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Is COVID-19 Causing Diabetes?

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When the prestigious medical journal The Lancet published a set of “practical recommendations for the management of diabetes in patients with COVID-19” (PDF), representing what must be the best up-to-the-minute consensus on the topic, the authors briefly noted one curious but potentially consequential aspect of treatment:

All patients without diabetes and particularly when at high risk for metabolic disease who have contracted the viral infection need to be monitored for new onset diabetes that might be triggered by the virus.  

“New onset diabetes?”

Is the new coronavirus … giving people diabetes?

The answer appears to be yes. The mechanisms by which this may occur are not yet verified, and the prevailing theories are probably only truly comprehensible to those with graduate level biochemistry experience, but I’ll take a crack at it. You may have heard of ACE2, a receptor that the coronavirus “hijacks” in order to gain entry to the body’s cells and multiply. ACE2 is highly expressed in the pancreas and on the beta cells themselves, which means that when the coronavirus attacks, the beta cells are among the primary fields of battle. Direct damage to the beta cells impairs their ability to release insulin, leading to heightened glucose intolerance and, in a word, diabetes.

The theory that COVID-19 attacks the Beta cells is supported by “frequent” reports of patients suffering from diabetic ketoacidosis (DKA), a condition almost unknown outside of the presence of type 1 diabetes, attested to by Italian colleagues of the authors of the Lancet paper. The authors further go on to emphasize the “tremendous insulin requirements” of patients: “the extent of insulin resistance in patients with diabetes seems disproportionate compared with critical illness caused by other conditions.”

The day after the Lancet letter was published online, the same link was considered in a Chinese case study, in which COVID-19 was seen to “precipitate” a case of DKA.

Neither paper speculates on the duration of new onset diabetes, although the Lancet letter does note that “SARS-CoV-2 can induce long-term metabolic alterations in patients,” and that cardiometabolic monitoring during is called for during recovery.

Apparently, there is some precedence for this. The SARS coronavirus which caused a 2003 pandemic evidently acted in a similar way, damaging the pancreatic islets and causing in some patients a temporary state of “acute” insulin-dependent diabetes. One study followed 20 patients that developed diabetes while hospitalized with SARS, and found that 18 of them had regained healthy glucose metabolism three years later. Two remained diabetic. The details and ramifications of these two fascinating cases were left unexplored, leaving us to wonder whether or not SARS had actually caused chronic diabetes to develop, or perhaps if the virus had merely hastened the inevitable progress of incipient diabetes.

Unfortunately, it turns out that the hyperglycemia that can develop as a result of severe COVID-19 may be especially dangerous. A recent study (PDF) of American patients analyzed the prevalence of “uncontrolled hyperglycemia” among hospitalized COVID-19 patients. This paper did not use the term “new onset diabetes,” but by looking at patients with high blood sugars during infection (multiple readings above 180 mg/dL) and without any previous history of diabetes (average A1c of 5.9% upon admission), it can be presumed to address the same phenomenon. In the study sample, 14.8% of patients with known type 2 diabetes died as a result of COVID-19, itself a distressingly high number. But by contrast, among those patients that were not suspected to have diabetes upon admission but did develop rampant hyperglycemia during hospitalization, an astonishing 41.7% died.

This data dovetails with the testimony of one Dr. Antonio Ceriello, a professor and researcher in Milan, Italy, one of the pandemic’s earliest epicenters. In late April, Dr. Ceriello authored an editorial arguing for the necessity of rapid blood glucose control in COVID-19 patients. In an interview this week with Endocrinology Advisor, Dr. Ceriello stated that glucose control “is even more important in patients without diabetes.”

The authors of the American study conclude:

Clinicians should treat hyperglycemia to achieve BG targets < 180 mg/dl for most patients. This equates to basal-bolus insulin therapy in most non-ICU patients and continuous insulin infusion in the critically ill…

In essence, the researchers have suggested that “most” COVID-19 patients – whether they have diabetes or not –should be treated as if they had insulin-dependent diabetes, with frequent blood sugar measurement and aggressive insulin therapy in order to bring glucose back in range.

Complicating all of this is that fact that there are literally millions of Americans with undiagnosed type 2 diabetes. The American Diabetes Association reports that 20% of the 34 million American adults with diabetes have not been diagnosed, and some research has suggested that even more, as many as one-third of all cases, are undiagnosed. More stories like this one, in which a San Francisco man hospitalized with COVID-19 learned that he also had diabetes, are inevitable.

Only this week we published an article titled Why Blood Sugar Matters, which focused on the importance of good glucose control for people with diabetes under the threat of COVID-19 infection. The fact is that blood sugar matters not just for people with diabetes, but for everyone. If the recommendations of the researchers quoted in this article are widely accepted, blood sugar and insulin treatment may soon become topics of surpassing importance across the entire globe.

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