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COVID-19-Related Stress Could Trigger Increased Insulin Resistance, Transient Diabetes

A retrospective review with nearly a year of follow-up indicates nearly 40% of newly diagnosed diabetes at COVID-19 admission regressed to prediabetes or normoglycemia at follow-up, suggesting stress hyperglycemia induced by COVID-19-related acute stress could be driving rates of diagnosis.

A new study from investigators at Massachusetts General Hospital (MGH) suggests elevated rates of newly diagnosed diabetes among patients presenting with COVID-19 may be the result of a transitory condition caused by acute physiological stress.

Based on the results of their retrospective review, investigators purport increased inflammatory markers and lower glucose at admission point to stress hyperglycemia as a major mechanism driving increased rates of new-onset diabetes, with approximately half of these newly diagnosed patients eventually experiencing regression of diabetes.

“Instead of directly causing diabetes, COVID-19 may push patients with pre-existing but undiagnosed diabetes to see a physician for the first time, where their blood sugar disorder can be clinically diagnosed. Our study showed these individuals had higher inflammatory markers and more frequently required admission to hospital ICUs than COVID-19 patients with pre-existing diabetes,” said lead investigator Sara Cromer, MD, an investigator with the Department of Medicine-Endocrinology, Diabetes and Metabolism at MGH, in a statement. “This suggests to us that newly diagnosed diabetes may be a transitory condition related to the acute stress of COVID-19 infection.”

Citing reports detailing increased rates of newly diagnosed diabetes among patients admitted with COVID-19 but a lack of knowledge related to patient characteristics and outcomes among these patients, Cromer and a team of colleagues designed the current study as a retrospective review of patients with COVID-19 and diabetes admitted to MGH from March-September 2020, with follow-up through July 2021. During this period, 1902 individuals were admitted with OCIVD-19 including 594 with diabetes. Of the 594, 77 (13.0%) had newly diagnosed diabetes.

Of the 77 patients admitted with newly diagnosed diabetes, 33 had evidence of prediabetes prior to admission. Of those with preexisting diabetes, the majority (92.8%) had type 2 diabetes, 2.1% had type 1 diabetes, 2.5% had gestational diabetes, 1.4% had secondary diabetes, and 0.6% had pancreatic diabetes.

Outcomes of interest for investigators included diabetes type, glycemic trajectory, and diabetes persistence versus regression among patients with preexisting diabetes compared to their counterparts with newly diagnosed diabetes. For the purpose of analysis, regression to prediabetes at follow-up was defined as an HbA1c of 5.7-6.4% without the use of diabetes medications and the absence of discussions or treatment in clinical notes at the most recent follow-up. Persistence of diabetes was defined as an HbA1c of 6.5% or greater.

Compared to those with preexisting diabetes, patients with newly diagnosed diabetes were younger, less likely to be non-Hispanic White, less likely to have Medicare insurance, and more likely to have Medicaid insurance at the time of admission in univariate analyses. Additionally, patients with newly diagnosed diabetes had lower glycemic parameters but elevated inflammatory markers and markers of COVID-19 severity, including C-reactive protein, ferritin, lactate dehydrogenase, aspartate, and alanine aminotransferase.

Of the 77 individuals diagnosed with diabetes at admission, 10 died during the initial COVID-19 admission and 3 were lost to follow-up within 30 days of admission. At a median of 323 (IQR, 205-385) days of follow-up, results suggested 56.3% of the 64 survivors continued to have diabetes, but regression to normoglycemia or prediabetes was observed among 40.6%. Of the 26 individuals with regression, 20 regressed to normoglycemia and had a median HbA1c of 5.6% and 6 regressed to prediabetes and had a median HbA1c of 5.9%.

In the aforementioned statement, investigators noted their results underline the importance of close follow-up for patients who were diagnosed with diabetes during admission for COVID-19.

“Our results suggest that acute insulin resistance is the major mechanism underlying newly diagnosed diabetes in most patients with COVID-19, and that insulin deficiency, if it occurs at all, is generally not permanent,” Cromer added. “These patients may only need insulin or other medications for a short time, and it’s therefore critical that physicians closely follow them to see if and when their conditions improve.”

This study, “Newly diagnosed diabetes vs. pre-existing diabetes upon admission for COVID-19: Associated factors, short-term outcomes, and long-term glycemic phenotypes,” was published in the Journal of Diabetes and its Complications.