How COVID-19 Can Lead to Diabetes
Posted on by Dr. Francis Collins
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
There may also be adverse effects on the beta cells secondary to “insulin resistance” produced by infection. This may result in a syndrome similar to what occurs in type 2 diabetes where the beta cell de-differentiate resulting in glycemic decompensation in the face of the metabolic inflammation. We have found it interesting that individuals with metabolic syndrome (overweight plus hypertension, fatty liver, type 2 diabetes) appear to be at greatest risk for many if not all of the adverse sequelea of SAR-CoV2 infection. Based on our work on new “insulin sensitizers” I suspect important interactions with adipose, adipose-like cells, and the immune system contribute to adverse response to SARS-CoV2 as well as many other infections.
Thank you Jerry, for this explanation…………………I was diagnosed with Type2 Diabetes about three months ago, and having difficulty with my sugars, etc. I am taking insulin……………….I had both of my Covid shots recently……………..I am going to talk with my Doctor about this……………….thanks.
Has there been extensive research on whether family history of autoimmune disease (multiple sclerosis, Type 1 Diabetes, Rheumatoid Arthritis) would dictate the need to either a. Avoid Vaccination OR … b. Select Pfizer/Moderna over J&J? One Physician told me to wait another 6 months before being vaccinated for more data – as her autoimmune patients had a flare up after vaccination while others did not have a flare up…
Given that all current vaccines encode the spike protein (mRNA and the adenoviral ones), the question to ask may in fact be how long are these spike proteins then being expressed in vivo, and whether that may cause an autoimmune scenario in those susceptible at a later yet undetermined time point.
mRNA vaccines use PEG to enhance half-life. Interestingly, Lilly had a PhIII pegylated product for diabetes that was pulled. PEG is also used in basic science to make hybridomas which are fused B-cells producing antibodies and is commonly used in industrials and other products including things such as toothpaste and cosmetics. Contra-indications for other commonly used marketed pegylated drugs such as interferon can be informative.
In a virus, the surrounding and 3-dimensional structure of the spike protein is different than the surrounding and of the spike protein being expressed on the surface of human cell that takes up the vaccine. Depending on other factors, post translational modifications of the spike by the virus may be slightly different than the modifications by the vaccine. There is the nucleotide aspect, but also for consideration is the epigenetics.
I have servers autoimmune conditions. had a flare up after getting Covid. It was manageable. I had a plan. I started Ivm day 4 and I got the monoclonal antibodies day 5. Felt much better day 6. I can only imagine my flare up if I had gotten vaccines. So many spike protein being produced in your body at one eye.
Thank you so much for this article, I have been looking into this heavily since last November when our 8 year old was diagnosed with Type 1. I continue to believe COVID caused/triggered his diagnosis. no one in our family has type 1.
Hi Kristina,
My nephew now 10 recovered from COVID a month ago has been having acute weight loss was last week diagnosed with Type 1. We also think it maybe covid related and trying to understand if it can/will be reversed. Would like to stay in touch and see if we can help each other we the information we gather.
Kristina, does your family have any history of other autoimmune diseases? There are over 100 known autoimmune diseases, they often manifest as different types among family members.
In my 35 years of Family Medicine practice have seen may children develop DM type 1 post viral infections without a family history. I have always believed the viral agent and cytokine storm in those cases happened to target the pancreas. have also seen pericarditis with viral infections. COVID-19 has demonstrated to many of us the myriad of chronic diseases post viral infections in a very concentrated timeline. I hope we make a bigger effort at teaching hand hygiene behavior consistently from Head Start ages onward into adulthood to minimize viral infections and subsequent chronic disease manifestations.
Is it possible this issue is related to the spike protein itself and not the virus, and if so, could this same problem occur as a result of vaccination?
There is clinival evidence that viral infection, particularly SARS cause acutely hepatic and endothelial (vascular) insulin-resistance. Iron increase the viral replication; and If iron oveload promotes apoptosis in pancreatic beta-cells, particularly in insulin resistante men and post-menopausal women, SARS-COV-2 may promotes beta-cell-de-differentation and apoptosis in iron-repleted cells (expressed in high ferritin levels), The more ferritin levels, the more prone to suddendly diabetes. May catalytic iron increase the ACE-2 receptors density in pancreatic beta-cells?
Very interesting. It is indeed frightening how many systems this terrible virus can affect
Yes DM 1 can be a consequence of many other viruses as well. I have seen this in my 35 years of Family Medicine practice. As such I am a staunch advocate for teaching the Public the 4 Principles of Hand Awareness to help patients reduce respiratory infections, hence stay well.
I have been recently diagnosed with type 2 diabetes. This came out of no where. Is it possible that covid caused it? If so what should I do? Will it go away naturally? I’ve been on insulin for about 5 months now.
Could a nursing mother’s vaccine somehow be responsible for an enfant’s type one diabetes diagnosis? (11 months old)
the covid shot cant give u something that u had when u got the shot!
I was diagnosed last year in April
at age 59 with Type 1 diabetes. I have never had any indication of being a diabetic with my annual bloodwork in the past years. My endocrinologist stated he believes a virus attacked my pancreas and caused this! I was diagnosed with a respiratory condition in February of 2020. I am now insulin dependent and will be the rest of my life.
Would increased expression of ACE2 or recombinant ACE2 compensate for COVID-19 infection?
I ended up in ICU three days after my second shot (Moderna), my blood sugar spiked @ 1272 and I was diagnosed with Acute Diabetes. No history of Diabetes in my family nor any related Glucose issues in my medical profiles. I am a firm believer the vaccine was the culprit!
This message is a question I am posing to anyone who doesn’t have diabetes but has family who does and is therefore predisposed to developing diabetes. After you have received the vaccine, do you think that your symptoms for diabetes accelerated to the point where you are now with diabetes whereas prior to the vaccine you were not? Just want to open a dialogue about this since I haven’t seen any posts related. For me, it seems that the shot triggered something in my body to now experience Diabetes Stiff Hand Syndrome, this happened the morning after receiving the shot.
Any virus or cold can trigger anti-bodys to attack the cells that produce insulin in people that have the autoimmune gene. That is primarily with Type 1 diabetes. Is it possible that Covid-19 can do this, absolutely but not anymore than any other cold or virus. Stop the fear mongering.
The past four+ months I have had long COVID symptoms and it may have been triggered by the Pfizer vaccines. My heart,liver, thyroid and pancreas were all affected. I’m on a blood thinner because my inflammatory markers were persistently elevated. I’m checking my glucose levels now as well. I was hoping this would be temporary and would resolve with time-I think I am wrong. Thank you to all the medical researchers studying this plague.
I wonder how the cells that express spike protein, as a result of vaccination, are regarded by the white cells that destroy invaders. Would they be attacked and destroyed, too?
I haven’t read all of the research, but I’m aware of the concern for COVID related diabetes. In the course of your research was any thought given to the massive doses and combination of drugs used to treat hospitalized SARS-COV2 patients? What percentage of patients studied were hospitalized & what were the treatment commonalities?
Thanks! Very interestingly written is both research and the effect of beta cell infection. In addition to losing beta cells, infection also changes the fate of the surviving cells. The real effects of beta cell infections have not yet been proven. Anything that could potentially exacerbate insulin deficiency and raise blood glucose levels. So it is important to remind yourself once again of the need for protection against Covid-19. You need to adhere to the mask regime, self-isolation and many more protection instructions.
I hope this reasearch will drive additional studies into the role of viruses in triggering Type I diabetes. My son has had Type I for a decade and he was diagnosed after a viral illness. I have always thought there was a connection.
I’m a Covid long hauler and never had an issue with insulin resistance or diabetes. Recently bloodwork reveals elevated BS and elevated HgBA1C. I’ve had 5 hyperbaric oxygen treatments in addition to IV Vitamin C and glutathione. Any thoughts as to HBOT and improvement of beta cell function?
Great info ! I absolutely love this content about how COVID-19 can lead to diabetes . . .