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10% with diabetes hospitalized for COVID-19 die within a week
Data from the CORONADO (French Coronavirus SARS-CoV-2 and Diabetes Outcomes) study also revealed that body mass index (BMI) was independently associated with death or intubation at 7 days, while A1c and use of renin-angiotensin-aldosterone system (RAAS) blockers and dipeptidyl peptidase–4 inhibitors were not.
The presence of diabetes-related complications and older age also increased the risk of death.
The findings were published online Diabetologia by Bertrand Cariou, MD, PhD, of the department of endocrinology at the Hôpital Guillaume et René Laennec in Nantes, France, and colleagues.
First study to examine specific characteristics at time of admission
Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview.
“Before the CORONADO study it was ‘all diabetes [patients] are the same.’ Now we can surely consider more precisely the risk, taking age, sex, BMI, complications, and [obstructive sleep apnea] as clear ‘very high-risk situations,’” said Dr. Hadjadj, of the same institution as Dr. Cariou.
Another clinical message, Dr. Hadjadj said, is that, “even in diabetes, each increase in BMI is associated with an increase in the risk of intubation and/or death in the 7 days following admission for COVID-19. So let’s target this population as a really important population to keep social distancing and stay alert on avoiding the virus.”
But he urged caution regarding the A1c finding. “A1c might be associated with admission to hospital but other factors far beyond A1c drive the prognosis as soon as a patient is admitted. It’s surprising but reasonable speculation can explain this.”
And Dr. Hadjadj said that no obvious signals were identified with regard to medication use.
“Insulin is not suspected of having adverse effects closely related to COVID-19. RAAS blockers are not deleterious but indicative of hypertension, which is a comorbidity even in diabetes patients,” he said. (None of the patients studied were taking sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide receptor agonists.)
Yet again, high BMI emerges as a major risk factor
The study included 1,317 patients with diabetes and confirmed COVID-19 admitted to 53 French hospitals during March 10-31, 2020. Participants included 88.5% with type 2 diabetes, 3% with type 1 diabetes, and 3.1% newly diagnosed on admission. Mean age was 69.8 years.
Diabetes-related disorders on admission were reported in 11.1% of participants overall. These included 132 episodes of severe hyperglycemia, including 40 of ketosis, of which 19 were ketoacidosis, and 14 hypoglycemic events. Severe anorexia was reported in 6.3%.
The composite primary endpoint, tracheal intubation for mechanical ventilation and/or death within 7 days of admission, occurred in 29% of patients (n = 382).
Of the secondary outcomes, 31.1% (n = 410) were admitted to ICUs within 7 days of hospital admission, including 20.3% (n = 267) who required tracheal intubation for mechanical ventilation.
On day 7, 10.6% (n = 140) had died and 18.0% (n = 237) were discharged.
In the univariate analysis, the primary outcome was more frequent in men (69.1% vs. 63.2%; P = .0420) and those taking RAAS blockers (61.5% vs. 55.3%; P = .0386). Median BMI was significantly higher in those in whom the primary outcome occurred (29.1 vs 28.1 kg/m2; P = .0009),
Other characteristics prior to admission associated with risk of death on day 7 included age, hypertension, micro- and macrovascular diabetes-related complications, and comorbidities such as heart failure and treated obstructive sleep apnea.
Over 40% of those admitted had such complications. Of the patients analyzed, microvascular complications (eye, kidney, and neuropathy) were present in 47% and macrovascular complications (arteries of the heart, brain, and legs) were present in 41%.
Encouragingly, there were no deaths in patients aged under 65 years with type 1 diabetes, but only 39 participants had type 1 diabetes. Other work is ongoing to establish the effect of COVID-19 in this specific population, the researchers wrote.
Among prior medications, metformin use was lower in people who died, while insulin use, RAAS blockers, beta-blockers, loop diuretics, and mineralocorticoid-receptor antagonists were associated with death on day 7. The medication findings didn’t reach statistical significance, however.
When asked about the hint of a protective effect of metformin (odds ratio, 0.80; P = .4532), given that some experts have advised stopping it in the setting of COVID-19 because of the risk of lactic acidosis, Dr. Hadjadj said he wouldn’t necessarily stop it in all patients with COVID-19, but said, “let’s stop it in cases of severe condition.”
Analysis ongoing, ‘some new messages might pop up’
After adjustment for age and sex, BMI was significantly and positively associated with the primary outcome (P = .0001) but not with death on day 7 (P = .1488), and A1c wasn’t associated with either outcome.
In a multivariable analysis that included characteristics prior to admission, BMI remained the only independent preadmission predictor associated with the primary outcome (adjusted odds ratio, 1.28), while factors independently associated with risk of death on day 7 included age, diabetes complication history, and treated obstructive sleep apnea.
And after adjustment for age and sex, admission plasma glucose level was significantly and positively associated with both the primary outcome (P = .0001) and death on day 7 (P = .0059).
In the multivariate analysis, admission characteristics that predicted the primary outcome were dyspnea, lymphopenia, increased AST, and increased C-reactive protein.
Dr. Hadjadj said his team is now “focusing on specific risk factors such as obesity, age, vascular complications, medications ... to perform some deeper analyses.”
“We look forward to analyzing the data on in-hospital stay up to day 28 after admission. Some new messages might well pop up,” he added.
But in the meantime, “Elderly populations with long-term diabetes with advanced diabetes-related complications and/or treated obstructive sleep apnea were particularly at risk of early death and might require specific management to avoid infection with the novel coronavirus,” the researchers stressed.
The study received funding from the Fondation Francophone de Recherche sur le Diabète and was supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly, and the Fédération Française des Diabétiques; Société Francophone du Diabète; and Air Liquide Healthcare International. Dr. Hadjadj reported receiving grants, personal fees, and/or nonfinancial support from AstraZeneca, Bayer, Boehringer Ingelheim, Dinno Santé, Eli Lilly, LVL, MSD, Novartis, Pierre Fabre Santé, Sanofi, Servier, and Valbiotis.
A version of this article originally appeared on Medscape.com.
Data from the CORONADO (French Coronavirus SARS-CoV-2 and Diabetes Outcomes) study also revealed that body mass index (BMI) was independently associated with death or intubation at 7 days, while A1c and use of renin-angiotensin-aldosterone system (RAAS) blockers and dipeptidyl peptidase–4 inhibitors were not.
The presence of diabetes-related complications and older age also increased the risk of death.
The findings were published online Diabetologia by Bertrand Cariou, MD, PhD, of the department of endocrinology at the Hôpital Guillaume et René Laennec in Nantes, France, and colleagues.
First study to examine specific characteristics at time of admission
Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview.
“Before the CORONADO study it was ‘all diabetes [patients] are the same.’ Now we can surely consider more precisely the risk, taking age, sex, BMI, complications, and [obstructive sleep apnea] as clear ‘very high-risk situations,’” said Dr. Hadjadj, of the same institution as Dr. Cariou.
Another clinical message, Dr. Hadjadj said, is that, “even in diabetes, each increase in BMI is associated with an increase in the risk of intubation and/or death in the 7 days following admission for COVID-19. So let’s target this population as a really important population to keep social distancing and stay alert on avoiding the virus.”
But he urged caution regarding the A1c finding. “A1c might be associated with admission to hospital but other factors far beyond A1c drive the prognosis as soon as a patient is admitted. It’s surprising but reasonable speculation can explain this.”
And Dr. Hadjadj said that no obvious signals were identified with regard to medication use.
“Insulin is not suspected of having adverse effects closely related to COVID-19. RAAS blockers are not deleterious but indicative of hypertension, which is a comorbidity even in diabetes patients,” he said. (None of the patients studied were taking sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide receptor agonists.)
Yet again, high BMI emerges as a major risk factor
The study included 1,317 patients with diabetes and confirmed COVID-19 admitted to 53 French hospitals during March 10-31, 2020. Participants included 88.5% with type 2 diabetes, 3% with type 1 diabetes, and 3.1% newly diagnosed on admission. Mean age was 69.8 years.
Diabetes-related disorders on admission were reported in 11.1% of participants overall. These included 132 episodes of severe hyperglycemia, including 40 of ketosis, of which 19 were ketoacidosis, and 14 hypoglycemic events. Severe anorexia was reported in 6.3%.
The composite primary endpoint, tracheal intubation for mechanical ventilation and/or death within 7 days of admission, occurred in 29% of patients (n = 382).
Of the secondary outcomes, 31.1% (n = 410) were admitted to ICUs within 7 days of hospital admission, including 20.3% (n = 267) who required tracheal intubation for mechanical ventilation.
On day 7, 10.6% (n = 140) had died and 18.0% (n = 237) were discharged.
In the univariate analysis, the primary outcome was more frequent in men (69.1% vs. 63.2%; P = .0420) and those taking RAAS blockers (61.5% vs. 55.3%; P = .0386). Median BMI was significantly higher in those in whom the primary outcome occurred (29.1 vs 28.1 kg/m2; P = .0009),
Other characteristics prior to admission associated with risk of death on day 7 included age, hypertension, micro- and macrovascular diabetes-related complications, and comorbidities such as heart failure and treated obstructive sleep apnea.
Over 40% of those admitted had such complications. Of the patients analyzed, microvascular complications (eye, kidney, and neuropathy) were present in 47% and macrovascular complications (arteries of the heart, brain, and legs) were present in 41%.
Encouragingly, there were no deaths in patients aged under 65 years with type 1 diabetes, but only 39 participants had type 1 diabetes. Other work is ongoing to establish the effect of COVID-19 in this specific population, the researchers wrote.
Among prior medications, metformin use was lower in people who died, while insulin use, RAAS blockers, beta-blockers, loop diuretics, and mineralocorticoid-receptor antagonists were associated with death on day 7. The medication findings didn’t reach statistical significance, however.
When asked about the hint of a protective effect of metformin (odds ratio, 0.80; P = .4532), given that some experts have advised stopping it in the setting of COVID-19 because of the risk of lactic acidosis, Dr. Hadjadj said he wouldn’t necessarily stop it in all patients with COVID-19, but said, “let’s stop it in cases of severe condition.”
Analysis ongoing, ‘some new messages might pop up’
After adjustment for age and sex, BMI was significantly and positively associated with the primary outcome (P = .0001) but not with death on day 7 (P = .1488), and A1c wasn’t associated with either outcome.
In a multivariable analysis that included characteristics prior to admission, BMI remained the only independent preadmission predictor associated with the primary outcome (adjusted odds ratio, 1.28), while factors independently associated with risk of death on day 7 included age, diabetes complication history, and treated obstructive sleep apnea.
And after adjustment for age and sex, admission plasma glucose level was significantly and positively associated with both the primary outcome (P = .0001) and death on day 7 (P = .0059).
In the multivariate analysis, admission characteristics that predicted the primary outcome were dyspnea, lymphopenia, increased AST, and increased C-reactive protein.
Dr. Hadjadj said his team is now “focusing on specific risk factors such as obesity, age, vascular complications, medications ... to perform some deeper analyses.”
“We look forward to analyzing the data on in-hospital stay up to day 28 after admission. Some new messages might well pop up,” he added.
But in the meantime, “Elderly populations with long-term diabetes with advanced diabetes-related complications and/or treated obstructive sleep apnea were particularly at risk of early death and might require specific management to avoid infection with the novel coronavirus,” the researchers stressed.
The study received funding from the Fondation Francophone de Recherche sur le Diabète and was supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly, and the Fédération Française des Diabétiques; Société Francophone du Diabète; and Air Liquide Healthcare International. Dr. Hadjadj reported receiving grants, personal fees, and/or nonfinancial support from AstraZeneca, Bayer, Boehringer Ingelheim, Dinno Santé, Eli Lilly, LVL, MSD, Novartis, Pierre Fabre Santé, Sanofi, Servier, and Valbiotis.
A version of this article originally appeared on Medscape.com.
Data from the CORONADO (French Coronavirus SARS-CoV-2 and Diabetes Outcomes) study also revealed that body mass index (BMI) was independently associated with death or intubation at 7 days, while A1c and use of renin-angiotensin-aldosterone system (RAAS) blockers and dipeptidyl peptidase–4 inhibitors were not.
The presence of diabetes-related complications and older age also increased the risk of death.
The findings were published online Diabetologia by Bertrand Cariou, MD, PhD, of the department of endocrinology at the Hôpital Guillaume et René Laennec in Nantes, France, and colleagues.
First study to examine specific characteristics at time of admission
Previous studies have linked diabetes to worse outcomes in COVID-19, but this is the first to examine specific characteristics before and at the time of hospital admission that predict worse outcomes among people with diabetes, study coauthor Samy Hadjadj, MD, PhD, said in an interview.
“Before the CORONADO study it was ‘all diabetes [patients] are the same.’ Now we can surely consider more precisely the risk, taking age, sex, BMI, complications, and [obstructive sleep apnea] as clear ‘very high-risk situations,’” said Dr. Hadjadj, of the same institution as Dr. Cariou.
Another clinical message, Dr. Hadjadj said, is that, “even in diabetes, each increase in BMI is associated with an increase in the risk of intubation and/or death in the 7 days following admission for COVID-19. So let’s target this population as a really important population to keep social distancing and stay alert on avoiding the virus.”
But he urged caution regarding the A1c finding. “A1c might be associated with admission to hospital but other factors far beyond A1c drive the prognosis as soon as a patient is admitted. It’s surprising but reasonable speculation can explain this.”
And Dr. Hadjadj said that no obvious signals were identified with regard to medication use.
“Insulin is not suspected of having adverse effects closely related to COVID-19. RAAS blockers are not deleterious but indicative of hypertension, which is a comorbidity even in diabetes patients,” he said. (None of the patients studied were taking sodium-glucose cotransporter 2 inhibitors or glucagonlike peptide receptor agonists.)
Yet again, high BMI emerges as a major risk factor
The study included 1,317 patients with diabetes and confirmed COVID-19 admitted to 53 French hospitals during March 10-31, 2020. Participants included 88.5% with type 2 diabetes, 3% with type 1 diabetes, and 3.1% newly diagnosed on admission. Mean age was 69.8 years.
Diabetes-related disorders on admission were reported in 11.1% of participants overall. These included 132 episodes of severe hyperglycemia, including 40 of ketosis, of which 19 were ketoacidosis, and 14 hypoglycemic events. Severe anorexia was reported in 6.3%.
The composite primary endpoint, tracheal intubation for mechanical ventilation and/or death within 7 days of admission, occurred in 29% of patients (n = 382).
Of the secondary outcomes, 31.1% (n = 410) were admitted to ICUs within 7 days of hospital admission, including 20.3% (n = 267) who required tracheal intubation for mechanical ventilation.
On day 7, 10.6% (n = 140) had died and 18.0% (n = 237) were discharged.
In the univariate analysis, the primary outcome was more frequent in men (69.1% vs. 63.2%; P = .0420) and those taking RAAS blockers (61.5% vs. 55.3%; P = .0386). Median BMI was significantly higher in those in whom the primary outcome occurred (29.1 vs 28.1 kg/m2; P = .0009),
Other characteristics prior to admission associated with risk of death on day 7 included age, hypertension, micro- and macrovascular diabetes-related complications, and comorbidities such as heart failure and treated obstructive sleep apnea.
Over 40% of those admitted had such complications. Of the patients analyzed, microvascular complications (eye, kidney, and neuropathy) were present in 47% and macrovascular complications (arteries of the heart, brain, and legs) were present in 41%.
Encouragingly, there were no deaths in patients aged under 65 years with type 1 diabetes, but only 39 participants had type 1 diabetes. Other work is ongoing to establish the effect of COVID-19 in this specific population, the researchers wrote.
Among prior medications, metformin use was lower in people who died, while insulin use, RAAS blockers, beta-blockers, loop diuretics, and mineralocorticoid-receptor antagonists were associated with death on day 7. The medication findings didn’t reach statistical significance, however.
When asked about the hint of a protective effect of metformin (odds ratio, 0.80; P = .4532), given that some experts have advised stopping it in the setting of COVID-19 because of the risk of lactic acidosis, Dr. Hadjadj said he wouldn’t necessarily stop it in all patients with COVID-19, but said, “let’s stop it in cases of severe condition.”
Analysis ongoing, ‘some new messages might pop up’
After adjustment for age and sex, BMI was significantly and positively associated with the primary outcome (P = .0001) but not with death on day 7 (P = .1488), and A1c wasn’t associated with either outcome.
In a multivariable analysis that included characteristics prior to admission, BMI remained the only independent preadmission predictor associated with the primary outcome (adjusted odds ratio, 1.28), while factors independently associated with risk of death on day 7 included age, diabetes complication history, and treated obstructive sleep apnea.
And after adjustment for age and sex, admission plasma glucose level was significantly and positively associated with both the primary outcome (P = .0001) and death on day 7 (P = .0059).
In the multivariate analysis, admission characteristics that predicted the primary outcome were dyspnea, lymphopenia, increased AST, and increased C-reactive protein.
Dr. Hadjadj said his team is now “focusing on specific risk factors such as obesity, age, vascular complications, medications ... to perform some deeper analyses.”
“We look forward to analyzing the data on in-hospital stay up to day 28 after admission. Some new messages might well pop up,” he added.
But in the meantime, “Elderly populations with long-term diabetes with advanced diabetes-related complications and/or treated obstructive sleep apnea were particularly at risk of early death and might require specific management to avoid infection with the novel coronavirus,” the researchers stressed.
The study received funding from the Fondation Francophone de Recherche sur le Diabète and was supported by Novo Nordisk, MSD, Abbott, AstraZeneca, Lilly, and the Fédération Française des Diabétiques; Société Francophone du Diabète; and Air Liquide Healthcare International. Dr. Hadjadj reported receiving grants, personal fees, and/or nonfinancial support from AstraZeneca, Bayer, Boehringer Ingelheim, Dinno Santé, Eli Lilly, LVL, MSD, Novartis, Pierre Fabre Santé, Sanofi, Servier, and Valbiotis.
A version of this article originally appeared on Medscape.com.
FDA recalls extended-release metformin due to NDMA impurities
The US Food and Drug Administration (FDA) has recommended voluntary recall of certain extended-release (ER) versions of metformin because testing has revealed excessive levels of N-nitrosodimethylamine (NDMA) in these products.
Metformin is the most commonly prescribed drug used to treat type 2 diabetes worldwide.
NDMA is a contaminant with the potential to be carcinogenic if there is exposure to above-acceptable levels over the long-term.
Five pharmaceutical firms in particular are being contacted by the FDA with notices (posted on the FDA website) recommending they voluntarily recall their products. At the time of writing, only one was listed, Apotex Corp and its metformin hydrochloride ER tablets, USP 500 mg.
The recall does not apply to immediate-release metformin products, the most commonly prescribed ones for diabetes, the agency stresses.
It also recommends that clinicians continue to prescribe metformin when clinically appropriate.
In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the US supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 2 years.
By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA, as reported by Medscape Medical News.
“Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” Patrizia Cavazzoni, MD, acting director of the FDA Center for Drug Evaluation and Research, said in a press release.
Requests for recall apply only to affected products
The recall was instigated after the FDA became aware of reports of higher levels of NDMA in certain ER formulations of metformin through a citizen petition filed by a private laboratory. The agency confirmed unacceptable NDMA levels in some, but not all, of those lots.
“In other instances, our laboratory detected NDMA in lots that the private laboratory did not,” it notes.
The FDA says it is working closely with manufacturers of the recalled tablets to identify the source of the NDMA impurity and ensure appropriate testing is carried out.
Elevated levels of NDMA have been found in some finished-dose tablets of the ER formulations but NDMA has not been detected in samples of the metformin active pharmaceutical ingredient.
The FDA also stresses there are many other additional manufacturers that supply metformin ER products to much of the US market, and they are not being asked to recall their products.
Work is also ongoing to determine whether the drug recalls will result in shortages, and if so, the agency says it will collaborate with manufacturers to prevent or reduce any impact of shortages.
“We understand that patients may have concerns about possible impurities in their medicines and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers,” Cavazzoni said.
For more information about NDMA, visit the FDA nitrosamines web page.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has recommended voluntary recall of certain extended-release (ER) versions of metformin because testing has revealed excessive levels of N-nitrosodimethylamine (NDMA) in these products.
Metformin is the most commonly prescribed drug used to treat type 2 diabetes worldwide.
NDMA is a contaminant with the potential to be carcinogenic if there is exposure to above-acceptable levels over the long-term.
Five pharmaceutical firms in particular are being contacted by the FDA with notices (posted on the FDA website) recommending they voluntarily recall their products. At the time of writing, only one was listed, Apotex Corp and its metformin hydrochloride ER tablets, USP 500 mg.
The recall does not apply to immediate-release metformin products, the most commonly prescribed ones for diabetes, the agency stresses.
It also recommends that clinicians continue to prescribe metformin when clinically appropriate.
In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the US supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 2 years.
By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA, as reported by Medscape Medical News.
“Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” Patrizia Cavazzoni, MD, acting director of the FDA Center for Drug Evaluation and Research, said in a press release.
Requests for recall apply only to affected products
The recall was instigated after the FDA became aware of reports of higher levels of NDMA in certain ER formulations of metformin through a citizen petition filed by a private laboratory. The agency confirmed unacceptable NDMA levels in some, but not all, of those lots.
“In other instances, our laboratory detected NDMA in lots that the private laboratory did not,” it notes.
The FDA says it is working closely with manufacturers of the recalled tablets to identify the source of the NDMA impurity and ensure appropriate testing is carried out.
Elevated levels of NDMA have been found in some finished-dose tablets of the ER formulations but NDMA has not been detected in samples of the metformin active pharmaceutical ingredient.
The FDA also stresses there are many other additional manufacturers that supply metformin ER products to much of the US market, and they are not being asked to recall their products.
Work is also ongoing to determine whether the drug recalls will result in shortages, and if so, the agency says it will collaborate with manufacturers to prevent or reduce any impact of shortages.
“We understand that patients may have concerns about possible impurities in their medicines and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers,” Cavazzoni said.
For more information about NDMA, visit the FDA nitrosamines web page.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has recommended voluntary recall of certain extended-release (ER) versions of metformin because testing has revealed excessive levels of N-nitrosodimethylamine (NDMA) in these products.
Metformin is the most commonly prescribed drug used to treat type 2 diabetes worldwide.
NDMA is a contaminant with the potential to be carcinogenic if there is exposure to above-acceptable levels over the long-term.
Five pharmaceutical firms in particular are being contacted by the FDA with notices (posted on the FDA website) recommending they voluntarily recall their products. At the time of writing, only one was listed, Apotex Corp and its metformin hydrochloride ER tablets, USP 500 mg.
The recall does not apply to immediate-release metformin products, the most commonly prescribed ones for diabetes, the agency stresses.
It also recommends that clinicians continue to prescribe metformin when clinically appropriate.
In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the US supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 2 years.
By February 2020, the agency had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of metformin exceeded the acceptable intake limit for NDMA, as reported by Medscape Medical News.
“Now that we have identified some metformin products that do not meet our standards, we’re taking action. As we have been doing since this impurity was first identified, we will communicate as new scientific information becomes available and will take further action, if appropriate,” Patrizia Cavazzoni, MD, acting director of the FDA Center for Drug Evaluation and Research, said in a press release.
Requests for recall apply only to affected products
The recall was instigated after the FDA became aware of reports of higher levels of NDMA in certain ER formulations of metformin through a citizen petition filed by a private laboratory. The agency confirmed unacceptable NDMA levels in some, but not all, of those lots.
“In other instances, our laboratory detected NDMA in lots that the private laboratory did not,” it notes.
The FDA says it is working closely with manufacturers of the recalled tablets to identify the source of the NDMA impurity and ensure appropriate testing is carried out.
Elevated levels of NDMA have been found in some finished-dose tablets of the ER formulations but NDMA has not been detected in samples of the metformin active pharmaceutical ingredient.
The FDA also stresses there are many other additional manufacturers that supply metformin ER products to much of the US market, and they are not being asked to recall their products.
Work is also ongoing to determine whether the drug recalls will result in shortages, and if so, the agency says it will collaborate with manufacturers to prevent or reduce any impact of shortages.
“We understand that patients may have concerns about possible impurities in their medicines and want to assure the public that we have been looking closely at this problem over many months in order to provide patients and healthcare professionals with clear and accurate answers,” Cavazzoni said.
For more information about NDMA, visit the FDA nitrosamines web page.
This article first appeared on Medscape.com.
‘The story unfolding is worrisome’ for diabetes and COVID-19
The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.
“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.
Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.
Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”
Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.
“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
Although rapidly collected, data “offer important clues”
Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.
Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.
“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”
Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”
Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.
“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
Existing insulin use linked to COVID-19 death risk
One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).
“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.
Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
Remote glucose monitoring a novel tool for COVID-19 isolation
Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.
Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.
“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.
“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.
Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”
Key question: Does glycemic management make a difference?
With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.
They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.
In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.
And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”
Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”
“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
More on obesity and COVID-19, this time from China
Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.
An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.
A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
Emerging from the crisis: Protect the vulnerable, increase knowledge base
As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.
Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”
Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.
“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.
Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.
Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”
Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.
“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
Although rapidly collected, data “offer important clues”
Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.
Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.
“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”
Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”
Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.
“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
Existing insulin use linked to COVID-19 death risk
One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).
“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.
Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
Remote glucose monitoring a novel tool for COVID-19 isolation
Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.
Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.
“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.
“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.
Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”
Key question: Does glycemic management make a difference?
With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.
They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.
In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.
And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”
Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”
“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
More on obesity and COVID-19, this time from China
Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.
An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.
A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
Emerging from the crisis: Protect the vulnerable, increase knowledge base
As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.
Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”
Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.
“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.
Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.
Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”
Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.
“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
Although rapidly collected, data “offer important clues”
Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.
Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.
“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”
Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”
Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.
“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
Existing insulin use linked to COVID-19 death risk
One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).
“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.
Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
Remote glucose monitoring a novel tool for COVID-19 isolation
Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.
Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.
“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.
“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.
Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”
Key question: Does glycemic management make a difference?
With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.
They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.
In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.
And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”
Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”
“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
More on obesity and COVID-19, this time from China
Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.
An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.
A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
Emerging from the crisis: Protect the vulnerable, increase knowledge base
As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.
Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”
Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Medicare will offer a $35/month insulin-cost cap in 2021
U.S. Medicare beneficiaries with diabetes will be able to cap their out-of-pocket cost for insulin at no more than $35/month starting in January 2021 under a new coverage option in the Senior Savings Model, according to program details released by the Centers for Medicare & Medicaid Services on May 26.
This facet of the Senior Savings Model for Medicare drug benefits depends on voluntary participation by insurers offering Part D (drug) coverage to Medicare beneficiaries. As of May 26, 2020, 88 insurers had agreed to participate with a total of roughly 1,750 different drug-coverage plan options with this benefit starting next year, either as part of standalone Part D policies or as part of Medicare Advantage, or “enhanced” plans with drug coverage, said Seema Verma, administrator of the CMS, during a press conference.
Beneficiaries who opt for Part D coverage with this benefit will see a cap at $35 a month for their out-of-pocket insulin costs regardless of what phase of drug coverage they are in during the course of a benefit year: the 100% responsibility phase until their annual plan deductible is met, their initial coverage phase, their coverage gap phase (which kicks in after a total of $4,020 is spent on all prescription drugs), and the catastrophic coverage phase.
A recently published analysis of average, annual, out-of-pocket insulin costs for U.S. Medicare beneficiaries with “typical” Part D plans during 2019 found that, under this four-phase pricing scheme, the 1-year total cost to patients for their insulin came to just over $1,140 (N Engl J Med. 2020 May 14;382[20]:1878-80). For 2021 participants in the new model, annual out-of-pocket cost should be no greater than $420, and could possibly be less as the $35/month rate is not set but a cost ceiling.
A written statement from CMS about the new program predicted an average, estimated out-of-pocket cost savings of $446 per beneficiary. In addition to reducing overall out-of-pocket costs, another goal of the program is to give beneficiaries month-to-month consistency in their insulin costs. Under current coverage rules, costs fluctuate from month to month depending on the phase of coverage a beneficiary qualifies for at a given time.
The change to insulin copays in 2021 for beneficiaries in participating plans will cover “all common forms of insulin,” said Ms. Verma during the press conference. “If it goes well, we’ll extend that to other drugs,” she added. “We’re starting with insulin, but depending on the progress of this, we will consider offering this flexibility to manufacturers and plans with other drugs, depending on the results. We think that this creates a foundation and a platform to fix things, some of the problems that we have in the Part D plans. It’s time for that program to be updated. A lot of the provisions just don’t work anymore, and it’s standing in the way of free-market completion and negotiation that can lower prices for seniors.”
But “only 54% of all Medicare beneficiaries are enrolled in enhanced plans that are eligible to participate in the model, and only 44% of those plans have agreed to participate,” according to a statement from Public Citizen, a consumer-rights group based in Washington. Furthermore, the statement’s author, Peter Maybarduk, director of the organizations Access to Medicines Program, cited an analysis by Public Citizen that found that the program did nothing prevent pharmaceutical corporations from setting exorbitant prices for insulin. He added that the plan leaves out younger patients with diabetes, many of whom have been forced to ration their insulin because of the “outrageous insulin price gouging.”
CMS also recently announced on May 22 that it had finalized a rule that allows for expanded use of telehealth consultations for beneficiaries in Advantage programs. The agency said that telehealth consults had become possible for a variety of medical subspecialties, including endocrinology, dermatology, cardiology, gynecology, psychiatry, and primary care. In March, CMS announced a waiver to its prior rules on use of telehealth consults effective March 6, 2020. Kellyanne Conway, a senior counselor to President Donald Trump, said during the May 26 press conference that Medicare-covered telehealth visits rose from about 12,000 per week prior to issuance of the waiver to “well into the six figures,” in recent weeks.
U.S. Medicare beneficiaries with diabetes will be able to cap their out-of-pocket cost for insulin at no more than $35/month starting in January 2021 under a new coverage option in the Senior Savings Model, according to program details released by the Centers for Medicare & Medicaid Services on May 26.
This facet of the Senior Savings Model for Medicare drug benefits depends on voluntary participation by insurers offering Part D (drug) coverage to Medicare beneficiaries. As of May 26, 2020, 88 insurers had agreed to participate with a total of roughly 1,750 different drug-coverage plan options with this benefit starting next year, either as part of standalone Part D policies or as part of Medicare Advantage, or “enhanced” plans with drug coverage, said Seema Verma, administrator of the CMS, during a press conference.
Beneficiaries who opt for Part D coverage with this benefit will see a cap at $35 a month for their out-of-pocket insulin costs regardless of what phase of drug coverage they are in during the course of a benefit year: the 100% responsibility phase until their annual plan deductible is met, their initial coverage phase, their coverage gap phase (which kicks in after a total of $4,020 is spent on all prescription drugs), and the catastrophic coverage phase.
A recently published analysis of average, annual, out-of-pocket insulin costs for U.S. Medicare beneficiaries with “typical” Part D plans during 2019 found that, under this four-phase pricing scheme, the 1-year total cost to patients for their insulin came to just over $1,140 (N Engl J Med. 2020 May 14;382[20]:1878-80). For 2021 participants in the new model, annual out-of-pocket cost should be no greater than $420, and could possibly be less as the $35/month rate is not set but a cost ceiling.
A written statement from CMS about the new program predicted an average, estimated out-of-pocket cost savings of $446 per beneficiary. In addition to reducing overall out-of-pocket costs, another goal of the program is to give beneficiaries month-to-month consistency in their insulin costs. Under current coverage rules, costs fluctuate from month to month depending on the phase of coverage a beneficiary qualifies for at a given time.
The change to insulin copays in 2021 for beneficiaries in participating plans will cover “all common forms of insulin,” said Ms. Verma during the press conference. “If it goes well, we’ll extend that to other drugs,” she added. “We’re starting with insulin, but depending on the progress of this, we will consider offering this flexibility to manufacturers and plans with other drugs, depending on the results. We think that this creates a foundation and a platform to fix things, some of the problems that we have in the Part D plans. It’s time for that program to be updated. A lot of the provisions just don’t work anymore, and it’s standing in the way of free-market completion and negotiation that can lower prices for seniors.”
But “only 54% of all Medicare beneficiaries are enrolled in enhanced plans that are eligible to participate in the model, and only 44% of those plans have agreed to participate,” according to a statement from Public Citizen, a consumer-rights group based in Washington. Furthermore, the statement’s author, Peter Maybarduk, director of the organizations Access to Medicines Program, cited an analysis by Public Citizen that found that the program did nothing prevent pharmaceutical corporations from setting exorbitant prices for insulin. He added that the plan leaves out younger patients with diabetes, many of whom have been forced to ration their insulin because of the “outrageous insulin price gouging.”
CMS also recently announced on May 22 that it had finalized a rule that allows for expanded use of telehealth consultations for beneficiaries in Advantage programs. The agency said that telehealth consults had become possible for a variety of medical subspecialties, including endocrinology, dermatology, cardiology, gynecology, psychiatry, and primary care. In March, CMS announced a waiver to its prior rules on use of telehealth consults effective March 6, 2020. Kellyanne Conway, a senior counselor to President Donald Trump, said during the May 26 press conference that Medicare-covered telehealth visits rose from about 12,000 per week prior to issuance of the waiver to “well into the six figures,” in recent weeks.
U.S. Medicare beneficiaries with diabetes will be able to cap their out-of-pocket cost for insulin at no more than $35/month starting in January 2021 under a new coverage option in the Senior Savings Model, according to program details released by the Centers for Medicare & Medicaid Services on May 26.
This facet of the Senior Savings Model for Medicare drug benefits depends on voluntary participation by insurers offering Part D (drug) coverage to Medicare beneficiaries. As of May 26, 2020, 88 insurers had agreed to participate with a total of roughly 1,750 different drug-coverage plan options with this benefit starting next year, either as part of standalone Part D policies or as part of Medicare Advantage, or “enhanced” plans with drug coverage, said Seema Verma, administrator of the CMS, during a press conference.
Beneficiaries who opt for Part D coverage with this benefit will see a cap at $35 a month for their out-of-pocket insulin costs regardless of what phase of drug coverage they are in during the course of a benefit year: the 100% responsibility phase until their annual plan deductible is met, their initial coverage phase, their coverage gap phase (which kicks in after a total of $4,020 is spent on all prescription drugs), and the catastrophic coverage phase.
A recently published analysis of average, annual, out-of-pocket insulin costs for U.S. Medicare beneficiaries with “typical” Part D plans during 2019 found that, under this four-phase pricing scheme, the 1-year total cost to patients for their insulin came to just over $1,140 (N Engl J Med. 2020 May 14;382[20]:1878-80). For 2021 participants in the new model, annual out-of-pocket cost should be no greater than $420, and could possibly be less as the $35/month rate is not set but a cost ceiling.
A written statement from CMS about the new program predicted an average, estimated out-of-pocket cost savings of $446 per beneficiary. In addition to reducing overall out-of-pocket costs, another goal of the program is to give beneficiaries month-to-month consistency in their insulin costs. Under current coverage rules, costs fluctuate from month to month depending on the phase of coverage a beneficiary qualifies for at a given time.
The change to insulin copays in 2021 for beneficiaries in participating plans will cover “all common forms of insulin,” said Ms. Verma during the press conference. “If it goes well, we’ll extend that to other drugs,” she added. “We’re starting with insulin, but depending on the progress of this, we will consider offering this flexibility to manufacturers and plans with other drugs, depending on the results. We think that this creates a foundation and a platform to fix things, some of the problems that we have in the Part D plans. It’s time for that program to be updated. A lot of the provisions just don’t work anymore, and it’s standing in the way of free-market completion and negotiation that can lower prices for seniors.”
But “only 54% of all Medicare beneficiaries are enrolled in enhanced plans that are eligible to participate in the model, and only 44% of those plans have agreed to participate,” according to a statement from Public Citizen, a consumer-rights group based in Washington. Furthermore, the statement’s author, Peter Maybarduk, director of the organizations Access to Medicines Program, cited an analysis by Public Citizen that found that the program did nothing prevent pharmaceutical corporations from setting exorbitant prices for insulin. He added that the plan leaves out younger patients with diabetes, many of whom have been forced to ration their insulin because of the “outrageous insulin price gouging.”
CMS also recently announced on May 22 that it had finalized a rule that allows for expanded use of telehealth consultations for beneficiaries in Advantage programs. The agency said that telehealth consults had become possible for a variety of medical subspecialties, including endocrinology, dermatology, cardiology, gynecology, psychiatry, and primary care. In March, CMS announced a waiver to its prior rules on use of telehealth consults effective March 6, 2020. Kellyanne Conway, a senior counselor to President Donald Trump, said during the May 26 press conference that Medicare-covered telehealth visits rose from about 12,000 per week prior to issuance of the waiver to “well into the six figures,” in recent weeks.
Seek safe strategies to diagnose gestational diabetes during pandemic
Clinicians and pregnant women are less likely to prescribe and undergo the oral glucose tolerance test (OGTT) to diagnose gestational diabetes in the context of the COVID-19 pandemic, according to a review by H. David McIntyre, MD, of the University of Queensland, Brisbane, Australia, and Robert G. Moses, MD, of Wollongong (Australia) Hospital.
National and international discussions of whether a one- or two-step test for gestational diabetes mellitus (GDM) is optimal, and which women should be tested are ongoing, but the potential for exposure risks to COVID-19 are impacting the test process, they wrote in a commentary published in Diabetes Care.
“Any national or local guidelines should be developed with the primary aim of being protective for pregnant women and workable in the current health crisis,” they wrote.
Key concerns expressed by women and health care providers include the need for travel to be tested, the possible need for two visits, and the several hours spent in a potentially high-risk specimen collection center.
“Further, a GDM diagnosis generally involves additional health service visits for diabetes education, glucose monitoring review, and fetal ultrasonography, all of which carry exposure risks during a pandemic,” Dr. McIntyre and Dr. Moses noted.
Professional societies in the United Kingdom, Canada, and Australia have issued guidance to clinicians for modifying GDM diagnoses criteria during the pandemic that aim to reduce the need for the oral glucose tolerance test both during and after pregnancy.
Pandemic guidelines for all three of these countries support the identification of GDM using early pregnancy hemoglobin A1c (HbA1c) of at least 41 mmol/mol (5.9%).
Then, professionals in the United Kingdom recommend testing based on risk factors and diagnosing GDM based on any of these criteria: HbA1c of at least 39 mmol/mol (5.7%), fasting venous plasma glucose of at least 5.6 mmol/L (preferred), or random VPG of at least 9.0 mmol/L.
The revised testing pathway for Canada accepts an HbA1c of at least 39 mmol/mol (5.7%) and/or random VPG of at least 11.1 mmol/L.
“The revised Australian pathway does not include HbA1c but recommends a fasting VPG with progression to OGTT only if this result is 4.7-5.0 mmol/L,” Dr. McIntyre and Dr. Moses explained.
Overall, the revised guidelines for GDM testing will likely miss some women and only identify those with higher levels of hyperglycemia, the authors wrote. In addition, “the evidence base for these revised pathways is limited and that each alternative strategy should be evaluated over the course of the current pandemic.”
Validation of new testing strategies are needed, and the pandemic may provide and opportunity to adopt an alternative to the OGTT. The World Health Organization has not issued revised guidance for other methods of testing, but fasting VPG alone may be the simplest and most cost effective, at least for the short term, they noted.
“In this ‘new COVID world,’ GDM should not be ignored but pragmatically merits a lower priority than the avoidance of exposure to the COVID-19 virus,” although no single alternative strategy applies in all countries and situations, the authors concluded. Pragmatic measures and documentation of outcomes at the local level will offer the “least worst” solution while the pandemic continues.
The authors had no relevant financial disclosures.
SOURCE: McIntyre HD, Moses RG. Diabetes Care. 2020 May. doi: 10.2337/dci20-0026.
A major concern against the backdrop of COVID-19 is ensuring long-term health while urgent care is – understandably so – being prioritized over preventive care. We can already see the impact that the decrease in primary care has had: Rates of childhood vaccination appear to have dropped; the cancellation or indefinite delay of elective medical procedures has meant a reduction in preventive cancer screenings, such as colonoscopies and mammograms; and concerns about COVID-19 may be keeping those experiencing cardiac events from seeking emergency care.
However, an outcropping of the coronavirus pandemic is an ingenuity to adapt to our new “normal.” Medical licenses have been recognized across state lines to allow much-needed professionals to practice in the hardest-hit areas. Doctors retrofitted a sleep apnea machine to be used as a makeshift ventilator. Those in the wearable device market now have a greater onus to deliver on quality, utility, security, and accuracy.
Obstetricians have had to dramatically change delivery of ante-, intra- and postpartum care. The recent commentary by Dr. McIntyre and Dr. Moses focuses on one particular area of concern: screening, diagnosis, and management of gestational diabetes mellitus (GDM).
Screening and diagnosis are mainstays to reduce the adverse maternal and neonatal outcomes of diabetes in pregnancy. Although there is no universally accepted approach to evaluating GDM, all current methods utilize an oral glucose tolerance test (OGTT), which requires significant time spent in a clinical office setting, thus increasing risk for COVID-19 exposure.
Several countries have adopted modified GDM criteria within the last months. At the time of this writing, the United States has not. Although not testing women for GDM, which is what Dr. McIntyre and Dr. Moses point out may be happening in countries with modified guidelines, seems questionable, perhaps we should think differently about our approach.
More than 20 years ago, it was reported that jelly beans could be used as an alternative to the 50-g GDM screening test (Am J Obstet Gynecol. 1999 Nov;181[5 Pt 1]:1154‐7; Am J Obstet Gynecol. 1995 Dec;173[6]:1889‐92); more recently, candy twists were used with similar results (Am J Obstet Gynecol. 2015 Apr;212[4]:522.e1-5). In addition, a number of articles have reported on the utility of capillary whole blood glucose measurements to screen for GDM in developing and resource-limited countries (Diabetes Technol Ther. 2011;13[5]:586‐91; Acta Diabetol. 2016 Feb;53[1]:91‐7; Diabetes Technol Ther. 2012 Feb;14[2]:131-4). Therefore, rather than forgo GDM screening, women could self-administer a jelly bean test at home, measure blood sugar with a glucometer, and depending on the results, have an OGTT. Importantly, this would allow ob.gyns. to maintain medical standards while managing patients via telemedicine.
We have evidence that GDM can establish poor health for generations. We know that people with underlying conditions have greater morbidity and mortality from infectious diseases. We recognize that accurate screening and diagnosis is the key to prevention and management. Rather than accept a “least worst” scenario, as Dr. McIntyre and Dr. Moses state, we must find ways to provide the best possible care under the current circumstances.
E. Albert Reece, MD, PhD, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. He said he had no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
A major concern against the backdrop of COVID-19 is ensuring long-term health while urgent care is – understandably so – being prioritized over preventive care. We can already see the impact that the decrease in primary care has had: Rates of childhood vaccination appear to have dropped; the cancellation or indefinite delay of elective medical procedures has meant a reduction in preventive cancer screenings, such as colonoscopies and mammograms; and concerns about COVID-19 may be keeping those experiencing cardiac events from seeking emergency care.
However, an outcropping of the coronavirus pandemic is an ingenuity to adapt to our new “normal.” Medical licenses have been recognized across state lines to allow much-needed professionals to practice in the hardest-hit areas. Doctors retrofitted a sleep apnea machine to be used as a makeshift ventilator. Those in the wearable device market now have a greater onus to deliver on quality, utility, security, and accuracy.
Obstetricians have had to dramatically change delivery of ante-, intra- and postpartum care. The recent commentary by Dr. McIntyre and Dr. Moses focuses on one particular area of concern: screening, diagnosis, and management of gestational diabetes mellitus (GDM).
Screening and diagnosis are mainstays to reduce the adverse maternal and neonatal outcomes of diabetes in pregnancy. Although there is no universally accepted approach to evaluating GDM, all current methods utilize an oral glucose tolerance test (OGTT), which requires significant time spent in a clinical office setting, thus increasing risk for COVID-19 exposure.
Several countries have adopted modified GDM criteria within the last months. At the time of this writing, the United States has not. Although not testing women for GDM, which is what Dr. McIntyre and Dr. Moses point out may be happening in countries with modified guidelines, seems questionable, perhaps we should think differently about our approach.
More than 20 years ago, it was reported that jelly beans could be used as an alternative to the 50-g GDM screening test (Am J Obstet Gynecol. 1999 Nov;181[5 Pt 1]:1154‐7; Am J Obstet Gynecol. 1995 Dec;173[6]:1889‐92); more recently, candy twists were used with similar results (Am J Obstet Gynecol. 2015 Apr;212[4]:522.e1-5). In addition, a number of articles have reported on the utility of capillary whole blood glucose measurements to screen for GDM in developing and resource-limited countries (Diabetes Technol Ther. 2011;13[5]:586‐91; Acta Diabetol. 2016 Feb;53[1]:91‐7; Diabetes Technol Ther. 2012 Feb;14[2]:131-4). Therefore, rather than forgo GDM screening, women could self-administer a jelly bean test at home, measure blood sugar with a glucometer, and depending on the results, have an OGTT. Importantly, this would allow ob.gyns. to maintain medical standards while managing patients via telemedicine.
We have evidence that GDM can establish poor health for generations. We know that people with underlying conditions have greater morbidity and mortality from infectious diseases. We recognize that accurate screening and diagnosis is the key to prevention and management. Rather than accept a “least worst” scenario, as Dr. McIntyre and Dr. Moses state, we must find ways to provide the best possible care under the current circumstances.
E. Albert Reece, MD, PhD, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. He said he had no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
A major concern against the backdrop of COVID-19 is ensuring long-term health while urgent care is – understandably so – being prioritized over preventive care. We can already see the impact that the decrease in primary care has had: Rates of childhood vaccination appear to have dropped; the cancellation or indefinite delay of elective medical procedures has meant a reduction in preventive cancer screenings, such as colonoscopies and mammograms; and concerns about COVID-19 may be keeping those experiencing cardiac events from seeking emergency care.
However, an outcropping of the coronavirus pandemic is an ingenuity to adapt to our new “normal.” Medical licenses have been recognized across state lines to allow much-needed professionals to practice in the hardest-hit areas. Doctors retrofitted a sleep apnea machine to be used as a makeshift ventilator. Those in the wearable device market now have a greater onus to deliver on quality, utility, security, and accuracy.
Obstetricians have had to dramatically change delivery of ante-, intra- and postpartum care. The recent commentary by Dr. McIntyre and Dr. Moses focuses on one particular area of concern: screening, diagnosis, and management of gestational diabetes mellitus (GDM).
Screening and diagnosis are mainstays to reduce the adverse maternal and neonatal outcomes of diabetes in pregnancy. Although there is no universally accepted approach to evaluating GDM, all current methods utilize an oral glucose tolerance test (OGTT), which requires significant time spent in a clinical office setting, thus increasing risk for COVID-19 exposure.
Several countries have adopted modified GDM criteria within the last months. At the time of this writing, the United States has not. Although not testing women for GDM, which is what Dr. McIntyre and Dr. Moses point out may be happening in countries with modified guidelines, seems questionable, perhaps we should think differently about our approach.
More than 20 years ago, it was reported that jelly beans could be used as an alternative to the 50-g GDM screening test (Am J Obstet Gynecol. 1999 Nov;181[5 Pt 1]:1154‐7; Am J Obstet Gynecol. 1995 Dec;173[6]:1889‐92); more recently, candy twists were used with similar results (Am J Obstet Gynecol. 2015 Apr;212[4]:522.e1-5). In addition, a number of articles have reported on the utility of capillary whole blood glucose measurements to screen for GDM in developing and resource-limited countries (Diabetes Technol Ther. 2011;13[5]:586‐91; Acta Diabetol. 2016 Feb;53[1]:91‐7; Diabetes Technol Ther. 2012 Feb;14[2]:131-4). Therefore, rather than forgo GDM screening, women could self-administer a jelly bean test at home, measure blood sugar with a glucometer, and depending on the results, have an OGTT. Importantly, this would allow ob.gyns. to maintain medical standards while managing patients via telemedicine.
We have evidence that GDM can establish poor health for generations. We know that people with underlying conditions have greater morbidity and mortality from infectious diseases. We recognize that accurate screening and diagnosis is the key to prevention and management. Rather than accept a “least worst” scenario, as Dr. McIntyre and Dr. Moses state, we must find ways to provide the best possible care under the current circumstances.
E. Albert Reece, MD, PhD, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. He said he had no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
Clinicians and pregnant women are less likely to prescribe and undergo the oral glucose tolerance test (OGTT) to diagnose gestational diabetes in the context of the COVID-19 pandemic, according to a review by H. David McIntyre, MD, of the University of Queensland, Brisbane, Australia, and Robert G. Moses, MD, of Wollongong (Australia) Hospital.
National and international discussions of whether a one- or two-step test for gestational diabetes mellitus (GDM) is optimal, and which women should be tested are ongoing, but the potential for exposure risks to COVID-19 are impacting the test process, they wrote in a commentary published in Diabetes Care.
“Any national or local guidelines should be developed with the primary aim of being protective for pregnant women and workable in the current health crisis,” they wrote.
Key concerns expressed by women and health care providers include the need for travel to be tested, the possible need for two visits, and the several hours spent in a potentially high-risk specimen collection center.
“Further, a GDM diagnosis generally involves additional health service visits for diabetes education, glucose monitoring review, and fetal ultrasonography, all of which carry exposure risks during a pandemic,” Dr. McIntyre and Dr. Moses noted.
Professional societies in the United Kingdom, Canada, and Australia have issued guidance to clinicians for modifying GDM diagnoses criteria during the pandemic that aim to reduce the need for the oral glucose tolerance test both during and after pregnancy.
Pandemic guidelines for all three of these countries support the identification of GDM using early pregnancy hemoglobin A1c (HbA1c) of at least 41 mmol/mol (5.9%).
Then, professionals in the United Kingdom recommend testing based on risk factors and diagnosing GDM based on any of these criteria: HbA1c of at least 39 mmol/mol (5.7%), fasting venous plasma glucose of at least 5.6 mmol/L (preferred), or random VPG of at least 9.0 mmol/L.
The revised testing pathway for Canada accepts an HbA1c of at least 39 mmol/mol (5.7%) and/or random VPG of at least 11.1 mmol/L.
“The revised Australian pathway does not include HbA1c but recommends a fasting VPG with progression to OGTT only if this result is 4.7-5.0 mmol/L,” Dr. McIntyre and Dr. Moses explained.
Overall, the revised guidelines for GDM testing will likely miss some women and only identify those with higher levels of hyperglycemia, the authors wrote. In addition, “the evidence base for these revised pathways is limited and that each alternative strategy should be evaluated over the course of the current pandemic.”
Validation of new testing strategies are needed, and the pandemic may provide and opportunity to adopt an alternative to the OGTT. The World Health Organization has not issued revised guidance for other methods of testing, but fasting VPG alone may be the simplest and most cost effective, at least for the short term, they noted.
“In this ‘new COVID world,’ GDM should not be ignored but pragmatically merits a lower priority than the avoidance of exposure to the COVID-19 virus,” although no single alternative strategy applies in all countries and situations, the authors concluded. Pragmatic measures and documentation of outcomes at the local level will offer the “least worst” solution while the pandemic continues.
The authors had no relevant financial disclosures.
SOURCE: McIntyre HD, Moses RG. Diabetes Care. 2020 May. doi: 10.2337/dci20-0026.
Clinicians and pregnant women are less likely to prescribe and undergo the oral glucose tolerance test (OGTT) to diagnose gestational diabetes in the context of the COVID-19 pandemic, according to a review by H. David McIntyre, MD, of the University of Queensland, Brisbane, Australia, and Robert G. Moses, MD, of Wollongong (Australia) Hospital.
National and international discussions of whether a one- or two-step test for gestational diabetes mellitus (GDM) is optimal, and which women should be tested are ongoing, but the potential for exposure risks to COVID-19 are impacting the test process, they wrote in a commentary published in Diabetes Care.
“Any national or local guidelines should be developed with the primary aim of being protective for pregnant women and workable in the current health crisis,” they wrote.
Key concerns expressed by women and health care providers include the need for travel to be tested, the possible need for two visits, and the several hours spent in a potentially high-risk specimen collection center.
“Further, a GDM diagnosis generally involves additional health service visits for diabetes education, glucose monitoring review, and fetal ultrasonography, all of which carry exposure risks during a pandemic,” Dr. McIntyre and Dr. Moses noted.
Professional societies in the United Kingdom, Canada, and Australia have issued guidance to clinicians for modifying GDM diagnoses criteria during the pandemic that aim to reduce the need for the oral glucose tolerance test both during and after pregnancy.
Pandemic guidelines for all three of these countries support the identification of GDM using early pregnancy hemoglobin A1c (HbA1c) of at least 41 mmol/mol (5.9%).
Then, professionals in the United Kingdom recommend testing based on risk factors and diagnosing GDM based on any of these criteria: HbA1c of at least 39 mmol/mol (5.7%), fasting venous plasma glucose of at least 5.6 mmol/L (preferred), or random VPG of at least 9.0 mmol/L.
The revised testing pathway for Canada accepts an HbA1c of at least 39 mmol/mol (5.7%) and/or random VPG of at least 11.1 mmol/L.
“The revised Australian pathway does not include HbA1c but recommends a fasting VPG with progression to OGTT only if this result is 4.7-5.0 mmol/L,” Dr. McIntyre and Dr. Moses explained.
Overall, the revised guidelines for GDM testing will likely miss some women and only identify those with higher levels of hyperglycemia, the authors wrote. In addition, “the evidence base for these revised pathways is limited and that each alternative strategy should be evaluated over the course of the current pandemic.”
Validation of new testing strategies are needed, and the pandemic may provide and opportunity to adopt an alternative to the OGTT. The World Health Organization has not issued revised guidance for other methods of testing, but fasting VPG alone may be the simplest and most cost effective, at least for the short term, they noted.
“In this ‘new COVID world,’ GDM should not be ignored but pragmatically merits a lower priority than the avoidance of exposure to the COVID-19 virus,” although no single alternative strategy applies in all countries and situations, the authors concluded. Pragmatic measures and documentation of outcomes at the local level will offer the “least worst” solution while the pandemic continues.
The authors had no relevant financial disclosures.
SOURCE: McIntyre HD, Moses RG. Diabetes Care. 2020 May. doi: 10.2337/dci20-0026.
ARBs didn't raise suicide risk in large VA study
Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.
The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.
The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.
The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.
The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.
Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.
Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.
A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.
Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.
Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.
The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.
The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.
The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.
The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.
Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.
Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.
A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.
Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.
Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.
The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.
The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.
The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.
The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.
Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.
Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.
A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.
Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.
FROM AAS20
Glucose control linked to COVID-19 outcomes in largest-yet study
The strong link between glucose control and COVID-19 outcomes has been reaffirmed in the largest study thus far of hospitalized patients with preexisting type 2 diabetes.
The retrospective, multicenter study, from 7,337 hospitalized patients with COVID-19, was published online in Cell Metabolism by Lihua Zhu, Renmin Hospital of Wuhan University, China, and colleagues.
The study finds that, while the presence of type 2 diabetes per se is a risk factor for worse COVID-19 outcomes, better glycemic control among those with preexisting type 2 diabetes appears to be associated with significant reductions in adverse outcomes and death.
“We were surprised to see such favorable outcomes in the well-controlled blood glucose group among patients with COVID-19 and preexisting type 2 diabetes,” senior author Hongliang Li, also of Renmin Hospital, said in a statement.
“Considering that people with diabetes had much higher risk for death and various complications, and there are no specific drugs for COVID-19, our findings indicate that controlling blood glucose well may act as an effective auxiliary approach to improve the prognosis of patients with COVID-19 and preexisting diabetes,” Dr. Li added.
Asked to comment on the findings, David Klonoff, MD, medical director of the Diabetes Research Institute at Mills–Peninsula Medical Center, San Mateo, Calif., cautioned that the way in which the “well-controlled” diabetes group was distinguished from the “poorly controlled” one in this study used a “nonstandard method for distinguishing these groups based on variability.”
So “there was a great deal of overlap between the two groups,” he observed.
Diabetes itself was associated with worse COVID-19 outcomes
Of the 7,337 participants with confirmed COVID-19 in the Chinese study, 13% (952) had preexisting type 2 diabetes while the other 6,385 did not have diabetes.
Median ages were 62 years for those with and 53 years for those without diabetes. As has been reported several times since the pandemic began, the presence of diabetes was associated with a worse COVID-19 prognosis.
Those with preexisting diabetes received significantly more antibiotics, antifungals, systemic corticosteroids, immunoglobulin, antihypertensive drugs, and vasoactive drugs than did those without diabetes. They were also more likely to receive oxygen inhalation (76.9% vs. 61.2%), noninvasive ventilation (10.2% vs. 3.9%), and invasive ventilation (3.6% vs. 0.7%).
Over 28 days starting with the day of admission, the type 2 diabetes group was significantly more likely to die compared with those without diabetes (7.8% vs. 2.7%; P < .001), with a crude hazard ratio of 2.90 (P < .001). After adjustments for age, gender, and COVID-19 severity, the diabetes group was still significantly more likely to die, with a hazard ratio of 1.49 (P = .005).
Those with diabetes were also significantly more likely to develop acute respiratory distress syndrome (adjusted hazard ratio, 1.44), acute kidney injury (3.01), and septic shock (1.95).
“The results were unequivocal to implicate diabetes mellitus in higher risk of death and other detrimental outcomes of COVID-19,” the authors wrote, although they caution “there were notable differences in the covariate distributions between the two groups.”
With T2D, tighter glycemic control predicted better outcome
Among the 952 with COVID-19 and type 2 diabetes, 282 individuals had “well-controlled” blood glucose, ranging from 3.9 to 10.0 mmol/L (~70 - 180 mg/dL) with median 6.4 mmol/L (115 mg/dL) and hemoglobin A1c of 7.3%.
The other 528 were “poorly controlled,” defined as the lowest fasting glucose level 3.9 mmol/L or above and the highest 2-hour postprandial glucose exceeding 10.0 mmol/L, with median 10.9 mmol/L (196 mg/dL) and HbA1c of 8.1%.
Just as with the diabetes vs. no diabetes comparison, those in the “well-controlled” blood glucose group had lower use of antivirals, antibiotics, antifungals, systemic corticosteroids, immunoglobulin, and vasoactive drugs.
They also were less likely to require oxygen inhalation (70.2% vs. 83.5%), non-invasive ventilation (4.6% vs. 11.9%), invasive ventilation (0% vs. 4.2%), and extracorporeal membrane oxygenation (0% vs. 0.8%).
In-hospital death was significantly lower in the “well-controlled” group (1.1% vs. 11.0%; crude hazard ratio, 0.09; P < .001). After adjustments for the previous factors plus site effect, the difference remained significant (0.13; P < .001). Adjusted hazard ratio for acute respiratory distress syndrome was 0.41 (P < .001) and for acute heart injury it was 0.21 (P = .003).
Stress hyperglycemia in COVID-19 associated with greater mortality
Klonoff was senior author on a previous study from the United States that showed that both diabetes and uncontrolled hyperglycemia among people without prior diabetes – the latter “presumably due to stress,” he said – were strong predictors of mortality among hospitalized patients with COVID-19.
The new Chinese research only looks at individuals with previously diagnosed type 2 diabetes, Klonoff pointed out in an interview.
“The article by Zhu et al. did not look at outcomes of hospitalized COVID-19 patients with uncontrolled hyperglycemia. Per [the U.S. study], in COVID-19 stress hyperglycemia, compared to diabetes, was associated with greater mortality.”
In addition, although international guidance now advises optimizing blood glucose levels in all patients with hyperglycemia and COVID-19, it’s actually not yet totally clear which in-target range improves COVID-19 prognosis the best, Dr. Klonoff said.
He is now working on a study aimed at answering that question.
The researchers have disclosed no relevant financial relationships. Dr. Klonoff is a consultant to Abbott, Ascensia, Dexcom, EOFlow, Fractyl, Lifecare, Novo, Roche, and ThirdWayv.
A version of this article originally appeared on Medscape.com.
The strong link between glucose control and COVID-19 outcomes has been reaffirmed in the largest study thus far of hospitalized patients with preexisting type 2 diabetes.
The retrospective, multicenter study, from 7,337 hospitalized patients with COVID-19, was published online in Cell Metabolism by Lihua Zhu, Renmin Hospital of Wuhan University, China, and colleagues.
The study finds that, while the presence of type 2 diabetes per se is a risk factor for worse COVID-19 outcomes, better glycemic control among those with preexisting type 2 diabetes appears to be associated with significant reductions in adverse outcomes and death.
“We were surprised to see such favorable outcomes in the well-controlled blood glucose group among patients with COVID-19 and preexisting type 2 diabetes,” senior author Hongliang Li, also of Renmin Hospital, said in a statement.
“Considering that people with diabetes had much higher risk for death and various complications, and there are no specific drugs for COVID-19, our findings indicate that controlling blood glucose well may act as an effective auxiliary approach to improve the prognosis of patients with COVID-19 and preexisting diabetes,” Dr. Li added.
Asked to comment on the findings, David Klonoff, MD, medical director of the Diabetes Research Institute at Mills–Peninsula Medical Center, San Mateo, Calif., cautioned that the way in which the “well-controlled” diabetes group was distinguished from the “poorly controlled” one in this study used a “nonstandard method for distinguishing these groups based on variability.”
So “there was a great deal of overlap between the two groups,” he observed.
Diabetes itself was associated with worse COVID-19 outcomes
Of the 7,337 participants with confirmed COVID-19 in the Chinese study, 13% (952) had preexisting type 2 diabetes while the other 6,385 did not have diabetes.
Median ages were 62 years for those with and 53 years for those without diabetes. As has been reported several times since the pandemic began, the presence of diabetes was associated with a worse COVID-19 prognosis.
Those with preexisting diabetes received significantly more antibiotics, antifungals, systemic corticosteroids, immunoglobulin, antihypertensive drugs, and vasoactive drugs than did those without diabetes. They were also more likely to receive oxygen inhalation (76.9% vs. 61.2%), noninvasive ventilation (10.2% vs. 3.9%), and invasive ventilation (3.6% vs. 0.7%).
Over 28 days starting with the day of admission, the type 2 diabetes group was significantly more likely to die compared with those without diabetes (7.8% vs. 2.7%; P < .001), with a crude hazard ratio of 2.90 (P < .001). After adjustments for age, gender, and COVID-19 severity, the diabetes group was still significantly more likely to die, with a hazard ratio of 1.49 (P = .005).
Those with diabetes were also significantly more likely to develop acute respiratory distress syndrome (adjusted hazard ratio, 1.44), acute kidney injury (3.01), and septic shock (1.95).
“The results were unequivocal to implicate diabetes mellitus in higher risk of death and other detrimental outcomes of COVID-19,” the authors wrote, although they caution “there were notable differences in the covariate distributions between the two groups.”
With T2D, tighter glycemic control predicted better outcome
Among the 952 with COVID-19 and type 2 diabetes, 282 individuals had “well-controlled” blood glucose, ranging from 3.9 to 10.0 mmol/L (~70 - 180 mg/dL) with median 6.4 mmol/L (115 mg/dL) and hemoglobin A1c of 7.3%.
The other 528 were “poorly controlled,” defined as the lowest fasting glucose level 3.9 mmol/L or above and the highest 2-hour postprandial glucose exceeding 10.0 mmol/L, with median 10.9 mmol/L (196 mg/dL) and HbA1c of 8.1%.
Just as with the diabetes vs. no diabetes comparison, those in the “well-controlled” blood glucose group had lower use of antivirals, antibiotics, antifungals, systemic corticosteroids, immunoglobulin, and vasoactive drugs.
They also were less likely to require oxygen inhalation (70.2% vs. 83.5%), non-invasive ventilation (4.6% vs. 11.9%), invasive ventilation (0% vs. 4.2%), and extracorporeal membrane oxygenation (0% vs. 0.8%).
In-hospital death was significantly lower in the “well-controlled” group (1.1% vs. 11.0%; crude hazard ratio, 0.09; P < .001). After adjustments for the previous factors plus site effect, the difference remained significant (0.13; P < .001). Adjusted hazard ratio for acute respiratory distress syndrome was 0.41 (P < .001) and for acute heart injury it was 0.21 (P = .003).
Stress hyperglycemia in COVID-19 associated with greater mortality
Klonoff was senior author on a previous study from the United States that showed that both diabetes and uncontrolled hyperglycemia among people without prior diabetes – the latter “presumably due to stress,” he said – were strong predictors of mortality among hospitalized patients with COVID-19.
The new Chinese research only looks at individuals with previously diagnosed type 2 diabetes, Klonoff pointed out in an interview.
“The article by Zhu et al. did not look at outcomes of hospitalized COVID-19 patients with uncontrolled hyperglycemia. Per [the U.S. study], in COVID-19 stress hyperglycemia, compared to diabetes, was associated with greater mortality.”
In addition, although international guidance now advises optimizing blood glucose levels in all patients with hyperglycemia and COVID-19, it’s actually not yet totally clear which in-target range improves COVID-19 prognosis the best, Dr. Klonoff said.
He is now working on a study aimed at answering that question.
The researchers have disclosed no relevant financial relationships. Dr. Klonoff is a consultant to Abbott, Ascensia, Dexcom, EOFlow, Fractyl, Lifecare, Novo, Roche, and ThirdWayv.
A version of this article originally appeared on Medscape.com.
The strong link between glucose control and COVID-19 outcomes has been reaffirmed in the largest study thus far of hospitalized patients with preexisting type 2 diabetes.
The retrospective, multicenter study, from 7,337 hospitalized patients with COVID-19, was published online in Cell Metabolism by Lihua Zhu, Renmin Hospital of Wuhan University, China, and colleagues.
The study finds that, while the presence of type 2 diabetes per se is a risk factor for worse COVID-19 outcomes, better glycemic control among those with preexisting type 2 diabetes appears to be associated with significant reductions in adverse outcomes and death.
“We were surprised to see such favorable outcomes in the well-controlled blood glucose group among patients with COVID-19 and preexisting type 2 diabetes,” senior author Hongliang Li, also of Renmin Hospital, said in a statement.
“Considering that people with diabetes had much higher risk for death and various complications, and there are no specific drugs for COVID-19, our findings indicate that controlling blood glucose well may act as an effective auxiliary approach to improve the prognosis of patients with COVID-19 and preexisting diabetes,” Dr. Li added.
Asked to comment on the findings, David Klonoff, MD, medical director of the Diabetes Research Institute at Mills–Peninsula Medical Center, San Mateo, Calif., cautioned that the way in which the “well-controlled” diabetes group was distinguished from the “poorly controlled” one in this study used a “nonstandard method for distinguishing these groups based on variability.”
So “there was a great deal of overlap between the two groups,” he observed.
Diabetes itself was associated with worse COVID-19 outcomes
Of the 7,337 participants with confirmed COVID-19 in the Chinese study, 13% (952) had preexisting type 2 diabetes while the other 6,385 did not have diabetes.
Median ages were 62 years for those with and 53 years for those without diabetes. As has been reported several times since the pandemic began, the presence of diabetes was associated with a worse COVID-19 prognosis.
Those with preexisting diabetes received significantly more antibiotics, antifungals, systemic corticosteroids, immunoglobulin, antihypertensive drugs, and vasoactive drugs than did those without diabetes. They were also more likely to receive oxygen inhalation (76.9% vs. 61.2%), noninvasive ventilation (10.2% vs. 3.9%), and invasive ventilation (3.6% vs. 0.7%).
Over 28 days starting with the day of admission, the type 2 diabetes group was significantly more likely to die compared with those without diabetes (7.8% vs. 2.7%; P < .001), with a crude hazard ratio of 2.90 (P < .001). After adjustments for age, gender, and COVID-19 severity, the diabetes group was still significantly more likely to die, with a hazard ratio of 1.49 (P = .005).
Those with diabetes were also significantly more likely to develop acute respiratory distress syndrome (adjusted hazard ratio, 1.44), acute kidney injury (3.01), and septic shock (1.95).
“The results were unequivocal to implicate diabetes mellitus in higher risk of death and other detrimental outcomes of COVID-19,” the authors wrote, although they caution “there were notable differences in the covariate distributions between the two groups.”
With T2D, tighter glycemic control predicted better outcome
Among the 952 with COVID-19 and type 2 diabetes, 282 individuals had “well-controlled” blood glucose, ranging from 3.9 to 10.0 mmol/L (~70 - 180 mg/dL) with median 6.4 mmol/L (115 mg/dL) and hemoglobin A1c of 7.3%.
The other 528 were “poorly controlled,” defined as the lowest fasting glucose level 3.9 mmol/L or above and the highest 2-hour postprandial glucose exceeding 10.0 mmol/L, with median 10.9 mmol/L (196 mg/dL) and HbA1c of 8.1%.
Just as with the diabetes vs. no diabetes comparison, those in the “well-controlled” blood glucose group had lower use of antivirals, antibiotics, antifungals, systemic corticosteroids, immunoglobulin, and vasoactive drugs.
They also were less likely to require oxygen inhalation (70.2% vs. 83.5%), non-invasive ventilation (4.6% vs. 11.9%), invasive ventilation (0% vs. 4.2%), and extracorporeal membrane oxygenation (0% vs. 0.8%).
In-hospital death was significantly lower in the “well-controlled” group (1.1% vs. 11.0%; crude hazard ratio, 0.09; P < .001). After adjustments for the previous factors plus site effect, the difference remained significant (0.13; P < .001). Adjusted hazard ratio for acute respiratory distress syndrome was 0.41 (P < .001) and for acute heart injury it was 0.21 (P = .003).
Stress hyperglycemia in COVID-19 associated with greater mortality
Klonoff was senior author on a previous study from the United States that showed that both diabetes and uncontrolled hyperglycemia among people without prior diabetes – the latter “presumably due to stress,” he said – were strong predictors of mortality among hospitalized patients with COVID-19.
The new Chinese research only looks at individuals with previously diagnosed type 2 diabetes, Klonoff pointed out in an interview.
“The article by Zhu et al. did not look at outcomes of hospitalized COVID-19 patients with uncontrolled hyperglycemia. Per [the U.S. study], in COVID-19 stress hyperglycemia, compared to diabetes, was associated with greater mortality.”
In addition, although international guidance now advises optimizing blood glucose levels in all patients with hyperglycemia and COVID-19, it’s actually not yet totally clear which in-target range improves COVID-19 prognosis the best, Dr. Klonoff said.
He is now working on a study aimed at answering that question.
The researchers have disclosed no relevant financial relationships. Dr. Klonoff is a consultant to Abbott, Ascensia, Dexcom, EOFlow, Fractyl, Lifecare, Novo, Roche, and ThirdWayv.
A version of this article originally appeared on Medscape.com.
Health care costs nearly doubled for patients with NAFLD
The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.
Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.
The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.
Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.
Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.
“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”
They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.
The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.
SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.
The possibility of FDA approval of NASH-modifying drugs later this year brings the hope of improving outcomes for patients with NAFLD. Inevitably, the cost effectiveness of those drugs also will be scrutinized as we evaluate their impact in the coming years. To that end, Hagstrom et al. provide useful insight regarding the real-world costs of medical care among patients with histologically staged NAFLD in Sweden.
Their main finding is that medical costs for a patient with NAFLD over 20 years is double that for a random control patient from the general population.
It is worth taking a deeper dive into the factors that drove the cost differential. First, higher inpatient and outpatient specialty care costs accounted for the incremental cost of NAFLD care; drug costs were materially similar in the two groups, albeit examined over a very short time period in the study due to limited national registry data. Second, the cost differential was largest in the first year of diagnosis and attributed to the cost of liver biopsy and related expenses. Last, as one would expect, the cost differential was largest between patients who had stage 3-4 fibrosis, possibly explained by the costs of NASH-related complications.
While we hope that NASH-modifying drugs will reduce the risk of liver-specific complications, the cumulative financial impact of such therapies remains to be seen. On the one hand, short-term costs may increase because of the direct expense of the NASH-modifying drugs plus additional expenses related to management of side effects. In addition, it is likely patients treated with NASH-modifying drugs will need more frequent assessments of liver disease severity to evaluate whether the medication is working, which even if done noninvasively, is likely the add to medical costs. In the long term however, NASH-modifying treatments may reduce the risk of NAFLD complications over time, mitigating the cumulative cost of NAFLD care. The true net effect remains to be seen. In the meantime, we need further studies that quantify costs of NAFLD care - ideally by disease severity and that provide greater insight into the cost of caring for the complications of NASH progression, including liver disease clinical decompensations and transplant.
Maya Balakrishnan, MD, MPH, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, Houston, and director of hepatology at Ben Taub General Hospital, Houston. She has no conflicts of interest.
The possibility of FDA approval of NASH-modifying drugs later this year brings the hope of improving outcomes for patients with NAFLD. Inevitably, the cost effectiveness of those drugs also will be scrutinized as we evaluate their impact in the coming years. To that end, Hagstrom et al. provide useful insight regarding the real-world costs of medical care among patients with histologically staged NAFLD in Sweden.
Their main finding is that medical costs for a patient with NAFLD over 20 years is double that for a random control patient from the general population.
It is worth taking a deeper dive into the factors that drove the cost differential. First, higher inpatient and outpatient specialty care costs accounted for the incremental cost of NAFLD care; drug costs were materially similar in the two groups, albeit examined over a very short time period in the study due to limited national registry data. Second, the cost differential was largest in the first year of diagnosis and attributed to the cost of liver biopsy and related expenses. Last, as one would expect, the cost differential was largest between patients who had stage 3-4 fibrosis, possibly explained by the costs of NASH-related complications.
While we hope that NASH-modifying drugs will reduce the risk of liver-specific complications, the cumulative financial impact of such therapies remains to be seen. On the one hand, short-term costs may increase because of the direct expense of the NASH-modifying drugs plus additional expenses related to management of side effects. In addition, it is likely patients treated with NASH-modifying drugs will need more frequent assessments of liver disease severity to evaluate whether the medication is working, which even if done noninvasively, is likely the add to medical costs. In the long term however, NASH-modifying treatments may reduce the risk of NAFLD complications over time, mitigating the cumulative cost of NAFLD care. The true net effect remains to be seen. In the meantime, we need further studies that quantify costs of NAFLD care - ideally by disease severity and that provide greater insight into the cost of caring for the complications of NASH progression, including liver disease clinical decompensations and transplant.
Maya Balakrishnan, MD, MPH, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, Houston, and director of hepatology at Ben Taub General Hospital, Houston. She has no conflicts of interest.
The possibility of FDA approval of NASH-modifying drugs later this year brings the hope of improving outcomes for patients with NAFLD. Inevitably, the cost effectiveness of those drugs also will be scrutinized as we evaluate their impact in the coming years. To that end, Hagstrom et al. provide useful insight regarding the real-world costs of medical care among patients with histologically staged NAFLD in Sweden.
Their main finding is that medical costs for a patient with NAFLD over 20 years is double that for a random control patient from the general population.
It is worth taking a deeper dive into the factors that drove the cost differential. First, higher inpatient and outpatient specialty care costs accounted for the incremental cost of NAFLD care; drug costs were materially similar in the two groups, albeit examined over a very short time period in the study due to limited national registry data. Second, the cost differential was largest in the first year of diagnosis and attributed to the cost of liver biopsy and related expenses. Last, as one would expect, the cost differential was largest between patients who had stage 3-4 fibrosis, possibly explained by the costs of NASH-related complications.
While we hope that NASH-modifying drugs will reduce the risk of liver-specific complications, the cumulative financial impact of such therapies remains to be seen. On the one hand, short-term costs may increase because of the direct expense of the NASH-modifying drugs plus additional expenses related to management of side effects. In addition, it is likely patients treated with NASH-modifying drugs will need more frequent assessments of liver disease severity to evaluate whether the medication is working, which even if done noninvasively, is likely the add to medical costs. In the long term however, NASH-modifying treatments may reduce the risk of NAFLD complications over time, mitigating the cumulative cost of NAFLD care. The true net effect remains to be seen. In the meantime, we need further studies that quantify costs of NAFLD care - ideally by disease severity and that provide greater insight into the cost of caring for the complications of NASH progression, including liver disease clinical decompensations and transplant.
Maya Balakrishnan, MD, MPH, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, Houston, and director of hepatology at Ben Taub General Hospital, Houston. She has no conflicts of interest.
The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.
Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.
The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.
Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.
Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.
“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”
They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.
The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.
SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.
The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.
Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.
The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.
Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.
Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.
“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”
They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.
The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.
SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Adolescent obesity, diabetes linked to atherosclerotic signs
significantly greater than their normal-weight peers, according to a longitudinal study published online in the Journal of the American Heart Association.
The study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.
“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.
The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.
Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.
The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.
Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.
“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.
The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.
“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”
The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”
The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”
They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”
Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.
SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.
significantly greater than their normal-weight peers, according to a longitudinal study published online in the Journal of the American Heart Association.
The study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.
“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.
The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.
Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.
The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.
Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.
“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.
The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.
“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”
The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”
The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”
They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”
Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.
SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.
significantly greater than their normal-weight peers, according to a longitudinal study published online in the Journal of the American Heart Association.
The study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.
“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.
The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.
Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.
The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.
Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.
“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.
The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.
“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”
The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”
The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”
They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”
Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.
SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
More guidance on inpatient management of blood glucose in COVID-19
“The glycemic management of many COVID-19–positive patients with diabetes is proving extremely complex, with huge fluctuations in glucose control and the need for very high doses of insulin,” says Diabetes UK’s National Diabetes Inpatient COVID Response Team.
“Intravenous infusion pumps, also required for inotropes, are at a premium and there may be the need to consider the use of subcutaneous or intramuscular insulin protocols,” they note.
Updated as of April 29, all of the information of the National Diabetes Inpatient COVID Response Team is available on the Diabetes UK website.
The new inpatient management graphic adds more detail to the previous “front-door” guidance, as reported by Medscape Medical News.
The document stressed that, as well as identifying patients with known diabetes, it is imperative that all newly admitted patients with COVID-19 are evaluated for diabetes, as the infection is known to cause new-onset diabetes.
Subcutaneous insulin dosing
The new graphic gives extensive details on subcutaneous insulin dosing in place of variable rate intravenous insulin when infusion pumps are not available, and when the patient has a glucose level above 12 mmol/L (216 mg/dL) but does not have DKA or hyperosmolar hyperglycemic state.
However, the advice is not intended for people with COVID-19 causing severe insulin resistance in the intensive care unit.
The other new guidance graphic on managing DKA or hyperosmolar state in people with COVID-19 using subcutaneous insulin is also intended for situations where intravenous infusion isn’t available.
Seek help from specialist diabetes team when needed
This is not to be used for mixed DKA/hyperosmolar state or for patients who are pregnant, have severe metabolic derangement, other significant comorbidity, or impaired consciousness, however.
For those situations, the advice is to seek help from a specialist diabetes team, says Diabetes UK.
Specialist teams will be available to answer diabetes queries, both by signposting to relevant existing local documents and also by providing patient-specific advice.
Indeed, NHS England recommends that such a team be available in every hospital, with a lead consultant designated each day to co-ordinate these services who must be free of other clinical duties when doing so. The role involves co-ordination of the whole service from the emergency department through to liaison with other specialties and managers.
Also newly updated is a page with extensive information for patients, including advice for staying at home, medication use, self-isolating, shielding, hospital and doctor appointments, need for urgent medical advice, and going to the hospital.
It also covers how coronavirus can affect people with diabetes, children and school, pregnancy, work situations, and tips for picking up prescriptions.
Another, shorter document with COVID-19 advice for patients has been posted by the JDRF and Beyond Type 1 Alliance.
It has also been endorsed by the American Diabetes Association, Harvard Medical School, and International Society for Pediatric and Adolescent Diabetes, in partnership with many other professional organizations, including the International Diabetes Federation, American Association of Clinical Endocrinologists, and Association of Diabetes Care & Education Specialists.
The shorter document covers topics such as personal hygiene, distancing, diabetes management, and seeking treatment, as well as links to other resources on what to do when health insurance is lost and legal rights.
This article first appeared on Medscape.com.
“The glycemic management of many COVID-19–positive patients with diabetes is proving extremely complex, with huge fluctuations in glucose control and the need for very high doses of insulin,” says Diabetes UK’s National Diabetes Inpatient COVID Response Team.
“Intravenous infusion pumps, also required for inotropes, are at a premium and there may be the need to consider the use of subcutaneous or intramuscular insulin protocols,” they note.
Updated as of April 29, all of the information of the National Diabetes Inpatient COVID Response Team is available on the Diabetes UK website.
The new inpatient management graphic adds more detail to the previous “front-door” guidance, as reported by Medscape Medical News.
The document stressed that, as well as identifying patients with known diabetes, it is imperative that all newly admitted patients with COVID-19 are evaluated for diabetes, as the infection is known to cause new-onset diabetes.
Subcutaneous insulin dosing
The new graphic gives extensive details on subcutaneous insulin dosing in place of variable rate intravenous insulin when infusion pumps are not available, and when the patient has a glucose level above 12 mmol/L (216 mg/dL) but does not have DKA or hyperosmolar hyperglycemic state.
However, the advice is not intended for people with COVID-19 causing severe insulin resistance in the intensive care unit.
The other new guidance graphic on managing DKA or hyperosmolar state in people with COVID-19 using subcutaneous insulin is also intended for situations where intravenous infusion isn’t available.
Seek help from specialist diabetes team when needed
This is not to be used for mixed DKA/hyperosmolar state or for patients who are pregnant, have severe metabolic derangement, other significant comorbidity, or impaired consciousness, however.
For those situations, the advice is to seek help from a specialist diabetes team, says Diabetes UK.
Specialist teams will be available to answer diabetes queries, both by signposting to relevant existing local documents and also by providing patient-specific advice.
Indeed, NHS England recommends that such a team be available in every hospital, with a lead consultant designated each day to co-ordinate these services who must be free of other clinical duties when doing so. The role involves co-ordination of the whole service from the emergency department through to liaison with other specialties and managers.
Also newly updated is a page with extensive information for patients, including advice for staying at home, medication use, self-isolating, shielding, hospital and doctor appointments, need for urgent medical advice, and going to the hospital.
It also covers how coronavirus can affect people with diabetes, children and school, pregnancy, work situations, and tips for picking up prescriptions.
Another, shorter document with COVID-19 advice for patients has been posted by the JDRF and Beyond Type 1 Alliance.
It has also been endorsed by the American Diabetes Association, Harvard Medical School, and International Society for Pediatric and Adolescent Diabetes, in partnership with many other professional organizations, including the International Diabetes Federation, American Association of Clinical Endocrinologists, and Association of Diabetes Care & Education Specialists.
The shorter document covers topics such as personal hygiene, distancing, diabetes management, and seeking treatment, as well as links to other resources on what to do when health insurance is lost and legal rights.
This article first appeared on Medscape.com.
“The glycemic management of many COVID-19–positive patients with diabetes is proving extremely complex, with huge fluctuations in glucose control and the need for very high doses of insulin,” says Diabetes UK’s National Diabetes Inpatient COVID Response Team.
“Intravenous infusion pumps, also required for inotropes, are at a premium and there may be the need to consider the use of subcutaneous or intramuscular insulin protocols,” they note.
Updated as of April 29, all of the information of the National Diabetes Inpatient COVID Response Team is available on the Diabetes UK website.
The new inpatient management graphic adds more detail to the previous “front-door” guidance, as reported by Medscape Medical News.
The document stressed that, as well as identifying patients with known diabetes, it is imperative that all newly admitted patients with COVID-19 are evaluated for diabetes, as the infection is known to cause new-onset diabetes.
Subcutaneous insulin dosing
The new graphic gives extensive details on subcutaneous insulin dosing in place of variable rate intravenous insulin when infusion pumps are not available, and when the patient has a glucose level above 12 mmol/L (216 mg/dL) but does not have DKA or hyperosmolar hyperglycemic state.
However, the advice is not intended for people with COVID-19 causing severe insulin resistance in the intensive care unit.
The other new guidance graphic on managing DKA or hyperosmolar state in people with COVID-19 using subcutaneous insulin is also intended for situations where intravenous infusion isn’t available.
Seek help from specialist diabetes team when needed
This is not to be used for mixed DKA/hyperosmolar state or for patients who are pregnant, have severe metabolic derangement, other significant comorbidity, or impaired consciousness, however.
For those situations, the advice is to seek help from a specialist diabetes team, says Diabetes UK.
Specialist teams will be available to answer diabetes queries, both by signposting to relevant existing local documents and also by providing patient-specific advice.
Indeed, NHS England recommends that such a team be available in every hospital, with a lead consultant designated each day to co-ordinate these services who must be free of other clinical duties when doing so. The role involves co-ordination of the whole service from the emergency department through to liaison with other specialties and managers.
Also newly updated is a page with extensive information for patients, including advice for staying at home, medication use, self-isolating, shielding, hospital and doctor appointments, need for urgent medical advice, and going to the hospital.
It also covers how coronavirus can affect people with diabetes, children and school, pregnancy, work situations, and tips for picking up prescriptions.
Another, shorter document with COVID-19 advice for patients has been posted by the JDRF and Beyond Type 1 Alliance.
It has also been endorsed by the American Diabetes Association, Harvard Medical School, and International Society for Pediatric and Adolescent Diabetes, in partnership with many other professional organizations, including the International Diabetes Federation, American Association of Clinical Endocrinologists, and Association of Diabetes Care & Education Specialists.
The shorter document covers topics such as personal hygiene, distancing, diabetes management, and seeking treatment, as well as links to other resources on what to do when health insurance is lost and legal rights.
This article first appeared on Medscape.com.