Diabetes

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 A_1c (HbA_1c) 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: HbA_1c 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 HbA_1c 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 HbA_1c 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 A_1c (HbA_1c) 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: HbA_1c 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 HbA_1c 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 HbA_1c 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 A_1c (HbA_1c) 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: HbA_1c 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 HbA_1c 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 HbA_1c 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.

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.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. 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.

[email protected]

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.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. 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.

[email protected]

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.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. 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.

[email protected]

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 A_1c 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 HbA_1c 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 A_1c 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 HbA_1c 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 A_1c 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 HbA_1c 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 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.

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.

Adolescents with obesity, type 2 diabetes, and systolic hypertension show accelerated development of signs of atherosclerosis 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.

Adolescents with obesity, type 2 diabetes, and systolic hypertension show accelerated development of signs of atherosclerosis 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.

Adolescents with obesity, type 2 diabetes, and systolic hypertension show accelerated development of signs of atherosclerosis 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.

New guidance is available for managing inpatient hyperglycemia and diabetic ketoacidosis (DKA) in COVID-19 patients with diabetes using subcutaneous insulin.

“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.

New guidance is available for managing inpatient hyperglycemia and diabetic ketoacidosis (DKA) in COVID-19 patients with diabetes using subcutaneous insulin.

“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.

New guidance is available for managing inpatient hyperglycemia and diabetic ketoacidosis (DKA) in COVID-19 patients with diabetes using subcutaneous insulin.

“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 Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

[email protected]

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

[email protected]

The sodium-glucose transporter 2 (SGLT-2) inhibitor ertugliflozin broke ranks with the other drugs in its class and failed to produce statistically significant drops in the both the combined incidence of cardiovascular (CV) death or heart failure hospitalization, and the rate of adverse renal outcomes, in the mandated CV outcomes trial run for ertugliflozin with more than 8,200 patients with type 2 diabetes and established CV disease.

Merck, one of the companies that markets the drug, announced the topline results in a quarterly financial report released on April 28, 2020.

According to the report, the results from the ertugliflozin cardiovascular outcomes trial “achieved its primary endpoint of noninferiority for major adverse CV events (MACE), compared to placebo in patients with type 2 diabetes mellitus and established atherosclerotic CV disease,” but “the key secondary endpoints of superiority” of ertugliflozin, compared with placebo, “for time to the composite of CV death or hospitalization for heart failure, CV death alone, and the composite of renal death, dialysis/transplant or doubling of serum creatinine from baseline were not met.”

However, the report added that, “while not a prespecified hypothesis for statistical testing, a reduction in hospitalization for heart failure was observed” with ertugliflozin treatment, and the report further said that the drug’s safety profile in the trial “was consistent with that reported in previous studies.” The statement closed by saying that detailed results from the trial are scheduled to be presented on June 16, 2020, at the virtual American Diabetes Association’s 80th Scientific Sessions.

These results came from the VERTIS CV (Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes) trial, which researchers said in 2018 had administered at least one investigational dose to 8,238 randomized patients at centers in any of 34 countries during two enrollment periods in 2013-2015 and 2016-2017 (Am Heart J. 2018 Dec;206:11-23). The tested agent, ertugliflozin (Steglatro) received Food and Drug Administration marketing approval late in 2017 for the indication of improving glycemic control in patients with type 2 diabetes.

The FDA mandated cardiovascular outcomes trials for new glycemic control drugs in guidance the agency issued in 2008 (the FDA released in March 2020 a draft of updated guidance on this topic).

Other FDA-approved agents from the SGLT2 inhibitor class include canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance), and all three showed evidence for a statistically significant effect on reducing the incidence of CV disease death and heart failure hospitalizations, as well as renal complications (Can J Diabetes. 2020 Feb;44[1]:61-7). The evidence showing that several SGLT2 drugs have important and consistent effects on endpoints like CV death, heart failure hospitalizations, and renal complications has helped propel this class of agents to the forefront of glycemic control treatments. More recently, one agent from this group, dapagliflozin, also significantly cut the rate of heart failure worsening or CV disease death in patients with heart failure with reduced ejection fraction but without diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). Based on this evidence, the FDA is currently considering adding a new indication for dapagliflozin that would also label it for use in patients with heart failure with reduced ejection fraction but without diabetes.

[email protected]

Hypersomnolence, or excessive daytime sleepiness, in older adults is a risk factor for developing several serious medical conditions, including hypertension, heart disease, cancer, and diabetes, new research suggests. A study of almost 11,000 participants shows those who reported excessive sleepiness were twice as likely as their nonsleepy counterparts to develop these conditions. Hypersomnolence was also linked to development of musculoskeletal and connective tissue conditions.

“Paying attention to sleepiness in older adults could help doctors predict and prevent future medical conditions,” study investigator Maurice M. Ohayon, MD, PhD, Stanford University, California, said in a news release.

The findings were released March 1 ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology. The AAN canceled the meeting and released abstracts and access to presenters for press coverage.
 

Early warning sign

Prior research has suggested an association between hypersomnolence and several psychiatric disorders, as well as cognitive decline and Alzheimer’s disease. However, its role in the development of other medical conditions is not as well studied.

The current investigation included 10,930 adults who were interviewed by phone on two separate occasions 3 years apart. At the second interview, 3,701 participants were at least 65 years old and 59% were women.

About 23% of the elderly participants reported hypersomnolence in the first interview and 24% reported it in the second interview. Of these individuals, 41% said during the first and second interviews that excessive daytime sleepiness was a chronic problem.

After adjusting for gender and obstructive sleep apnea status, participants who reported hypersomnolence in the first interview had more than a twofold greater risk of developing diabetes (relative risk [RR], 2.3; 95% CI, 1.5 - 3.4) or hypertension (RR, 2.3; 95% CI, 1.5 - 3.4) 3 years later than those who did not report this problem. They were also twice as likely to develop cancer (RR, 2.0; 95% CI, 1.1 - 3.8).

Of the 840 participants who reported hypersomnolence at the first interview, 52 (6.2%) developed diabetes compared with 74 (2.9%) who did not have excessive daytime sleepiness. Twenty (2.4%) individuals who reported hypersomnolence developed cancer compared with 21 (0.8%) who did not have it. Chronic hypersomnolence was associated with a greater than twofold increased risk of developing heart disease (RR, 2.5; 95% CI, 1.8 - 3.4).

Those who reported hypersomnolence at the second interview also were 50% more likely to have diseases of the musculoskeletal system and connective tissue, such as arthritis, tendinitis, and lupus, than their peers who did not have excessive daytime sleepiness.

The findings suggest that hypersomnolence in the elderly “can be an early sign of a developing medical condition,” the investigators wrote.

A limitation of the study is that it relied on participants’ memories rather than monitoring their sleep length and quality and daytime sleepiness in a sleep clinic, they noted.

Sleep as a vital sign?

Commenting on the findings, Harly Greenberg, MD, medical director at the Northwell Health Sleep Disorders Center, New York City, called the study “informative.”

However, because the findings were associations, “the study does not necessarily indicate that hypersomnolence itself is causal for these conditions. Rather excessive sleepiness may be a marker of sleep disorders that can cause sleepiness as well as contribute to the risk of these medical conditions,” said Dr. Greenberg, who was not involved with the research.

“The takeaway point from this study is that excessive sleepiness should not be ignored. Not only does it impair quality of life, daytime function, and vigilance and increase risk of sleepiness-related accidents, it may also be a marker for serious sleep disorders that can increase risk for medical disorders,” he said.

Also commenting on the study, Nathaniel Watson, MD, professor of neurology at the University of Washington (UW) and director of the UW Medicine Sleep Clinic, said it is “not surprising” that excessive daytime sleepiness might contribute to diabetes, hypertension, and other diseases.

“Sleep is something we spend a third of our lives doing. It impacts nearly every aspect of human physiology and we have a lot of basic science and epidemiologic research that shows when sleep is either inadequate or of poor quality or not timed correctly it can be associated with some of these untoward health outcomes,” said Watson, who is a past president of the American Academy of Sleep Medicine.

“This research just provides further evidence in support of the importance of sleep for overall health and well-being,” he added.

Asking patients about sleepiness, sleep, or sleep quality should be a “vital sign just like temperature, blood pressure, weight, and these other measures,” Dr. Watson said.

The study was supported by the Arrillaga Foundation. Drs. Ohayon, Greenberg, and Watson have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Hypersomnolence, or excessive daytime sleepiness, in older adults is a risk factor for developing several serious medical conditions, including hypertension, heart disease, cancer, and diabetes, new research suggests. A study of almost 11,000 participants shows those who reported excessive sleepiness were twice as likely as their nonsleepy counterparts to develop these conditions. Hypersomnolence was also linked to development of musculoskeletal and connective tissue conditions.

“Paying attention to sleepiness in older adults could help doctors predict and prevent future medical conditions,” study investigator Maurice M. Ohayon, MD, PhD, Stanford University, California, said in a news release.

The findings were released March 1 ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology. The AAN canceled the meeting and released abstracts and access to presenters for press coverage.
 

Early warning sign

Prior research has suggested an association between hypersomnolence and several psychiatric disorders, as well as cognitive decline and Alzheimer’s disease. However, its role in the development of other medical conditions is not as well studied.

The current investigation included 10,930 adults who were interviewed by phone on two separate occasions 3 years apart. At the second interview, 3,701 participants were at least 65 years old and 59% were women.

About 23% of the elderly participants reported hypersomnolence in the first interview and 24% reported it in the second interview. Of these individuals, 41% said during the first and second interviews that excessive daytime sleepiness was a chronic problem.

After adjusting for gender and obstructive sleep apnea status, participants who reported hypersomnolence in the first interview had more than a twofold greater risk of developing diabetes (relative risk [RR], 2.3; 95% CI, 1.5 - 3.4) or hypertension (RR, 2.3; 95% CI, 1.5 - 3.4) 3 years later than those who did not report this problem. They were also twice as likely to develop cancer (RR, 2.0; 95% CI, 1.1 - 3.8).

Of the 840 participants who reported hypersomnolence at the first interview, 52 (6.2%) developed diabetes compared with 74 (2.9%) who did not have excessive daytime sleepiness. Twenty (2.4%) individuals who reported hypersomnolence developed cancer compared with 21 (0.8%) who did not have it. Chronic hypersomnolence was associated with a greater than twofold increased risk of developing heart disease (RR, 2.5; 95% CI, 1.8 - 3.4).

Those who reported hypersomnolence at the second interview also were 50% more likely to have diseases of the musculoskeletal system and connective tissue, such as arthritis, tendinitis, and lupus, than their peers who did not have excessive daytime sleepiness.

The findings suggest that hypersomnolence in the elderly “can be an early sign of a developing medical condition,” the investigators wrote.

A limitation of the study is that it relied on participants’ memories rather than monitoring their sleep length and quality and daytime sleepiness in a sleep clinic, they noted.

Sleep as a vital sign?

Commenting on the findings, Harly Greenberg, MD, medical director at the Northwell Health Sleep Disorders Center, New York City, called the study “informative.”

However, because the findings were associations, “the study does not necessarily indicate that hypersomnolence itself is causal for these conditions. Rather excessive sleepiness may be a marker of sleep disorders that can cause sleepiness as well as contribute to the risk of these medical conditions,” said Dr. Greenberg, who was not involved with the research.

“The takeaway point from this study is that excessive sleepiness should not be ignored. Not only does it impair quality of life, daytime function, and vigilance and increase risk of sleepiness-related accidents, it may also be a marker for serious sleep disorders that can increase risk for medical disorders,” he said.

Also commenting on the study, Nathaniel Watson, MD, professor of neurology at the University of Washington (UW) and director of the UW Medicine Sleep Clinic, said it is “not surprising” that excessive daytime sleepiness might contribute to diabetes, hypertension, and other diseases.

“Sleep is something we spend a third of our lives doing. It impacts nearly every aspect of human physiology and we have a lot of basic science and epidemiologic research that shows when sleep is either inadequate or of poor quality or not timed correctly it can be associated with some of these untoward health outcomes,” said Watson, who is a past president of the American Academy of Sleep Medicine.

“This research just provides further evidence in support of the importance of sleep for overall health and well-being,” he added.

Asking patients about sleepiness, sleep, or sleep quality should be a “vital sign just like temperature, blood pressure, weight, and these other measures,” Dr. Watson said.

The study was supported by the Arrillaga Foundation. Drs. Ohayon, Greenberg, and Watson have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Hypersomnolence, or excessive daytime sleepiness, in older adults is a risk factor for developing several serious medical conditions, including hypertension, heart disease, cancer, and diabetes, new research suggests. A study of almost 11,000 participants shows those who reported excessive sleepiness were twice as likely as their nonsleepy counterparts to develop these conditions. Hypersomnolence was also linked to development of musculoskeletal and connective tissue conditions.

“Paying attention to sleepiness in older adults could help doctors predict and prevent future medical conditions,” study investigator Maurice M. Ohayon, MD, PhD, Stanford University, California, said in a news release.

The findings were released March 1 ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology. The AAN canceled the meeting and released abstracts and access to presenters for press coverage.
 

Early warning sign

Prior research has suggested an association between hypersomnolence and several psychiatric disorders, as well as cognitive decline and Alzheimer’s disease. However, its role in the development of other medical conditions is not as well studied.

The current investigation included 10,930 adults who were interviewed by phone on two separate occasions 3 years apart. At the second interview, 3,701 participants were at least 65 years old and 59% were women.

About 23% of the elderly participants reported hypersomnolence in the first interview and 24% reported it in the second interview. Of these individuals, 41% said during the first and second interviews that excessive daytime sleepiness was a chronic problem.

After adjusting for gender and obstructive sleep apnea status, participants who reported hypersomnolence in the first interview had more than a twofold greater risk of developing diabetes (relative risk [RR], 2.3; 95% CI, 1.5 - 3.4) or hypertension (RR, 2.3; 95% CI, 1.5 - 3.4) 3 years later than those who did not report this problem. They were also twice as likely to develop cancer (RR, 2.0; 95% CI, 1.1 - 3.8).

Of the 840 participants who reported hypersomnolence at the first interview, 52 (6.2%) developed diabetes compared with 74 (2.9%) who did not have excessive daytime sleepiness. Twenty (2.4%) individuals who reported hypersomnolence developed cancer compared with 21 (0.8%) who did not have it. Chronic hypersomnolence was associated with a greater than twofold increased risk of developing heart disease (RR, 2.5; 95% CI, 1.8 - 3.4).

Those who reported hypersomnolence at the second interview also were 50% more likely to have diseases of the musculoskeletal system and connective tissue, such as arthritis, tendinitis, and lupus, than their peers who did not have excessive daytime sleepiness.

The findings suggest that hypersomnolence in the elderly “can be an early sign of a developing medical condition,” the investigators wrote.

A limitation of the study is that it relied on participants’ memories rather than monitoring their sleep length and quality and daytime sleepiness in a sleep clinic, they noted.

Sleep as a vital sign?

Commenting on the findings, Harly Greenberg, MD, medical director at the Northwell Health Sleep Disorders Center, New York City, called the study “informative.”

However, because the findings were associations, “the study does not necessarily indicate that hypersomnolence itself is causal for these conditions. Rather excessive sleepiness may be a marker of sleep disorders that can cause sleepiness as well as contribute to the risk of these medical conditions,” said Dr. Greenberg, who was not involved with the research.

“The takeaway point from this study is that excessive sleepiness should not be ignored. Not only does it impair quality of life, daytime function, and vigilance and increase risk of sleepiness-related accidents, it may also be a marker for serious sleep disorders that can increase risk for medical disorders,” he said.

Also commenting on the study, Nathaniel Watson, MD, professor of neurology at the University of Washington (UW) and director of the UW Medicine Sleep Clinic, said it is “not surprising” that excessive daytime sleepiness might contribute to diabetes, hypertension, and other diseases.

“Sleep is something we spend a third of our lives doing. It impacts nearly every aspect of human physiology and we have a lot of basic science and epidemiologic research that shows when sleep is either inadequate or of poor quality or not timed correctly it can be associated with some of these untoward health outcomes,” said Watson, who is a past president of the American Academy of Sleep Medicine.

“This research just provides further evidence in support of the importance of sleep for overall health and well-being,” he added.

Asking patients about sleepiness, sleep, or sleep quality should be a “vital sign just like temperature, blood pressure, weight, and these other measures,” Dr. Watson said.

The study was supported by the Arrillaga Foundation. Drs. Ohayon, Greenberg, and Watson have reported no relevant financial relationships.

This article first appeared on Medscape.com.