Study explores link between COVID-19 and new-onset diabetes

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A recent study revealed that the novel coronavirus (COVID-19) activates a specific gene that disrupts insulin signals, leading to problems with blood sugar metabolism, and sometimes diabetes.

The study, published in the journal Metabolism, was led by Iichiro Shimomura, MD, PhD, of the department of metabolic medicine at the Graduate School of Medicine at Osaka University in Japan.  According to the authors, previous studies have shown that COVID-19 can lead to organ damage and metabolic abnormalities, among them, hyperglycemia, insulin resistance, and diabetes. For this study, researchers set out to discover how a COVID-19 infection impacts the insulin/insulin-like growth factor (IGF) signaling pathway which contributes to the regulation of energy metabolism and cell survival, according to the authors.

Researchers analyzed gene expression data from various sources including infected human cells and tissues, human lungs, and animal models, and compared them to the uninfected counterpart. To understand the association between COVID-19 risk factors like old age, obesity, and diabetes, researchers observed transcriptomes of human raspatory, as well as metabolic and endocrine cells and tissues. Finally, to determine whether there was an association between COVID-19 severity and the insulin/IGF signaling pathway, scientists compared whole blood transcriptomes of critical patients with COVID-19 with those of hospitalized noncritical COVID-19 patients.

“The results were striking,” said Shimomura. “Infection with SARS-CoV-2 affected the expression of insulin/IGF signaling pathway components in the lung, liver, adipose tissue, and pancreatic cells. Moreover, these changes were attributed in part to activation of interferon regulatory factor 1 (IRF1).”

The study found that several insulin/IGF signaling pathway genes were impaired such as IRS, PI3K, AKT, mTOR, and MARK. In addition, compared with noncritical patients, the investigation showed that critical COVID-19 patients had higher levels of IRF1 and lower insulin/IGF signal pathway genes in whole blood transcriptomes.

“Our findings suggest that SARS-CoV-2 infection impairs insulin/IGF signaling by increasing IRF1 expression, thereby disrupting blood sugar metabolism. Decreasing IRF1 expression by treatment with factors such as dihydrotestosterone and dexamethasone could help mitigate the effects of COVID-19,” said corresponding author Jihoon Shin, MD, of the Graduate School of Medicine at Osaka University.