Question: Is there a specific link between diabetes and increased risk and severity of COVID infection?
Takeaway: The impact of diabetes on angiotensin-converting enzyme receptor activity may directly increase risk of infection and the impact of the infection across multiple organs. These specific effects are in addition to any generalized deficits in immune function, vascular function, and other organ systems.
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 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, 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.
Notes
- Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS; Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020
- Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection; COVID-19: consider cytokine storm syndromes and immunosuppression
- ACE2, angiotensin-(1–7) and Mas receptor axis in inflammation and fibrosis
- Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes
Endocrine and Metabolic Link to Coronavirus Infection