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How COVID-19 Can Lead to Diabetes

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Human abdominal anatomy with highlighted pancreas. Cluster of Infected Beta Cells with cornaviruses are in foreground.

Along with the pneumonia, blood clots, and other serious health concerns caused by SARS-CoV-2, the COVID-19 virus, some studies have also identified another troubling connection. Some people can develop diabetes after an acute COVID-19 infection.

What’s going on? Two new NIH-supported studies, now available as pre-proofs in the journal Cell Metabolism [1,2], help to answer this important question, confirming that SARS-CoV-2 can target and impair the body’s insulin-producing cells.

Type 1 diabetes occurs when beta cells in the pancreas don’t secrete enough insulin to allow the body to metabolize food optimally after a meal. As a result of this insulin insufficiency, blood glucose levels go up, the hallmark of diabetes.

Earlier lab studies had suggested that SARS-CoV-2 can infect human beta cells [3]. They also showed that this dangerous virus can replicate in these insulin-producing beta cells, to make more copies of itself and spread to other cells [4].

The latest work builds on these earlier studies to discover more about the connection between COVID-19 and diabetes. The work involved two independent NIH-funded teams, one led by Peter Jackson, Stanford University School of Medicine, Palo Alto, CA, and the other by Shuibing Chen, Weill Cornell Medicine, New York. I’m actually among the co-authors on the study by the Chen team, as some of the studies were conducted in my lab at NIH’s National Human Genome Research Institute, Bethesda, MD.

Both studies confirmed infection of pancreatic beta cells in autopsy samples from people who died of COVID-19. Additional studies by the Jackson team suggest that the coronavirus may preferentially infect the insulin-producing beta cells.

This also makes biological sense. Beta cells and other cell types in the pancreas express the ACE2 receptor protein, the TMPRSS2 enzyme protein, and neuropilin 1 (NRP1), all of which SARS-CoV-2 depends upon to enter and infect human cells. Indeed, the Chen team saw signs of the coronavirus in both insulin-producing beta cells and several other pancreatic cell types in the studies of autopsied pancreatic tissue.

The new findings also show that the coronavirus infection changes the function of islets—the pancreatic tissue that contains beta cells. Both teams report evidence that infection with SARS-CoV-2 leads to reduced production and release of insulin from pancreatic islet tissue. The Jackson team also found that the infection leads directly to the death of some of those all-important beta cells. Encouragingly, they showed this could avoided by blocking NRP1.

In addition to the loss of beta cells, the infection also appears to change the fate of the surviving cells. Chen’s team performed single-cell analysis to get a careful look at changes in the gene activity within pancreatic cells following SARS-CoV-2 infection. These studies showed that beta cells go through a process of transdifferentiation, in which they appeared to get reprogrammed.

In this process, the cells begin producing less insulin and more glucagon, a hormone that encourages glycogen in the liver to be broken down into glucose. They also began producing higher levels of a digestive enzyme called trypsin 1. Importantly, they also showed that this transdifferentiation process could be reversed by a chemical (called trans-ISRIB) known to reduce an important cellular response to stress.

The consequences of this transdifferentiation of beta cells aren’t yet clear, but would be predicted to worsen insulin deficiency and raise blood glucose levels. More study is needed to understand how SARS-CoV-2 reaches the pancreas and what role the immune system might play in the resulting damage. Above all, this work provides yet another reminder of the importance of protecting yourself, your family members, and your community from COVID-19 by getting vaccinated if you haven’t already—and encouraging your loved ones to do the same.

References:

[1] SARS-CoV-2 infection induces beta cell transdifferentiation. Tang et al. Cell Metab 2021 May 19;S1550-4131(21)00232-1.

[2] SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment. Wu et al. Cell Metab. 2021 May 18;S1550-4131(21)00230-8.

[3] A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids. Yang L, Han Y, Nilsson-Payant BE, Evans T, Schwartz RE, Chen S, et al. Cell Stem Cell. 2020 Jul 2;27(1):125-136.e7.

[4] SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Müller JA, Groß R, Conzelmann C, Münch J, Heller S, Kleger A, et al. Nat Metab. 2021 Feb;3(2):149-165.

Links:

COVID-19 Research (NIH)

Type 1 Diabetes (National Institute of Diabetes, Digestive and Kidney Disorders/NIH)

Jackson Lab (Stanford Medicine, Palo Alto, CA)

Shuibing Chen Laboratory (Weill Cornell Medicine, New York City)

NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases; National Human Genome Research Institute; National Institute of General Medical Sciences; National Cancer Institute; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development

37 Comments

  • Scott Greenbaum, MD FACS says:

    Very interesting work – thank you for sharing it Dr. Collins – it raises the applicability of another NIH-NICHD sponsored project-that of RNA Replicase inhibition by Tempol. https://www.nih.gov/news-events/news-releases/nih-researchers-identify-potential-new-antiviral-drug-covid-19 The wider the scope of SARSCoV2 infection, the greater the need for broad spectrum therapeutics. In my view the inhibition of replicase is as broad as they come. What do you think?

  • m says:

    this vaccines HAS NOT been tested long enough to know whats going to happen in the long run … i will not get one.

    • Joseph E Loyd says:

      It is the disease Covid-19, not the vaccination, that is associated with these after effects! Get the vaccination to PREVENT COVID-19 and these potential sequalae!

  • M Grossman says:

    Is there any evidence that an asymptomatic COVID-19 infection can lead to type 1 diabetes?

  • Ahmed says:

    Would it be temporary or permanent??
    I got diabetes type 1 after Covid-19

    • Kevin says:

      same here. No family history whatsoever then i thought i had a cold and couple months later type 1 diagnosis.

    • Amit Pratap Singh says:

      I too want to know whether diabetes type 1 after covid 19 is temporary or permanent and what type of measure could be adopted.

  • Cheryl Kennedy says:

    Yes, this is what happened with my 10th grade daughter. Diagnosed with Covid 9/11/2020, and with Type 1 Diabetes on 12/7/2020. Children’s Healthcare of Atlanta staff mentioned many times a >300% increase in new T1D diagnoses that fall. Children weren’t typically as severely symptomatic, perhaps not as well documented, but they were rather sure Covid was the cause. My daughter’s symptoms were not severe – only a low-grade fever, mostly headache and sore throat, fatigue. I don’t even think she coughed much. 3 months later, craving sweets, increasingly thirsty, having to use the restroom every hour or so, lost 15 lbs., using shoelaces in her belt loops to hold her jeans up. I’m glad I knew about these signs, and that her school nurse knew what to do.

    • Karan Goel says:

      Quite similar happened to my 9 year child. Got mild covid fever in April 2021, and got diagnosed with T1D couple of weeks back, with similar story Cheryl. We do not have any family history. We don’t know a single child in our circle with this condition.
      Is it temporary, reversible? Are there other side effects?

  • A. says:

    For more than a year, the whole planet is suffering from the corona pandemic. It caused a lot of panic, fear, and anxiety.
    People started to worry more about themselves, their families, and their beloved ones, which led them to take some more protective actions.
    A lot of our daily routine has changed; staying home is all we can do now. And if we have to go out a lot of precautions must be taken. i hope to be safe soon

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