This short April 2020 review highlights specific links between diabetes and increased risk of COVID infection, morbidity, and mortality.

Diabetes has been well established as a risk factor for COVID-19, just as it was for previous coronaviruses SARS and MERS-CoV (1). In patients with SARS or MERS-CoV, diabetes was thought to increase risk of infection and death by increasing inflammation and distorting the immune and cytokine responses, all of which impaired an effective healing response and accelerated multi-organ failure (2).

The authors argue two specific factors related to COVID-19 increase risk in diabetics; both factors are related to the impact of diabetes on angiotensin-converting enzyme (ACE) activity. ACE receptors regulate the renin-angiotensin system (i.e., blood pressure and fluid volume) by controlling the relative levels of angiotensin I and angiotensin II production. (ACE inhibitors, a widely prescribed class of high blood pressure medications, increase levels of angiotensin I relative to levels of angiotensin II.) Diabetics and hypertensive and insulin-resistant individuals display increased levels of angiotensin I and decreased levels of angiotensin II — changes associated with increased blood pressure, inflammation, and vascular permeability. These changes directly increase the risk of respiratory distress syndrome (3).

ACE2 receptors are present in many organs, including the pancreas, lungs, liver, and heart. Coronavirus binds to ACE2 receptors, a phenomenon clearly seen in SARS-CoV patients who became diabetic while infected due to the virus infecting and damaging their pancreas (4). Mouse studies have shown that diabetic subjects have increased ACE expression across multiple organs. This may have two negative consequences for diabetics. First, the increased ACE expression will increase susceptibility to infection in diabetic subjects. Second, increased rates of infection across multiple organs may further accelerate multi-organ damage.

These two mechanisms indicate diabetics may be particularly susceptible to infection and harm from the coronavirus. This may explain the increased rates of COVID morbidity and mortality seen in diabetics.

 

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