Diabetes and COVID-19

As of 2014, more than 422 million people suffer from the chronic condition of diabetes. Being such a prevalent condition in today’s world, the question arises as to whether or not diabetes is yet another of the many conditions being recently linked to increased risk of  the severity of COVID-19 symptoms. 

Perhaps the first step towards answering this question is understanding the mechanisms behind diabetes. Type 1 diabetes is a result of an auto-immune response against the islet cells in the pancreas that produce the hormone insulin, which is responsible for triggering a signaling pathway that results in the uptake of glucose in the blood by tissues. Type 1 diabetes prevents insulin production, causing blood sugar levels to rise without glucose being absorbed into surrounding tissues. On the other hand, type 2 diabetics still have some amount of produced insulin; however, this insulin may not be enough to carry out its function or may not trigger the correct or complete pathways required for glucose uptake. 

While diabetic patients do not have a higher chance of contracting the disease, they are more susceptible to experience more severe symptoms, which is in large part due to the high blood sugar that characterizes this condition. High blood sugar often leads to a weakened immune system. Researchers attribute this to the production of molecules known as dicarbonyls, particularly the methylglyoxal (MGO) and glyoxal (GO) dicarbonyls, that are a biproduct of the breakdown of glucose and are elevated in diabetic patients. These dicarbonyls affect the structure of human beta-defensin-2 (hBD-2) peptides, which could normally prevent entry of harmful pathogens and kickstart the immune response in the presence of a foreign invader. In non-diabetic people, hBD-2 also marks antigens for destruction through chemoattraction; research showed that the changes in structure due to dicarbonyls affect both of these processes. The effects of diabetes on hBD-2 lead to a weakened immune system that is less able to mount a defense against the novel coronavirus, thus leading to more severe symptoms. 

Type 2 diabetes and insulin resistance has also been connected to inflammation. Combined with the inflammation caused by infection with the virus, this can lead to organ damage and plaque buildup in arteries due to immune cells. In turn, this can lead to cardiovascular complications. 

Photo: Effect of dicarbonyls on immune function.

Not only does diabetes exacerbate the symptoms of the coronavirus, but the coronavirus can also exacerbate the symptoms of diabetes. Type 1 diabetics often experience diabetic ketoacidosis, in which the body begins to burn fat in the absence of glucose (due to the lack of insulin). This leads to the production of ketones that acidify the blood and can lead to a diabetic coma and without treatment, death.  Research shows that infection with the novel coronavirus often leads to or worsens the symptoms of diabetic ketoacidosis

A recent case study proposes that the link to diabetic ketoacidosis may be angiotensin-converting enzyme 2 (ACE2). This enzyme is an entry point for the virus; after endocytosis of the virus, its expression is downregulated. Since ACE2 acts as a catalyst to convert angiotensin II to angiotensin 1-7, downregulation due to coronavirus infection leads to the abundance of angiotensin II which affects pancreatic beta cell function. This in turn affects insulin production and contributes to diabetic ketoacidosis. The virus itself may also damage pancreatic beta cells causing similar effects. 

Understanding these various connections between diabetes and the 2019 novel coronavirus could prove crucial to developing treatment strategies and possible cures, especially for patients who may have pre-existing conditions.

Photo: SARS-CoV-2 pathway playing a role in diabetic ketoacidosis.

References:

What is Diabetes?” Diabetes Research Institute Foundation. 

Gisela Wilcox. “Insulin and Insulin Resistance.” The Clinical Biochemist Reviews (May 2005).

How COVID-19 Impacts People with Diabetes.” American Diabetes Association. 

Jordyn Imhoff. “What to Know About COVID-19 if You Have Diabetes.” Michigan Health (April 2020).

Derek Le Roith. “Recent Advances in Our Understanding of Insulin Action and Insulin Resistance..” Diabetes Care (March 2001). 

Janna G. Kilesar. “Modification of β-Defensin-2 by Dicarbonyls Methylglyoxal and Glyoxal Inhibits Antibacterial and Chemotactic Function In Vitro.” PLOS ONE (August 2015). 

Periathamby Antony Raj. “Current status of defensins and their role in innate and adaptive immunity.” FEMS Microbiology Letters (January 2002). 

Paul DiCorleto. “Why You Should Pay Attention to Chronic Inflammation.” Cleveland Clinic: Cancer Care (October 2014).

Ying Jie Chee. “Diabetic ketoacidosis precipitated by Covid-19 in a patient with newly diagnosed diabetes mellitus.” Diabetes Research and Clinical Practice (April 2020). 

 “DKA (ketoacidosis) and Ketones.” American Diabetes Association. 

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