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
Comments on Endocrine and Metabolic Link to Coronavirus Infection
I know I’m not alone in doing this, but when I hear about young and healthy people dying of coronavirus, I almost always try to find a picture. Generally, what I see is “normal”, but not healthy. When I hear they “watch their diet”, I wonder if they look at healthy food and eat something else.
Then again, the dietary advice of the WHO and CDC is woefully bad. Lots of good people are harmed by the bad dietary advice of these and other health organizations.
After age, severe obesity is the second most common predictor of hospitalization. It’s number one for people under 65. This article gives us several important clues why.
Barry Sears (author of the Zone Diet) wrote an interesting article on covid-19 and how immune responses work. He is in complete agreement that covid-19 is exacerbated by chronic inflammation. When the immune system attacks invaders, collateral damage is unavoidable. The people with the most severe cases are unable to shut down the inflammatory response once it has started. This results in a cytokine storm and damage to multiple organ systems.
A paper on influenza and obesity reports that obese subjects are more contagious. They shed the virus for a longer duration and they also expel more infectious virus with each breath. This paper also proposes that exercise is the most potent non-pharmacological immunomudulatory intervention. It reduces inflammation and improves the hormonal milieu that drives inflammatory responses. Some of this paper should probably be ignored. The paper refers to marathon running as “high intensity exercise” and recommends metformin for its anti-inflammatory benefits. CrossFit has previously posted an article that metformin blunts adaptation to endurance exercise.
Another cause for concern is vaccine response. Vaccines are known to be less effective in both of these populations, who are sadly the ones most in need. The vaccines which will supposedly bring the world back to normalcy in 18 months might not be as effective as we hope.
We should do everything we can to spread the word that our diet and exercise recommendations are perhaps the best defense we have now and might even improve our vaccine response when that eventually arrives. I’m optimistic that many people are making positive changes in their lives. I just hope they follow us and not the “low fat diet plus moderate activity” plan promoted by the CDC/AHA/WHO.
Thanks once again for the continued effort to get the truth about illness and this COVID fiasco out to everyone. It is absolutely mind boggling to me that we allowed governors the power to shut down our nation to protect people who basically made choices to neglect their health. As a doctor who has tried for over 30 years to motivate people to get off sugar and exercise I don’t think it is uncaring to allow someone to face the consequences of their own behavior. I believe it is a terrible policy to make those who take the time and make the effort to get fit suffer fir those who have not
Could not agree more, John Sullivan.
Endocrine and Metabolic Link to Coronavirus Infection
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