Miriam E. Tucker

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

Neither diabetes per se nor hyperglycemia appear to impair the antibody response to SARS-CoV-2, suggesting that a COVID-19 vaccine would be just as effective in people with diabetes as in those without, new research finds.

Results from a study involving 480 patients with confirmed COVID-19 seen at an Italian hospital between February 25 and April 19 were published online October 8 in Diabetologia by Vito Lampasona, MD, and colleagues.

Antibody responses against multiple SARS-CoV-2 antigens among the 27% of patients with COVID-19 and diabetes (preexisting and newly diagnosed) were similar with regard to timing, titers, and classes to those of patients with COVID-19 and without diabetes, and the results did not differ by glucose levels.

Moreover, positivity for immunoglobulin G (IgG) against the SARS-CoV-2 spike receptor-binding domain (RBD) was associated with improved survival regardless of diabetes status.

And as previously shown, high blood glucose levels were strongly associated with greater COVID-19 mortality even in those without diabetes.

This is the first study of the immunologic humoral response against SARS-CoV-2 in patients with hyperglycemia, the authors say.

“The immunological response to a future SARS-CoV-2 vaccine will be assessed when the vaccine becomes available. However, our data allow a cautious optimism regarding effective immunization in individuals with diabetes, as well as in the general population,” wrote Dr. Lampasona of San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele in Milan, and colleagues.
 

Diabetes and hyperglycemia worsen COVID-19 outcomes

The investigators analyzed the presence of three types of antibody to multiple SARS-CoV-2 antigens in 509 participants: IgG, which is evidence of past infection; IgM, which indicates more recent or current infection; and IgA, which is involved in the mucosal immune response, for example, in the nose where the virus enters the body.

Overall, 452 (88.8%) patients were hospitalized, 79 (15.5%) patients were admitted to intensive care, and 93 (18.3%) patients died during follow-up.

Of the 139 patients with diabetes, 90 (17.7% of the study cohort) already had a diagnosis of diabetes, and 49 (9.6%) were newly diagnosed.

Those with diabetes were older, had a higher body mass index (BMI), and were more likely to have cardiovascular comorbidities, hypertension, and chronic kidney disease. As has been previously reported for diabetes and COVID-19, diabetes was also associated with increased levels of inflammatory biomarkers, hypercoagulopathy, leukocytosis, and neutrophilia.

In multivariate analysis, diabetes status (hazard ratio, 2.32; P = .001), mean fasting plasma glucose (P < .001), and glucose variability (P = .002) were all independently associated with increased mortality and ICU admission. And fasting plasma glucose was associated with increased mortality risk even among those without diabetes (P < .001).
 

Antibody response similar in patients with and without diabetes

The humoral response against SARS-CoV-2 in patients with diabetes was present and superimposable in terms of timing and antibody titers to that of patients without diabetes, with marginal differences, and was not influenced by glucose levels.

After adjustment for sex, age, and diabetes status and stratification by symptom duration at time of sampling, the development of SARS-CoV-2 RBD IgG antibodies was associated with improved survival, with an HR for time to death of 0.4 (P = .002).

“Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival rate, both in the presence or absence of diabetes,” the authors stressed, with similar HRs for those with diabetes (0.37; P = .013) and without diabetes (0.43; P = .038).

These data confirm “the relevance for patient survival rate of the specific antigen response against spike RBD even in the presence of diabetes, and it underlines how the mechanism explaining the worse clinical outcome in patients with diabetes is unrelated to the antibody response,” they explain.

They added, “This, together with evidence that increased blood glucose levels do predict a poor prognosis even in nondiabetic individuals and the association with increased levels of inflammatory biomarkers and hypercoagulopathy, as well as leukocytosis and neutrophilia, support the speculation that glucose per se could be an independent biological negative factor, acting as a direct regulator of innate immunity.”

“The observed increased severity and mortality risk of COVID-19 pneumonia in patients with hyperglycemia was not the result of an impaired humoral response against SARS-CoV-2.”

“RBD IgG positivity was associated with a remarkable protective effect, allowing for a cautious optimism about the efficacy of future vaccines against SARS-COV-2 in people with diabetes,” they reiterated.

The authors have reported no relevant financial relationships.
 

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

A protocol developed in the United Kingdom that allows commercial pilots with insulin-treated diabetes to fly airplanes has resulted in precise glycemic control during flight and no safety issues, new research finds.

©mico_images/Thinkstock

The results are believed to be the largest-ever dataset for people with insulin-treated diabetes in “safety-critical” occupations, said Gillian L. Garden, MD, who presented the findings this week at the virtual annual meeting of the European Association for the Study of Diabetes.

The protocol, which involves multiple glucose measurements before and throughout flights and corrective action for out-of-range values, resulted in 98% of glucose values in target range with no pilot incapacitation. The results were also published in Diabetes Care earlier this year, noted Dr. Garden, a clinical fellow in diabetes and endocrinology at the Royal Surrey NHS Foundation Trust, Guildford, England.

“There were no safety concerns at all and certainly no episodes of pilot incapacitation throughout the [7.5] years of the study. Our study proves that the protocol is feasible, is practical to implement, and is easily understood by both pilots and copilots,” she observed.

Dr. Garden foresees wider use of this approach: “We believe the study is of international importance and this protocol could be adopted by other aviation authorities to allow more insulin-treated pilots worldwide to be able to fly commercial aircraft.”

“With proper oversight and a defined protocol such as the one that we’ve been working to produce it is possible for anybody with insulin-treated diabetes to, in fact, adequately perform other safety-critical occupations as well, and it would be good to see fewer people being discriminated against on the basis of their diabetes,” she emphasized.
 

‘Impressive’ study of highly motivated individuals

Historically, insulin-treated patients – with both types of diabetes – had been barred from many “safety-critical” occupations, including commercial airline piloting. This was out of concern both for the potential immediate effects of hypoglycemia, including cognitive impairment and slowing of reaction times, as well as the long-term effects of diabetes, including vision loss and nerve damage, Dr. Garden explained.

However, “with advances in diabetes management, including different insulin types, methods of delivery, and glucose-monitoring systems, it’s now possible for individuals to have excellent glycemic control. This, along with the implementation of legislation against discrimination, has allowed insulin-treated people to no longer be debarred from certain employments,” she explained during an EASD press briefing on Sept. 24.

An expert panel convened in 2010 by the U.K. Civil Aviation Authority developed the protocol, and in 2012, the CAA began issuing class 1 medical certificates to insulin-treated pilots. The protocol was subsequently adopted by Ireland in 2015 and by Austria in 2016.

Initial results from nearly 9,000 glucose readings of 26 U.K. pilots who received a certificate between 2012 and 2015 were reported at the EASD 2016 Annual Meeting and published in 2017.

The current study is far larger, with 38,621 glucose readings from 49 pilots from the United Kingdom, Ireland, and Austria who have been using the protocol since 2012. 

Mark Evans, MD, of Addenbrookes Hospital, Cambridge, England, said in an interview that “I thought this was a fascinating paper. ... I was deeply impressed by the data.”

Dr. Evans, who chairs the U.K. Department of Transport advisory panel on driving and diabetes, also noted: “The group of people with insulin-treated diabetes flying planes are a phenomenally motivated group who are prepared to do things that probably most drivers of motor vehicles would find oppressive or very difficult to do.”

“I thought the outcomes were really impressive in terms of the amount of time they were able to maintain themselves within glucose target ranges.”

Indeed, Dr. Garden said, “pilots are typically very organized and used to dealing with strict protocols with regard to all of the processes they have to follow before they fly and the safety checks they have to do. They adapted to this additional safety measure really well.”
 

Traffic light protocol keeps pilots in range

The protocol requires pilots to perform fingerstick glucose checks 30 minutes prior to flight, every hour during flight, and 30 minutes before landing. They must also attend clinical reviews every 6 months.

A traffic light system is used to denote acceptable pre- and in-flight glucose levels, with green meaning acceptable (5.0-15.0 mmol/L [90-270 mg/dL]), amber indicating caution for low (4.0-4.9 mmol/L [72-88 mg/dL]) or high (15.1-20.0 mmol/L [272-360 mg/dL]) blood glucose. Red requires immediate action (low blood glucose <4 mmol/L [72 mg/dL] and high >20 mmol/L [>360 mg/dL]).

Low amber values require the pilot to ingest 10-15 fast-acting carbohydrates and retest after 30 minutes. Low red values indicate the pilot must hand over the controls to the copilot. High readings of >15.0 mmol/L (>270 mg/dL) require an insulin dosing review. A high red value also requires the pilot to hand over the controls.

Of the 49 pilots, 84% had type 1 diabetes and 16% had insulin-treated type 2 diabetes. Most (61%) had class 1 medical certificates (required to validate a commercial pilot license) and 39% had class 2 medical certificates (required to validate a private pilot’s license). Median diabetes duration was 10.9 years.

Of note, all had become pilots prior to diabetes onset. As of now, the EU Aviation Safety Agency doesn’t allow people with preexisting insulin-treated diabetes to become pilots.

“We are fighting to change that, but with the U.K. leaving the EU, the Civil Aviation Authority might pursue it [separately]. We don’t know how that will pan out,” Dr. Garden noted during the briefing.

Over the 7.5 years, 97.7% of readings were within the green range, while just 1.42% were in the low amber range and 0.75% in the high amber range. Just 48 readings (0.12%) were in the low red range and 6 (0.02%) in the high red range. Of the 48 low reds, just 14 were recorded during flight. Of the six high reds, only two occurred during flight.

There were no instances of pilot incapacitation or changes in average hemoglobin A1c.

The results should alleviate concerns expressed after a prior report that pilots’ overall glycemic control could worsen if they pushed too hard to avoid lows, Dr. Garden noted.

The proportion of out-of-range values declined from 5.7% in 2013 to 1.2% in 2019. Low red values didn’t change (0.2% in 2013 and 0.1% in 2019) but high red values had completely disappeared by 2017.
 

What about CGM?

In response to a question during the briefing about use of continuous glucose monitoring, Dr. Garden said that some of the pilots were using CGM in addition to following the fingerstick protocol.

At the time the protocol was developed a decade ago, CGM wasn’t considered accurate enough and there wasn’t evidence for its use at high altitude.

But there has been a great deal more data since then, she said, noting “we believe it would be safer to use now because of how good that equipment is. ... Certainly, there’s a good number [of pilots] using CGM, and hopefully that will increase and the protocol will change to allow them all to use CGM if they want to.

“I think we’ll probably see CGM in the protocol within the next year to 2 years. Hopefully, that will make things a lot easier, so pilots won’t have to prick their fingers while they’re flying.”

Her group is currently conducting a study (DEXFLY) on use of the Dexcom G6 in addition to fingersticks in commercial pilots with insulin-treated diabetes. Results are expected by the end of the year.

Dr. Evans commented: “I think it’s a no-brainer that CGM will become the gold standard. I understand why they’re going to want to be cautious about this, but if they can generate data to show it will be a low-risk change, I think it will come.”

He also noted that it was only a couple of years ago that U.K. law was changed to allow car drivers with insulin-treated diabetes to use CGM as part of their glucose-testing requirements (before driving and every 2 hours). CGM still isn’t approved for use by drivers of trucks or other large vehicles, but “I think at some point in the future it will become more accepted,” Dr. Evans commented.

Dr. Garden reported no relevant financial relationships. Dr. Evans has reported being an advisory board member of, speaker for, and/or grant recipient from Novo Nordisk, Dexcom, Medtronic, Abbott, Eli Lilly, and Roche. 

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

A protocol developed in the United Kingdom that allows commercial pilots with insulin-treated diabetes to fly airplanes has resulted in precise glycemic control during flight and no safety issues, new research finds.

©mico_images/Thinkstock

The results are believed to be the largest-ever dataset for people with insulin-treated diabetes in “safety-critical” occupations, said Gillian L. Garden, MD, who presented the findings this week at the virtual annual meeting of the European Association for the Study of Diabetes.

The protocol, which involves multiple glucose measurements before and throughout flights and corrective action for out-of-range values, resulted in 98% of glucose values in target range with no pilot incapacitation. The results were also published in Diabetes Care earlier this year, noted Dr. Garden, a clinical fellow in diabetes and endocrinology at the Royal Surrey NHS Foundation Trust, Guildford, England.

“There were no safety concerns at all and certainly no episodes of pilot incapacitation throughout the [7.5] years of the study. Our study proves that the protocol is feasible, is practical to implement, and is easily understood by both pilots and copilots,” she observed.

Dr. Garden foresees wider use of this approach: “We believe the study is of international importance and this protocol could be adopted by other aviation authorities to allow more insulin-treated pilots worldwide to be able to fly commercial aircraft.”

“With proper oversight and a defined protocol such as the one that we’ve been working to produce it is possible for anybody with insulin-treated diabetes to, in fact, adequately perform other safety-critical occupations as well, and it would be good to see fewer people being discriminated against on the basis of their diabetes,” she emphasized.
 

‘Impressive’ study of highly motivated individuals

Historically, insulin-treated patients – with both types of diabetes – had been barred from many “safety-critical” occupations, including commercial airline piloting. This was out of concern both for the potential immediate effects of hypoglycemia, including cognitive impairment and slowing of reaction times, as well as the long-term effects of diabetes, including vision loss and nerve damage, Dr. Garden explained.

However, “with advances in diabetes management, including different insulin types, methods of delivery, and glucose-monitoring systems, it’s now possible for individuals to have excellent glycemic control. This, along with the implementation of legislation against discrimination, has allowed insulin-treated people to no longer be debarred from certain employments,” she explained during an EASD press briefing on Sept. 24.

An expert panel convened in 2010 by the U.K. Civil Aviation Authority developed the protocol, and in 2012, the CAA began issuing class 1 medical certificates to insulin-treated pilots. The protocol was subsequently adopted by Ireland in 2015 and by Austria in 2016.

Initial results from nearly 9,000 glucose readings of 26 U.K. pilots who received a certificate between 2012 and 2015 were reported at the EASD 2016 Annual Meeting and published in 2017.

The current study is far larger, with 38,621 glucose readings from 49 pilots from the United Kingdom, Ireland, and Austria who have been using the protocol since 2012. 

Mark Evans, MD, of Addenbrookes Hospital, Cambridge, England, said in an interview that “I thought this was a fascinating paper. ... I was deeply impressed by the data.”

Dr. Evans, who chairs the U.K. Department of Transport advisory panel on driving and diabetes, also noted: “The group of people with insulin-treated diabetes flying planes are a phenomenally motivated group who are prepared to do things that probably most drivers of motor vehicles would find oppressive or very difficult to do.”

“I thought the outcomes were really impressive in terms of the amount of time they were able to maintain themselves within glucose target ranges.”

Indeed, Dr. Garden said, “pilots are typically very organized and used to dealing with strict protocols with regard to all of the processes they have to follow before they fly and the safety checks they have to do. They adapted to this additional safety measure really well.”
 

Traffic light protocol keeps pilots in range

The protocol requires pilots to perform fingerstick glucose checks 30 minutes prior to flight, every hour during flight, and 30 minutes before landing. They must also attend clinical reviews every 6 months.

A traffic light system is used to denote acceptable pre- and in-flight glucose levels, with green meaning acceptable (5.0-15.0 mmol/L [90-270 mg/dL]), amber indicating caution for low (4.0-4.9 mmol/L [72-88 mg/dL]) or high (15.1-20.0 mmol/L [272-360 mg/dL]) blood glucose. Red requires immediate action (low blood glucose <4 mmol/L [72 mg/dL] and high >20 mmol/L [>360 mg/dL]).

Low amber values require the pilot to ingest 10-15 fast-acting carbohydrates and retest after 30 minutes. Low red values indicate the pilot must hand over the controls to the copilot. High readings of >15.0 mmol/L (>270 mg/dL) require an insulin dosing review. A high red value also requires the pilot to hand over the controls.

Of the 49 pilots, 84% had type 1 diabetes and 16% had insulin-treated type 2 diabetes. Most (61%) had class 1 medical certificates (required to validate a commercial pilot license) and 39% had class 2 medical certificates (required to validate a private pilot’s license). Median diabetes duration was 10.9 years.

Of note, all had become pilots prior to diabetes onset. As of now, the EU Aviation Safety Agency doesn’t allow people with preexisting insulin-treated diabetes to become pilots.

“We are fighting to change that, but with the U.K. leaving the EU, the Civil Aviation Authority might pursue it [separately]. We don’t know how that will pan out,” Dr. Garden noted during the briefing.

Over the 7.5 years, 97.7% of readings were within the green range, while just 1.42% were in the low amber range and 0.75% in the high amber range. Just 48 readings (0.12%) were in the low red range and 6 (0.02%) in the high red range. Of the 48 low reds, just 14 were recorded during flight. Of the six high reds, only two occurred during flight.

There were no instances of pilot incapacitation or changes in average hemoglobin A1c.

The results should alleviate concerns expressed after a prior report that pilots’ overall glycemic control could worsen if they pushed too hard to avoid lows, Dr. Garden noted.

The proportion of out-of-range values declined from 5.7% in 2013 to 1.2% in 2019. Low red values didn’t change (0.2% in 2013 and 0.1% in 2019) but high red values had completely disappeared by 2017.
 

What about CGM?

In response to a question during the briefing about use of continuous glucose monitoring, Dr. Garden said that some of the pilots were using CGM in addition to following the fingerstick protocol.

At the time the protocol was developed a decade ago, CGM wasn’t considered accurate enough and there wasn’t evidence for its use at high altitude.

But there has been a great deal more data since then, she said, noting “we believe it would be safer to use now because of how good that equipment is. ... Certainly, there’s a good number [of pilots] using CGM, and hopefully that will increase and the protocol will change to allow them all to use CGM if they want to.

“I think we’ll probably see CGM in the protocol within the next year to 2 years. Hopefully, that will make things a lot easier, so pilots won’t have to prick their fingers while they’re flying.”

Her group is currently conducting a study (DEXFLY) on use of the Dexcom G6 in addition to fingersticks in commercial pilots with insulin-treated diabetes. Results are expected by the end of the year.

Dr. Evans commented: “I think it’s a no-brainer that CGM will become the gold standard. I understand why they’re going to want to be cautious about this, but if they can generate data to show it will be a low-risk change, I think it will come.”

He also noted that it was only a couple of years ago that U.K. law was changed to allow car drivers with insulin-treated diabetes to use CGM as part of their glucose-testing requirements (before driving and every 2 hours). CGM still isn’t approved for use by drivers of trucks or other large vehicles, but “I think at some point in the future it will become more accepted,” Dr. Evans commented.

Dr. Garden reported no relevant financial relationships. Dr. Evans has reported being an advisory board member of, speaker for, and/or grant recipient from Novo Nordisk, Dexcom, Medtronic, Abbott, Eli Lilly, and Roche. 

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

A protocol developed in the United Kingdom that allows commercial pilots with insulin-treated diabetes to fly airplanes has resulted in precise glycemic control during flight and no safety issues, new research finds.

©mico_images/Thinkstock

The results are believed to be the largest-ever dataset for people with insulin-treated diabetes in “safety-critical” occupations, said Gillian L. Garden, MD, who presented the findings this week at the virtual annual meeting of the European Association for the Study of Diabetes.

The protocol, which involves multiple glucose measurements before and throughout flights and corrective action for out-of-range values, resulted in 98% of glucose values in target range with no pilot incapacitation. The results were also published in Diabetes Care earlier this year, noted Dr. Garden, a clinical fellow in diabetes and endocrinology at the Royal Surrey NHS Foundation Trust, Guildford, England.

“There were no safety concerns at all and certainly no episodes of pilot incapacitation throughout the [7.5] years of the study. Our study proves that the protocol is feasible, is practical to implement, and is easily understood by both pilots and copilots,” she observed.

Dr. Garden foresees wider use of this approach: “We believe the study is of international importance and this protocol could be adopted by other aviation authorities to allow more insulin-treated pilots worldwide to be able to fly commercial aircraft.”

“With proper oversight and a defined protocol such as the one that we’ve been working to produce it is possible for anybody with insulin-treated diabetes to, in fact, adequately perform other safety-critical occupations as well, and it would be good to see fewer people being discriminated against on the basis of their diabetes,” she emphasized.
 

‘Impressive’ study of highly motivated individuals

Historically, insulin-treated patients – with both types of diabetes – had been barred from many “safety-critical” occupations, including commercial airline piloting. This was out of concern both for the potential immediate effects of hypoglycemia, including cognitive impairment and slowing of reaction times, as well as the long-term effects of diabetes, including vision loss and nerve damage, Dr. Garden explained.

However, “with advances in diabetes management, including different insulin types, methods of delivery, and glucose-monitoring systems, it’s now possible for individuals to have excellent glycemic control. This, along with the implementation of legislation against discrimination, has allowed insulin-treated people to no longer be debarred from certain employments,” she explained during an EASD press briefing on Sept. 24.

An expert panel convened in 2010 by the U.K. Civil Aviation Authority developed the protocol, and in 2012, the CAA began issuing class 1 medical certificates to insulin-treated pilots. The protocol was subsequently adopted by Ireland in 2015 and by Austria in 2016.

Initial results from nearly 9,000 glucose readings of 26 U.K. pilots who received a certificate between 2012 and 2015 were reported at the EASD 2016 Annual Meeting and published in 2017.

The current study is far larger, with 38,621 glucose readings from 49 pilots from the United Kingdom, Ireland, and Austria who have been using the protocol since 2012. 

Mark Evans, MD, of Addenbrookes Hospital, Cambridge, England, said in an interview that “I thought this was a fascinating paper. ... I was deeply impressed by the data.”

Dr. Evans, who chairs the U.K. Department of Transport advisory panel on driving and diabetes, also noted: “The group of people with insulin-treated diabetes flying planes are a phenomenally motivated group who are prepared to do things that probably most drivers of motor vehicles would find oppressive or very difficult to do.”

“I thought the outcomes were really impressive in terms of the amount of time they were able to maintain themselves within glucose target ranges.”

Indeed, Dr. Garden said, “pilots are typically very organized and used to dealing with strict protocols with regard to all of the processes they have to follow before they fly and the safety checks they have to do. They adapted to this additional safety measure really well.”
 

Traffic light protocol keeps pilots in range

The protocol requires pilots to perform fingerstick glucose checks 30 minutes prior to flight, every hour during flight, and 30 minutes before landing. They must also attend clinical reviews every 6 months.

A traffic light system is used to denote acceptable pre- and in-flight glucose levels, with green meaning acceptable (5.0-15.0 mmol/L [90-270 mg/dL]), amber indicating caution for low (4.0-4.9 mmol/L [72-88 mg/dL]) or high (15.1-20.0 mmol/L [272-360 mg/dL]) blood glucose. Red requires immediate action (low blood glucose <4 mmol/L [72 mg/dL] and high >20 mmol/L [>360 mg/dL]).

Low amber values require the pilot to ingest 10-15 fast-acting carbohydrates and retest after 30 minutes. Low red values indicate the pilot must hand over the controls to the copilot. High readings of >15.0 mmol/L (>270 mg/dL) require an insulin dosing review. A high red value also requires the pilot to hand over the controls.

Of the 49 pilots, 84% had type 1 diabetes and 16% had insulin-treated type 2 diabetes. Most (61%) had class 1 medical certificates (required to validate a commercial pilot license) and 39% had class 2 medical certificates (required to validate a private pilot’s license). Median diabetes duration was 10.9 years.

Of note, all had become pilots prior to diabetes onset. As of now, the EU Aviation Safety Agency doesn’t allow people with preexisting insulin-treated diabetes to become pilots.

“We are fighting to change that, but with the U.K. leaving the EU, the Civil Aviation Authority might pursue it [separately]. We don’t know how that will pan out,” Dr. Garden noted during the briefing.

Over the 7.5 years, 97.7% of readings were within the green range, while just 1.42% were in the low amber range and 0.75% in the high amber range. Just 48 readings (0.12%) were in the low red range and 6 (0.02%) in the high red range. Of the 48 low reds, just 14 were recorded during flight. Of the six high reds, only two occurred during flight.

There were no instances of pilot incapacitation or changes in average hemoglobin A1c.

The results should alleviate concerns expressed after a prior report that pilots’ overall glycemic control could worsen if they pushed too hard to avoid lows, Dr. Garden noted.

The proportion of out-of-range values declined from 5.7% in 2013 to 1.2% in 2019. Low red values didn’t change (0.2% in 2013 and 0.1% in 2019) but high red values had completely disappeared by 2017.
 

What about CGM?

In response to a question during the briefing about use of continuous glucose monitoring, Dr. Garden said that some of the pilots were using CGM in addition to following the fingerstick protocol.

At the time the protocol was developed a decade ago, CGM wasn’t considered accurate enough and there wasn’t evidence for its use at high altitude.

But there has been a great deal more data since then, she said, noting “we believe it would be safer to use now because of how good that equipment is. ... Certainly, there’s a good number [of pilots] using CGM, and hopefully that will increase and the protocol will change to allow them all to use CGM if they want to.

“I think we’ll probably see CGM in the protocol within the next year to 2 years. Hopefully, that will make things a lot easier, so pilots won’t have to prick their fingers while they’re flying.”

Her group is currently conducting a study (DEXFLY) on use of the Dexcom G6 in addition to fingersticks in commercial pilots with insulin-treated diabetes. Results are expected by the end of the year.

Dr. Evans commented: “I think it’s a no-brainer that CGM will become the gold standard. I understand why they’re going to want to be cautious about this, but if they can generate data to show it will be a low-risk change, I think it will come.”

He also noted that it was only a couple of years ago that U.K. law was changed to allow car drivers with insulin-treated diabetes to use CGM as part of their glucose-testing requirements (before driving and every 2 hours). CGM still isn’t approved for use by drivers of trucks or other large vehicles, but “I think at some point in the future it will become more accepted,” Dr. Evans commented.

Dr. Garden reported no relevant financial relationships. Dr. Evans has reported being an advisory board member of, speaker for, and/or grant recipient from Novo Nordisk, Dexcom, Medtronic, Abbott, Eli Lilly, and Roche. 

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

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

Dr. Rosenstock reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander reported no relevant financial relationships.

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

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

Dr. Rosenstock reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander reported no relevant financial relationships.

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

Phase 2 data for the investigational, once-weekly basal insulin analog icodec (Novo Nordisk) showing comparable efficacy and safety to once-daily insulin glargine U100 have been published in the New England Journal of Medicine.

“Insulin icodec could potentially improve acceptance and likely would facilitate management in type 2 diabetes patients needing basal insulin, and I think it will be transformational in the way we manage people with type 2 diabetes requiring insulin,” said lead author Julio Rosenstock, MD, University of Texas Southwestern Medical Center, Dallas, who also presented the data at the virtual annual meeting of the European Association for the Study of Diabetes.

Insulin icodec binds to albumin to create a circulating depot with a 196-hour (8.1 days) half-life, so the once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week, with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.

In the 26-week, randomized, phase 2 trial involving 247 insulin-naive patients with type 2 diabetes, once-weekly icodec’s glucose-lowering and safety profiles were similar to those of once-daily insulin glargine U100. These results were previously presented by Dr. Rosenstock in June at the virtual American Diabetes Association conference, as reported by Medscape Medical News.

In addition, new data in a poster at EASD 2020 showed that switching to icodec from other basal insulins is efficacious without causing significant hypoglycemia, as reported by Harpreet Bajaj, MD, MPH, director of the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto.

Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said in an interview that “some patients will find once-weekly basal insulin an attractive option, while other patients will be indifferent to its availability.”

Dr. Alexander also pointed out that “payers are not going to be very interested in paying for a once-weekly basal insulin when daily basal insulins have been available for many years, unless the cost is the same or less. Resource-constrained health plans will wait until the price is [similar].”
 

The phase 2 study: Once weekly is just as good as daily

In the phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial, the patients had baseline hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with or without a dipeptidyl peptidase–4 inhibitor.

They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, down to 6.7% and 6.9%, respectively. The difference wasn’t significant (P = .08). Fasting plasma glucose levels dropped by 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).

Time in range (70-140 mg/dL or 3.9-7.8 mmol/L) as assessed by flash glucose monitoring (FreeStyle Libre Pro) was greater with Icodec, by 5.4 percentage points, corresponding to an extra 78 minutes per day in range.

Mild hypoglycemia was more common with icodec than glargine (509 vs. 211 events per 100 patient-years, but rates of moderate/clinically significant hypoglycemia (52.5 vs. 46 per 100 patient-years, respectively) and severe hypoglycemia (1.4 vs. 0 per 100 patient-years) did not differ significantly (P = .85).

And the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.

Rates of other adverse events were similar between the groups.

Use of a once-weekly basal insulin could reduce the number of annual insulin injections from 365 to just 52, the authors noted in their paper.
 

New data: Switching to icodec is effective, safe

The new data on switching came from a 16-week, open-label, phase 2 trial of 154 patients with type 2 diabetes with insufficient glycemic control (mean A1c 7.9%) while taking oral medication and basal insulin. They were randomized to once-weekly icodec with or without an initial loading dose, or once-daily glargine U100.

Insulin doses were titrated weekly based on blood glucose levels as measured by continuous glucose monitoring (Dexcom G6).

The primary endpoint, time in range (70-180 mg/dL or 3.9-10.0 mmol/L) during weeks 15-16 was significantly better for icodec plus loading dose, compared with glargine U100 (72.9% vs 65.0%, P = .01) and similar between icodec and glargine U100 (66.0% vs 65.0%, P = .75).

Estimated mean percentage point reductions in A1c were 0.77 for icodec plus loading dose, 0.47 for icodec without the loading dose, and 0.54 for glargine U100.

Rates of moderate to severe hypoglycemia were similar between icodec plus loading dose and glargine U100 (78.0 and 79.4 events per 100 patient-years, respectively), and lower for icodec without the loading dose (14.8/100 patient-years).

There were no unexpected safety findings.

Novo Nordisk’s phase 3 trial for icodec is set to begin in late November.

The company is also developing a coformulation of icodec with its glucagonlike peptide–1 receptor agonist semaglutide, currently in phase 1 testing. Meanwhile, Eli Lilly is also developing a once-weekly basal analog, LY3209590, currently in phase 2 trials.

Dr. Rosenstock reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander reported no relevant financial relationships.

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

This year’s virtual meeting of the European Association for the Study of Diabetes (EASD) offers new data and insights regarding the use of newer glucose-lowering agents for treating people with, and without, diabetes, as well as updates on diabetes technology, a symposium on COVID-19, and much more.

The meeting takes place live online September 22-25, Central European time, because it was to have been located in Vienna before the COVID-19 pandemic, which forced nearly all medical meetings to go virtual. However, as in years past, videos of all the sessions will be available to registrants for later viewing and to the public a month after the meeting ends. The registration fee is less than half the cost for previous years.

In fact, EASD was better prepared to go virtual than many other medical societies, and not just because they had more time to plan since the pandemic began, EASD president Stefano Del Prato, MD, told Medscape Medical News. “Starting in 2013 we already had a virtual congress in parallel to the face-to-face meeting. Everything at the congress was simultaneously available on streaming. That made us more confident in what we could achieve with a virtual meeting.”

Last year, the EASD meeting held in Barcelona was the first for which the number of virtual attendees equaled the number who attended in person, about 15,000 each. Another 80,000 people have accessed the video content in the year since.

“Maybe this is a unique occasion for reaching out to a really global audience,” said Del Prato, professor of endocrinology and metabolism and chief of the section of diabetes at the University of Pisa School of Medicine, Italy.  

EASD Honorary Secretary Mikael Rydén, MD, PhD, the meeting’s program chair, told Medscape Medical News, “I’m really looking forward to this meeting because of the interactivity. I hope that, lacking the possibility of having a physical meeting, this is absolutely the best one can do.”
 

More cardiovascular and renal outcomes for SGLT2 inhibitors 

The impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor drug class beyond glucose-lowering has dominated the agenda of diabetes meetings for the past 5 years, and this EASD is no exception.

Here, new data will be presented for the previously reported EMPEROR-Reduced trial of empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) for patients with heart failure with or without diabetes; DAPA-CKD, on renal outcomes for dapagliflozin (Farxiga, AstraZeneca); and renal results from the VERTIS CV outcome trial of ertugliflozin (Steglatro, Merck).

Regarding DAPA-CKD, Del Prato noted, “We will have a greater opportunity ... to go deeper into the results during a 1-hour session.”

A related session, a joint EASD/European Society of Cardiology (ESC) symposium on the “dawn of cardiovascular risk reduction in type 2 diabetes” will review the development of SGLT2 inhibitors and the data accumulated for the drug class over the past 5 years since the landmark EMPA-REG OUTCOME trial was first reported at EASD in 2015.

The joint symposium, Rydénsaid, will be “extremely important for clinicians. It’s a revolution in type 2 diabetes treatment, and perhaps in those without diabetes who have heart failure...It’s not about a single company, but experts involved in all the different trials of the different SGLT2 inhibitors...We’re still seeing the huge impact that the SGLT2 inhibitors have made, and the incretins as well. We’re still living in these rumbling years after these huge trials.”

Del Prato also named that symposium as a meeting highlight.

“From a clinical point of view, I think the EMPA-REG 5-year session will be of great interest. That was really a turning point not only in the field of diabetes, but also in cardiology and nephrology. I think that will be a great opportunity to see how quickly and how importantly SGLT2 inhibition has turned into a great opportunity for many people.”
 

Who’s “right” – diabetologists or cardiologists?

Another session likely to draw a crowd of clinicians is a debate about which guidelines are “right”: the ESC’s, which advise first-line use of an SGLT2 inhibitor or glucagon-like peptide-1 (GLP-1) agonist for patients with established CVD or those at high risk, or the more conservative EASD/American Diabetes Association’s, which still advise metformin as first-line therapy for type 2 diabetes.

Rydén, who is professor and senior consultant in endocrinology at the Karolinska University Hospital and Karolinska Institute, Sweden, commented, “The difference is in how aggressive to be in treatment and when adding drugs...I think we have slightly different ways of seeing things and how we implement them.”

Del Prato noted, “We need to clear the fog about what are the current indications for people with diabetes. There is definitely a point of contact between cardiology and diabetology. ... We like to split [the disciplines] up, but discussion is a good way to get people thinking.”

“It will be very important to address the importance of glucose control but yet also leverage a new form of treatment that will have properties above and beyond glucose-lowering capacity.”
 

Other big trial results: CGM after MI, semaglutide for obesity

Other major new trial results to be presented in dedicated sessions include LIBERATES (Improving Glucose Control in Patients With Diabetes Following Myocardial Infarction: The Role of a Novel Glycaemic Monitoring), and STEP program (Semaglutide for the Treatment of Obesity).

LIBERATES will compare glycemic control with the Abbott FreeStyle Libre 14-day sensor and standard fingerstick glucose monitoring versus blinded continuous glucose monitoring (CGM) for 90 days after a heart attack. It was a late addition to the meeting program, Rydén noted.

The semaglutide study is looking at weight loss associated with a higher dose of the GLP-1 agonist than is currently approved for diabetes, similar to the way in which liraglutide was developed as an obesity agent after first gaining approval for type 2 diabetes.

Regarding semaglutide, Rydén said, “I’ve heard this one is quite efficient. It will be interesting.”
 

Personalized medicine, COVID-19, intermittent fasting, and much more

Both Rydén and Del Prato also said they were looking forward to a joint EASD/American Diabetes Association symposium on a newly launched precision medicine initiative. The session will include talks on subclassifications of diabetes, genetics, and precision diabetes medicine in practice, as well as lessons on the latter from Greenland.

Rydén noted, “I think it’s interesting for everyone, from the primary healthcare physician to the basic scientist. We’re trying to understand why we have this huge diabetic panorama and how do we identify the subject who should have a specific treatment, or perhaps [will] develop a specific complication of diabetes.”

This field, he predicted, “will grow enormously in the next 10 years.”

Del Prato pointed out, “Diabetes is more heterogeneous than we tend to believe for both types. Better guidance for individualization of treatments could be a great opportunity. ... Ways to better genotype and phenotype the population are becoming less expensive and easier to access. It will be a different way to treat diabetes in the future.”

Other noteworthy conference sessions will address COVID-19 and diabetes, intermittent fasting, new technologies, diabetes and cancer, the role of liver surveillance in patients with diabetes, medicines that can cause diabetes, exercise in type 1 diabetes, and the burden of hypoglycemia.  

There will also be opportunities for networking, Del Prato said. “You’ll be able to walk around with your own avatar. You’ll be assisted by [artificial intelligence] to build your own program based on what you’ve been following. You can participate in discussion rooms. You can walk in and out.”

“We hope people will appreciate the science and the spirit of the congress – mingling, interacting, chatting to start discussion and maybe collaboration. It will be lots of fun. I would like to invite all Medscape readers to come and register.

Rydén has reported being a consultant, speaker, and/or advisory board member for Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Novartis, and AstraZeneca. Del Prato has reported being a speaker, advisory board member, and/or receiving research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier, and Takeda. 

This article first appeared on Medscape.com.

This year’s virtual meeting of the European Association for the Study of Diabetes (EASD) offers new data and insights regarding the use of newer glucose-lowering agents for treating people with, and without, diabetes, as well as updates on diabetes technology, a symposium on COVID-19, and much more.

The meeting takes place live online September 22-25, Central European time, because it was to have been located in Vienna before the COVID-19 pandemic, which forced nearly all medical meetings to go virtual. However, as in years past, videos of all the sessions will be available to registrants for later viewing and to the public a month after the meeting ends. The registration fee is less than half the cost for previous years.

In fact, EASD was better prepared to go virtual than many other medical societies, and not just because they had more time to plan since the pandemic began, EASD president Stefano Del Prato, MD, told Medscape Medical News. “Starting in 2013 we already had a virtual congress in parallel to the face-to-face meeting. Everything at the congress was simultaneously available on streaming. That made us more confident in what we could achieve with a virtual meeting.”

Last year, the EASD meeting held in Barcelona was the first for which the number of virtual attendees equaled the number who attended in person, about 15,000 each. Another 80,000 people have accessed the video content in the year since.

“Maybe this is a unique occasion for reaching out to a really global audience,” said Del Prato, professor of endocrinology and metabolism and chief of the section of diabetes at the University of Pisa School of Medicine, Italy.  

EASD Honorary Secretary Mikael Rydén, MD, PhD, the meeting’s program chair, told Medscape Medical News, “I’m really looking forward to this meeting because of the interactivity. I hope that, lacking the possibility of having a physical meeting, this is absolutely the best one can do.”
 

More cardiovascular and renal outcomes for SGLT2 inhibitors 

The impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor drug class beyond glucose-lowering has dominated the agenda of diabetes meetings for the past 5 years, and this EASD is no exception.

Here, new data will be presented for the previously reported EMPEROR-Reduced trial of empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) for patients with heart failure with or without diabetes; DAPA-CKD, on renal outcomes for dapagliflozin (Farxiga, AstraZeneca); and renal results from the VERTIS CV outcome trial of ertugliflozin (Steglatro, Merck).

Regarding DAPA-CKD, Del Prato noted, “We will have a greater opportunity ... to go deeper into the results during a 1-hour session.”

A related session, a joint EASD/European Society of Cardiology (ESC) symposium on the “dawn of cardiovascular risk reduction in type 2 diabetes” will review the development of SGLT2 inhibitors and the data accumulated for the drug class over the past 5 years since the landmark EMPA-REG OUTCOME trial was first reported at EASD in 2015.

The joint symposium, Rydénsaid, will be “extremely important for clinicians. It’s a revolution in type 2 diabetes treatment, and perhaps in those without diabetes who have heart failure...It’s not about a single company, but experts involved in all the different trials of the different SGLT2 inhibitors...We’re still seeing the huge impact that the SGLT2 inhibitors have made, and the incretins as well. We’re still living in these rumbling years after these huge trials.”

Del Prato also named that symposium as a meeting highlight.

“From a clinical point of view, I think the EMPA-REG 5-year session will be of great interest. That was really a turning point not only in the field of diabetes, but also in cardiology and nephrology. I think that will be a great opportunity to see how quickly and how importantly SGLT2 inhibition has turned into a great opportunity for many people.”
 

Who’s “right” – diabetologists or cardiologists?

Another session likely to draw a crowd of clinicians is a debate about which guidelines are “right”: the ESC’s, which advise first-line use of an SGLT2 inhibitor or glucagon-like peptide-1 (GLP-1) agonist for patients with established CVD or those at high risk, or the more conservative EASD/American Diabetes Association’s, which still advise metformin as first-line therapy for type 2 diabetes.

Rydén, who is professor and senior consultant in endocrinology at the Karolinska University Hospital and Karolinska Institute, Sweden, commented, “The difference is in how aggressive to be in treatment and when adding drugs...I think we have slightly different ways of seeing things and how we implement them.”

Del Prato noted, “We need to clear the fog about what are the current indications for people with diabetes. There is definitely a point of contact between cardiology and diabetology. ... We like to split [the disciplines] up, but discussion is a good way to get people thinking.”

“It will be very important to address the importance of glucose control but yet also leverage a new form of treatment that will have properties above and beyond glucose-lowering capacity.”
 

Other big trial results: CGM after MI, semaglutide for obesity

Other major new trial results to be presented in dedicated sessions include LIBERATES (Improving Glucose Control in Patients With Diabetes Following Myocardial Infarction: The Role of a Novel Glycaemic Monitoring), and STEP program (Semaglutide for the Treatment of Obesity).

LIBERATES will compare glycemic control with the Abbott FreeStyle Libre 14-day sensor and standard fingerstick glucose monitoring versus blinded continuous glucose monitoring (CGM) for 90 days after a heart attack. It was a late addition to the meeting program, Rydén noted.

The semaglutide study is looking at weight loss associated with a higher dose of the GLP-1 agonist than is currently approved for diabetes, similar to the way in which liraglutide was developed as an obesity agent after first gaining approval for type 2 diabetes.

Regarding semaglutide, Rydén said, “I’ve heard this one is quite efficient. It will be interesting.”
 

Personalized medicine, COVID-19, intermittent fasting, and much more

Both Rydén and Del Prato also said they were looking forward to a joint EASD/American Diabetes Association symposium on a newly launched precision medicine initiative. The session will include talks on subclassifications of diabetes, genetics, and precision diabetes medicine in practice, as well as lessons on the latter from Greenland.

Rydén noted, “I think it’s interesting for everyone, from the primary healthcare physician to the basic scientist. We’re trying to understand why we have this huge diabetic panorama and how do we identify the subject who should have a specific treatment, or perhaps [will] develop a specific complication of diabetes.”

This field, he predicted, “will grow enormously in the next 10 years.”

Del Prato pointed out, “Diabetes is more heterogeneous than we tend to believe for both types. Better guidance for individualization of treatments could be a great opportunity. ... Ways to better genotype and phenotype the population are becoming less expensive and easier to access. It will be a different way to treat diabetes in the future.”

Other noteworthy conference sessions will address COVID-19 and diabetes, intermittent fasting, new technologies, diabetes and cancer, the role of liver surveillance in patients with diabetes, medicines that can cause diabetes, exercise in type 1 diabetes, and the burden of hypoglycemia.  

There will also be opportunities for networking, Del Prato said. “You’ll be able to walk around with your own avatar. You’ll be assisted by [artificial intelligence] to build your own program based on what you’ve been following. You can participate in discussion rooms. You can walk in and out.”

“We hope people will appreciate the science and the spirit of the congress – mingling, interacting, chatting to start discussion and maybe collaboration. It will be lots of fun. I would like to invite all Medscape readers to come and register.

Rydén has reported being a consultant, speaker, and/or advisory board member for Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Novartis, and AstraZeneca. Del Prato has reported being a speaker, advisory board member, and/or receiving research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier, and Takeda. 

This article first appeared on Medscape.com.

This year’s virtual meeting of the European Association for the Study of Diabetes (EASD) offers new data and insights regarding the use of newer glucose-lowering agents for treating people with, and without, diabetes, as well as updates on diabetes technology, a symposium on COVID-19, and much more.

The meeting takes place live online September 22-25, Central European time, because it was to have been located in Vienna before the COVID-19 pandemic, which forced nearly all medical meetings to go virtual. However, as in years past, videos of all the sessions will be available to registrants for later viewing and to the public a month after the meeting ends. The registration fee is less than half the cost for previous years.

In fact, EASD was better prepared to go virtual than many other medical societies, and not just because they had more time to plan since the pandemic began, EASD president Stefano Del Prato, MD, told Medscape Medical News. “Starting in 2013 we already had a virtual congress in parallel to the face-to-face meeting. Everything at the congress was simultaneously available on streaming. That made us more confident in what we could achieve with a virtual meeting.”

Last year, the EASD meeting held in Barcelona was the first for which the number of virtual attendees equaled the number who attended in person, about 15,000 each. Another 80,000 people have accessed the video content in the year since.

“Maybe this is a unique occasion for reaching out to a really global audience,” said Del Prato, professor of endocrinology and metabolism and chief of the section of diabetes at the University of Pisa School of Medicine, Italy.  

EASD Honorary Secretary Mikael Rydén, MD, PhD, the meeting’s program chair, told Medscape Medical News, “I’m really looking forward to this meeting because of the interactivity. I hope that, lacking the possibility of having a physical meeting, this is absolutely the best one can do.”
 

More cardiovascular and renal outcomes for SGLT2 inhibitors 

The impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor drug class beyond glucose-lowering has dominated the agenda of diabetes meetings for the past 5 years, and this EASD is no exception.

Here, new data will be presented for the previously reported EMPEROR-Reduced trial of empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) for patients with heart failure with or without diabetes; DAPA-CKD, on renal outcomes for dapagliflozin (Farxiga, AstraZeneca); and renal results from the VERTIS CV outcome trial of ertugliflozin (Steglatro, Merck).

Regarding DAPA-CKD, Del Prato noted, “We will have a greater opportunity ... to go deeper into the results during a 1-hour session.”

A related session, a joint EASD/European Society of Cardiology (ESC) symposium on the “dawn of cardiovascular risk reduction in type 2 diabetes” will review the development of SGLT2 inhibitors and the data accumulated for the drug class over the past 5 years since the landmark EMPA-REG OUTCOME trial was first reported at EASD in 2015.

The joint symposium, Rydénsaid, will be “extremely important for clinicians. It’s a revolution in type 2 diabetes treatment, and perhaps in those without diabetes who have heart failure...It’s not about a single company, but experts involved in all the different trials of the different SGLT2 inhibitors...We’re still seeing the huge impact that the SGLT2 inhibitors have made, and the incretins as well. We’re still living in these rumbling years after these huge trials.”

Del Prato also named that symposium as a meeting highlight.

“From a clinical point of view, I think the EMPA-REG 5-year session will be of great interest. That was really a turning point not only in the field of diabetes, but also in cardiology and nephrology. I think that will be a great opportunity to see how quickly and how importantly SGLT2 inhibition has turned into a great opportunity for many people.”
 

Who’s “right” – diabetologists or cardiologists?

Another session likely to draw a crowd of clinicians is a debate about which guidelines are “right”: the ESC’s, which advise first-line use of an SGLT2 inhibitor or glucagon-like peptide-1 (GLP-1) agonist for patients with established CVD or those at high risk, or the more conservative EASD/American Diabetes Association’s, which still advise metformin as first-line therapy for type 2 diabetes.

Rydén, who is professor and senior consultant in endocrinology at the Karolinska University Hospital and Karolinska Institute, Sweden, commented, “The difference is in how aggressive to be in treatment and when adding drugs...I think we have slightly different ways of seeing things and how we implement them.”

Del Prato noted, “We need to clear the fog about what are the current indications for people with diabetes. There is definitely a point of contact between cardiology and diabetology. ... We like to split [the disciplines] up, but discussion is a good way to get people thinking.”

“It will be very important to address the importance of glucose control but yet also leverage a new form of treatment that will have properties above and beyond glucose-lowering capacity.”
 

Other big trial results: CGM after MI, semaglutide for obesity

Other major new trial results to be presented in dedicated sessions include LIBERATES (Improving Glucose Control in Patients With Diabetes Following Myocardial Infarction: The Role of a Novel Glycaemic Monitoring), and STEP program (Semaglutide for the Treatment of Obesity).

LIBERATES will compare glycemic control with the Abbott FreeStyle Libre 14-day sensor and standard fingerstick glucose monitoring versus blinded continuous glucose monitoring (CGM) for 90 days after a heart attack. It was a late addition to the meeting program, Rydén noted.

The semaglutide study is looking at weight loss associated with a higher dose of the GLP-1 agonist than is currently approved for diabetes, similar to the way in which liraglutide was developed as an obesity agent after first gaining approval for type 2 diabetes.

Regarding semaglutide, Rydén said, “I’ve heard this one is quite efficient. It will be interesting.”
 

Personalized medicine, COVID-19, intermittent fasting, and much more

Both Rydén and Del Prato also said they were looking forward to a joint EASD/American Diabetes Association symposium on a newly launched precision medicine initiative. The session will include talks on subclassifications of diabetes, genetics, and precision diabetes medicine in practice, as well as lessons on the latter from Greenland.

Rydén noted, “I think it’s interesting for everyone, from the primary healthcare physician to the basic scientist. We’re trying to understand why we have this huge diabetic panorama and how do we identify the subject who should have a specific treatment, or perhaps [will] develop a specific complication of diabetes.”

This field, he predicted, “will grow enormously in the next 10 years.”

Del Prato pointed out, “Diabetes is more heterogeneous than we tend to believe for both types. Better guidance for individualization of treatments could be a great opportunity. ... Ways to better genotype and phenotype the population are becoming less expensive and easier to access. It will be a different way to treat diabetes in the future.”

Other noteworthy conference sessions will address COVID-19 and diabetes, intermittent fasting, new technologies, diabetes and cancer, the role of liver surveillance in patients with diabetes, medicines that can cause diabetes, exercise in type 1 diabetes, and the burden of hypoglycemia.  

There will also be opportunities for networking, Del Prato said. “You’ll be able to walk around with your own avatar. You’ll be assisted by [artificial intelligence] to build your own program based on what you’ve been following. You can participate in discussion rooms. You can walk in and out.”

“We hope people will appreciate the science and the spirit of the congress – mingling, interacting, chatting to start discussion and maybe collaboration. It will be lots of fun. I would like to invite all Medscape readers to come and register.

Rydén has reported being a consultant, speaker, and/or advisory board member for Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Novartis, and AstraZeneca. Del Prato has reported being a speaker, advisory board member, and/or receiving research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier, and Takeda. 

This article first appeared on Medscape.com.

Under the U.S. Medicare system, the cost of insulin is about 50% higher for beneficiaries who use insulin pumps than those who inject insulin, a new analysis reveals.

Courtesy Wikimedia Commons/Mbbradford/CC-by-3.0

A call to action as price of insulin rose, suddenly shifted, in 2017

In the article, the authors call for the Centers for Medicare & Medicaid Services to fix the situation with a series of actions, including better aligning the cost of insulin under Parts B and D, and determining reimbursement rates on a drug-by-drug basis, rather than lumping together all infused drugs.

The CMS said in a statement: “As with all relevant and topical research, CMS appreciates the input of the journal authors and considers external research in all potential future policymaking and initiatives.”

As outlined by the authors, the overall price of insulin in the United States has dramatically increased in the past 2 decades. For example, the average list price of one vial of insulin rose from $9.61 to $25.38 between January 2013 and July 2018, a 164% increase.

A provision in the 21st Century Cures Act, which went into effect Jan. 1, 2017, attempted to remedy past overpayment for DME-infused drugs covered under Medicare Part B by changing the pricing methodology. Prior to 2017, the drugs had been reimbursed based on 95% of the 2003 average wholesale price. With the new law, payments have been set to average sales price plus 6%.

As a result, the price of insulin rose by 251% overnight from Dec. 31, 2016, to Jan. 1, 2017, for Medicare beneficiaries using insulin pumps, whereas there was no change for those injecting their insulin.

And then in 2018, insulin manufacturers raised the price by another 53%, resulting in an overall 304% price increase under Part B over 2 years.

Meanwhile, on March 11, 2020, CMS announced a cap on insulin copays in Part D to $35 a month, which doesn’t apply to pump users.

Thus, as of now, the average monthly copay for insulin for pump users in Medicare is about $54.26, about 50% more than the $35 maximum for those who inject insulin.

“This is in the setting of patients skimping on insulin anyway because of the high cost. There’s reasonably good evidence that patients stretch out their insulin because of cost, including those in Medicare,” Dr. Vigersky emphasized.
 

What can be done?

The problem could have been avoided, the authors wrote in their commentary, if payments had simply been adjusted for the two pre-2017 most highly overpaid DME-infused drugs, milrinone lactate and immune globulin, rather than all of them. Doing that would have addressed 95% of the overpayments and saved $267 million without affecting insulin cost.

Unlike insulin, nearly all of the other infused drugs are used only for short periods of time, such as pain medications, antibiotics, or chemotherapy.

“People get these for a few months, but not for years and years. Some aren’t used much at all. It was sort of a wholesale way to change things, and insulin got caught in it, with more extensive consequences,” Dr. Vigersky noted.

He and his coauthors advised the CMS to test pricing methodologies before implementation to prevent further unintended consequences going forward, to ask the Inspector General’s office to reanalyze costs to see if savings targets are being met, and to notify patients and health care providers in advance of a change so that they can better prepare for increased costs.

For now, Dr. Vigersky advised that, when considering pump therapy for a given patient, “from a clinical standpoint, this is a shared decision with the patient.

“As much as the reality of costs is shared with the patient, there is good evidence that pump therapy is cost-effective. The patient has to make the decision as to whether this extra amount is worth the benefits in the long run that they will get from pump therapy.”

A version of this article was originally published on Medscape.com.

Under the U.S. Medicare system, the cost of insulin is about 50% higher for beneficiaries who use insulin pumps than those who inject insulin, a new analysis reveals.

Courtesy Wikimedia Commons/Mbbradford/CC-by-3.0

A call to action as price of insulin rose, suddenly shifted, in 2017

In the article, the authors call for the Centers for Medicare & Medicaid Services to fix the situation with a series of actions, including better aligning the cost of insulin under Parts B and D, and determining reimbursement rates on a drug-by-drug basis, rather than lumping together all infused drugs.

The CMS said in a statement: “As with all relevant and topical research, CMS appreciates the input of the journal authors and considers external research in all potential future policymaking and initiatives.”

As outlined by the authors, the overall price of insulin in the United States has dramatically increased in the past 2 decades. For example, the average list price of one vial of insulin rose from $9.61 to $25.38 between January 2013 and July 2018, a 164% increase.

A provision in the 21st Century Cures Act, which went into effect Jan. 1, 2017, attempted to remedy past overpayment for DME-infused drugs covered under Medicare Part B by changing the pricing methodology. Prior to 2017, the drugs had been reimbursed based on 95% of the 2003 average wholesale price. With the new law, payments have been set to average sales price plus 6%.

As a result, the price of insulin rose by 251% overnight from Dec. 31, 2016, to Jan. 1, 2017, for Medicare beneficiaries using insulin pumps, whereas there was no change for those injecting their insulin.

And then in 2018, insulin manufacturers raised the price by another 53%, resulting in an overall 304% price increase under Part B over 2 years.

Meanwhile, on March 11, 2020, CMS announced a cap on insulin copays in Part D to $35 a month, which doesn’t apply to pump users.

Thus, as of now, the average monthly copay for insulin for pump users in Medicare is about $54.26, about 50% more than the $35 maximum for those who inject insulin.

“This is in the setting of patients skimping on insulin anyway because of the high cost. There’s reasonably good evidence that patients stretch out their insulin because of cost, including those in Medicare,” Dr. Vigersky emphasized.
 

What can be done?

The problem could have been avoided, the authors wrote in their commentary, if payments had simply been adjusted for the two pre-2017 most highly overpaid DME-infused drugs, milrinone lactate and immune globulin, rather than all of them. Doing that would have addressed 95% of the overpayments and saved $267 million without affecting insulin cost.

Unlike insulin, nearly all of the other infused drugs are used only for short periods of time, such as pain medications, antibiotics, or chemotherapy.

“People get these for a few months, but not for years and years. Some aren’t used much at all. It was sort of a wholesale way to change things, and insulin got caught in it, with more extensive consequences,” Dr. Vigersky noted.

He and his coauthors advised the CMS to test pricing methodologies before implementation to prevent further unintended consequences going forward, to ask the Inspector General’s office to reanalyze costs to see if savings targets are being met, and to notify patients and health care providers in advance of a change so that they can better prepare for increased costs.

For now, Dr. Vigersky advised that, when considering pump therapy for a given patient, “from a clinical standpoint, this is a shared decision with the patient.

“As much as the reality of costs is shared with the patient, there is good evidence that pump therapy is cost-effective. The patient has to make the decision as to whether this extra amount is worth the benefits in the long run that they will get from pump therapy.”

A version of this article was originally published on Medscape.com.

Under the U.S. Medicare system, the cost of insulin is about 50% higher for beneficiaries who use insulin pumps than those who inject insulin, a new analysis reveals.

Courtesy Wikimedia Commons/Mbbradford/CC-by-3.0

A call to action as price of insulin rose, suddenly shifted, in 2017

In the article, the authors call for the Centers for Medicare & Medicaid Services to fix the situation with a series of actions, including better aligning the cost of insulin under Parts B and D, and determining reimbursement rates on a drug-by-drug basis, rather than lumping together all infused drugs.

The CMS said in a statement: “As with all relevant and topical research, CMS appreciates the input of the journal authors and considers external research in all potential future policymaking and initiatives.”

As outlined by the authors, the overall price of insulin in the United States has dramatically increased in the past 2 decades. For example, the average list price of one vial of insulin rose from $9.61 to $25.38 between January 2013 and July 2018, a 164% increase.

A provision in the 21st Century Cures Act, which went into effect Jan. 1, 2017, attempted to remedy past overpayment for DME-infused drugs covered under Medicare Part B by changing the pricing methodology. Prior to 2017, the drugs had been reimbursed based on 95% of the 2003 average wholesale price. With the new law, payments have been set to average sales price plus 6%.

As a result, the price of insulin rose by 251% overnight from Dec. 31, 2016, to Jan. 1, 2017, for Medicare beneficiaries using insulin pumps, whereas there was no change for those injecting their insulin.

And then in 2018, insulin manufacturers raised the price by another 53%, resulting in an overall 304% price increase under Part B over 2 years.

Meanwhile, on March 11, 2020, CMS announced a cap on insulin copays in Part D to $35 a month, which doesn’t apply to pump users.

Thus, as of now, the average monthly copay for insulin for pump users in Medicare is about $54.26, about 50% more than the $35 maximum for those who inject insulin.

“This is in the setting of patients skimping on insulin anyway because of the high cost. There’s reasonably good evidence that patients stretch out their insulin because of cost, including those in Medicare,” Dr. Vigersky emphasized.
 

What can be done?

The problem could have been avoided, the authors wrote in their commentary, if payments had simply been adjusted for the two pre-2017 most highly overpaid DME-infused drugs, milrinone lactate and immune globulin, rather than all of them. Doing that would have addressed 95% of the overpayments and saved $267 million without affecting insulin cost.

Unlike insulin, nearly all of the other infused drugs are used only for short periods of time, such as pain medications, antibiotics, or chemotherapy.

“People get these for a few months, but not for years and years. Some aren’t used much at all. It was sort of a wholesale way to change things, and insulin got caught in it, with more extensive consequences,” Dr. Vigersky noted.

He and his coauthors advised the CMS to test pricing methodologies before implementation to prevent further unintended consequences going forward, to ask the Inspector General’s office to reanalyze costs to see if savings targets are being met, and to notify patients and health care providers in advance of a change so that they can better prepare for increased costs.

For now, Dr. Vigersky advised that, when considering pump therapy for a given patient, “from a clinical standpoint, this is a shared decision with the patient.

“As much as the reality of costs is shared with the patient, there is good evidence that pump therapy is cost-effective. The patient has to make the decision as to whether this extra amount is worth the benefits in the long run that they will get from pump therapy.”

A version of this article was originally published on Medscape.com.

A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.

The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.

Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).

OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.

Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.

“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.

He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.

Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”

Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy

Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.

They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.

“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.

Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.

IVIG May Be a Potential Treatment

Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.

In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.

Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.

Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”

Whelan and Chu have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.

The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.

Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).

OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.

Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.

“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.

He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.

Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”

Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy

Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.

They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.

“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.

Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.

IVIG May Be a Potential Treatment

Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.

In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.

Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.

Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”

Whelan and Chu have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.

The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.

Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).

OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.

Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.

“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.

He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.

Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”

Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy

Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.

They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.

“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.

Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.

IVIG May Be a Potential Treatment

Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.

In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.

Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.

Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”

Whelan and Chu have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the MiniMed 770G (Medtronic) automated insulin delivery system for children aged 2-6 years.

The 770G system adds Bluetooth smartphone connectivity to the SmartGuard technology that is present in the hybrid closed-loop MiniMed 670G system, which has been available in the United States since 2016 for individuals aged 14 years and older who have type 1 diabetes. It has been available since 2018 for children aged 7 years.

The 770G will also be available to older children and adults once it has been launched.

As with other so-called artificial pancreas systems, the 770G is made up of an insulin pump and continuous glucose monitor that are connected via software that allows the pump to deliver or withhold insulin on the basis of glucose readings.

It is a “hybrid closed-loop” system in that users or caregivers must still manually signal carbohydrate consumption.

The 770G includes a “share” feature that allows health care providers, users, and caregivers to follow the user’s glucose levels remotely via smartphones. In-app notices indicate when glucose levels are out of range. The data can be uploaded prior to telehealth visits.

The approval was based on a 3-month study of 151 children aged 2-6 years who showed improvement in outcomes comparable with those seen in 124 older adolescents and adults with the 770G system as compared to patients who used manual (nonlooped) mode over a 2-week period. There were no episodes of severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events while in hybrid closed-loop mode.

The FDA will require Medtronic to conduct a postmarketing study to evaluate the 770G in real-world settings. It is not approved for use in children younger than 2 years nor in any patient who requires less than 8 units of insulin per day.

The next-generation Medtronic closed-loop system, the 780G, has already been approved in Europe. It improves on the technology by delivering automated bolus correction doses in addition to basal insulin every 5 minutes. The company is preparing to submit the 780G for approval in the United States.

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

The Food and Drug Administration has approved the MiniMed 770G (Medtronic) automated insulin delivery system for children aged 2-6 years.

The 770G system adds Bluetooth smartphone connectivity to the SmartGuard technology that is present in the hybrid closed-loop MiniMed 670G system, which has been available in the United States since 2016 for individuals aged 14 years and older who have type 1 diabetes. It has been available since 2018 for children aged 7 years.

The 770G will also be available to older children and adults once it has been launched.

As with other so-called artificial pancreas systems, the 770G is made up of an insulin pump and continuous glucose monitor that are connected via software that allows the pump to deliver or withhold insulin on the basis of glucose readings.

It is a “hybrid closed-loop” system in that users or caregivers must still manually signal carbohydrate consumption.

The 770G includes a “share” feature that allows health care providers, users, and caregivers to follow the user’s glucose levels remotely via smartphones. In-app notices indicate when glucose levels are out of range. The data can be uploaded prior to telehealth visits.

The approval was based on a 3-month study of 151 children aged 2-6 years who showed improvement in outcomes comparable with those seen in 124 older adolescents and adults with the 770G system as compared to patients who used manual (nonlooped) mode over a 2-week period. There were no episodes of severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events while in hybrid closed-loop mode.

The FDA will require Medtronic to conduct a postmarketing study to evaluate the 770G in real-world settings. It is not approved for use in children younger than 2 years nor in any patient who requires less than 8 units of insulin per day.

The next-generation Medtronic closed-loop system, the 780G, has already been approved in Europe. It improves on the technology by delivering automated bolus correction doses in addition to basal insulin every 5 minutes. The company is preparing to submit the 780G for approval in the United States.

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

The Food and Drug Administration has approved the MiniMed 770G (Medtronic) automated insulin delivery system for children aged 2-6 years.

The 770G system adds Bluetooth smartphone connectivity to the SmartGuard technology that is present in the hybrid closed-loop MiniMed 670G system, which has been available in the United States since 2016 for individuals aged 14 years and older who have type 1 diabetes. It has been available since 2018 for children aged 7 years.

The 770G will also be available to older children and adults once it has been launched.

As with other so-called artificial pancreas systems, the 770G is made up of an insulin pump and continuous glucose monitor that are connected via software that allows the pump to deliver or withhold insulin on the basis of glucose readings.

It is a “hybrid closed-loop” system in that users or caregivers must still manually signal carbohydrate consumption.

The 770G includes a “share” feature that allows health care providers, users, and caregivers to follow the user’s glucose levels remotely via smartphones. In-app notices indicate when glucose levels are out of range. The data can be uploaded prior to telehealth visits.

The approval was based on a 3-month study of 151 children aged 2-6 years who showed improvement in outcomes comparable with those seen in 124 older adolescents and adults with the 770G system as compared to patients who used manual (nonlooped) mode over a 2-week period. There were no episodes of severe hypoglycemia or diabetic ketoacidosis and no serious device-related adverse events while in hybrid closed-loop mode.

The FDA will require Medtronic to conduct a postmarketing study to evaluate the 770G in real-world settings. It is not approved for use in children younger than 2 years nor in any patient who requires less than 8 units of insulin per day.

The next-generation Medtronic closed-loop system, the 780G, has already been approved in Europe. It improves on the technology by delivering automated bolus correction doses in addition to basal insulin every 5 minutes. The company is preparing to submit the 780G for approval in the United States.

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

The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.

“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.

However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”

“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”

However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”

Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”

Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
 

No significant differences in multiple parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
 

Study limitations: Small, not randomized, long diabetes duration

The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.

Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”

Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

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

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity. 

The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.

“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.

However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”

“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”

However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”

Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”

Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
 

No significant differences in multiple parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
 

Study limitations: Small, not randomized, long diabetes duration

The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.

Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”

Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

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

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity. 

The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in the New England Journal of Medicine. The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (about 18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” Dr. Yoshino and colleagues wrote.

“The similar findings in participants in the two groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” they added.

However, they acknowledged, “the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and type 2 diabetes.”

“This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients – reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes,” stated the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and Massachusetts General Hospital, both in Boston, said in an interview that the study was “very elegant” and “well designed.”

However, he pointed out, “the reality is diet alone has been shown over and over that it’s not sustainable. For a very small few it is, but for the vast majority, that’s not the case.”

Dr. Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study “doesn’t look at how effective [dieting] is in the real world.”

Bariatric surgery, on the other hand, “is very effective for treating type 2 diabetes. It’s a good long-term solution.”
 

No significant differences in multiple parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16%-18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiological range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved hemoglobin A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group. Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups. However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.
 

Study limitations: Small, not randomized, long diabetes duration

The authors acknowledged some of the study’s limitations, including the fact that it wasn’t randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists – endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy editor for the New England Journal of Medicine Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston – pointed out that today more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Dr. Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: “What phase you’re in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time.”

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

“The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early versus later disease, but you would need a larger sample size to do that,” he said.

Dr. Hutter noted: “I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we’re still trying to figure out how it works.”

Dr. Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

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

The AGA Practice guide on Obesity and Weight management, Education and Resources (POWER) white paper provides physicians with a comprehensive, multi-disciplinary process to guide and personalize innovative obesity care for safe and effective weight management. Learn more at www.gastro.org/obesity. 

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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