degludec, at 36.7% versus 26.8% (P = .0223). Other adverse events were equivalent between the two groups, Dr. Philis-Tsimikas reported.

Scores on the diabetes treatment satisfaction questionnaire, which addresses convenience, flexibility, satisfaction, and willingness to recommend treatment to others, were significantly higher for icodec than degludec, at 4.22 versus 2.96 (P = .0036).

“For me, this is one of the most important outcomes,” she commented.  
 

Benefit in type 2 diabetes, potential concern in type 1 diabetes

Top-line results from ONWARDS 1, a phase 3a 78-week trial in 984 drug-naive people with type 2 diabetes and ONWARDS 6, a 52-week trial in 583 people with type 1 diabetes, were presented earlier this year at the American Diabetes Association 81st Scientific Sessions.

In ONWARDS 1, icodec achieved noninferiority to daily insulin glargine, reducing A1c by 1.55 versus 1.35 percentage points, with superior time in range and no significant differences in hypoglycemia rates.

However, in ONWARDS 6, while noninferiority in A1c lowering compared with daily degludec was achieved, with reductions of 0.47 versus 0.51 percentage points from a baseline A1c of 7.6%, there was a significantly greater rate of severe or clinically significant hypoglycemia with icodec, at 19.93 versus 10.37 events per patient-year with degludec.

Dr. Philis-Tsimikas has reported performing research and serving as an advisor on behalf of her employer for Abbott, Bayer, Dexcom, Eli Lilly, Medtronic, Merck, Novo Nordisk, and Sanofi. All reimbursements go to her employer. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum.

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

STOCKHOLM – The number of people living with type 1 diabetes worldwide is expected to double by 2040, with most new cases among adults living in low- and middle-income countries, new modeling data suggest.

The forecast, developed from available data collected in the newly established open-source Type 1 Diabetes Index, provides estimates for type 1 diabetes prevalence, incidence, associated mortality, and life expectancy for 201 countries for 2021.

The model also projects estimates for prevalent cases in 2040. It is the first type 1 diabetes dataset to account for the lack of prevalence because of premature mortality, particularly in low- and middle-income countries.

“The worldwide prevalence of type 1 diabetes is substantial and growing. Improved surveillance – particularly in adults who make up most of the population living with type 1 diabetes – is essential to enable improvements to care and outcomes. There is an opportunity to save millions of lives in the coming decades by raising the standard of care (including ensuring universal access to insulin and other essential supplies) and increasing awareness of the signs and symptoms of type 1 diabetes to enable a 100% rate of diagnosis in all countries,” the authors write.

“This work spells out the need for early diagnosis of type 1 diabetes and timely access to quality care,” said Chantal Mathieu, MD, at the European Association for the Study of Diabetes annual meeting.
 

One in five deaths from type 1 diabetes in under 25s

The new findings were published in Lancet Diabetes & Endocrinology by Gabriel A. Gregory, MD, of Life for a Child Program, New South Wales, Australia, and colleagues. The T1D Index Project database was published Sept. 21, 2022.

According to the model, about 8.4 million people were living with type 1 diabetes in 2021, with one-fifth from low- and middle-income countries. An additional 3.7 million died prematurely and would have been added to that count had they lived. One in five of all deaths caused by type 1 diabetes in 2021 is estimated to have occurred in people younger than age 25 years because of nondiagnosis.

“It is unacceptable that, in 2022, some 35,000 people worldwide are dying undiagnosed within a year of onset of symptoms. There also continues to be a huge disparity in life expectancy for people with type 1 diabetes, hitting those in the poorest countries hardest,” noted Dr. Mathieu, who is senior vice-president of EASD and an endocrinologist based at KU Leuven, Belgium.

By 2040, the model predicts that between 13.5 million and 17.4 million people will be living with the condition, with the largest relative increase from 2021 in low-income and lower-middle-income countries. The majority of incident and prevalent cases of type 1 diabetes are in adults, with an estimated 62% of 510,000 new diagnoses worldwide in 2021 occurring in people aged 20 years and older.
 

Type 1 diabetes is not predominantly a disease of childhood

Dr. Mathieu also noted that the data dispute the long-held view of type 1 diabetes as a predominantly pediatric condition. Indeed, worldwide, the median age for a person living with type 1 diabetes is 37 years.

“While type 1 diabetes is often referred to as ‘child-onset’ diabetes, this important study shows that only around one in five living with the condition are aged 20 years or younger, two-thirds are aged 20-64 years, and a further one in five are aged 65 years or older.”

“This condition does not stop at age 18 years – the children become adults, and the adults become elderly. All countries must examine and strengthen their diagnosis and care pathways for people of all ages living with type 1 diabetes,” Dr. Mathieu emphasized.

And in an accompanying editorial, Serena Jingchuan Guo, MD, PhD, and Hui Shao, MD, PhD, point out that most studies that estimate diabetes burden have focused on type 2 diabetes, noting, “type 1 diabetes faces the challenges of misdiagnosis, underdiagnosis, high risk of complications, and premature mortality.”

The insulin affordability issue is central, point out Dr. Guo and Dr. Shao of the Center for Drug Evaluation and Safety, department of pharmaceutical evaluation and policy, University of Florida College of Pharmacy, Gainesville.

“Countries need to strengthen the price regulation and reimbursement policy for insulin while building subsidy programs to ensure insulin access and to cope with the growing demand for insulin. Meanwhile, optimizing the insulin supply chain between manufacturers and patients while seeking alternative treatment options (for example, biosimilar products) will also improve the current situation,” they conclude.   

The study was funded by JDRF, of which four coauthors are employees. The editorialists have reported no relevant financial relationships.

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

STOCKHOLM – The number of people living with type 1 diabetes worldwide is expected to double by 2040, with most new cases among adults living in low- and middle-income countries, new modeling data suggest.

The forecast, developed from available data collected in the newly established open-source Type 1 Diabetes Index, provides estimates for type 1 diabetes prevalence, incidence, associated mortality, and life expectancy for 201 countries for 2021.

The model also projects estimates for prevalent cases in 2040. It is the first type 1 diabetes dataset to account for the lack of prevalence because of premature mortality, particularly in low- and middle-income countries.

“The worldwide prevalence of type 1 diabetes is substantial and growing. Improved surveillance – particularly in adults who make up most of the population living with type 1 diabetes – is essential to enable improvements to care and outcomes. There is an opportunity to save millions of lives in the coming decades by raising the standard of care (including ensuring universal access to insulin and other essential supplies) and increasing awareness of the signs and symptoms of type 1 diabetes to enable a 100% rate of diagnosis in all countries,” the authors write.

“This work spells out the need for early diagnosis of type 1 diabetes and timely access to quality care,” said Chantal Mathieu, MD, at the European Association for the Study of Diabetes annual meeting.
 

One in five deaths from type 1 diabetes in under 25s

The new findings were published in Lancet Diabetes & Endocrinology by Gabriel A. Gregory, MD, of Life for a Child Program, New South Wales, Australia, and colleagues. The T1D Index Project database was published Sept. 21, 2022.

According to the model, about 8.4 million people were living with type 1 diabetes in 2021, with one-fifth from low- and middle-income countries. An additional 3.7 million died prematurely and would have been added to that count had they lived. One in five of all deaths caused by type 1 diabetes in 2021 is estimated to have occurred in people younger than age 25 years because of nondiagnosis.

“It is unacceptable that, in 2022, some 35,000 people worldwide are dying undiagnosed within a year of onset of symptoms. There also continues to be a huge disparity in life expectancy for people with type 1 diabetes, hitting those in the poorest countries hardest,” noted Dr. Mathieu, who is senior vice-president of EASD and an endocrinologist based at KU Leuven, Belgium.

By 2040, the model predicts that between 13.5 million and 17.4 million people will be living with the condition, with the largest relative increase from 2021 in low-income and lower-middle-income countries. The majority of incident and prevalent cases of type 1 diabetes are in adults, with an estimated 62% of 510,000 new diagnoses worldwide in 2021 occurring in people aged 20 years and older.
 

Type 1 diabetes is not predominantly a disease of childhood

Dr. Mathieu also noted that the data dispute the long-held view of type 1 diabetes as a predominantly pediatric condition. Indeed, worldwide, the median age for a person living with type 1 diabetes is 37 years.

“While type 1 diabetes is often referred to as ‘child-onset’ diabetes, this important study shows that only around one in five living with the condition are aged 20 years or younger, two-thirds are aged 20-64 years, and a further one in five are aged 65 years or older.”

“This condition does not stop at age 18 years – the children become adults, and the adults become elderly. All countries must examine and strengthen their diagnosis and care pathways for people of all ages living with type 1 diabetes,” Dr. Mathieu emphasized.

And in an accompanying editorial, Serena Jingchuan Guo, MD, PhD, and Hui Shao, MD, PhD, point out that most studies that estimate diabetes burden have focused on type 2 diabetes, noting, “type 1 diabetes faces the challenges of misdiagnosis, underdiagnosis, high risk of complications, and premature mortality.”

The insulin affordability issue is central, point out Dr. Guo and Dr. Shao of the Center for Drug Evaluation and Safety, department of pharmaceutical evaluation and policy, University of Florida College of Pharmacy, Gainesville.

“Countries need to strengthen the price regulation and reimbursement policy for insulin while building subsidy programs to ensure insulin access and to cope with the growing demand for insulin. Meanwhile, optimizing the insulin supply chain between manufacturers and patients while seeking alternative treatment options (for example, biosimilar products) will also improve the current situation,” they conclude.   

The study was funded by JDRF, of which four coauthors are employees. The editorialists have reported no relevant financial relationships.

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

STOCKHOLM – The number of people living with type 1 diabetes worldwide is expected to double by 2040, with most new cases among adults living in low- and middle-income countries, new modeling data suggest.

The forecast, developed from available data collected in the newly established open-source Type 1 Diabetes Index, provides estimates for type 1 diabetes prevalence, incidence, associated mortality, and life expectancy for 201 countries for 2021.

The model also projects estimates for prevalent cases in 2040. It is the first type 1 diabetes dataset to account for the lack of prevalence because of premature mortality, particularly in low- and middle-income countries.

“The worldwide prevalence of type 1 diabetes is substantial and growing. Improved surveillance – particularly in adults who make up most of the population living with type 1 diabetes – is essential to enable improvements to care and outcomes. There is an opportunity to save millions of lives in the coming decades by raising the standard of care (including ensuring universal access to insulin and other essential supplies) and increasing awareness of the signs and symptoms of type 1 diabetes to enable a 100% rate of diagnosis in all countries,” the authors write.

“This work spells out the need for early diagnosis of type 1 diabetes and timely access to quality care,” said Chantal Mathieu, MD, at the European Association for the Study of Diabetes annual meeting.
 

One in five deaths from type 1 diabetes in under 25s

The new findings were published in Lancet Diabetes & Endocrinology by Gabriel A. Gregory, MD, of Life for a Child Program, New South Wales, Australia, and colleagues. The T1D Index Project database was published Sept. 21, 2022.

According to the model, about 8.4 million people were living with type 1 diabetes in 2021, with one-fifth from low- and middle-income countries. An additional 3.7 million died prematurely and would have been added to that count had they lived. One in five of all deaths caused by type 1 diabetes in 2021 is estimated to have occurred in people younger than age 25 years because of nondiagnosis.

“It is unacceptable that, in 2022, some 35,000 people worldwide are dying undiagnosed within a year of onset of symptoms. There also continues to be a huge disparity in life expectancy for people with type 1 diabetes, hitting those in the poorest countries hardest,” noted Dr. Mathieu, who is senior vice-president of EASD and an endocrinologist based at KU Leuven, Belgium.

By 2040, the model predicts that between 13.5 million and 17.4 million people will be living with the condition, with the largest relative increase from 2021 in low-income and lower-middle-income countries. The majority of incident and prevalent cases of type 1 diabetes are in adults, with an estimated 62% of 510,000 new diagnoses worldwide in 2021 occurring in people aged 20 years and older.
 

Type 1 diabetes is not predominantly a disease of childhood

Dr. Mathieu also noted that the data dispute the long-held view of type 1 diabetes as a predominantly pediatric condition. Indeed, worldwide, the median age for a person living with type 1 diabetes is 37 years.

“While type 1 diabetes is often referred to as ‘child-onset’ diabetes, this important study shows that only around one in five living with the condition are aged 20 years or younger, two-thirds are aged 20-64 years, and a further one in five are aged 65 years or older.”

“This condition does not stop at age 18 years – the children become adults, and the adults become elderly. All countries must examine and strengthen their diagnosis and care pathways for people of all ages living with type 1 diabetes,” Dr. Mathieu emphasized.

And in an accompanying editorial, Serena Jingchuan Guo, MD, PhD, and Hui Shao, MD, PhD, point out that most studies that estimate diabetes burden have focused on type 2 diabetes, noting, “type 1 diabetes faces the challenges of misdiagnosis, underdiagnosis, high risk of complications, and premature mortality.”

The insulin affordability issue is central, point out Dr. Guo and Dr. Shao of the Center for Drug Evaluation and Safety, department of pharmaceutical evaluation and policy, University of Florida College of Pharmacy, Gainesville.

“Countries need to strengthen the price regulation and reimbursement policy for insulin while building subsidy programs to ensure insulin access and to cope with the growing demand for insulin. Meanwhile, optimizing the insulin supply chain between manufacturers and patients while seeking alternative treatment options (for example, biosimilar products) will also improve the current situation,” they conclude.   

The study was funded by JDRF, of which four coauthors are employees. The editorialists have reported no relevant financial relationships.

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

STOCKHOLM – Weight loss should be a co–primary management goal for type 2 diabetes in adults, according to a new comprehensive joint consensus report from the European Association for the Study of Diabetes and the American Diabetes Association.

And while metformin is still recommended as first-line therapy for patients with type 2 diabetes with no other comorbidities, the statement expands the indications for use of other agents or combinations of agents as initial therapy for subgroups of patients, as part of individualized and patient-centered decision-making.

Last updated in 2019, the new “Management of Hyperglycemia in Type 2 Diabetes” statement also places increased emphasis on social determinants of health, incorporates recent clinical trial data for cardiovascular and kidney outcomes for sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists to broaden recommendations for cardiorenal protection, and discusses health behaviors such as sleep and sitting. It also targets a wider audience than in the past by addressing health system organization to optimize delivery of diabetes care.

The new statement was presented during a 90-minute session at the annual meeting of the EASD, with 12 of its 14 European and American authors as presenters. The document was simultaneously published in Diabetologia and Diabetes Care.

During the discussion, panel member Jennifer Brigitte Green, MD, commented: “Many of these recommendations are not new. They’re modest revisions of recommendations that have been in place for years, but we know that actual implementation rates of use of these drugs in patients with established comorbidities are very low.”

“I think it’s time for communities, health care systems, etc, to actually introduce these as expectations of care... to assess quality because unless it’s considered formally to be a requirement of care I just don’t think we’re going to move that needle very much,” added Dr. Green, who is professor of medicine at Duke University, Durham, N.C.

Vanita R. Aroda, MD, of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, commented: “In the past, sometimes these recommendations created fodder for debate, but I don’t think this one will. It’s just really solidly evidence based, with the rationales presented throughout, including the figures. I think just having very clear evidence-based directions should support their dissemination and use.”
 

Weight management plays a prominent role in treatment

In an interview, writing panel cochair John B. Buse, MD, PhD, said: “We are saying that the four major components of type 2 diabetes care are glycemic management, cardiovascular risk management, weight management, and prevention of end-organ damage, particularly with regard to cardiorenal risk.”

“The weight management piece is much more explicit now,” said Dr. Buse, director of the Diabetes Center at the University of North Carolina at Chapel Hill.

He noted that recent evidence from the intensive lifestyle trial DiRECT, conducted in the United Kingdom, the bariatric surgery literature, and the emergence of potent weight-loss drugs have meant that “achieving 10%-15% body weight loss is now possible.

“So, aiming for remission is something that might be attractive to patients and providers. This could be based on weight management, with the [chosen] method based on shared decision-making.”

According to the new report: “Weight loss of 5%-10% confers metabolic improvement; weight loss of 10%-15% or more can have a disease-modifying effect and lead to remission of diabetes, defined as normal blood glucose levels for 3 months or more in the absence of pharmacological therapy in a 2021 consensus report.”

“Weight loss may exert benefits that extend beyond glycemic management to improve risk factors for cardiometabolic disease and quality of life,” it adds.
 

Individualization featured throughout

The report’s sections cover principles of care, including the importance of diabetes self-management education and support and avoidance of therapeutic inertia. Detailed guidance addresses therapeutic options including lifestyle, weight management, and pharmacotherapy for treating type 2 diabetes.

Another entire section is devoted to personalizing treatment approaches based on individual characteristics, including new evidence from cardiorenal outcomes studies for SGLT2 inhibitors and GLP-1 agonists that have come out since the last consensus report.

The document advises: “Consider initial combination therapy with glucose-lowering agents, especially in those with high [hemoglobin] A1c at diagnosis (that is, > 70 mmol/mol [> 8.5%]), in younger people with type 2 diabetes (regardless of A1c), and in those in whom a stepwise approach would delay access to agents that provide cardiorenal protection beyond their glucose-lowering effects.”
 

Designed to be used and user-friendly

Under the “Putting it all together: strategies for implementation” section, several lists of “practical tips for clinicians” are provided for many of the topics covered.

A series of colorful infographics are included as well, addressing the “decision cycle for person-centered glycemic management in type 2 diabetes,” including a chart summarizing characteristics of available glucose-lowering medications, including cardiorenal protection.

Also mentioned is the importance of 24-hour physical behaviors (including sleep, sitting, and sweating) and the impact on cardiometabolic health, use of a “holistic person-centered approach” to type 2 diabetes management, and an algorithm on insulin use.

Dr. Buse has financial ties to numerous drug and device companies. Dr. Green is a consultant for AstraZeneca, Pfizer, Boehringer Ingelheim/Lilly, Bayer, Sanofi, Anji, Vertex/ICON, and Valo. Dr. Aroda has served as a consultant for Applied Therapeutics, Duke, Fractyl, Novo Nordisk, Pfizer, and Sanofi.

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

STOCKHOLM – Weight loss should be a co–primary management goal for type 2 diabetes in adults, according to a new comprehensive joint consensus report from the European Association for the Study of Diabetes and the American Diabetes Association.

And while metformin is still recommended as first-line therapy for patients with type 2 diabetes with no other comorbidities, the statement expands the indications for use of other agents or combinations of agents as initial therapy for subgroups of patients, as part of individualized and patient-centered decision-making.

Last updated in 2019, the new “Management of Hyperglycemia in Type 2 Diabetes” statement also places increased emphasis on social determinants of health, incorporates recent clinical trial data for cardiovascular and kidney outcomes for sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists to broaden recommendations for cardiorenal protection, and discusses health behaviors such as sleep and sitting. It also targets a wider audience than in the past by addressing health system organization to optimize delivery of diabetes care.

The new statement was presented during a 90-minute session at the annual meeting of the EASD, with 12 of its 14 European and American authors as presenters. The document was simultaneously published in Diabetologia and Diabetes Care.

During the discussion, panel member Jennifer Brigitte Green, MD, commented: “Many of these recommendations are not new. They’re modest revisions of recommendations that have been in place for years, but we know that actual implementation rates of use of these drugs in patients with established comorbidities are very low.”

“I think it’s time for communities, health care systems, etc, to actually introduce these as expectations of care... to assess quality because unless it’s considered formally to be a requirement of care I just don’t think we’re going to move that needle very much,” added Dr. Green, who is professor of medicine at Duke University, Durham, N.C.

Vanita R. Aroda, MD, of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, commented: “In the past, sometimes these recommendations created fodder for debate, but I don’t think this one will. It’s just really solidly evidence based, with the rationales presented throughout, including the figures. I think just having very clear evidence-based directions should support their dissemination and use.”
 

Weight management plays a prominent role in treatment

In an interview, writing panel cochair John B. Buse, MD, PhD, said: “We are saying that the four major components of type 2 diabetes care are glycemic management, cardiovascular risk management, weight management, and prevention of end-organ damage, particularly with regard to cardiorenal risk.”

“The weight management piece is much more explicit now,” said Dr. Buse, director of the Diabetes Center at the University of North Carolina at Chapel Hill.

He noted that recent evidence from the intensive lifestyle trial DiRECT, conducted in the United Kingdom, the bariatric surgery literature, and the emergence of potent weight-loss drugs have meant that “achieving 10%-15% body weight loss is now possible.

“So, aiming for remission is something that might be attractive to patients and providers. This could be based on weight management, with the [chosen] method based on shared decision-making.”

According to the new report: “Weight loss of 5%-10% confers metabolic improvement; weight loss of 10%-15% or more can have a disease-modifying effect and lead to remission of diabetes, defined as normal blood glucose levels for 3 months or more in the absence of pharmacological therapy in a 2021 consensus report.”

“Weight loss may exert benefits that extend beyond glycemic management to improve risk factors for cardiometabolic disease and quality of life,” it adds.
 

Individualization featured throughout

The report’s sections cover principles of care, including the importance of diabetes self-management education and support and avoidance of therapeutic inertia. Detailed guidance addresses therapeutic options including lifestyle, weight management, and pharmacotherapy for treating type 2 diabetes.

Another entire section is devoted to personalizing treatment approaches based on individual characteristics, including new evidence from cardiorenal outcomes studies for SGLT2 inhibitors and GLP-1 agonists that have come out since the last consensus report.

The document advises: “Consider initial combination therapy with glucose-lowering agents, especially in those with high [hemoglobin] A1c at diagnosis (that is, > 70 mmol/mol [> 8.5%]), in younger people with type 2 diabetes (regardless of A1c), and in those in whom a stepwise approach would delay access to agents that provide cardiorenal protection beyond their glucose-lowering effects.”
 

Designed to be used and user-friendly

Under the “Putting it all together: strategies for implementation” section, several lists of “practical tips for clinicians” are provided for many of the topics covered.

A series of colorful infographics are included as well, addressing the “decision cycle for person-centered glycemic management in type 2 diabetes,” including a chart summarizing characteristics of available glucose-lowering medications, including cardiorenal protection.

Also mentioned is the importance of 24-hour physical behaviors (including sleep, sitting, and sweating) and the impact on cardiometabolic health, use of a “holistic person-centered approach” to type 2 diabetes management, and an algorithm on insulin use.

Dr. Buse has financial ties to numerous drug and device companies. Dr. Green is a consultant for AstraZeneca, Pfizer, Boehringer Ingelheim/Lilly, Bayer, Sanofi, Anji, Vertex/ICON, and Valo. Dr. Aroda has served as a consultant for Applied Therapeutics, Duke, Fractyl, Novo Nordisk, Pfizer, and Sanofi.

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

STOCKHOLM – Weight loss should be a co–primary management goal for type 2 diabetes in adults, according to a new comprehensive joint consensus report from the European Association for the Study of Diabetes and the American Diabetes Association.

And while metformin is still recommended as first-line therapy for patients with type 2 diabetes with no other comorbidities, the statement expands the indications for use of other agents or combinations of agents as initial therapy for subgroups of patients, as part of individualized and patient-centered decision-making.

Last updated in 2019, the new “Management of Hyperglycemia in Type 2 Diabetes” statement also places increased emphasis on social determinants of health, incorporates recent clinical trial data for cardiovascular and kidney outcomes for sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagonlike peptide–1 (GLP-1) agonists to broaden recommendations for cardiorenal protection, and discusses health behaviors such as sleep and sitting. It also targets a wider audience than in the past by addressing health system organization to optimize delivery of diabetes care.

The new statement was presented during a 90-minute session at the annual meeting of the EASD, with 12 of its 14 European and American authors as presenters. The document was simultaneously published in Diabetologia and Diabetes Care.

During the discussion, panel member Jennifer Brigitte Green, MD, commented: “Many of these recommendations are not new. They’re modest revisions of recommendations that have been in place for years, but we know that actual implementation rates of use of these drugs in patients with established comorbidities are very low.”

“I think it’s time for communities, health care systems, etc, to actually introduce these as expectations of care... to assess quality because unless it’s considered formally to be a requirement of care I just don’t think we’re going to move that needle very much,” added Dr. Green, who is professor of medicine at Duke University, Durham, N.C.

Vanita R. Aroda, MD, of the division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, commented: “In the past, sometimes these recommendations created fodder for debate, but I don’t think this one will. It’s just really solidly evidence based, with the rationales presented throughout, including the figures. I think just having very clear evidence-based directions should support their dissemination and use.”
 

Weight management plays a prominent role in treatment

In an interview, writing panel cochair John B. Buse, MD, PhD, said: “We are saying that the four major components of type 2 diabetes care are glycemic management, cardiovascular risk management, weight management, and prevention of end-organ damage, particularly with regard to cardiorenal risk.”

“The weight management piece is much more explicit now,” said Dr. Buse, director of the Diabetes Center at the University of North Carolina at Chapel Hill.

He noted that recent evidence from the intensive lifestyle trial DiRECT, conducted in the United Kingdom, the bariatric surgery literature, and the emergence of potent weight-loss drugs have meant that “achieving 10%-15% body weight loss is now possible.

“So, aiming for remission is something that might be attractive to patients and providers. This could be based on weight management, with the [chosen] method based on shared decision-making.”

According to the new report: “Weight loss of 5%-10% confers metabolic improvement; weight loss of 10%-15% or more can have a disease-modifying effect and lead to remission of diabetes, defined as normal blood glucose levels for 3 months or more in the absence of pharmacological therapy in a 2021 consensus report.”

“Weight loss may exert benefits that extend beyond glycemic management to improve risk factors for cardiometabolic disease and quality of life,” it adds.
 

Individualization featured throughout

The report’s sections cover principles of care, including the importance of diabetes self-management education and support and avoidance of therapeutic inertia. Detailed guidance addresses therapeutic options including lifestyle, weight management, and pharmacotherapy for treating type 2 diabetes.

Another entire section is devoted to personalizing treatment approaches based on individual characteristics, including new evidence from cardiorenal outcomes studies for SGLT2 inhibitors and GLP-1 agonists that have come out since the last consensus report.

The document advises: “Consider initial combination therapy with glucose-lowering agents, especially in those with high [hemoglobin] A1c at diagnosis (that is, > 70 mmol/mol [> 8.5%]), in younger people with type 2 diabetes (regardless of A1c), and in those in whom a stepwise approach would delay access to agents that provide cardiorenal protection beyond their glucose-lowering effects.”
 

Designed to be used and user-friendly

Under the “Putting it all together: strategies for implementation” section, several lists of “practical tips for clinicians” are provided for many of the topics covered.

A series of colorful infographics are included as well, addressing the “decision cycle for person-centered glycemic management in type 2 diabetes,” including a chart summarizing characteristics of available glucose-lowering medications, including cardiorenal protection.

Also mentioned is the importance of 24-hour physical behaviors (including sleep, sitting, and sweating) and the impact on cardiometabolic health, use of a “holistic person-centered approach” to type 2 diabetes management, and an algorithm on insulin use.

Dr. Buse has financial ties to numerous drug and device companies. Dr. Green is a consultant for AstraZeneca, Pfizer, Boehringer Ingelheim/Lilly, Bayer, Sanofi, Anji, Vertex/ICON, and Valo. Dr. Aroda has served as a consultant for Applied Therapeutics, Duke, Fractyl, Novo Nordisk, Pfizer, and Sanofi.

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

Long-term A1c from the time of type 1 diabetes diagnosis strongly predicts the development of severe retinopathy and nephropathy, new data suggest.

“[Weighted] HbA1c followed from diagnosis is a very strong biomarker for pan-retinal laser-treated diabetic retinopathy (PDR) and nephropathy, [and] the prevalence of both is still increasing 32 years after diagnosis,” say Hans J. Arnqvist, MD, and colleagues in their study published online Sept. 12 in Diabetes Care.

The results are from a 32-year follow-up of 447 patients from time of diagnosis of type 1 diabetes at age 0-34 in the Vascular Diabetic Complications in Southeast Sweden study.

“To avoid PDR and macroalbuminuria in patients with type 1 diabetes, A1c less than 7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life,” stress Dr. Arnqvist, department of endocrinology, Linköping University (Sweden), and coauthors.

At the time of the 20- to 24-year VISS follow-up, severe eye complications, defined as PDR, or nephropathy, defined as macroalbuminuria, were not present in participants with a long-term weighted mean A1c less than 7.6% (60 mmol/mol), they write.
 

Is explanation an increase in glycemic burden with diabetes duration?

By years 32-36, the prevalence of PDR had risen from 14% to 27%, and macroalbuminuria from 4% to 8%, with prevalence strongly correlated with A1c levels. At the same time, the threshold for the appearance of those severe complications dropped, with the lowest A1c values for appearance of PDR decreasing from 7.6% to 7.3% and for macroalbuminuria from 8.4% to 8.1%.

“A possible explanation for the lowered threshold for development of severe microangiopathy is the increase in ‘glycemic burden’ with diabetes duration,” the authors speculate.

In all A1c categories above 6.7% (> 50 mmol/mol), the cumulative proportion with PDR and/or macroproteinuria continued to increase up to at least 32 years of diabetes duration.

At the highest A1c quintile, greater than 9.5% (> 80mmol/mol), 75% had developed PDR and 44.2% had macroalbuminuria.

These findings align with guidelines from both the International Society for Pediatric and Adolescent Diabetes, which recommend A1c less than 7% (53 mmol/mol) as a treatment goal, and the UK National Institute for Health and Care Excellence, which advises a target A1c of 6.5% (48 mmol/mol) or lower in children and adults with type 1 diabetes.

The American Diabetes Association recommends individualized A1c targets ranging from 6.5% to 8.0%.

The study was supported by Barndiabetesfonden (Swedish Children’s Diabetes Foundation) and Region Ostergotlands Stiftelsefonder. The authors reported no further disclosures.

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

Long-term A1c from the time of type 1 diabetes diagnosis strongly predicts the development of severe retinopathy and nephropathy, new data suggest.

“[Weighted] HbA1c followed from diagnosis is a very strong biomarker for pan-retinal laser-treated diabetic retinopathy (PDR) and nephropathy, [and] the prevalence of both is still increasing 32 years after diagnosis,” say Hans J. Arnqvist, MD, and colleagues in their study published online Sept. 12 in Diabetes Care.

The results are from a 32-year follow-up of 447 patients from time of diagnosis of type 1 diabetes at age 0-34 in the Vascular Diabetic Complications in Southeast Sweden study.

“To avoid PDR and macroalbuminuria in patients with type 1 diabetes, A1c less than 7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life,” stress Dr. Arnqvist, department of endocrinology, Linköping University (Sweden), and coauthors.

At the time of the 20- to 24-year VISS follow-up, severe eye complications, defined as PDR, or nephropathy, defined as macroalbuminuria, were not present in participants with a long-term weighted mean A1c less than 7.6% (60 mmol/mol), they write.
 

Is explanation an increase in glycemic burden with diabetes duration?

By years 32-36, the prevalence of PDR had risen from 14% to 27%, and macroalbuminuria from 4% to 8%, with prevalence strongly correlated with A1c levels. At the same time, the threshold for the appearance of those severe complications dropped, with the lowest A1c values for appearance of PDR decreasing from 7.6% to 7.3% and for macroalbuminuria from 8.4% to 8.1%.

“A possible explanation for the lowered threshold for development of severe microangiopathy is the increase in ‘glycemic burden’ with diabetes duration,” the authors speculate.

In all A1c categories above 6.7% (> 50 mmol/mol), the cumulative proportion with PDR and/or macroproteinuria continued to increase up to at least 32 years of diabetes duration.

At the highest A1c quintile, greater than 9.5% (> 80mmol/mol), 75% had developed PDR and 44.2% had macroalbuminuria.

These findings align with guidelines from both the International Society for Pediatric and Adolescent Diabetes, which recommend A1c less than 7% (53 mmol/mol) as a treatment goal, and the UK National Institute for Health and Care Excellence, which advises a target A1c of 6.5% (48 mmol/mol) or lower in children and adults with type 1 diabetes.

The American Diabetes Association recommends individualized A1c targets ranging from 6.5% to 8.0%.

The study was supported by Barndiabetesfonden (Swedish Children’s Diabetes Foundation) and Region Ostergotlands Stiftelsefonder. The authors reported no further disclosures.

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

Long-term A1c from the time of type 1 diabetes diagnosis strongly predicts the development of severe retinopathy and nephropathy, new data suggest.

“[Weighted] HbA1c followed from diagnosis is a very strong biomarker for pan-retinal laser-treated diabetic retinopathy (PDR) and nephropathy, [and] the prevalence of both is still increasing 32 years after diagnosis,” say Hans J. Arnqvist, MD, and colleagues in their study published online Sept. 12 in Diabetes Care.

The results are from a 32-year follow-up of 447 patients from time of diagnosis of type 1 diabetes at age 0-34 in the Vascular Diabetic Complications in Southeast Sweden study.

“To avoid PDR and macroalbuminuria in patients with type 1 diabetes, A1c less than 7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life,” stress Dr. Arnqvist, department of endocrinology, Linköping University (Sweden), and coauthors.

At the time of the 20- to 24-year VISS follow-up, severe eye complications, defined as PDR, or nephropathy, defined as macroalbuminuria, were not present in participants with a long-term weighted mean A1c less than 7.6% (60 mmol/mol), they write.
 

Is explanation an increase in glycemic burden with diabetes duration?

By years 32-36, the prevalence of PDR had risen from 14% to 27%, and macroalbuminuria from 4% to 8%, with prevalence strongly correlated with A1c levels. At the same time, the threshold for the appearance of those severe complications dropped, with the lowest A1c values for appearance of PDR decreasing from 7.6% to 7.3% and for macroalbuminuria from 8.4% to 8.1%.

“A possible explanation for the lowered threshold for development of severe microangiopathy is the increase in ‘glycemic burden’ with diabetes duration,” the authors speculate.

In all A1c categories above 6.7% (> 50 mmol/mol), the cumulative proportion with PDR and/or macroproteinuria continued to increase up to at least 32 years of diabetes duration.

At the highest A1c quintile, greater than 9.5% (> 80mmol/mol), 75% had developed PDR and 44.2% had macroalbuminuria.

These findings align with guidelines from both the International Society for Pediatric and Adolescent Diabetes, which recommend A1c less than 7% (53 mmol/mol) as a treatment goal, and the UK National Institute for Health and Care Excellence, which advises a target A1c of 6.5% (48 mmol/mol) or lower in children and adults with type 1 diabetes.

The American Diabetes Association recommends individualized A1c targets ranging from 6.5% to 8.0%.

The study was supported by Barndiabetesfonden (Swedish Children’s Diabetes Foundation) and Region Ostergotlands Stiftelsefonder. The authors reported no further disclosures.

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

STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.

“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.

baibaz/iStock/Getty Images

She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.

The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.

Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.

“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.

The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.

Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”

And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.

“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
 

Red meat damages, dairy protects

The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.

Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).

The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).

Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.

And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.

Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
 

What are the mechanisms?

The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.

In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”

Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”

Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”

And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.

What about vegan diets? The devil is in the details

Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”

“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”

Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.

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

STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.

“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.

baibaz/iStock/Getty Images

She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.

The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.

Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.

“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.

The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.

Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”

And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.

“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
 

Red meat damages, dairy protects

The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.

Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).

The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).

Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.

And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.

Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
 

What are the mechanisms?

The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.

In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”

Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”

Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”

And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.

What about vegan diets? The devil is in the details

Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”

“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”

Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.

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

STOCKHOLM – Among animal protein foods, low-fat dairy consumption may minimize the risk of developing type 2 diabetes while red meat raises that risk, a new analysis finds.

“A plant-based dietary pattern with limited intake of meat, moderate intake of fish, eggs, and full-fat dairy, and habitual consumption of yogurt, milk, or low-fat dairy, might represent the most feasible, sustainable, and successful population strategy to optimize the prevention of type 2 diabetes,” lead author Annalisa Giosuè, MD, of the University of Naples (Italy) Federico II, told this news organization.

baibaz/iStock/Getty Images

She presented the findings from an umbrella review of 13 dose-response meta-analyses of prospective cohort studies at the annual meeting of the European Association for the Study of Diabetes.

The study is believed to be the first comprehensive overview of the available evidence from all published meta-analyses on the relationship between well-defined amounts of animal-origin foods and the risk of type 2 diabetes.

Dr. Giosuè and colleagues focused on animal-based foods because they represent a gap in most guidelines for type 2 diabetes prevention, she explained.

“The existing evidence and dietary recommendations for type 2 diabetes prevention are mainly based on the appropriate consumption of plant foods: high amounts of the fiber-rich ones and low consumption of the refined ones as well as those rich in free sugars. And also on the adequate choice among fat sources – reduction of saturated fat sources like butter and cream and replacement with plant-based poly- and monounsaturated fat sources like nontropical vegetable oils. But not on the most suitable choices among different animal foods for the prevention of type 2 diabetes,” she explained.

The new findings are in line with the Mediterranean diet in that, while plant based, it also limits red-meat consumption, but not all animal-based foods, and has consistently been associated with a reduced risk of type 2 diabetes. Vegetarian diets have also been associated with a reduced risk of type 2 diabetes, but far less evidence is available for that, she said.

Asked for comment, session moderator Matthias Schulze, MD, head of the department of molecular epidemiology at the German Institute of Human Nutrition, Berlin, said: “Decreasing intake of red and processed meat is already a strong recommendation, and these data support that. You have to make choices for and against [certain] foods. So, if you decide to eat less red meat, then the question is what do you eat instead? This study shows that specifically other animal products, like dairy and ... fish or white meat sources ... are healthy among the animal-based foods. But you could also obviously look at plant-based foods as protein sources as well.”

And Dr. Schulze noted that the data suggest another dimension to type 2 diabetes prevention beyond simply focusing on weight loss.

“You can achieve weight loss with very different diets. Diet quality plays an important role. These data support that if you look at diabetes prevention, then you would focus on people with high intakes of specific animal-based foods, besides looking at overweight and obesity. Then you could intervene to reduce this intake, with potential substitutions with other animal foods like fish or white meat, or plant-based sources of proteins.”
 

Red meat damages, dairy protects

The 13 meta-analyses included 175 summary risk ratios for type 2 diabetes incidence for the consumption of total meat, red meat, white meat, processed meats, fish, total dairy, full-fat dairy, low-fat dairy, milk, cheese, yogurt, or eggs.

Significant increases in the risk of developing type 2 diabetes were found for consumption of 100 g/day of total meat (SRR, 1.20; 20% increase) and red meat (SRR, 1.22, 22% increase) and with 50 g/day of processed meats (SRR, 1.30; 30% increase). A borderline increased risk was also seen for 50 g/day of white meat (SRR, 1.04; 4% increase).

The opposite was found for dairy foods. Inverse associations for type 2 diabetes development were found for an intake of 200 g/day of total dairy (SRR, 0.95; 5% reduction), low-fat dairy (SRR, 0.96; 4% reduction), milk (SRR, 0.90; 10% reduction), and for 100 g/day of yogurt (SRR, 0.94, 6% reduction).

Neutral (nonsignificant) effects were found for 200 g/day of full-fat dairy (SRR, 0.98) and for 30 g/day of cheese (SRR, 0.97). Fish consumption also had a neutral association with type 2 diabetes risk (SRR, 1.04 for 100 g/day) as did one egg per day (SRR, 1.07), but evidence quality was low.

And, Dr. Giosuè noted during her presentation, these relationships could change with alterations in the amounts consumed.

Dr. Schulze commented: “Fish is more clearly related to reduced cardiovascular risk than for preventing type 2 diabetes, where we’ve had mixed results. They might not always be the same.”
 

What are the mechanisms?

The reasons for these positive and negative associations aren’t entirely clear, but Dr. Giosuè noted that dairy products contain several nutrients, vitamins, and other components, such as calcium and vitamin D, that have potential beneficial effects on glucose metabolism.

In particular, she said, “Whey proteins in milk have a well-known beneficial effect on the regulation of the rise of glucose levels in the blood after meals, and also on the control of appetite and body weight.”

Moreover, probiotics found in yogurt have been linked to protective effects against weight gain and obesity, which “may in part [explain] the beneficial role of yogurt in type 2 diabetes prevention.”

Meat, in contrast, is full of cholesterol, saturated fatty acids, and heme iron, which can promote subclinical inflammation and oxidative stress, which may in turn, affect insulin sensitivity, Dr. Giosuè explained. What’s more, “processed meats also contain nitrates, nitrites, and sodium that can contribute to pancreatic cell damage and vascular dysfunction, thus affecting insulin sensitivity.”

And white meat (poultry) has a lower fat content than red meats such as beef, lamb, and pork, as well as a more favorable fatty acid profile and a lower heme-iron content, she said in an interview.

What about vegan diets? The devil is in the details

Asked about the relative health benefits of diets that completely eliminate animal-based foods, Dr. Giosuè replied: “What is important to keep in mind when hearing about the potential of vegan diets to prevent, or manage, or induce the remission of type 2 diabetes, is that the inclusion in the diet of solely foods of plant origin does not mean ‘automatically’ to eat only foods that are good for diabetes prevention.”

“Just like the exclusion of all foods of animal origin is not equivalent to reduce the risk of type 2 diabetes ... Solid evidence has demonstrated that plant foods which are refined and/or rich in free sugars like white bread, biscuits, and sweetened beverages are as harmful as red and processed meats for diabetes incidence and progression.”

Dr. Giosuè and Dr. Schulze have reported no relevant financial relationships.

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

Highlights of the European Association for the Study of Diabetes 2022 annual meeting include new data on weight loss with the blockbuster twincretin tirzepatide and on the effects of dapagliflozin on heart failure in people with diabetes, as well as updated guidelines for type 2 diabetes management.

The EASD meeting will take place Sept. 19-23 in Stockholm. It will be the first in-person meeting since 2019 but will also feature live-streamed content for participants around the world.

“The EASD congress will cover all the different areas and aspects of diabetes research – clinical, basic, epidemiologic, and psychological,” EASD President Stefano Del Prato, MD, told this news organization.

What attendees should expect, said Del Prato of the University of Pisa (Italy), “is the pleasure to be able to participate in person at a meeting and get useful information, not only in terms of the knowledge and intellectual aspects of diabetes, but also something that can be implemented the following day in their daily clinical activities.”  

EASD Honorary Secretary Mikael Rydén, MD, added: “I think meeting attendees will really be able to get the absolutely latest developments in all the areas that are relevant to diabetes treatments. It’s the best way to keep yourself up to date.”

This year, in particular, there’s a focus on past, present, and future trends in type 2 diabetes management, along with the co-occurring conditions of obesity, heart failure, and metabolic fatty liver disease.  
 

DELIVER: The diabetes side

On Sept. 22, new data will be presented from the DELIVER trial on the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) in patients with heart failure with preserved ejection fraction, comparing data for participants with diabetes, prediabetes, and normoglycemia.

Primary results from DELIVER were presented Aug. 26 at the European Society of Cardiology Congress 2022 in Barcelona and simultaneously published in the New England Journal of Medicine. The results showed that dapagliflozin benefits patients with heart failure with preserved ejection fraction, as previously demonstrated in those with reduced ejection fraction in the DAPA-HF trial.

“This information is quite important and is becoming of major interest in the field of diabetes,” Dr. Del Prato said, adding that a related joint EASD/ESC symposium will take place the next morning, on Sept. 23, entitled, “New perspectives on heart function and failure in diabetes.”

“So, within the congress, you get the background, pathophysiology, the diagnostic aspects, and the results of the effect of dapagliflozin on those individuals.”

Dr. Rydén commented, “I think this underlines how important it is for diabetologists to screen our patients better for heart failure because we can actually treat them now.”

However, Dr. Rydén of the Karolinska Institute, Stockholm, also cautioned about use of SGLT2 inhibitors in people with diabetes who use insulin, given the risk of euglycemic diabetic ketoacidosis. “These drugs have side effects and you have to be wary who you prescribe them to. For those on multiple daily [insulin] injections, the side effects probably outweigh the benefits.”
 

Tirzepatide, weight loss, and type 2 diabetes remission

On Sept. 21, a symposium will provide new data for the dual glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, approved for the treatment of type 2 diabetes in the United States in May with the brand name Mounjaro. The agent is now being studied as an obesity treatment.

Data from the SURMOUNT-1 trial presented at the ADA meeting in June showed the drug produced “unprecedented” weight loss of up to 22.5%.

At EASD, those findings will be reviewed and new data presented on morbidity and mortality, along with a new commentary. The degree of weight loss seen with this new twincretin has furthered discussion about the concept of remission in type 2 diabetes, Dr. Rydén noted. That will also be the subject of the Diabetologia symposium on Sept. 21, entitled, “Remission of type 2 diabetes – fact or fiction?”

Regarding tirzepatide, Dr. Rydén said: “It’s amazing, the most powerful antiobesity drug we have at our disposal. These drugs slow gastric emptying and have other beneficial effects. … We’re now closing in on drugs that produce more than 15% weight loss. That appears to be the ‘magic bullet’ where you can achieve type 2 diabetes remission.” He pointed to a symposium sponsored by The Lancet on this topic at last year’s EASD meeting.

“I think what we want with our drugs is not to treat but actually to combat type 2 diabetes and really to achieve remission. Of course, if you’ve had it for many decades that might be impossible, but we know that particularly in the first 5-10 years it’s very important to have good glucose control and we know we can also achieve remission.”

Dr. Del Prato noted the importance of weight reduction at the time of type 2 diabetes diagnosis will be emphasized in the ADA/EASD consensus document on the management of hyperglycemia in type 2 diabetes, to be presented in its final form on Sept. 23.

“I think we’ll be learning more about potential remission in the future, both because of metabolic surgery and agents like tirzepatide. The reduction in body weight that can be achieved [with these newer drugs], or that has been reported so far, is the closest to what can be obtained with metabolic surgery. I think there will be more and more information and a lot of discussion about this, and of course about the definition of remission and what to do after remission has occurred,” Dr. Del Prato said.  

The revised ADA/EASD consensus document is expected to endorse weight loss as a “co-primary goal” of care for those without cardiorenal disease, along with early initiation of combination therapies – for example, taking two drugs immediately upon diagnosis, rather than just metformin – as opposed to the prior stepwise approach. The document will also cover use of newer glucose-lowering therapies, surgery, and behavioral interventions.  

The key is a holistic approach, Dr. Del Prato said. “Of course, glucose control is important, but it’s not the only thing. The heterogeneity of the population with diabetes is also important. Some may already have microvascular complications, kidney dysfunction, are more or less obese, and older or younger. We need to keep these differences in mind to provide more and more individualized treatment.”

Related to that, he noted, will be a joint EASD/ADA symposium on Sept. 19, entitled, “Precision medicine in type 2 diabetes: How far can we get?”
 

COVID-19 and diabetes, UKPDS, type 1 diabetes, and much more

As always, there’s a whole lot more. On Sept. 21, there will be a symposium on COVID-19 and diabetes.

Another, on diabetes technology, has a somewhat cautionary theme: “A new hope (Star Wars) or strange new worlds (Star Trek): Submerging diabetes into emerging technologies.” One of the speakers will address the question: “Are we becoming robots? Automated insulin delivery (AID) systems for everyone with type 1 diabetes: Strengths and limitations.” And this year’s EASD/JDRF symposium topic will be prevention of type 1 diabetes.

Yet another symposium on Sept. 21 will present 44-year follow-up data from the landmark United Kingdom Prospective Diabetes Study (UKPDS), including an economic analysis and a look at dementia outcomes. “It’s a historical thing. This big trial represents a gold mine of information,” Dr. Del Prato commented.

On Sept. 22, new data will be presented for the investigational once-weekly insulins during a symposium entitled, “Re-inventing the insulin experience: Exploring the prospects of once-weekly insulins.”

And lest anyone was thinking of leaving the conference early, there’s a full agenda on Sept. 23, including symposia on diabetic nephropathy, type 1 diabetes, diabetes in old age, dietary management, and the role of primary care, among others. There will also be 12 separate oral presentation sessions that day.

Overall, the meeting will reflect the multidisciplinary direction the field is headed, Dr. Rydén said.

“We’re still in an era of medicine where a lot of things happen every year. Now we have the next generation of drugs that are coming that combine many areas of treatment – obesity, cardiology, and nephrology. So, we’re integrating. The future is integrating the diabetes world with our friends in other areas of clinical medicine.”

Dr. Del Prato has reported being a consultant, advisory board member, and/or lecturer for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Takeda, Eli Lilly, Abbott, and Applied Therapeutics. Dr. Rydén has reported receiving lecture fees from the Novo Nordisk Foundation and serving on advisory boards for MSD, Lilly, Boehringer Ingelheim, and AstraZeneca.

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

Highlights of the European Association for the Study of Diabetes 2022 annual meeting include new data on weight loss with the blockbuster twincretin tirzepatide and on the effects of dapagliflozin on heart failure in people with diabetes, as well as updated guidelines for type 2 diabetes management.

The EASD meeting will take place Sept. 19-23 in Stockholm. It will be the first in-person meeting since 2019 but will also feature live-streamed content for participants around the world.

“The EASD congress will cover all the different areas and aspects of diabetes research – clinical, basic, epidemiologic, and psychological,” EASD President Stefano Del Prato, MD, told this news organization.

What attendees should expect, said Del Prato of the University of Pisa (Italy), “is the pleasure to be able to participate in person at a meeting and get useful information, not only in terms of the knowledge and intellectual aspects of diabetes, but also something that can be implemented the following day in their daily clinical activities.”  

EASD Honorary Secretary Mikael Rydén, MD, added: “I think meeting attendees will really be able to get the absolutely latest developments in all the areas that are relevant to diabetes treatments. It’s the best way to keep yourself up to date.”

This year, in particular, there’s a focus on past, present, and future trends in type 2 diabetes management, along with the co-occurring conditions of obesity, heart failure, and metabolic fatty liver disease.  
 

DELIVER: The diabetes side

On Sept. 22, new data will be presented from the DELIVER trial on the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) in patients with heart failure with preserved ejection fraction, comparing data for participants with diabetes, prediabetes, and normoglycemia.

Primary results from DELIVER were presented Aug. 26 at the European Society of Cardiology Congress 2022 in Barcelona and simultaneously published in the New England Journal of Medicine. The results showed that dapagliflozin benefits patients with heart failure with preserved ejection fraction, as previously demonstrated in those with reduced ejection fraction in the DAPA-HF trial.

“This information is quite important and is becoming of major interest in the field of diabetes,” Dr. Del Prato said, adding that a related joint EASD/ESC symposium will take place the next morning, on Sept. 23, entitled, “New perspectives on heart function and failure in diabetes.”

“So, within the congress, you get the background, pathophysiology, the diagnostic aspects, and the results of the effect of dapagliflozin on those individuals.”

Dr. Rydén commented, “I think this underlines how important it is for diabetologists to screen our patients better for heart failure because we can actually treat them now.”

However, Dr. Rydén of the Karolinska Institute, Stockholm, also cautioned about use of SGLT2 inhibitors in people with diabetes who use insulin, given the risk of euglycemic diabetic ketoacidosis. “These drugs have side effects and you have to be wary who you prescribe them to. For those on multiple daily [insulin] injections, the side effects probably outweigh the benefits.”
 

Tirzepatide, weight loss, and type 2 diabetes remission

On Sept. 21, a symposium will provide new data for the dual glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, approved for the treatment of type 2 diabetes in the United States in May with the brand name Mounjaro. The agent is now being studied as an obesity treatment.

Data from the SURMOUNT-1 trial presented at the ADA meeting in June showed the drug produced “unprecedented” weight loss of up to 22.5%.

At EASD, those findings will be reviewed and new data presented on morbidity and mortality, along with a new commentary. The degree of weight loss seen with this new twincretin has furthered discussion about the concept of remission in type 2 diabetes, Dr. Rydén noted. That will also be the subject of the Diabetologia symposium on Sept. 21, entitled, “Remission of type 2 diabetes – fact or fiction?”

Regarding tirzepatide, Dr. Rydén said: “It’s amazing, the most powerful antiobesity drug we have at our disposal. These drugs slow gastric emptying and have other beneficial effects. … We’re now closing in on drugs that produce more than 15% weight loss. That appears to be the ‘magic bullet’ where you can achieve type 2 diabetes remission.” He pointed to a symposium sponsored by The Lancet on this topic at last year’s EASD meeting.

“I think what we want with our drugs is not to treat but actually to combat type 2 diabetes and really to achieve remission. Of course, if you’ve had it for many decades that might be impossible, but we know that particularly in the first 5-10 years it’s very important to have good glucose control and we know we can also achieve remission.”

Dr. Del Prato noted the importance of weight reduction at the time of type 2 diabetes diagnosis will be emphasized in the ADA/EASD consensus document on the management of hyperglycemia in type 2 diabetes, to be presented in its final form on Sept. 23.

“I think we’ll be learning more about potential remission in the future, both because of metabolic surgery and agents like tirzepatide. The reduction in body weight that can be achieved [with these newer drugs], or that has been reported so far, is the closest to what can be obtained with metabolic surgery. I think there will be more and more information and a lot of discussion about this, and of course about the definition of remission and what to do after remission has occurred,” Dr. Del Prato said.  

The revised ADA/EASD consensus document is expected to endorse weight loss as a “co-primary goal” of care for those without cardiorenal disease, along with early initiation of combination therapies – for example, taking two drugs immediately upon diagnosis, rather than just metformin – as opposed to the prior stepwise approach. The document will also cover use of newer glucose-lowering therapies, surgery, and behavioral interventions.  

The key is a holistic approach, Dr. Del Prato said. “Of course, glucose control is important, but it’s not the only thing. The heterogeneity of the population with diabetes is also important. Some may already have microvascular complications, kidney dysfunction, are more or less obese, and older or younger. We need to keep these differences in mind to provide more and more individualized treatment.”

Related to that, he noted, will be a joint EASD/ADA symposium on Sept. 19, entitled, “Precision medicine in type 2 diabetes: How far can we get?”
 

COVID-19 and diabetes, UKPDS, type 1 diabetes, and much more

As always, there’s a whole lot more. On Sept. 21, there will be a symposium on COVID-19 and diabetes.

Another, on diabetes technology, has a somewhat cautionary theme: “A new hope (Star Wars) or strange new worlds (Star Trek): Submerging diabetes into emerging technologies.” One of the speakers will address the question: “Are we becoming robots? Automated insulin delivery (AID) systems for everyone with type 1 diabetes: Strengths and limitations.” And this year’s EASD/JDRF symposium topic will be prevention of type 1 diabetes.

Yet another symposium on Sept. 21 will present 44-year follow-up data from the landmark United Kingdom Prospective Diabetes Study (UKPDS), including an economic analysis and a look at dementia outcomes. “It’s a historical thing. This big trial represents a gold mine of information,” Dr. Del Prato commented.

On Sept. 22, new data will be presented for the investigational once-weekly insulins during a symposium entitled, “Re-inventing the insulin experience: Exploring the prospects of once-weekly insulins.”

And lest anyone was thinking of leaving the conference early, there’s a full agenda on Sept. 23, including symposia on diabetic nephropathy, type 1 diabetes, diabetes in old age, dietary management, and the role of primary care, among others. There will also be 12 separate oral presentation sessions that day.

Overall, the meeting will reflect the multidisciplinary direction the field is headed, Dr. Rydén said.

“We’re still in an era of medicine where a lot of things happen every year. Now we have the next generation of drugs that are coming that combine many areas of treatment – obesity, cardiology, and nephrology. So, we’re integrating. The future is integrating the diabetes world with our friends in other areas of clinical medicine.”

Dr. Del Prato has reported being a consultant, advisory board member, and/or lecturer for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Takeda, Eli Lilly, Abbott, and Applied Therapeutics. Dr. Rydén has reported receiving lecture fees from the Novo Nordisk Foundation and serving on advisory boards for MSD, Lilly, Boehringer Ingelheim, and AstraZeneca.

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

Highlights of the European Association for the Study of Diabetes 2022 annual meeting include new data on weight loss with the blockbuster twincretin tirzepatide and on the effects of dapagliflozin on heart failure in people with diabetes, as well as updated guidelines for type 2 diabetes management.

The EASD meeting will take place Sept. 19-23 in Stockholm. It will be the first in-person meeting since 2019 but will also feature live-streamed content for participants around the world.

“The EASD congress will cover all the different areas and aspects of diabetes research – clinical, basic, epidemiologic, and psychological,” EASD President Stefano Del Prato, MD, told this news organization.

What attendees should expect, said Del Prato of the University of Pisa (Italy), “is the pleasure to be able to participate in person at a meeting and get useful information, not only in terms of the knowledge and intellectual aspects of diabetes, but also something that can be implemented the following day in their daily clinical activities.”  

EASD Honorary Secretary Mikael Rydén, MD, added: “I think meeting attendees will really be able to get the absolutely latest developments in all the areas that are relevant to diabetes treatments. It’s the best way to keep yourself up to date.”

This year, in particular, there’s a focus on past, present, and future trends in type 2 diabetes management, along with the co-occurring conditions of obesity, heart failure, and metabolic fatty liver disease.  
 

DELIVER: The diabetes side

On Sept. 22, new data will be presented from the DELIVER trial on the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) in patients with heart failure with preserved ejection fraction, comparing data for participants with diabetes, prediabetes, and normoglycemia.

Primary results from DELIVER were presented Aug. 26 at the European Society of Cardiology Congress 2022 in Barcelona and simultaneously published in the New England Journal of Medicine. The results showed that dapagliflozin benefits patients with heart failure with preserved ejection fraction, as previously demonstrated in those with reduced ejection fraction in the DAPA-HF trial.

“This information is quite important and is becoming of major interest in the field of diabetes,” Dr. Del Prato said, adding that a related joint EASD/ESC symposium will take place the next morning, on Sept. 23, entitled, “New perspectives on heart function and failure in diabetes.”

“So, within the congress, you get the background, pathophysiology, the diagnostic aspects, and the results of the effect of dapagliflozin on those individuals.”

Dr. Rydén commented, “I think this underlines how important it is for diabetologists to screen our patients better for heart failure because we can actually treat them now.”

However, Dr. Rydén of the Karolinska Institute, Stockholm, also cautioned about use of SGLT2 inhibitors in people with diabetes who use insulin, given the risk of euglycemic diabetic ketoacidosis. “These drugs have side effects and you have to be wary who you prescribe them to. For those on multiple daily [insulin] injections, the side effects probably outweigh the benefits.”
 

Tirzepatide, weight loss, and type 2 diabetes remission

On Sept. 21, a symposium will provide new data for the dual glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, approved for the treatment of type 2 diabetes in the United States in May with the brand name Mounjaro. The agent is now being studied as an obesity treatment.

Data from the SURMOUNT-1 trial presented at the ADA meeting in June showed the drug produced “unprecedented” weight loss of up to 22.5%.

At EASD, those findings will be reviewed and new data presented on morbidity and mortality, along with a new commentary. The degree of weight loss seen with this new twincretin has furthered discussion about the concept of remission in type 2 diabetes, Dr. Rydén noted. That will also be the subject of the Diabetologia symposium on Sept. 21, entitled, “Remission of type 2 diabetes – fact or fiction?”

Regarding tirzepatide, Dr. Rydén said: “It’s amazing, the most powerful antiobesity drug we have at our disposal. These drugs slow gastric emptying and have other beneficial effects. … We’re now closing in on drugs that produce more than 15% weight loss. That appears to be the ‘magic bullet’ where you can achieve type 2 diabetes remission.” He pointed to a symposium sponsored by The Lancet on this topic at last year’s EASD meeting.

“I think what we want with our drugs is not to treat but actually to combat type 2 diabetes and really to achieve remission. Of course, if you’ve had it for many decades that might be impossible, but we know that particularly in the first 5-10 years it’s very important to have good glucose control and we know we can also achieve remission.”

Dr. Del Prato noted the importance of weight reduction at the time of type 2 diabetes diagnosis will be emphasized in the ADA/EASD consensus document on the management of hyperglycemia in type 2 diabetes, to be presented in its final form on Sept. 23.

“I think we’ll be learning more about potential remission in the future, both because of metabolic surgery and agents like tirzepatide. The reduction in body weight that can be achieved [with these newer drugs], or that has been reported so far, is the closest to what can be obtained with metabolic surgery. I think there will be more and more information and a lot of discussion about this, and of course about the definition of remission and what to do after remission has occurred,” Dr. Del Prato said.  

The revised ADA/EASD consensus document is expected to endorse weight loss as a “co-primary goal” of care for those without cardiorenal disease, along with early initiation of combination therapies – for example, taking two drugs immediately upon diagnosis, rather than just metformin – as opposed to the prior stepwise approach. The document will also cover use of newer glucose-lowering therapies, surgery, and behavioral interventions.  

The key is a holistic approach, Dr. Del Prato said. “Of course, glucose control is important, but it’s not the only thing. The heterogeneity of the population with diabetes is also important. Some may already have microvascular complications, kidney dysfunction, are more or less obese, and older or younger. We need to keep these differences in mind to provide more and more individualized treatment.”

Related to that, he noted, will be a joint EASD/ADA symposium on Sept. 19, entitled, “Precision medicine in type 2 diabetes: How far can we get?”
 

COVID-19 and diabetes, UKPDS, type 1 diabetes, and much more

As always, there’s a whole lot more. On Sept. 21, there will be a symposium on COVID-19 and diabetes.

Another, on diabetes technology, has a somewhat cautionary theme: “A new hope (Star Wars) or strange new worlds (Star Trek): Submerging diabetes into emerging technologies.” One of the speakers will address the question: “Are we becoming robots? Automated insulin delivery (AID) systems for everyone with type 1 diabetes: Strengths and limitations.” And this year’s EASD/JDRF symposium topic will be prevention of type 1 diabetes.

Yet another symposium on Sept. 21 will present 44-year follow-up data from the landmark United Kingdom Prospective Diabetes Study (UKPDS), including an economic analysis and a look at dementia outcomes. “It’s a historical thing. This big trial represents a gold mine of information,” Dr. Del Prato commented.

On Sept. 22, new data will be presented for the investigational once-weekly insulins during a symposium entitled, “Re-inventing the insulin experience: Exploring the prospects of once-weekly insulins.”

And lest anyone was thinking of leaving the conference early, there’s a full agenda on Sept. 23, including symposia on diabetic nephropathy, type 1 diabetes, diabetes in old age, dietary management, and the role of primary care, among others. There will also be 12 separate oral presentation sessions that day.

Overall, the meeting will reflect the multidisciplinary direction the field is headed, Dr. Rydén said.

“We’re still in an era of medicine where a lot of things happen every year. Now we have the next generation of drugs that are coming that combine many areas of treatment – obesity, cardiology, and nephrology. So, we’re integrating. The future is integrating the diabetes world with our friends in other areas of clinical medicine.”

Dr. Del Prato has reported being a consultant, advisory board member, and/or lecturer for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi, Takeda, Eli Lilly, Abbott, and Applied Therapeutics. Dr. Rydén has reported receiving lecture fees from the Novo Nordisk Foundation and serving on advisory boards for MSD, Lilly, Boehringer Ingelheim, and AstraZeneca.

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

A new study provides yet more evidence that a significant subset of people who experience persistent fatigue and exercise intolerance following COVID-19 will meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Data from the prospective observational study of 42 patients with “post-COVID-19 syndrome (PCS),” including persistent fatigue and exercise intolerance, suggest that a large proportion will meet strict diagnostic criteria for ME/CFS, including the hallmark postexertional malaise (PEM). Still others may experience similar disability but lack duration and/or severity requirements for the diagnosis.

Moreover, disease severity and symptom burden were found similar in those with ME/CFS following COVID-19 and in a group of 19 age- and sex-matched individuals with ME/CFS that wasn’t associated with COVID-19.

“The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers,” senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, told this news organization.

Importantly, from a clinical standpoint, both diminished hand-grip strength (HGS) and orthostatic intolerance were common across all patient groups, as were several laboratory values, Claudia Kedor, MD, and colleagues at Charité report in the paper, published online in Nature Communications.

Of the 42 with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the rigorous Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, along with sleep dysfunction, significant persistent fatigue, pain, and several other symptoms from neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still experienced PEM but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all the Canadian criteria except for the neurological/cognitive symptoms. None of the 42 had evidence of severe depression.

The previously widely used 1994 “Fukuda” criteria for ME/CFS are no longer recommended because they don’t require PEM, which is now considered a key symptom. The more recent 2015 Institute (now Academy) of Medicine criteria don’t define the length of PEM, the authors note in the paper.

Dr. Scheibenbogen said, “Post-COVID has a spectrum of syndromes and conditions. We see that a subset of patients have similar symptoms of ME/CFS but don’t fulfill the CCC, although they may meet less stringent criteria. We think this is of relevance for both diagnostic markers and development of therapy, because there may be different pathomechanisms between the subsets of post-COVID patients.”

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that goes on to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. «At the moment, it’s quite complex, and I don’t think in the end we will have just one pathomechanism. So I think we’ll need to develop various treatment strategies.”

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, both in Boston, and editor in chief of the Harvard Health Letter, told this news organization, “This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home.”

But, Dr. Komaroff also cautioned, “the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the health care system, and the disability system could be substantial.”

He pointed to a recent report from the Brookings Institution (2022 Aug 24. “New data shows long Covid is keeping as many as 4 million people out of work” Katie Bach) “finding that “long COVID may be a major contributor to the shortage of job applicants plaguing many businesses.”
 

Biomarkers include hand-grip strength, orthostatic intolerance, lab measures

Hand-grip strength, as assessed by 10 repeat grips at maximum force and repeated after 60 minutes, were lower for all those meeting ME/CFS criteria, compared with the healthy controls. Hand-grip strength parameters were also positively correlated with laboratory hemoglobin measures in both PCS groups who did and didn’t meet the Canadian ME/CFS criteria.

A total of three patients with PCS who didn’t meet ME/CFS criteria and seven with PCS who met ME/CFS criteria had sitting blood pressures of greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS – four who met ME/CFS criteria and one who didn’t – fulfilled criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet ME/CFS criteria and the rest who did.

Among significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased infection susceptibility and found in only about 6% of historical controls, was found more frequently in both of the PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past among those with ME/CFS, compared with historical controls (15%).

There was only slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation within the last 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% with PCS and ME/CFS and in 48% with PCS who did not meet the ME/CFS criteria.

Elevated antinuclear antibodies, anti–thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies were all seen in small numbers of the PCS patients. Angiotensin-converting enzyme 1 levels were below the normal range in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients,” Dr. Kedor and colleagues write. “At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis. Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Dr. Scheibenbogen and Dr. Komaroff reported no relevant financial relationships.

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

A new study provides yet more evidence that a significant subset of people who experience persistent fatigue and exercise intolerance following COVID-19 will meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Data from the prospective observational study of 42 patients with “post-COVID-19 syndrome (PCS),” including persistent fatigue and exercise intolerance, suggest that a large proportion will meet strict diagnostic criteria for ME/CFS, including the hallmark postexertional malaise (PEM). Still others may experience similar disability but lack duration and/or severity requirements for the diagnosis.

Moreover, disease severity and symptom burden were found similar in those with ME/CFS following COVID-19 and in a group of 19 age- and sex-matched individuals with ME/CFS that wasn’t associated with COVID-19.

“The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers,” senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, told this news organization.

Importantly, from a clinical standpoint, both diminished hand-grip strength (HGS) and orthostatic intolerance were common across all patient groups, as were several laboratory values, Claudia Kedor, MD, and colleagues at Charité report in the paper, published online in Nature Communications.

Of the 42 with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the rigorous Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, along with sleep dysfunction, significant persistent fatigue, pain, and several other symptoms from neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still experienced PEM but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all the Canadian criteria except for the neurological/cognitive symptoms. None of the 42 had evidence of severe depression.

The previously widely used 1994 “Fukuda” criteria for ME/CFS are no longer recommended because they don’t require PEM, which is now considered a key symptom. The more recent 2015 Institute (now Academy) of Medicine criteria don’t define the length of PEM, the authors note in the paper.

Dr. Scheibenbogen said, “Post-COVID has a spectrum of syndromes and conditions. We see that a subset of patients have similar symptoms of ME/CFS but don’t fulfill the CCC, although they may meet less stringent criteria. We think this is of relevance for both diagnostic markers and development of therapy, because there may be different pathomechanisms between the subsets of post-COVID patients.”

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that goes on to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. «At the moment, it’s quite complex, and I don’t think in the end we will have just one pathomechanism. So I think we’ll need to develop various treatment strategies.”

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, both in Boston, and editor in chief of the Harvard Health Letter, told this news organization, “This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home.”

But, Dr. Komaroff also cautioned, “the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the health care system, and the disability system could be substantial.”

He pointed to a recent report from the Brookings Institution (2022 Aug 24. “New data shows long Covid is keeping as many as 4 million people out of work” Katie Bach) “finding that “long COVID may be a major contributor to the shortage of job applicants plaguing many businesses.”
 

Biomarkers include hand-grip strength, orthostatic intolerance, lab measures

Hand-grip strength, as assessed by 10 repeat grips at maximum force and repeated after 60 minutes, were lower for all those meeting ME/CFS criteria, compared with the healthy controls. Hand-grip strength parameters were also positively correlated with laboratory hemoglobin measures in both PCS groups who did and didn’t meet the Canadian ME/CFS criteria.

A total of three patients with PCS who didn’t meet ME/CFS criteria and seven with PCS who met ME/CFS criteria had sitting blood pressures of greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS – four who met ME/CFS criteria and one who didn’t – fulfilled criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet ME/CFS criteria and the rest who did.

Among significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased infection susceptibility and found in only about 6% of historical controls, was found more frequently in both of the PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past among those with ME/CFS, compared with historical controls (15%).

There was only slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation within the last 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% with PCS and ME/CFS and in 48% with PCS who did not meet the ME/CFS criteria.

Elevated antinuclear antibodies, anti–thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies were all seen in small numbers of the PCS patients. Angiotensin-converting enzyme 1 levels were below the normal range in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients,” Dr. Kedor and colleagues write. “At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis. Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Dr. Scheibenbogen and Dr. Komaroff reported no relevant financial relationships.

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

A new study provides yet more evidence that a significant subset of people who experience persistent fatigue and exercise intolerance following COVID-19 will meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Data from the prospective observational study of 42 patients with “post-COVID-19 syndrome (PCS),” including persistent fatigue and exercise intolerance, suggest that a large proportion will meet strict diagnostic criteria for ME/CFS, including the hallmark postexertional malaise (PEM). Still others may experience similar disability but lack duration and/or severity requirements for the diagnosis.

Moreover, disease severity and symptom burden were found similar in those with ME/CFS following COVID-19 and in a group of 19 age- and sex-matched individuals with ME/CFS that wasn’t associated with COVID-19.

“The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers,” senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, told this news organization.

Importantly, from a clinical standpoint, both diminished hand-grip strength (HGS) and orthostatic intolerance were common across all patient groups, as were several laboratory values, Claudia Kedor, MD, and colleagues at Charité report in the paper, published online in Nature Communications.

Of the 42 with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the rigorous Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, along with sleep dysfunction, significant persistent fatigue, pain, and several other symptoms from neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still experienced PEM but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all the Canadian criteria except for the neurological/cognitive symptoms. None of the 42 had evidence of severe depression.

The previously widely used 1994 “Fukuda” criteria for ME/CFS are no longer recommended because they don’t require PEM, which is now considered a key symptom. The more recent 2015 Institute (now Academy) of Medicine criteria don’t define the length of PEM, the authors note in the paper.

Dr. Scheibenbogen said, “Post-COVID has a spectrum of syndromes and conditions. We see that a subset of patients have similar symptoms of ME/CFS but don’t fulfill the CCC, although they may meet less stringent criteria. We think this is of relevance for both diagnostic markers and development of therapy, because there may be different pathomechanisms between the subsets of post-COVID patients.”

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that goes on to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. «At the moment, it’s quite complex, and I don’t think in the end we will have just one pathomechanism. So I think we’ll need to develop various treatment strategies.”

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, both in Boston, and editor in chief of the Harvard Health Letter, told this news organization, “This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home.”

But, Dr. Komaroff also cautioned, “the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the health care system, and the disability system could be substantial.”

He pointed to a recent report from the Brookings Institution (2022 Aug 24. “New data shows long Covid is keeping as many as 4 million people out of work” Katie Bach) “finding that “long COVID may be a major contributor to the shortage of job applicants plaguing many businesses.”
 

Biomarkers include hand-grip strength, orthostatic intolerance, lab measures

Hand-grip strength, as assessed by 10 repeat grips at maximum force and repeated after 60 minutes, were lower for all those meeting ME/CFS criteria, compared with the healthy controls. Hand-grip strength parameters were also positively correlated with laboratory hemoglobin measures in both PCS groups who did and didn’t meet the Canadian ME/CFS criteria.

A total of three patients with PCS who didn’t meet ME/CFS criteria and seven with PCS who met ME/CFS criteria had sitting blood pressures of greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS – four who met ME/CFS criteria and one who didn’t – fulfilled criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet ME/CFS criteria and the rest who did.

Among significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased infection susceptibility and found in only about 6% of historical controls, was found more frequently in both of the PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past among those with ME/CFS, compared with historical controls (15%).

There was only slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation within the last 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% with PCS and ME/CFS and in 48% with PCS who did not meet the ME/CFS criteria.

Elevated antinuclear antibodies, anti–thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies were all seen in small numbers of the PCS patients. Angiotensin-converting enzyme 1 levels were below the normal range in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients,” Dr. Kedor and colleagues write. “At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis. Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Dr. Scheibenbogen and Dr. Komaroff reported no relevant financial relationships.

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

Time-restricted eating during the earlier part of the day (eTRE) may promote weight loss and reduce blood pressure, new findings suggest.

Previous studies have produced mixed results regarding the weight-loss potential for intermittent fasting, the practice of alternating eating with extended fasting, and the “time-restricted eating” format, where eating is restricted to a specific, often 10-hour, time window during the day.

In a new randomized clinical trial of 90 people with obesity in which that time window was 7 AM through 3 PM, so 8 hours long, researchers report that “eTRE was more effective for losing weight and lowering diastolic blood pressure than was eating over a period of 12 or more hours at 14 weeks. The eTRE intervention may therefore be an effective treatment for both obesity and hypertension.” The study, by Humaira Jamshed, PhD, of the department of nutrition sciences, University of Alabama at Birmingham, and colleagues, was published in JAMA Internal Medicine.

In an accompanying invited commentary, Shalender Bhasin, MBBS, points out that the study findings differ from those of a previous trial published in April of 139 adults conducted in China, which did not find a significant weight loss benefit with TRE versus ad lib eating.

“The scientific premise and the preclinical data of the effects of TRE are promising, but the inconsistency among studies renders it difficult to draw strong inferences from these well-conducted but relatively small trials,” notes Dr. Bhasin, of Harvard Medical School, Boston.
 

Need for larger and longer trials of TRE

Dr. Bhasin says – and the study authors also acknowledge – that much larger randomized clinical trials of longer duration are needed “to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults.”

Commenting on the study for the U.K. Science Media Centre, Simon Steenson, PhD, nutrition scientist, British Nutrition Foundation, said “one of the strengths of this new study is the trial design and the number of people who were recruited compared to many of the previous trials to date.”

However, Dr. Steenson also pointed to the prior Chinese research as evidence that the inconsistencies across studies highlight the need for larger and longer trials, with cardiovascular as well as weight-loss endpoints.

Still, Dr. Steenson said, “For individuals who may find that this pattern of eating fits better with their lifestyle and preferences, time-restricted feeding is one option for reducing overall calorie intake that might be a suitable approach for some. Ultimately, it is about finding the best approach to moderate calorie intake that works for each person, as successful and sustained weight loss is about ensuring the diet is feasible to follow in the long-term.”
 

Differences in weight loss, diastolic BP, but not all measures

The study population included 90 adults seen at the Weight Loss Medicine clinic at the University of Alabama at Birmingham between August 2018 and December 2019. Participants had a body mass index of 30-60 kg/m², and none had diabetes. 

They were randomized to eTRE with the 7 AM to PM eating window or a control schedule with eating across 12 hours or more, mimicking U.S. median mealtimes, at least 6 days a week. All participants received 30-minute weight-loss counseling sessions at baseline and at weeks 2, 6, and 10 and were advised to follow a diet of 500 kcal/day below their resting energy expenditure and exercise 75-150 minutes per week.

The eTRE group adhered with their schedule a mean of 6 days per week, lower than the 6.3 days among controls (P = .03), and adherence declined by about 0.4 days per week in the eTRE group over the 14 weeks (P = .001).  

At 14 weeks, both the eTRE group and controls had lost clinically meaningful amounts of weight, at –6.3 kg and –4.0 kg, respectively, but the –2.3 kg difference was significant (P = .002).

However, there was no difference in absolute fat loss (P = .09) or ratio of fat loss to weight loss (P = .43). There were also no significant differences in changes in other body composition parameters, including visceral fat and waist circumference.

Diastolic blood pressure was lowered by an additional 4 mmHg in the eTRE group, compared with controls at 14 weeks (P = .04), but there were no significant differences in systolic blood pressure, heart rate, glucose, A1c levels, insulin levels, measures of insulin resistance, or plasma lipids.

There were no differences between the two groups in self-reported physical activity, energy intake, or dietary macronutrient composition either. However, weight-loss modeling in 77 participants with at least two weight measurements indicated that the eTRE group reduced their intake by about 214 kcal/day, compared with controls (P = .04).

Those in the eTRE group also showed greater improvements in measures of mood disturbance, vigor-activity, fatigue-inertia, and depression-dejection. Other mood and sleep endpoints were similar between groups.

In a secondary analysis of just the 59 participants who completed the study, eTRE was also more effective at reducing body fat (P = .047) and trunk fat (P = .03).

About 41% of the eTRE completers planned to continue the practice after the study concluded.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Jamshed has reported no relevant financial relationships. Dr. Bhasin has reported receiving grants to his institution for research on which Dr. Bhasin is the principal investigator from AbbVie and MIB, receiving personal fees from OPKO and Aditum and holding equity interest in FPT and XYOne. Dr. Steenson has declared funding in support of the British Nutrition Foundation that comes from a range of sources.

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

Time-restricted eating during the earlier part of the day (eTRE) may promote weight loss and reduce blood pressure, new findings suggest.

Previous studies have produced mixed results regarding the weight-loss potential for intermittent fasting, the practice of alternating eating with extended fasting, and the “time-restricted eating” format, where eating is restricted to a specific, often 10-hour, time window during the day.

In a new randomized clinical trial of 90 people with obesity in which that time window was 7 AM through 3 PM, so 8 hours long, researchers report that “eTRE was more effective for losing weight and lowering diastolic blood pressure than was eating over a period of 12 or more hours at 14 weeks. The eTRE intervention may therefore be an effective treatment for both obesity and hypertension.” The study, by Humaira Jamshed, PhD, of the department of nutrition sciences, University of Alabama at Birmingham, and colleagues, was published in JAMA Internal Medicine.

In an accompanying invited commentary, Shalender Bhasin, MBBS, points out that the study findings differ from those of a previous trial published in April of 139 adults conducted in China, which did not find a significant weight loss benefit with TRE versus ad lib eating.

“The scientific premise and the preclinical data of the effects of TRE are promising, but the inconsistency among studies renders it difficult to draw strong inferences from these well-conducted but relatively small trials,” notes Dr. Bhasin, of Harvard Medical School, Boston.
 

Need for larger and longer trials of TRE

Dr. Bhasin says – and the study authors also acknowledge – that much larger randomized clinical trials of longer duration are needed “to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults.”

Commenting on the study for the U.K. Science Media Centre, Simon Steenson, PhD, nutrition scientist, British Nutrition Foundation, said “one of the strengths of this new study is the trial design and the number of people who were recruited compared to many of the previous trials to date.”

However, Dr. Steenson also pointed to the prior Chinese research as evidence that the inconsistencies across studies highlight the need for larger and longer trials, with cardiovascular as well as weight-loss endpoints.

Still, Dr. Steenson said, “For individuals who may find that this pattern of eating fits better with their lifestyle and preferences, time-restricted feeding is one option for reducing overall calorie intake that might be a suitable approach for some. Ultimately, it is about finding the best approach to moderate calorie intake that works for each person, as successful and sustained weight loss is about ensuring the diet is feasible to follow in the long-term.”
 

Differences in weight loss, diastolic BP, but not all measures

The study population included 90 adults seen at the Weight Loss Medicine clinic at the University of Alabama at Birmingham between August 2018 and December 2019. Participants had a body mass index of 30-60 kg/m², and none had diabetes. 

They were randomized to eTRE with the 7 AM to PM eating window or a control schedule with eating across 12 hours or more, mimicking U.S. median mealtimes, at least 6 days a week. All participants received 30-minute weight-loss counseling sessions at baseline and at weeks 2, 6, and 10 and were advised to follow a diet of 500 kcal/day below their resting energy expenditure and exercise 75-150 minutes per week.

The eTRE group adhered with their schedule a mean of 6 days per week, lower than the 6.3 days among controls (P = .03), and adherence declined by about 0.4 days per week in the eTRE group over the 14 weeks (P = .001).  

At 14 weeks, both the eTRE group and controls had lost clinically meaningful amounts of weight, at –6.3 kg and –4.0 kg, respectively, but the –2.3 kg difference was significant (P = .002).

However, there was no difference in absolute fat loss (P = .09) or ratio of fat loss to weight loss (P = .43). There were also no significant differences in changes in other body composition parameters, including visceral fat and waist circumference.

Diastolic blood pressure was lowered by an additional 4 mmHg in the eTRE group, compared with controls at 14 weeks (P = .04), but there were no significant differences in systolic blood pressure, heart rate, glucose, A1c levels, insulin levels, measures of insulin resistance, or plasma lipids.

There were no differences between the two groups in self-reported physical activity, energy intake, or dietary macronutrient composition either. However, weight-loss modeling in 77 participants with at least two weight measurements indicated that the eTRE group reduced their intake by about 214 kcal/day, compared with controls (P = .04).

Those in the eTRE group also showed greater improvements in measures of mood disturbance, vigor-activity, fatigue-inertia, and depression-dejection. Other mood and sleep endpoints were similar between groups.

In a secondary analysis of just the 59 participants who completed the study, eTRE was also more effective at reducing body fat (P = .047) and trunk fat (P = .03).

About 41% of the eTRE completers planned to continue the practice after the study concluded.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Jamshed has reported no relevant financial relationships. Dr. Bhasin has reported receiving grants to his institution for research on which Dr. Bhasin is the principal investigator from AbbVie and MIB, receiving personal fees from OPKO and Aditum and holding equity interest in FPT and XYOne. Dr. Steenson has declared funding in support of the British Nutrition Foundation that comes from a range of sources.

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

Time-restricted eating during the earlier part of the day (eTRE) may promote weight loss and reduce blood pressure, new findings suggest.

Previous studies have produced mixed results regarding the weight-loss potential for intermittent fasting, the practice of alternating eating with extended fasting, and the “time-restricted eating” format, where eating is restricted to a specific, often 10-hour, time window during the day.

In a new randomized clinical trial of 90 people with obesity in which that time window was 7 AM through 3 PM, so 8 hours long, researchers report that “eTRE was more effective for losing weight and lowering diastolic blood pressure than was eating over a period of 12 or more hours at 14 weeks. The eTRE intervention may therefore be an effective treatment for both obesity and hypertension.” The study, by Humaira Jamshed, PhD, of the department of nutrition sciences, University of Alabama at Birmingham, and colleagues, was published in JAMA Internal Medicine.

In an accompanying invited commentary, Shalender Bhasin, MBBS, points out that the study findings differ from those of a previous trial published in April of 139 adults conducted in China, which did not find a significant weight loss benefit with TRE versus ad lib eating.

“The scientific premise and the preclinical data of the effects of TRE are promising, but the inconsistency among studies renders it difficult to draw strong inferences from these well-conducted but relatively small trials,” notes Dr. Bhasin, of Harvard Medical School, Boston.
 

Need for larger and longer trials of TRE

Dr. Bhasin says – and the study authors also acknowledge – that much larger randomized clinical trials of longer duration are needed “to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults.”

Commenting on the study for the U.K. Science Media Centre, Simon Steenson, PhD, nutrition scientist, British Nutrition Foundation, said “one of the strengths of this new study is the trial design and the number of people who were recruited compared to many of the previous trials to date.”

However, Dr. Steenson also pointed to the prior Chinese research as evidence that the inconsistencies across studies highlight the need for larger and longer trials, with cardiovascular as well as weight-loss endpoints.

Still, Dr. Steenson said, “For individuals who may find that this pattern of eating fits better with their lifestyle and preferences, time-restricted feeding is one option for reducing overall calorie intake that might be a suitable approach for some. Ultimately, it is about finding the best approach to moderate calorie intake that works for each person, as successful and sustained weight loss is about ensuring the diet is feasible to follow in the long-term.”
 

Differences in weight loss, diastolic BP, but not all measures

The study population included 90 adults seen at the Weight Loss Medicine clinic at the University of Alabama at Birmingham between August 2018 and December 2019. Participants had a body mass index of 30-60 kg/m², and none had diabetes. 

They were randomized to eTRE with the 7 AM to PM eating window or a control schedule with eating across 12 hours or more, mimicking U.S. median mealtimes, at least 6 days a week. All participants received 30-minute weight-loss counseling sessions at baseline and at weeks 2, 6, and 10 and were advised to follow a diet of 500 kcal/day below their resting energy expenditure and exercise 75-150 minutes per week.

The eTRE group adhered with their schedule a mean of 6 days per week, lower than the 6.3 days among controls (P = .03), and adherence declined by about 0.4 days per week in the eTRE group over the 14 weeks (P = .001).  

At 14 weeks, both the eTRE group and controls had lost clinically meaningful amounts of weight, at –6.3 kg and –4.0 kg, respectively, but the –2.3 kg difference was significant (P = .002).

However, there was no difference in absolute fat loss (P = .09) or ratio of fat loss to weight loss (P = .43). There were also no significant differences in changes in other body composition parameters, including visceral fat and waist circumference.

Diastolic blood pressure was lowered by an additional 4 mmHg in the eTRE group, compared with controls at 14 weeks (P = .04), but there were no significant differences in systolic blood pressure, heart rate, glucose, A1c levels, insulin levels, measures of insulin resistance, or plasma lipids.

There were no differences between the two groups in self-reported physical activity, energy intake, or dietary macronutrient composition either. However, weight-loss modeling in 77 participants with at least two weight measurements indicated that the eTRE group reduced their intake by about 214 kcal/day, compared with controls (P = .04).

Those in the eTRE group also showed greater improvements in measures of mood disturbance, vigor-activity, fatigue-inertia, and depression-dejection. Other mood and sleep endpoints were similar between groups.

In a secondary analysis of just the 59 participants who completed the study, eTRE was also more effective at reducing body fat (P = .047) and trunk fat (P = .03).

About 41% of the eTRE completers planned to continue the practice after the study concluded.

The study was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Jamshed has reported no relevant financial relationships. Dr. Bhasin has reported receiving grants to his institution for research on which Dr. Bhasin is the principal investigator from AbbVie and MIB, receiving personal fees from OPKO and Aditum and holding equity interest in FPT and XYOne. Dr. Steenson has declared funding in support of the British Nutrition Foundation that comes from a range of sources.

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

People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.

Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.

Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.

A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.

Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.

“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.

Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”

Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.

“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.

Misdiagnosis, treatment delays led to life-threatening malnutrition

The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.

“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)

Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”

At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.

“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.

Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”

Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
 

Caring for the patient with severe or very severe ME/CFS

Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.

In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.

Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.

The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.

Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.

Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.

Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.

The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.

A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.

Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.

Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”

He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.

Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.

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

People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.

Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.

Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.

A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.

Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.

“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.

Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”

Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.

“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.

Misdiagnosis, treatment delays led to life-threatening malnutrition

The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.

“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)

Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”

At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.

“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.

Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”

Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
 

Caring for the patient with severe or very severe ME/CFS

Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.

In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.

Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.

The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.

Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.

Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.

Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.

The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.

A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.

Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.

Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”

He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.

Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.

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

People who are severely ill with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are often too sick to leave home, but clinicians can still support them in many ways, experts say.

Approximately 250,000 people in the United Kingdom (0.2%-0.4%) have ME/CFS – where it’s called “ME.” As many as 2.5 million in the United States have it. Those numbers are expected to dramatically increase with the addition of people with long COVID. An estimated 25% of patients with the condition are so severely impaired that they are housebound or bedbound to the point where they’re unable to attend medical office visits. There are very few data about them because they’re typically unable to participate in studies.

Speaking at the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME), patient advocate Helen Baxter, of the U.K. charity 25% ME Group, presented a case series of five patients bedbound with ME/CFS who became severely malnourished because of delays in the placement of feeding tubes. The delays occurred because it was not recognized that the patients were unable to eat. The inability to eat may be due to a variety of factors, including gastrointestinal dysfunction, dysphagia, nausea, or lack of sufficient energy to eat or drink.

A report of those cases was included in a special issue of Healthcare, devoted to the topic of severe and very severe ME/CFS. The issue, which was published in April 2021, included 25 articles on the pathophysiology of severe ME/CFS, ways that clinicians can support patients who are too sick to make office visits, and psychosocial aspects of the condition that result from physical debilitation.

Two additional articles by specialist physicians aim to counter the skepticism about ME/CFS that has long persisted among some in the medical community.

“ME/CFS is under-researched and has historically received insufficient funding for research, particularly when compared to other chronic conditions, such as multiple sclerosis. And most of the research that has been done about it has focused on patients who are able to attend clinics. Patients with severe ME/CFS have largely been excluded from research due to the severity of their illness and are often described as ‘hard to reach.’ Consequently, research into severe ME is very limited,” Ms. Baxter said.

Asked to comment, Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, told this news organization, “It’s a big gap, even in the knowledgeable community. The research is totally skewed towards people who can get up and go participate in research. ... I don’t think most clinicians have any idea how sick people can get with ME/CFS.”

Cardiopulmonary exercise testing (CPET), which is commonly used in research, is intended to elicit objective biomarker responses. Such testing, which is considered the gold standard for determining disability, is impossible for the most severely ill patients with ME/CFS and is potentially harmful to these patients because of the hallmark postexertional malaise (PEM) phenomenon, Dr. Bateman noted.

“If we want to use CPET for research, we have to remember that it harms people to some degree and that we’re only studying the people who aren’t as sick. ... It’s one of the reasons I’ve been aggressively pursuing medical education about orthostatic testing, because it’s a clear objective marker, not as deleterious, and potentially leads to treatment options,” she said.

Misdiagnosis, treatment delays led to life-threatening malnutrition

The five patients that Ms. Baxter presented had become severely malnourished and dehydrated. There was evidence of clinical inertia for each of them.

“All were judged to have anorexia nervosa, and psychiatrists were involved, which was an added delay to starting tube feeding. ... In each case, the doctors resorted to making inappropriate psychological diagnoses without positive evidence of psychopathology, failing to recognize the significance of the malnutrition,” Ms. Baxter said. (Urgent tube feeding would have been warranted even had anorexia nervosa been the correct diagnosis, she pointed out.)

Once the problem was finally recognized, “all participants saw an improvement in their situation following the allocation of a home enteral nutrition dietician.”

At the IACFS/ME conference, Ms. Baxter described the painstaking methods used for gathering information, which were described in the same journal. These involved a combination of online, telephone, and text communications with patients or their caregivers. Efforts were made to avoid overtaxing the patients and triggering PEM.

“An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake, prompt action is taken, and tube feeding started, thereby avoiding undernutrition in patients with very severe ME,” Ms. Baxter and colleagues write.

Indeed, coauthor and semiretired pediatric ME/CFS specialist physician Nigel Speight, of Durham, United Kingdom, said in an interview, “In most of my patients, I used tube feeding early simply to avoid using unnecessary energy and causing stress to the patient.”

Dr. Speight added, “Patients can also die from sheer weakness leading to lack of respiratory drive. Also, and very understandably, some commit suicide.”
 

Caring for the patient with severe or very severe ME/CFS

Appearing in the special issue is an article entitled, “Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome”. It was authored by a multidisciplinary group led by Jose G. Montoya, MD, of the Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Calif.

In that article, four levels of severity are defined: mild, moderate, severe, and very severe. Included in the “severe” category are patients who are mostly homebound and whose activities of daily living are limited. They may have severe cognitive difficulties. Patients in the “very severe” caregory are bedbound and are unable to care for themselves.

Clinical features include more extreme versions of the core ME/CFS criteria: profound fatigue/weakness, PEM, unrefreshing sleep, orthostatic intolerance, and cognitive impairment. Additional symptoms in those with severe/very severe ME can include extreme hypersensitivity to light, sound, touch, and/or odors. Even small amounts of physical, mental, emotional, and orthostatic stressors can trigger PEM and increased weakness.

The authors recommend a “patient-centered, collaborative approach that is grounded in compassion and respect for the patient in all interactions,” and they provide lists of steps providers can take. These include seeing patients at home if possible and considerations regarding that care, such as partnering with the patient’s caregivers and other health care providers, who may include physical and occupational therapists, home health nurses, and social workers who understand the condition. Home visits by optometrists or ophthalmologists and dentists may be required.

Documenting limitations in activities of daily living is particularly important for helping patients to obtain homecare and disability benefits, Dr. Montoya and colleagues say.

Clinicians should investigate any medical problems that may be amenable to treatment, including orthostatic intolerance, pain, sleep difficulties, comorbidities, or gastrointestinal problems. For patients with pain, bloating, and diarrhea who are found on assessment to have mast cell activation disorder (MCAD), a trial of sodium cromoglicate may be tried, Ms. Baxter told this news organization.

Nonmedical problems that may be contributing to the patient’s morbidity should also be assessed, including a lack of caretaking, social services, transportation, food, and/or supportive devices, such as wheelchairs, bedpans, feeding tubes, and catheters.

The article provides additional detailed recommendations regarding pharmacologic treatments, follow-up visits – in-person or virtual – and hospitalization, as well as recommendations for energy conservation and management.

A section titled Practical Considerations for Busy Providers includes advice to be aware of any regulatory or insurance requirements for providing home visits and to maximize reimbursement by diagnosing any comorbidities, such as postural orthostatic tachycardia syndrome, Ehlers-Danlos syndrome, or MCAD.

Dr. Speight, who authored an article in the special issue on the management of ME in children, called the article by Dr. Montoya and colleagues “absolutely excellent,” and added his own advice, which included not “overinvestigating to cover your back but at the expense of causing stress to the patient” and considering a trial of immunoglobulin.

Importantly, Dr. Speight stressed, “avoid referral to psychiatrists unless specifically indicated for additional psychiatric morbidity; in which case, make clear that the psychiatrist accepts [that the] basic illness is medical.”

He also advised that clinicians stop using the term “chronic fatigue syndrome” because it suggests the illness is mild and/or psychosomatic. “Maybe the United States should embrace the term ME once and for all,” he said.

Dr. Baxter, Dr. Speight, and Dr. Montoya have disclosed no relevant financial relationships. Dr. Bateman is conducting research for Terra Biological.

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

Emerging evidence is shedding light on the common underlying mechanisms contributing to the overlapping clinical phenomena of “long COVID,” myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFSME), speakers presented data showing similar pathophysiologic abnormalities in people with systemic symptoms associated with ME/CFS who had a prior SARS-CoV-2 infection and those who did not, including individuals whose illness preceded the COVID-19 pandemic.

Core clinical diagnostic criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for 6 months or longer, postexertional malaise, or a worsening of symptoms following even minor exertion (often described by patients as “crashes”), unrefreshing sleep, and cognitive dysfunction and/or orthostatic intolerance that are frequent and severe.

Long COVID has been defined in several different ways using different terminology. The U.S. Centers for Disease Control and Prevention, for example, defines “post-COVID conditions” as those continuing four or more weeks beyond first symptoms. The World Health Organization’s clinical case definition of “post COVID-19 condition” includes otherwise unexplained symptoms 3 months from COVID-19 onset and lasting longer than 2 months.

Both ME/CFS and long COVID commonly involve numerous symptoms beyond the defining ones, affecting nearly every organ system in the body, including systemic, neurocognitive, endocrine, cardiovascular, pulmonary, musculoskeletal, and gastrointestinal, with wide variation among individuals. Autonomic dysfunction is common to both conditions, particularly postural orthostatic tachycardia syndrome (POTS).

“My way of understanding these illnesses is that they’re not just multisystem illnesses, but all these interactive systems that lean on each other are dysregulated. … I would say that a very common underlying mediator of both ME/CFS and long COVID is autonomic dysfunction, and it presents as POTS,” Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University, Fort Lauderdale, Fla., told this news organization.

Dr. Klimas, who is also director of Clinical Immunology Research at the Miami Veterans Affairs Medical Center, added that “if basic bioenergetics are disrupted and in an oxidative-stress state [then] they have downregulated energy production at the cellular level, which seems to be the case in ME/CFS and now in long COVID.”
 

New ICD-10 codes better characterize the syndromes

New ICD-10 codes for 2023, being implemented on Oct. 1, will enable clinicians to better document all of these interrelated conditions.

Under the existing G93.3, Postviral and related fatigue syndromes, there will now be:

• G93.31 – Postviral fatigue syndrome.
• G93.32 – Myalgic encephalomyelitis/chronic fatigue syndrome (and the separate terms).
• G93.39 – Other postinfection and related fatigue syndromes.

The old R53.82, “Chronic fatigue, unspecified” code now excludes all of the above conditions.

The additional code U09.9 for “post COVID-19 condition, unspecified,” may also be used if applicable.

In addition, a new code for POTS, G90.A, which wasn’t previously mentioned in ICD-10, may also be used starting Oct. 1.

Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, advises using all applicable codes for a given patient. “If a patient came into my office with long COVID and met criteria for ME/CFS, we would code both, and also any other syndrome criteria that they may meet, such as POTS or fibromyalgia.

“If people use the codes appropriately, then you can understand the overlap better. It increases the likelihood of reimbursement, creates a more accurate medical record for the patient, and provides them with a better tool should they require disability benefits.”

Dr. Bateman advises in-office orthostatic evaluation for all patients with this symptom constellation, using a passive standing evaluation such as the 10-minute NASA Lean test.

“Clinicians should take the time to do orthostatic testing in these patients because it provides objective markers and will help lead us to potential interventions to help improve people’s function.”

The Bateman Horne center offers clinician resources on management of ME/CFS and related conditions.
 

How common is ME/CFS after COVID-19?

According to one published meta-analysis, the global prevalence of “post-acute sequelae of SARS-CoV-2,” defined by any symptom, is about 43% of patients overall following infection, and 49% at 120 days. Fatigue was the most commonly reported symptom, followed by memory problems. As of March 22, the World Health Organization estimated that there have been more than 470 million COVID-19 cases, which would give a figure of about 200 million people who are experiencing a wide range of long-COVID symptoms. 

On the final day of the IACFSME conference, Luis Nacul, MD, of the University of British Columbia, Vancouver, presented several sets of data from his group and others aiming to determine the proportion of individuals who develop symptoms suggestive of ME/CFS following a COVID-19 infection.   

Among a cohort of 88 adults hospitalized with confirmed SARS-CoV-2 infections during the first pandemic wave in 2020 and followed up in the respiratory clinic, rates of reported generalized fatigue were 67% at 3 months and 59.5% at 6 months. Substantial fatigue (that is, present most days and affecting activity levels) were reported by 16% at 3 months and 7% at 6 months. “This should represent in principle the maximum prevalence of cases who would meet the criteria for ME/CFS,” Dr. Nacul said.

Baseline age was indirectly associated with fatigue at 3 and 6 months, while the number of comorbidities a patient had was directly associated. Comorbidities also predicted severe fatigue at 3 months, but the numbers were too small for assessment at 6 months.

Studies involving nonhospitalized patients suggested lower rates. One meta-analysis showed 1-year rates of fatigue in 32% and cognitive impairment in 22%. Another showed very similar rates, reporting fatigue in 28% and memory/concentration difficulties in 18%-19%.   

Dr. Nacul cautioned that these figures are likely overestimates since many of the study populations are taken from respiratory or long-COVID clinics. “The evidence on ‘post-COVID fatigue syndrome’ or ME/CFS following COVID is still evolving. There is a huge need for studies looking more closely at cases meeting well-defined ME/CFS criteria. This unfortunately hasn’t been done for most studies.”
 

Immune system dysfunction appears to underlie many cases

In a keynote address during the conference, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., pointed out that long COVID and ME/CFS are among many unexplained postacute infection syndromes associated with a long list of viral pathogens, including Ebola, the prior SARS viruses, Epstein-Barr virus, and Dengue, as well as nonviral pathogens such as Coxiella burnetii (Q fever syndrome) and Borrelia (posttreatment Lyme disease syndrome).

Dr. Iwasaki cited a recent Nature Medicine review article that she coauthored on this topic with an ME/CFS patient, noting: “We really need to understand why some people are failing to recover from these types of diseases.”

Emerging evidence supports four different hypotheses regarding pathogenesis: viral reservoir/viral pathogen-associated molecular pattern molecules, autoimmunity, dysbiosis/viral reactivation, and tissue damage

“Right now, it’s too early to exclude or make any conclusions about these. We need to have an open mind to dissect these various possibilities,” she said.

Two speakers reported findings of immune dysregulation in both ME/CFS and long COVID. Wakiro Sato, MD, PhD, of the National Center of Neurology and Psychiatry, Tokyo, reported that anti–G-protein coupled receptor antibodies were found in 33 (55%) of 60 patients with long COVID, and more than 40% had peripheral immune cell profile abnormalities. These findings were similar to those found in patients with ME/CFS, published by Sato’s team (Brain Behav Immun. 2021 Mar 29. doi: 10.1016/j.bbi.2021.03.023) and other researchers in Germany.  

Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, presented data for an analysis of peripheral blood mononuclear cells from 26 donors with ME/CFS (8 with long COVID) and 24 healthy controls. In both patient groups, they found altered expression of inflammatory markers and decreases in CD8 T-cell number and function. The patients with long COVID showed evidence of sustained activation of both T-cell populations with increased CD38 and HLA-DR, associated with a compensatory increased frequency of activated CD4+CD8+ T cells.

“These results are consistent with immune dysregulation associated with overactivation and exhaustion of CD8 T cells, as observed in chronic viral infections and tumor environments,” Dr. Selin said.
 

ME/CFS and long COVID ‘frighteningly similar, if not identical’

Data for a different system derangement in long COVID and ME/CFS, the pathophysiology of exercise intolerance, were presented in another keynote talk by David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital cardiopulmonary laboratory, both in Boston. He has conducted invasive cardiopulmonary exercise testing in patients with ME/CFS and patients with long COVID.

Previously, Dr. Systrom and his team found that patients with ME/CFS have distinct defects in both ventricular filling pressure and oxygen extraction from the muscles. Neither of those are features of deconditioning, which is often blamed for exercise intolerance in people with ME/CFS. Rather, the major defect in deconditioning is decreased stroke volume and cardiac output. In ME/CFS patients, he found supranormal pulmonary blood flow, compared with VO₂ max, suggesting peripheral left-to-right shunting.

In addition, Dr. Systrom and colleagues found that a large proportion of ME/CFS patients with these peripheral vascular defects also have biopsy-demonstrated small-fiber neuropathy, suggesting that acute exercise intolerance is related to underlying autonomic nervous system dysfunction.

In Dr. Systrom and colleagues’ long COVID study, invasive cardiopulmonary exercise testing in 10 patients who had recovered from COVID-19 at least 6 months prior and did not have cardiopulmonary disease had significantly revealed reduced peak exercise aerobic capacity (VO₂ max), compared with 10 age- and sex-matched controls. The reduction in peak VO₂ was associated with impaired systemic oxygen extraction, compared with the controls, despite a preserved peak cardiac index.

The long-COVID patients also showed greater ventilatory inefficiency, which “is entirely related to hyperventilation, not intrinsic lung disease,” Dr. Systrom said, adding that while there may be subsets of patients with interstitial lung disease after acute respiratory distress syndrome, these patients didn’t have that. “This for all the world looks like ME/CFS. We think they are frighteningly similar, if not identical,” Dr. Systrom said.  

In a third study for which Dr. Systrom was a coauthor, published in Annals of Neurology, multisystem involvement was found in nine patients following mild COVID-19 infection, using standardized autonomic assessments including Valsalva maneuver, sudomotor and tilt tests, and skin biopsies for small-fiber neuropathy. The findings included cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction, small-fiber neuropathy and related dysautonomia, respiratory dysregulation, and chronic inflammation.

Dr. Systrom’s conclusion: “Dyspnea and hyperventilation are common in ME/CFS and long COVID and there is significant overlap with POTS.”

Dr. Bateman disclosed that she is conducting research for Terra Biological. Dr. Systrom said he is conducting research for Astellas.

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

Emerging evidence is shedding light on the common underlying mechanisms contributing to the overlapping clinical phenomena of “long COVID,” myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFSME), speakers presented data showing similar pathophysiologic abnormalities in people with systemic symptoms associated with ME/CFS who had a prior SARS-CoV-2 infection and those who did not, including individuals whose illness preceded the COVID-19 pandemic.

Core clinical diagnostic criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for 6 months or longer, postexertional malaise, or a worsening of symptoms following even minor exertion (often described by patients as “crashes”), unrefreshing sleep, and cognitive dysfunction and/or orthostatic intolerance that are frequent and severe.

Long COVID has been defined in several different ways using different terminology. The U.S. Centers for Disease Control and Prevention, for example, defines “post-COVID conditions” as those continuing four or more weeks beyond first symptoms. The World Health Organization’s clinical case definition of “post COVID-19 condition” includes otherwise unexplained symptoms 3 months from COVID-19 onset and lasting longer than 2 months.

Both ME/CFS and long COVID commonly involve numerous symptoms beyond the defining ones, affecting nearly every organ system in the body, including systemic, neurocognitive, endocrine, cardiovascular, pulmonary, musculoskeletal, and gastrointestinal, with wide variation among individuals. Autonomic dysfunction is common to both conditions, particularly postural orthostatic tachycardia syndrome (POTS).

“My way of understanding these illnesses is that they’re not just multisystem illnesses, but all these interactive systems that lean on each other are dysregulated. … I would say that a very common underlying mediator of both ME/CFS and long COVID is autonomic dysfunction, and it presents as POTS,” Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University, Fort Lauderdale, Fla., told this news organization.

Dr. Klimas, who is also director of Clinical Immunology Research at the Miami Veterans Affairs Medical Center, added that “if basic bioenergetics are disrupted and in an oxidative-stress state [then] they have downregulated energy production at the cellular level, which seems to be the case in ME/CFS and now in long COVID.”
 

New ICD-10 codes better characterize the syndromes

New ICD-10 codes for 2023, being implemented on Oct. 1, will enable clinicians to better document all of these interrelated conditions.

Under the existing G93.3, Postviral and related fatigue syndromes, there will now be:

• G93.31 – Postviral fatigue syndrome.
• G93.32 – Myalgic encephalomyelitis/chronic fatigue syndrome (and the separate terms).
• G93.39 – Other postinfection and related fatigue syndromes.

The old R53.82, “Chronic fatigue, unspecified” code now excludes all of the above conditions.

The additional code U09.9 for “post COVID-19 condition, unspecified,” may also be used if applicable.

In addition, a new code for POTS, G90.A, which wasn’t previously mentioned in ICD-10, may also be used starting Oct. 1.

Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, advises using all applicable codes for a given patient. “If a patient came into my office with long COVID and met criteria for ME/CFS, we would code both, and also any other syndrome criteria that they may meet, such as POTS or fibromyalgia.

“If people use the codes appropriately, then you can understand the overlap better. It increases the likelihood of reimbursement, creates a more accurate medical record for the patient, and provides them with a better tool should they require disability benefits.”

Dr. Bateman advises in-office orthostatic evaluation for all patients with this symptom constellation, using a passive standing evaluation such as the 10-minute NASA Lean test.

“Clinicians should take the time to do orthostatic testing in these patients because it provides objective markers and will help lead us to potential interventions to help improve people’s function.”

The Bateman Horne center offers clinician resources on management of ME/CFS and related conditions.
 

How common is ME/CFS after COVID-19?

According to one published meta-analysis, the global prevalence of “post-acute sequelae of SARS-CoV-2,” defined by any symptom, is about 43% of patients overall following infection, and 49% at 120 days. Fatigue was the most commonly reported symptom, followed by memory problems. As of March 22, the World Health Organization estimated that there have been more than 470 million COVID-19 cases, which would give a figure of about 200 million people who are experiencing a wide range of long-COVID symptoms. 

On the final day of the IACFSME conference, Luis Nacul, MD, of the University of British Columbia, Vancouver, presented several sets of data from his group and others aiming to determine the proportion of individuals who develop symptoms suggestive of ME/CFS following a COVID-19 infection.   

Among a cohort of 88 adults hospitalized with confirmed SARS-CoV-2 infections during the first pandemic wave in 2020 and followed up in the respiratory clinic, rates of reported generalized fatigue were 67% at 3 months and 59.5% at 6 months. Substantial fatigue (that is, present most days and affecting activity levels) were reported by 16% at 3 months and 7% at 6 months. “This should represent in principle the maximum prevalence of cases who would meet the criteria for ME/CFS,” Dr. Nacul said.

Baseline age was indirectly associated with fatigue at 3 and 6 months, while the number of comorbidities a patient had was directly associated. Comorbidities also predicted severe fatigue at 3 months, but the numbers were too small for assessment at 6 months.

Studies involving nonhospitalized patients suggested lower rates. One meta-analysis showed 1-year rates of fatigue in 32% and cognitive impairment in 22%. Another showed very similar rates, reporting fatigue in 28% and memory/concentration difficulties in 18%-19%.   

Dr. Nacul cautioned that these figures are likely overestimates since many of the study populations are taken from respiratory or long-COVID clinics. “The evidence on ‘post-COVID fatigue syndrome’ or ME/CFS following COVID is still evolving. There is a huge need for studies looking more closely at cases meeting well-defined ME/CFS criteria. This unfortunately hasn’t been done for most studies.”
 

Immune system dysfunction appears to underlie many cases

In a keynote address during the conference, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., pointed out that long COVID and ME/CFS are among many unexplained postacute infection syndromes associated with a long list of viral pathogens, including Ebola, the prior SARS viruses, Epstein-Barr virus, and Dengue, as well as nonviral pathogens such as Coxiella burnetii (Q fever syndrome) and Borrelia (posttreatment Lyme disease syndrome).

Dr. Iwasaki cited a recent Nature Medicine review article that she coauthored on this topic with an ME/CFS patient, noting: “We really need to understand why some people are failing to recover from these types of diseases.”

Emerging evidence supports four different hypotheses regarding pathogenesis: viral reservoir/viral pathogen-associated molecular pattern molecules, autoimmunity, dysbiosis/viral reactivation, and tissue damage

“Right now, it’s too early to exclude or make any conclusions about these. We need to have an open mind to dissect these various possibilities,” she said.

Two speakers reported findings of immune dysregulation in both ME/CFS and long COVID. Wakiro Sato, MD, PhD, of the National Center of Neurology and Psychiatry, Tokyo, reported that anti–G-protein coupled receptor antibodies were found in 33 (55%) of 60 patients with long COVID, and more than 40% had peripheral immune cell profile abnormalities. These findings were similar to those found in patients with ME/CFS, published by Sato’s team (Brain Behav Immun. 2021 Mar 29. doi: 10.1016/j.bbi.2021.03.023) and other researchers in Germany.  

Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, presented data for an analysis of peripheral blood mononuclear cells from 26 donors with ME/CFS (8 with long COVID) and 24 healthy controls. In both patient groups, they found altered expression of inflammatory markers and decreases in CD8 T-cell number and function. The patients with long COVID showed evidence of sustained activation of both T-cell populations with increased CD38 and HLA-DR, associated with a compensatory increased frequency of activated CD4+CD8+ T cells.

“These results are consistent with immune dysregulation associated with overactivation and exhaustion of CD8 T cells, as observed in chronic viral infections and tumor environments,” Dr. Selin said.
 

ME/CFS and long COVID ‘frighteningly similar, if not identical’

Data for a different system derangement in long COVID and ME/CFS, the pathophysiology of exercise intolerance, were presented in another keynote talk by David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital cardiopulmonary laboratory, both in Boston. He has conducted invasive cardiopulmonary exercise testing in patients with ME/CFS and patients with long COVID.

Previously, Dr. Systrom and his team found that patients with ME/CFS have distinct defects in both ventricular filling pressure and oxygen extraction from the muscles. Neither of those are features of deconditioning, which is often blamed for exercise intolerance in people with ME/CFS. Rather, the major defect in deconditioning is decreased stroke volume and cardiac output. In ME/CFS patients, he found supranormal pulmonary blood flow, compared with VO₂ max, suggesting peripheral left-to-right shunting.

In addition, Dr. Systrom and colleagues found that a large proportion of ME/CFS patients with these peripheral vascular defects also have biopsy-demonstrated small-fiber neuropathy, suggesting that acute exercise intolerance is related to underlying autonomic nervous system dysfunction.

In Dr. Systrom and colleagues’ long COVID study, invasive cardiopulmonary exercise testing in 10 patients who had recovered from COVID-19 at least 6 months prior and did not have cardiopulmonary disease had significantly revealed reduced peak exercise aerobic capacity (VO₂ max), compared with 10 age- and sex-matched controls. The reduction in peak VO₂ was associated with impaired systemic oxygen extraction, compared with the controls, despite a preserved peak cardiac index.

The long-COVID patients also showed greater ventilatory inefficiency, which “is entirely related to hyperventilation, not intrinsic lung disease,” Dr. Systrom said, adding that while there may be subsets of patients with interstitial lung disease after acute respiratory distress syndrome, these patients didn’t have that. “This for all the world looks like ME/CFS. We think they are frighteningly similar, if not identical,” Dr. Systrom said.  

In a third study for which Dr. Systrom was a coauthor, published in Annals of Neurology, multisystem involvement was found in nine patients following mild COVID-19 infection, using standardized autonomic assessments including Valsalva maneuver, sudomotor and tilt tests, and skin biopsies for small-fiber neuropathy. The findings included cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction, small-fiber neuropathy and related dysautonomia, respiratory dysregulation, and chronic inflammation.

Dr. Systrom’s conclusion: “Dyspnea and hyperventilation are common in ME/CFS and long COVID and there is significant overlap with POTS.”

Dr. Bateman disclosed that she is conducting research for Terra Biological. Dr. Systrom said he is conducting research for Astellas.

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

Emerging evidence is shedding light on the common underlying mechanisms contributing to the overlapping clinical phenomena of “long COVID,” myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFSME), speakers presented data showing similar pathophysiologic abnormalities in people with systemic symptoms associated with ME/CFS who had a prior SARS-CoV-2 infection and those who did not, including individuals whose illness preceded the COVID-19 pandemic.

Core clinical diagnostic criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for 6 months or longer, postexertional malaise, or a worsening of symptoms following even minor exertion (often described by patients as “crashes”), unrefreshing sleep, and cognitive dysfunction and/or orthostatic intolerance that are frequent and severe.

Long COVID has been defined in several different ways using different terminology. The U.S. Centers for Disease Control and Prevention, for example, defines “post-COVID conditions” as those continuing four or more weeks beyond first symptoms. The World Health Organization’s clinical case definition of “post COVID-19 condition” includes otherwise unexplained symptoms 3 months from COVID-19 onset and lasting longer than 2 months.

Both ME/CFS and long COVID commonly involve numerous symptoms beyond the defining ones, affecting nearly every organ system in the body, including systemic, neurocognitive, endocrine, cardiovascular, pulmonary, musculoskeletal, and gastrointestinal, with wide variation among individuals. Autonomic dysfunction is common to both conditions, particularly postural orthostatic tachycardia syndrome (POTS).

“My way of understanding these illnesses is that they’re not just multisystem illnesses, but all these interactive systems that lean on each other are dysregulated. … I would say that a very common underlying mediator of both ME/CFS and long COVID is autonomic dysfunction, and it presents as POTS,” Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University, Fort Lauderdale, Fla., told this news organization.

Dr. Klimas, who is also director of Clinical Immunology Research at the Miami Veterans Affairs Medical Center, added that “if basic bioenergetics are disrupted and in an oxidative-stress state [then] they have downregulated energy production at the cellular level, which seems to be the case in ME/CFS and now in long COVID.”
 

New ICD-10 codes better characterize the syndromes

New ICD-10 codes for 2023, being implemented on Oct. 1, will enable clinicians to better document all of these interrelated conditions.

Under the existing G93.3, Postviral and related fatigue syndromes, there will now be:

• G93.31 – Postviral fatigue syndrome.
• G93.32 – Myalgic encephalomyelitis/chronic fatigue syndrome (and the separate terms).
• G93.39 – Other postinfection and related fatigue syndromes.

The old R53.82, “Chronic fatigue, unspecified” code now excludes all of the above conditions.

The additional code U09.9 for “post COVID-19 condition, unspecified,” may also be used if applicable.

In addition, a new code for POTS, G90.A, which wasn’t previously mentioned in ICD-10, may also be used starting Oct. 1.

Lucinda Bateman, MD, founder and director of the Bateman Horne Center, Salt Lake City, advises using all applicable codes for a given patient. “If a patient came into my office with long COVID and met criteria for ME/CFS, we would code both, and also any other syndrome criteria that they may meet, such as POTS or fibromyalgia.

“If people use the codes appropriately, then you can understand the overlap better. It increases the likelihood of reimbursement, creates a more accurate medical record for the patient, and provides them with a better tool should they require disability benefits.”

Dr. Bateman advises in-office orthostatic evaluation for all patients with this symptom constellation, using a passive standing evaluation such as the 10-minute NASA Lean test.

“Clinicians should take the time to do orthostatic testing in these patients because it provides objective markers and will help lead us to potential interventions to help improve people’s function.”

The Bateman Horne center offers clinician resources on management of ME/CFS and related conditions.
 

How common is ME/CFS after COVID-19?

According to one published meta-analysis, the global prevalence of “post-acute sequelae of SARS-CoV-2,” defined by any symptom, is about 43% of patients overall following infection, and 49% at 120 days. Fatigue was the most commonly reported symptom, followed by memory problems. As of March 22, the World Health Organization estimated that there have been more than 470 million COVID-19 cases, which would give a figure of about 200 million people who are experiencing a wide range of long-COVID symptoms. 

On the final day of the IACFSME conference, Luis Nacul, MD, of the University of British Columbia, Vancouver, presented several sets of data from his group and others aiming to determine the proportion of individuals who develop symptoms suggestive of ME/CFS following a COVID-19 infection.   

Among a cohort of 88 adults hospitalized with confirmed SARS-CoV-2 infections during the first pandemic wave in 2020 and followed up in the respiratory clinic, rates of reported generalized fatigue were 67% at 3 months and 59.5% at 6 months. Substantial fatigue (that is, present most days and affecting activity levels) were reported by 16% at 3 months and 7% at 6 months. “This should represent in principle the maximum prevalence of cases who would meet the criteria for ME/CFS,” Dr. Nacul said.

Baseline age was indirectly associated with fatigue at 3 and 6 months, while the number of comorbidities a patient had was directly associated. Comorbidities also predicted severe fatigue at 3 months, but the numbers were too small for assessment at 6 months.

Studies involving nonhospitalized patients suggested lower rates. One meta-analysis showed 1-year rates of fatigue in 32% and cognitive impairment in 22%. Another showed very similar rates, reporting fatigue in 28% and memory/concentration difficulties in 18%-19%.   

Dr. Nacul cautioned that these figures are likely overestimates since many of the study populations are taken from respiratory or long-COVID clinics. “The evidence on ‘post-COVID fatigue syndrome’ or ME/CFS following COVID is still evolving. There is a huge need for studies looking more closely at cases meeting well-defined ME/CFS criteria. This unfortunately hasn’t been done for most studies.”
 

Immune system dysfunction appears to underlie many cases

In a keynote address during the conference, Akiko Iwasaki, PhD, of Yale University, New Haven, Conn., pointed out that long COVID and ME/CFS are among many unexplained postacute infection syndromes associated with a long list of viral pathogens, including Ebola, the prior SARS viruses, Epstein-Barr virus, and Dengue, as well as nonviral pathogens such as Coxiella burnetii (Q fever syndrome) and Borrelia (posttreatment Lyme disease syndrome).

Dr. Iwasaki cited a recent Nature Medicine review article that she coauthored on this topic with an ME/CFS patient, noting: “We really need to understand why some people are failing to recover from these types of diseases.”

Emerging evidence supports four different hypotheses regarding pathogenesis: viral reservoir/viral pathogen-associated molecular pattern molecules, autoimmunity, dysbiosis/viral reactivation, and tissue damage

“Right now, it’s too early to exclude or make any conclusions about these. We need to have an open mind to dissect these various possibilities,” she said.

Two speakers reported findings of immune dysregulation in both ME/CFS and long COVID. Wakiro Sato, MD, PhD, of the National Center of Neurology and Psychiatry, Tokyo, reported that anti–G-protein coupled receptor antibodies were found in 33 (55%) of 60 patients with long COVID, and more than 40% had peripheral immune cell profile abnormalities. These findings were similar to those found in patients with ME/CFS, published by Sato’s team (Brain Behav Immun. 2021 Mar 29. doi: 10.1016/j.bbi.2021.03.023) and other researchers in Germany.  

Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, presented data for an analysis of peripheral blood mononuclear cells from 26 donors with ME/CFS (8 with long COVID) and 24 healthy controls. In both patient groups, they found altered expression of inflammatory markers and decreases in CD8 T-cell number and function. The patients with long COVID showed evidence of sustained activation of both T-cell populations with increased CD38 and HLA-DR, associated with a compensatory increased frequency of activated CD4+CD8+ T cells.

“These results are consistent with immune dysregulation associated with overactivation and exhaustion of CD8 T cells, as observed in chronic viral infections and tumor environments,” Dr. Selin said.
 

ME/CFS and long COVID ‘frighteningly similar, if not identical’

Data for a different system derangement in long COVID and ME/CFS, the pathophysiology of exercise intolerance, were presented in another keynote talk by David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital cardiopulmonary laboratory, both in Boston. He has conducted invasive cardiopulmonary exercise testing in patients with ME/CFS and patients with long COVID.

Previously, Dr. Systrom and his team found that patients with ME/CFS have distinct defects in both ventricular filling pressure and oxygen extraction from the muscles. Neither of those are features of deconditioning, which is often blamed for exercise intolerance in people with ME/CFS. Rather, the major defect in deconditioning is decreased stroke volume and cardiac output. In ME/CFS patients, he found supranormal pulmonary blood flow, compared with VO₂ max, suggesting peripheral left-to-right shunting.

In addition, Dr. Systrom and colleagues found that a large proportion of ME/CFS patients with these peripheral vascular defects also have biopsy-demonstrated small-fiber neuropathy, suggesting that acute exercise intolerance is related to underlying autonomic nervous system dysfunction.

In Dr. Systrom and colleagues’ long COVID study, invasive cardiopulmonary exercise testing in 10 patients who had recovered from COVID-19 at least 6 months prior and did not have cardiopulmonary disease had significantly revealed reduced peak exercise aerobic capacity (VO₂ max), compared with 10 age- and sex-matched controls. The reduction in peak VO₂ was associated with impaired systemic oxygen extraction, compared with the controls, despite a preserved peak cardiac index.

The long-COVID patients also showed greater ventilatory inefficiency, which “is entirely related to hyperventilation, not intrinsic lung disease,” Dr. Systrom said, adding that while there may be subsets of patients with interstitial lung disease after acute respiratory distress syndrome, these patients didn’t have that. “This for all the world looks like ME/CFS. We think they are frighteningly similar, if not identical,” Dr. Systrom said.  

In a third study for which Dr. Systrom was a coauthor, published in Annals of Neurology, multisystem involvement was found in nine patients following mild COVID-19 infection, using standardized autonomic assessments including Valsalva maneuver, sudomotor and tilt tests, and skin biopsies for small-fiber neuropathy. The findings included cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction, small-fiber neuropathy and related dysautonomia, respiratory dysregulation, and chronic inflammation.

Dr. Systrom’s conclusion: “Dyspnea and hyperventilation are common in ME/CFS and long COVID and there is significant overlap with POTS.”

Dr. Bateman disclosed that she is conducting research for Terra Biological. Dr. Systrom said he is conducting research for Astellas.

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