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FDA investigating potential sex differences in LAAO adverse outcomes
The agency said it is evaluating a real-world study, published in JAMA Cardiology, of 49,357 patients in the National Cardiovascular Data Registry LAAO Registry that suggested women might be at greater risk than men for procedural outcomes, including major adverse events after device implant.
“The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.,” the agency said in its letter to health care providers Sept. 27.
As reported last month, the study by Darden et al showed a significantly higher rate of adverse procedural events in women than in men, including any adverse events (6.3% vs. 3.9%; P < .001), any major adverse events (4.1% vs. 2.0%; P < .001), and hospital stay longer than 1 day (16.0% vs. 11.6%; P < .001). Procedure-associated death was 0.3% in women and 0.1% in men.
The agency noted that the number of patients in the LAAO Registry analysis was much larger than the number of patients in the premarket studies of the Watchman device that supported its approval and in the premarket studies for the other approved LAAO devices.
LAAO devices are indicated to reduce the risk for thromboembolism from the left atrial appendage in patients with nonvalvular atrial fibrillation who are not good candidates for long-term anticoagulation. LAAO devices currently marketed in the United States are Boston Scientific’s Watchman and Watchman FLX devices and Abbott Medical’s Amplatzer Amulet device.
“Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use,” the letter states.
The FDA will work with device manufacturers to evaluate the potential issue, including a review of available premarket and postapproval study data and other available real-world, postmarket datasets, the letter notes.
The agency will also work with device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.
In the letter, the FDA recommends health care providers continue monitoring patients who have been treated with LAAO devices in accordance with the current standard of care. They should also discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.
Any adverse events or suspected adverse events experienced by patients with LAAO devices should also be reported to the FDA through MedWatch, its adverse event reporting program.
A version of this article first appeared on Medscape.com.
The agency said it is evaluating a real-world study, published in JAMA Cardiology, of 49,357 patients in the National Cardiovascular Data Registry LAAO Registry that suggested women might be at greater risk than men for procedural outcomes, including major adverse events after device implant.
“The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.,” the agency said in its letter to health care providers Sept. 27.
As reported last month, the study by Darden et al showed a significantly higher rate of adverse procedural events in women than in men, including any adverse events (6.3% vs. 3.9%; P < .001), any major adverse events (4.1% vs. 2.0%; P < .001), and hospital stay longer than 1 day (16.0% vs. 11.6%; P < .001). Procedure-associated death was 0.3% in women and 0.1% in men.
The agency noted that the number of patients in the LAAO Registry analysis was much larger than the number of patients in the premarket studies of the Watchman device that supported its approval and in the premarket studies for the other approved LAAO devices.
LAAO devices are indicated to reduce the risk for thromboembolism from the left atrial appendage in patients with nonvalvular atrial fibrillation who are not good candidates for long-term anticoagulation. LAAO devices currently marketed in the United States are Boston Scientific’s Watchman and Watchman FLX devices and Abbott Medical’s Amplatzer Amulet device.
“Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use,” the letter states.
The FDA will work with device manufacturers to evaluate the potential issue, including a review of available premarket and postapproval study data and other available real-world, postmarket datasets, the letter notes.
The agency will also work with device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.
In the letter, the FDA recommends health care providers continue monitoring patients who have been treated with LAAO devices in accordance with the current standard of care. They should also discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.
Any adverse events or suspected adverse events experienced by patients with LAAO devices should also be reported to the FDA through MedWatch, its adverse event reporting program.
A version of this article first appeared on Medscape.com.
The agency said it is evaluating a real-world study, published in JAMA Cardiology, of 49,357 patients in the National Cardiovascular Data Registry LAAO Registry that suggested women might be at greater risk than men for procedural outcomes, including major adverse events after device implant.
“The FDA recognizes the limitations of these data, including that the study was not randomized, only included one LAAO device (the first-generation Watchman device), and did not include longer-term outcomes beyond in-hospital events. However, the analysis provides results from a large registry of patients treated with LAAO implants in the U.S.,” the agency said in its letter to health care providers Sept. 27.
As reported last month, the study by Darden et al showed a significantly higher rate of adverse procedural events in women than in men, including any adverse events (6.3% vs. 3.9%; P < .001), any major adverse events (4.1% vs. 2.0%; P < .001), and hospital stay longer than 1 day (16.0% vs. 11.6%; P < .001). Procedure-associated death was 0.3% in women and 0.1% in men.
The agency noted that the number of patients in the LAAO Registry analysis was much larger than the number of patients in the premarket studies of the Watchman device that supported its approval and in the premarket studies for the other approved LAAO devices.
LAAO devices are indicated to reduce the risk for thromboembolism from the left atrial appendage in patients with nonvalvular atrial fibrillation who are not good candidates for long-term anticoagulation. LAAO devices currently marketed in the United States are Boston Scientific’s Watchman and Watchman FLX devices and Abbott Medical’s Amplatzer Amulet device.
“Currently, the FDA believes the benefits continue to outweigh the risks for approved LAAO devices when used in accordance with their instructions for use,” the letter states.
The FDA will work with device manufacturers to evaluate the potential issue, including a review of available premarket and postapproval study data and other available real-world, postmarket datasets, the letter notes.
The agency will also work with device manufacturers, investigators, and the LAAO Registry to try to identify the causes of procedural outcome differences between women and men.
In the letter, the FDA recommends health care providers continue monitoring patients who have been treated with LAAO devices in accordance with the current standard of care. They should also discuss the risks and benefits of all available options for stroke prevention in patients with atrial fibrillation as part of shared clinical decision-making.
Any adverse events or suspected adverse events experienced by patients with LAAO devices should also be reported to the FDA through MedWatch, its adverse event reporting program.
A version of this article first appeared on Medscape.com.
‘Metabolically healthy obesity’ tied to substantial heart risk
In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.
There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.
“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.
“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
‘Metabolically healthy obesity’ – a misnomer?
‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m2 but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.
“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.
“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
Hospital discharge records checked
For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.
In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’
The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.
The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
Findings consistent with UK Biobank data
While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.
“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.
“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.
Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”
Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.
“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.
“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.”
Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”
Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.
In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.
There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.
“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.
“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
‘Metabolically healthy obesity’ – a misnomer?
‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m2 but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.
“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.
“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
Hospital discharge records checked
For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.
In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’
The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.
The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
Findings consistent with UK Biobank data
While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.
“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.
“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.
Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”
Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.
“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.
“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.”
Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”
Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.
In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.
There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.
“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.
“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
‘Metabolically healthy obesity’ – a misnomer?
‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m2 but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.
“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.
“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
Hospital discharge records checked
For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.
In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’
The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.
The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
Findings consistent with UK Biobank data
While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.
“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.
“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.
Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”
Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.
“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.
“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.”
Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”
Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.
FROM EASD 2021
Multiple Sclerosis: Presentation and Diagnosis
Age, C-reactive protein predict COVID-19 death in diabetes
The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.
The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.
“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.
“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”
“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.
“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
Kidney disease in younger patients also linked to poorer outcomes
The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.
They had a median BMI of 27.6 kg/m2, which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.
The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.
A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.
On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).
In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).
As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.
In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.
Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.
“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”
Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.
“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.
Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.
The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.
“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.
“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”
“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.
“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
Kidney disease in younger patients also linked to poorer outcomes
The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.
They had a median BMI of 27.6 kg/m2, which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.
The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.
A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.
On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).
In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).
As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.
In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.
Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.
“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”
Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.
“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.
Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.
The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.
“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.
“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”
“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.
“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
Kidney disease in younger patients also linked to poorer outcomes
The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.
They had a median BMI of 27.6 kg/m2, which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.
The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.
A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.
On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).
In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).
As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.
In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.
Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.
“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”
Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.
“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.
Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
Women with type 2 diabetes get fewer cardioprotective drugs than do men
At study entry, significantly fewer women received a statin, at 73%, or daily aspirin, at 44%, compared with men, who had treatment rates of 81% and 58%, respectively, Giulia Ferrannini, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
The data also show that significantly fewer women received treatment with an ACE inhibitor or angiotensin-receptor blocker (ARB), at 80%, than men, at 83%, although the absolute between-group difference was modest. Rates of a fourth metric of appropriate treatment, receipt of antihypertensive medications if systolic blood pressure was at least 130 mm Hg, were nearly identical among women and men.
Cardiovascular risk in women “less well managed”
“This is confirmation that women are less well managed than men when it comes to cardiovascular risk, especially if they have [type 2] diabetes,” Dr. Ferrannini said in an interview.
Similar observations have been documented before, including in a report in 2019.
The treatment disparity by sex among the 9901 women and men with type 2 diabetes enrolled in REWIND is particularly striking because in clinical trials “patients are generally better managed than in the real world,” Dr. Ferrannini noted. “Despite this, the pattern of disadvantage to women was still evident,” she added.
“In cardiovascular protection the gender issue is preponderant. Women are less well treated,” she said.
REWIND is the cardiovascular outcomes trial for the once-weekly injectable glucagonlike peptide–1 receptor agonist dulaglutide (Trulicity, Lilly) in patients with type 2 diabetes.
The primary results, reported at the 2019 scientific sessions of the American Diabetes Association and simultaneously published in The Lancet, showed dulaglutide significantly reduced major adverse cardiovascular events (MACE) by 12%, compared with placebo. The study ran at about 300 centers worldwide, including many U.S. and Canadian sites, and 46% of enrolled patients were women.
But despite undertreatment, women had significantly better outcomes in terms of MACE, the primary endpoint, during a median 5.4 years of follow-up compared with men. After adjustment for sex, other baseline characteristics, and study-treatment assignment, women had a significant 27% lower composite rate of nonfatal MI, nonfatal stroke, or death from either cardiovascular or unknown causes, compared with men, said Dr. Ferrannini, a researcher at the Karolinska Institute in Stockholm.
The analysis by sex also showed that women had a significant outcome advantage, compared with men, for three of the four components of the combined MACE outcome: nonfatal MI, cardiovascular death, and all-cause death, as well as for the outcome of hospitalization for heart failure, which was not part of the composite MACE outcome. The only MACE outcome component that showed no significant between-group difference was nonfatal stroke, which had roughly equal incidence rates among women and men.
Women had half the prevalence of CVD at baseline
The results also showed that the women with type 2 diabetes enrolled in REWIND had a prevalence of existing cardiovascular disease of 20%, which was half the rate of men at study entry, at 41%. However, the between-sex differences in the primary outcome, as well as each of the individual cardiovascular disease outcomes, didn’t change based on whether or not patients had a history of cardiovascular disease at baseline.
Only one outcome showed a between-sex difference linked to prevalent cardiovascular disease at study entry, the rate of all-cause mortality, which was not significantly different between men and women with a history of cardiovascular disease, but was 39% lower in women compared with men without such a history.
“The good news is that, at baseline and after 2 years, the majority of participants were meeting the relevant treatment targets regardless of sex,” commented Peter Novodvorsky, MUDr, a diabetes researcher at the University of Sheffield (England), who chaired the session during which Dr. Ferrannini presented her findings.
A role for geography, or selection bias?
The new analyses did not examine whether the overall pattern of undertreatment of women differed among each of the 24 participating countries, or by region of the world.
“We have to assume that these results reflect current [routine] practice” in the 24 countries that contributed patients to the trial, noted Dr. Novodvorsky.
There is also “the well-known issue of selection bias” in randomized trials. The current findings raise the question of whether the women willing to take part in the trial somehow differed from the men, he suggested.
Dr. Ferrannini added: “Even if we do observe a gender difference in management, if the majority of women with type 2 diabetes are appropriately treated, this ‘restores’ their cardiovascular risk advantage, compared with men, with the exception of stroke.”
The main hypothesis generated by the post hoc analysis of REWIND is that “women with diabetes have better outcomes than men if they are treated properly,” she stressed, noting that this “would have to be tested in a trial designed to ascertain gender differences.”
REWIND was sponsored by Eli Lilly. Dr. Ferrannini has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
At study entry, significantly fewer women received a statin, at 73%, or daily aspirin, at 44%, compared with men, who had treatment rates of 81% and 58%, respectively, Giulia Ferrannini, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
The data also show that significantly fewer women received treatment with an ACE inhibitor or angiotensin-receptor blocker (ARB), at 80%, than men, at 83%, although the absolute between-group difference was modest. Rates of a fourth metric of appropriate treatment, receipt of antihypertensive medications if systolic blood pressure was at least 130 mm Hg, were nearly identical among women and men.
Cardiovascular risk in women “less well managed”
“This is confirmation that women are less well managed than men when it comes to cardiovascular risk, especially if they have [type 2] diabetes,” Dr. Ferrannini said in an interview.
Similar observations have been documented before, including in a report in 2019.
The treatment disparity by sex among the 9901 women and men with type 2 diabetes enrolled in REWIND is particularly striking because in clinical trials “patients are generally better managed than in the real world,” Dr. Ferrannini noted. “Despite this, the pattern of disadvantage to women was still evident,” she added.
“In cardiovascular protection the gender issue is preponderant. Women are less well treated,” she said.
REWIND is the cardiovascular outcomes trial for the once-weekly injectable glucagonlike peptide–1 receptor agonist dulaglutide (Trulicity, Lilly) in patients with type 2 diabetes.
The primary results, reported at the 2019 scientific sessions of the American Diabetes Association and simultaneously published in The Lancet, showed dulaglutide significantly reduced major adverse cardiovascular events (MACE) by 12%, compared with placebo. The study ran at about 300 centers worldwide, including many U.S. and Canadian sites, and 46% of enrolled patients were women.
But despite undertreatment, women had significantly better outcomes in terms of MACE, the primary endpoint, during a median 5.4 years of follow-up compared with men. After adjustment for sex, other baseline characteristics, and study-treatment assignment, women had a significant 27% lower composite rate of nonfatal MI, nonfatal stroke, or death from either cardiovascular or unknown causes, compared with men, said Dr. Ferrannini, a researcher at the Karolinska Institute in Stockholm.
The analysis by sex also showed that women had a significant outcome advantage, compared with men, for three of the four components of the combined MACE outcome: nonfatal MI, cardiovascular death, and all-cause death, as well as for the outcome of hospitalization for heart failure, which was not part of the composite MACE outcome. The only MACE outcome component that showed no significant between-group difference was nonfatal stroke, which had roughly equal incidence rates among women and men.
Women had half the prevalence of CVD at baseline
The results also showed that the women with type 2 diabetes enrolled in REWIND had a prevalence of existing cardiovascular disease of 20%, which was half the rate of men at study entry, at 41%. However, the between-sex differences in the primary outcome, as well as each of the individual cardiovascular disease outcomes, didn’t change based on whether or not patients had a history of cardiovascular disease at baseline.
Only one outcome showed a between-sex difference linked to prevalent cardiovascular disease at study entry, the rate of all-cause mortality, which was not significantly different between men and women with a history of cardiovascular disease, but was 39% lower in women compared with men without such a history.
“The good news is that, at baseline and after 2 years, the majority of participants were meeting the relevant treatment targets regardless of sex,” commented Peter Novodvorsky, MUDr, a diabetes researcher at the University of Sheffield (England), who chaired the session during which Dr. Ferrannini presented her findings.
A role for geography, or selection bias?
The new analyses did not examine whether the overall pattern of undertreatment of women differed among each of the 24 participating countries, or by region of the world.
“We have to assume that these results reflect current [routine] practice” in the 24 countries that contributed patients to the trial, noted Dr. Novodvorsky.
There is also “the well-known issue of selection bias” in randomized trials. The current findings raise the question of whether the women willing to take part in the trial somehow differed from the men, he suggested.
Dr. Ferrannini added: “Even if we do observe a gender difference in management, if the majority of women with type 2 diabetes are appropriately treated, this ‘restores’ their cardiovascular risk advantage, compared with men, with the exception of stroke.”
The main hypothesis generated by the post hoc analysis of REWIND is that “women with diabetes have better outcomes than men if they are treated properly,” she stressed, noting that this “would have to be tested in a trial designed to ascertain gender differences.”
REWIND was sponsored by Eli Lilly. Dr. Ferrannini has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
At study entry, significantly fewer women received a statin, at 73%, or daily aspirin, at 44%, compared with men, who had treatment rates of 81% and 58%, respectively, Giulia Ferrannini, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
The data also show that significantly fewer women received treatment with an ACE inhibitor or angiotensin-receptor blocker (ARB), at 80%, than men, at 83%, although the absolute between-group difference was modest. Rates of a fourth metric of appropriate treatment, receipt of antihypertensive medications if systolic blood pressure was at least 130 mm Hg, were nearly identical among women and men.
Cardiovascular risk in women “less well managed”
“This is confirmation that women are less well managed than men when it comes to cardiovascular risk, especially if they have [type 2] diabetes,” Dr. Ferrannini said in an interview.
Similar observations have been documented before, including in a report in 2019.
The treatment disparity by sex among the 9901 women and men with type 2 diabetes enrolled in REWIND is particularly striking because in clinical trials “patients are generally better managed than in the real world,” Dr. Ferrannini noted. “Despite this, the pattern of disadvantage to women was still evident,” she added.
“In cardiovascular protection the gender issue is preponderant. Women are less well treated,” she said.
REWIND is the cardiovascular outcomes trial for the once-weekly injectable glucagonlike peptide–1 receptor agonist dulaglutide (Trulicity, Lilly) in patients with type 2 diabetes.
The primary results, reported at the 2019 scientific sessions of the American Diabetes Association and simultaneously published in The Lancet, showed dulaglutide significantly reduced major adverse cardiovascular events (MACE) by 12%, compared with placebo. The study ran at about 300 centers worldwide, including many U.S. and Canadian sites, and 46% of enrolled patients were women.
But despite undertreatment, women had significantly better outcomes in terms of MACE, the primary endpoint, during a median 5.4 years of follow-up compared with men. After adjustment for sex, other baseline characteristics, and study-treatment assignment, women had a significant 27% lower composite rate of nonfatal MI, nonfatal stroke, or death from either cardiovascular or unknown causes, compared with men, said Dr. Ferrannini, a researcher at the Karolinska Institute in Stockholm.
The analysis by sex also showed that women had a significant outcome advantage, compared with men, for three of the four components of the combined MACE outcome: nonfatal MI, cardiovascular death, and all-cause death, as well as for the outcome of hospitalization for heart failure, which was not part of the composite MACE outcome. The only MACE outcome component that showed no significant between-group difference was nonfatal stroke, which had roughly equal incidence rates among women and men.
Women had half the prevalence of CVD at baseline
The results also showed that the women with type 2 diabetes enrolled in REWIND had a prevalence of existing cardiovascular disease of 20%, which was half the rate of men at study entry, at 41%. However, the between-sex differences in the primary outcome, as well as each of the individual cardiovascular disease outcomes, didn’t change based on whether or not patients had a history of cardiovascular disease at baseline.
Only one outcome showed a between-sex difference linked to prevalent cardiovascular disease at study entry, the rate of all-cause mortality, which was not significantly different between men and women with a history of cardiovascular disease, but was 39% lower in women compared with men without such a history.
“The good news is that, at baseline and after 2 years, the majority of participants were meeting the relevant treatment targets regardless of sex,” commented Peter Novodvorsky, MUDr, a diabetes researcher at the University of Sheffield (England), who chaired the session during which Dr. Ferrannini presented her findings.
A role for geography, or selection bias?
The new analyses did not examine whether the overall pattern of undertreatment of women differed among each of the 24 participating countries, or by region of the world.
“We have to assume that these results reflect current [routine] practice” in the 24 countries that contributed patients to the trial, noted Dr. Novodvorsky.
There is also “the well-known issue of selection bias” in randomized trials. The current findings raise the question of whether the women willing to take part in the trial somehow differed from the men, he suggested.
Dr. Ferrannini added: “Even if we do observe a gender difference in management, if the majority of women with type 2 diabetes are appropriately treated, this ‘restores’ their cardiovascular risk advantage, compared with men, with the exception of stroke.”
The main hypothesis generated by the post hoc analysis of REWIND is that “women with diabetes have better outcomes than men if they are treated properly,” she stressed, noting that this “would have to be tested in a trial designed to ascertain gender differences.”
REWIND was sponsored by Eli Lilly. Dr. Ferrannini has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Time-restricted eating: An easy way to improve metabolic health?
Time-restricted eating – where caloric intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories – has “generated impressive [animal] data in preventing or reversing metabolic diseases associated with obesity,” and “more rigorous human studies are needed,” conclude the authors of a new review.
“Time-restricted eating is an easy-to-follow and effective dietary strategy that requires less mental math than counting calories,” said senior author Satchidananda Panda, PhD, of the Panda Lab at the Salk Institute for Biological Studies, La Jolla, Calif.
he noted in a press release from the Endocrine Society.
“People who are trying to lose weight and live a healthier lifestyle should pay more attention to when they eat as well as what they eat,” Dr. Panda advised.
Moreover, “eating at random times breaks the synchrony of our internal program [circadian clock] and make us prone to diseases,” so it is important to eat at consistent times.
Furthermore, time-restricted eating, a type of intermittent fasting, “is a lifestyle that anyone can adopt,” he noted, which “can help eliminate health disparities and lets everyone live a healthy and fulfilling life.”
The article, by Emily N. Manoogian, PhD, a postdoctoral fellow in the same lab, and colleagues was published online Sept. 22 in Endocrine Reviews.
The authors suggest that health care providers should encourage high-risk patients (such as those with obesity) to monitor their eating and sleeping times and make easy-to-implement behavior changes, such as decreasing after-dinner snacking and going to bed at the same time each day.
Animal experiments, early studies in humans
In animal experiments, time-restricted feeding without reducing caloric intake prevented or attenuated the severity of metabolic diseases including obesity, glucose intolerance, hepatic steatosis, dyslipidemia, and age-related decline in cardiac function, Dr. Manoogian and colleagues report.
In pilot human studies, time-restricted eating with or without explicit calorie reduction was associated with reductions in body weight, glucose intolerance, hypertension, and dyslipidemia.
Most studies did not restrict calories or provide dietary recommendations, yet participants commonly reduced their caloric intake by 7%-22%.
39 published clinical trials, many upcoming ones
The authors identified 39 clinical trials of time-restricted eating, which were mostly published in the past 2 years, with the earliest one published in 2013.
Most studies were short and small (4-12 weeks, 10-20 participants) and were of people with obesity, healthy adults, and athletes. Most of the trials had an 8- to 10-hour daily “eating window.”
Body weight decreased in 24 of 39 studies, and “importantly,” time-restricted eating was feasible and safe in all studies, the authors note.
“Larger randomized controlled trials are needed as many of the studies to date are smaller pre-post or crossover trials,” Dr. Manoogian and colleagues summarize. “Yet, the replication of findings, even in diverse patient populations, speaks to the potential impact of [time-restricted eating] as a health intervention.”
The many ongoing international clinical trials of time-restricted eating that are listed on clinicaltrials.gov should improve our understanding of time-restricted eating, they add.
Some of the larger trials are in participants with prediabetes (344 participants, NCT03504683), diabetes (144 participants, NCT04155619), metabolic syndrome (118 participants, NCT04057339), and firefighters on 24-hour shifts (150 participants, NCT03533023). There are also smaller pilot studies in participants with cancer (NCT04243512) and polycystic ovary syndrome (NCT03792282).
Be consistent; do not eat within 3 hours of bedtime
In the meantime, the review authors offer several tips:
- Because high melatonin levels (late at night or early morning) can inhibit proper response to food, choose a time to eat that starts at least an hour after waking and stops at least 3 hours before bedtime. If you sleep 8 hours, that leaves 12 hours for the time-restricted eating window.
- Try to eat within the same time window each day.
- Some research suggests eating earlier in the eating phase is better than eating later.
The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, the Larry l. Hillblom Foundation, the Wu Tsai Human Performance Alliance, the U.S. Department of Defense, and the Federal Emergency Management Agency. Dr. Panda has reported receiving royalties from his book, The Circadian Code. The other authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Time-restricted eating – where caloric intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories – has “generated impressive [animal] data in preventing or reversing metabolic diseases associated with obesity,” and “more rigorous human studies are needed,” conclude the authors of a new review.
“Time-restricted eating is an easy-to-follow and effective dietary strategy that requires less mental math than counting calories,” said senior author Satchidananda Panda, PhD, of the Panda Lab at the Salk Institute for Biological Studies, La Jolla, Calif.
he noted in a press release from the Endocrine Society.
“People who are trying to lose weight and live a healthier lifestyle should pay more attention to when they eat as well as what they eat,” Dr. Panda advised.
Moreover, “eating at random times breaks the synchrony of our internal program [circadian clock] and make us prone to diseases,” so it is important to eat at consistent times.
Furthermore, time-restricted eating, a type of intermittent fasting, “is a lifestyle that anyone can adopt,” he noted, which “can help eliminate health disparities and lets everyone live a healthy and fulfilling life.”
The article, by Emily N. Manoogian, PhD, a postdoctoral fellow in the same lab, and colleagues was published online Sept. 22 in Endocrine Reviews.
The authors suggest that health care providers should encourage high-risk patients (such as those with obesity) to monitor their eating and sleeping times and make easy-to-implement behavior changes, such as decreasing after-dinner snacking and going to bed at the same time each day.
Animal experiments, early studies in humans
In animal experiments, time-restricted feeding without reducing caloric intake prevented or attenuated the severity of metabolic diseases including obesity, glucose intolerance, hepatic steatosis, dyslipidemia, and age-related decline in cardiac function, Dr. Manoogian and colleagues report.
In pilot human studies, time-restricted eating with or without explicit calorie reduction was associated with reductions in body weight, glucose intolerance, hypertension, and dyslipidemia.
Most studies did not restrict calories or provide dietary recommendations, yet participants commonly reduced their caloric intake by 7%-22%.
39 published clinical trials, many upcoming ones
The authors identified 39 clinical trials of time-restricted eating, which were mostly published in the past 2 years, with the earliest one published in 2013.
Most studies were short and small (4-12 weeks, 10-20 participants) and were of people with obesity, healthy adults, and athletes. Most of the trials had an 8- to 10-hour daily “eating window.”
Body weight decreased in 24 of 39 studies, and “importantly,” time-restricted eating was feasible and safe in all studies, the authors note.
“Larger randomized controlled trials are needed as many of the studies to date are smaller pre-post or crossover trials,” Dr. Manoogian and colleagues summarize. “Yet, the replication of findings, even in diverse patient populations, speaks to the potential impact of [time-restricted eating] as a health intervention.”
The many ongoing international clinical trials of time-restricted eating that are listed on clinicaltrials.gov should improve our understanding of time-restricted eating, they add.
Some of the larger trials are in participants with prediabetes (344 participants, NCT03504683), diabetes (144 participants, NCT04155619), metabolic syndrome (118 participants, NCT04057339), and firefighters on 24-hour shifts (150 participants, NCT03533023). There are also smaller pilot studies in participants with cancer (NCT04243512) and polycystic ovary syndrome (NCT03792282).
Be consistent; do not eat within 3 hours of bedtime
In the meantime, the review authors offer several tips:
- Because high melatonin levels (late at night or early morning) can inhibit proper response to food, choose a time to eat that starts at least an hour after waking and stops at least 3 hours before bedtime. If you sleep 8 hours, that leaves 12 hours for the time-restricted eating window.
- Try to eat within the same time window each day.
- Some research suggests eating earlier in the eating phase is better than eating later.
The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, the Larry l. Hillblom Foundation, the Wu Tsai Human Performance Alliance, the U.S. Department of Defense, and the Federal Emergency Management Agency. Dr. Panda has reported receiving royalties from his book, The Circadian Code. The other authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Time-restricted eating – where caloric intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories – has “generated impressive [animal] data in preventing or reversing metabolic diseases associated with obesity,” and “more rigorous human studies are needed,” conclude the authors of a new review.
“Time-restricted eating is an easy-to-follow and effective dietary strategy that requires less mental math than counting calories,” said senior author Satchidananda Panda, PhD, of the Panda Lab at the Salk Institute for Biological Studies, La Jolla, Calif.
he noted in a press release from the Endocrine Society.
“People who are trying to lose weight and live a healthier lifestyle should pay more attention to when they eat as well as what they eat,” Dr. Panda advised.
Moreover, “eating at random times breaks the synchrony of our internal program [circadian clock] and make us prone to diseases,” so it is important to eat at consistent times.
Furthermore, time-restricted eating, a type of intermittent fasting, “is a lifestyle that anyone can adopt,” he noted, which “can help eliminate health disparities and lets everyone live a healthy and fulfilling life.”
The article, by Emily N. Manoogian, PhD, a postdoctoral fellow in the same lab, and colleagues was published online Sept. 22 in Endocrine Reviews.
The authors suggest that health care providers should encourage high-risk patients (such as those with obesity) to monitor their eating and sleeping times and make easy-to-implement behavior changes, such as decreasing after-dinner snacking and going to bed at the same time each day.
Animal experiments, early studies in humans
In animal experiments, time-restricted feeding without reducing caloric intake prevented or attenuated the severity of metabolic diseases including obesity, glucose intolerance, hepatic steatosis, dyslipidemia, and age-related decline in cardiac function, Dr. Manoogian and colleagues report.
In pilot human studies, time-restricted eating with or without explicit calorie reduction was associated with reductions in body weight, glucose intolerance, hypertension, and dyslipidemia.
Most studies did not restrict calories or provide dietary recommendations, yet participants commonly reduced their caloric intake by 7%-22%.
39 published clinical trials, many upcoming ones
The authors identified 39 clinical trials of time-restricted eating, which were mostly published in the past 2 years, with the earliest one published in 2013.
Most studies were short and small (4-12 weeks, 10-20 participants) and were of people with obesity, healthy adults, and athletes. Most of the trials had an 8- to 10-hour daily “eating window.”
Body weight decreased in 24 of 39 studies, and “importantly,” time-restricted eating was feasible and safe in all studies, the authors note.
“Larger randomized controlled trials are needed as many of the studies to date are smaller pre-post or crossover trials,” Dr. Manoogian and colleagues summarize. “Yet, the replication of findings, even in diverse patient populations, speaks to the potential impact of [time-restricted eating] as a health intervention.”
The many ongoing international clinical trials of time-restricted eating that are listed on clinicaltrials.gov should improve our understanding of time-restricted eating, they add.
Some of the larger trials are in participants with prediabetes (344 participants, NCT03504683), diabetes (144 participants, NCT04155619), metabolic syndrome (118 participants, NCT04057339), and firefighters on 24-hour shifts (150 participants, NCT03533023). There are also smaller pilot studies in participants with cancer (NCT04243512) and polycystic ovary syndrome (NCT03792282).
Be consistent; do not eat within 3 hours of bedtime
In the meantime, the review authors offer several tips:
- Because high melatonin levels (late at night or early morning) can inhibit proper response to food, choose a time to eat that starts at least an hour after waking and stops at least 3 hours before bedtime. If you sleep 8 hours, that leaves 12 hours for the time-restricted eating window.
- Try to eat within the same time window each day.
- Some research suggests eating earlier in the eating phase is better than eating later.
The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, the Larry l. Hillblom Foundation, the Wu Tsai Human Performance Alliance, the U.S. Department of Defense, and the Federal Emergency Management Agency. Dr. Panda has reported receiving royalties from his book, The Circadian Code. The other authors have reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Multiple Sclerosis: The Basics
FDA okays new oral CGRP antagonist for migraine prevention
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.