New-Onset Diabetes in COVID-19: An Unexpected Outcome

COVID-19 can cause diabetes, by interfering with the insulin signaling pathway that regulates energy metabolism and cell survival.

A pivotal gene that mediates the effects of COVID-19 infection on blood sugar metabolism is identified by researchers from Japan in a study published in Metabolism.

It has become abundantly clear that COVID-19 despite being transmitted by breathing in the SARS-CoV-2 virus, can have harmful effects far beyond the lungs.

COVID-19 May Trigger Diabetes Onset

COVID-19 is best known for causing respiratory disease, but can also damage other organ systems; notably, disruption of blood sugar regulation can lead to new-onset diabetes. However, it is unclear how infection with the virus results in these effects.

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COVID-19 infection activates the IRF1 gene and impairs insulin/IGF signaling in the lung, liver, adipose tissue, and pancreatic cells.

The insulin/IGF signaling pathway is a key pathway in the regulation of energy metabolism and cell survival and researchers suspected that COVID-19 affects this signaling pathway to cause problems with blood sugar regulation.

To test this, they analyzed datasets of gene expression from patients, as well as in vivo and in vitro models, infected with COVID-19. They specifically looked for genes that were noticeably over-or under-expressed compared with uninfected patients, animals, or cells.

Infection with COVID-19 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 the activation of interferon regulatory factor 1 (IRF1).

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Further investigation showed that IRF1 expression is elevated in older patients, men, obese individuals, and patients with diabetes. The synergistic effect of older age, male sex, obesity, and diabetes with SARS-CoV-2 means that the expression of IRF1 occurs at an increased rate which may explain why these patients are more vulnerable to COVID-19.

How To Treat COVID-19 Induced Diabetes?

In addition, critical patients with COVID-19 had higher IRF1 expression and lower insulin/IGF signaling pathway genes in their blood compared with non-critical patients. Finally, treating COVID-19 infected cells or an animal model with hormonal factors that decreased IRF1 expression enhanced insulin/IGF signaling.

These findings suggest that SARS-CoV-2 infection impairs insulin/IGF signaling by increasing IRF1 expression, thereby disrupting blood sugar metabolism.

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Decreasing IRF1 expression by treatment with factors such as dihydrotestosterone and dexamethasone could help mitigate the effects of COVID-19.

Given the devastating impact that COVID-19 can have on multiple organ systems, treatment strategies that could decrease the effect of the disease on blood sugar metabolism, could be vitally important.

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By identifying patients at greater risk of experiencing these effects and intervening to decrease IRF1 activation, some of the severe consequences of COVID-19 could be avoided in susceptible populations.

Source-Medindia