The COVID-19 infection is well known for its association with serious risks, severe disease, and death. For many, an emerging trend of hyperglycemia triggered by the disruption of essential metabolic signals appears to be another risk, according to researchers from Weill Cornell Medicine and New York-Presbyterian.

Dr. James Lo, a cardiologist at New York-Presbyterian/Weill Cornell Medical Center and an associate professor of medicine at the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine, and colleagues explored what they observed as a trend of hyperglycemia, with or without a diagnosis or history of diabetes, to be a strong predictor of adverse outcomes. These outcomes include a sevenfold higher mortality rate among patients infected with COVID-19 compared with patients with well-controlled blood glucose levels.

The research team set out to discover the potential physiologic mechanisms that may be responsible for the currently undefined emergence of hyperglycemia in COVID-19 patients. The team analyzed the records of 3,854 individuals who were hospitalized with COVID-19 at New York-Presbyterian /Weill Cornell Medical Center, New York-Presbyterian Queens, and New York-Presbyterian Lower Manhattan Hospital in the first few months of the pandemic in the United States.

"We normally don't think that fat cells are very active, but in fact they synthesize many protective proteins for your body—and it appears that SARS-CoV-2 may disable that protection in many patients," said Dr. Lo, who added, "Patients with obesity, for example, may be more vulnerable to COVID-19 because they may already have some degree of insulin resistance and fat cell dysfunction, and possibly their fat cells are more susceptible to infection."

The authors summarized their findings with the recognition that hyperglycemia is common in severe lung conditions such as acute respiratory distress syndrome (ARDS), including those not related to COVID-19, such as those seen with cases of severe seasonal influenza or pneumonia.  According to lead author Dr. Moritz Reiterer, who is a postdoctoral fellow in Dr. Lo's laboratory, "In contrast, hyperglycemia in COVID-19 patients is mainly caused by insulin resistance, in which insulin is present but the tissues it normally acts upon are no longer sensitive to it."

Further tests conducted on both patients with COVID-19 and hamsters infected with the same revealed that COVID-19-induced ARDS resulted in severe declines in blood levels of adiponectin, which is a hormone produced by fat cells that normally enhances insulin sensitivity, protecting against hyperglycemia. This discovery led the authors to conclude that viral disruption of normal adiponectin production may be the cause of insulin resistance in patients with severe COVID-19 infection and associated hyperglycemia.

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