COVID-19 May Trigger Hyperglycemia and Worsen Disease by Harming Fat Cells

COVID-19 may bring high risks of severe disease and death in many patients by disrupting key metabolic signals and thereby triggering hyperglycemia, according to a new study in Cell Metabolism.

Researchers led by James C. Lo, MD, PhD, an associate professor of medicine in the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center, found that hyperglycemia is common in hospitalized COVID-19 patients and is strongly associated with worse outcomes. The researchers also found evidence suggesting that SARS-CoV-2 can induce hyperglycemia by disrupting fat cells’ production of adiponectin, a hormone that helps regulate blood sugar levels. 

To better understand this important but mysterious aspect of COVID-19, Lo and colleagues – including Society member Laura Alonso, MD,  chief of the Division of Endocrinology, Diabetes and Metabolism at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center and the Herbert J. and Ann L. Siegel Distinguished Professor of Medicine at Weill Cornell Medicine — analyzed the records of 3,854 patients who were hospitalized with COVID-19 at NewYork-Presbyterian /Weill Cornell Medical Center, NewYork-Presbyterian Queens and NewYork-Presbyterian Lower Manhattan Hospital. in the first few months of the pandemic in the United States. 

They found that a remarkably high proportion (49.7 percent) of these patients presented with hyperglycemia or developed it during their hospital stays. 

Hyperglycemia in these COVID-19 patients was also strikingly associated with worse outcomes. Compared to patients with normal blood sugar levels, the patients with hyperglycemia were 9 times more likely to develop severe lung dysfunction (acute respiratory distress syndrome, or ARDS), 15 times more likely to be given mechanical ventilation, and three times more likely to die. 

Surprisingly, the researchers found that hyperglycemia and the dire risks it brings also occur in other, non-COVID-19 forms of severe lung dysfunction. They found it in the same proportion in ARDS cases associated with COVID-19 and in ARDS cases from non-COVID-19 causes such as severe influenza or bacterial pneumonia. However, hyperglycemia in the latter cases appeared to be caused mostly by the death or dysfunction of beta cells that produce insulin. Further tests revealed that the COVID-19 ARDS patients had severe declines in blood levels of adiponectin. 

How SARS-CoV-2 disrupts fat cells’ production of adiponectin isn’t yet clear. It may do so indirectly, by raising the general level of inflammation, which in turn disrupts fat cells. But the researchers demonstrated that SARS-CoV-2 can infect human and mouse fat cells, hinting at the possibility that the virus disrupts adiponectin production in this direct way in COVID-19 patients. The findings also suggest that a class of diabetes drugs called thiazolidinediones, which boost adiponectin production, may be useful in treating COVID-19 when it includes hyperglycemia. Further research is needed before this becomes clinically actionable.