Several beta cell receptors could explain link between COVID-19, new-onset diabetes
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SARS-CoV-2 may use ACE2 or other enzymes as a receptor to infect beta cells, providing a possible explanation behind new-onset diabetes occurring in people with COVID-19, according to a speaker.
“COVID-19 results in a significant increase in new-onset diabetes,” Irl Hirsch, MD, an endocrinologist and professor of medicine at the University of Washington School of Medicine, said during a presentation at the Cardiometabolic Health Congress. “The mechanisms for this are complex but appear to be related to specific beta cell toxicities, likely related from the ‘cytokine storm.’”
COVID-19 causes several metabolic and end-organ impacts. The release of cytokines can cause hepatocyte injury and impair glucose production, induce a stress response leading to more insulin resistance, and cause acute beta cell injury, Hirsch said.
Researchers are examining how SARS-CoV-2 is interacting with islets and affecting beta cells. A study published in Acta Diabetologica in 2010 discussed how the SARS coronavirus was able to enter islets using ACE2 as a receptor and damage them, causing acute diabetes. Hirsch noted while there are data both for and against ACE2 expression in beta cells, he believes SARS-CoV-2 might be able to damage them through a few different routes.
“Maybe it is more complicated than the ACE2 receptor,” Hirsch said. “Maybe there are other candidates when somebody is infected with COVID-19 that can cause beta cell toxicity. If we look at the beta cell as a whole, we know that in these infected individuals, interleukin-6 can cause the beta cell toxicity. We know there’s glucose toxicity from hyperglycemia, which we see both with and without preexisting diabetes. We know lipotoxicity with the high levels of free fatty acids, and of course, perhaps the ACE2 receptor itself. Maybe it’s a combination of these and not just COVID-19 and the ACE2 receptor itself.”
Several questions need to be answered regarding COVID-19 and new-onset diabetes, including what the phenotype is and whether it should be considered a new type of diabetes separate from typical type 2 diabetes. More research is also needed to explore the actual etiology and beta cell pathology of the entity, how COVID-19 therapies impact new-onset diabetes, and which type 2 diabetes treatments are most effective for new-onset diabetes after COVID-19 infection, Hirsch said. A group of international diabetes researchers have established the COVIdiab registry to compile data and answer some of those questions.
Unlike type 2 diabetes, COVID-19 has not been associated with an increase in new-onset type 1 diabetes in large population-based studies and there is no evidence the virus initiates beta cell autoimmunity. However, Hirsch said people have been presenting later with type 1 diabetes during the pandemic compared with before and are having more severe diabetic ketoacidosis.
“To date, there is no evidence that the SARS-CoV-2 virus initiates beta cell autoimmunity,” Hirsch said. “At least for now, we can scratch that off.”
Reference:
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Hirsch I. Rare Diabetes Disorders. Presented at: Cardiometabolic Health Congress; Oct. 14-17, 2021; National Harbor, Md. (hybrid meeting).
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