Better Glucose Status, Better COVID-19 Prognosis?

Hyperglycemia helps predict outcomes and mortality rates in COVID-19 patients both with and without diabetes

With Scott Isaacs MD and J. Michael Campoy-Gonzalez MD PhD

While type 2 diabetes is well-known to be a major comorbidity of COVID-19, much about how those with type 2 diabetes fare when infected and what role hyperglycemia may play has yet to be studied extensively.

Now, three new research studies from Chinese and U.S. doctors conclude that hyperglycemia, especially if it occurs early in the disease course, worsens the prognosis and the mortality rate. In one of the studies, researchers found that true in patients both with and without confirmed diabetes.

In an editorial, an Italian researcher says the findings call for a ''fast normalization of hyperglycemia during COVID-19" to decrease the inflammatory cytokines released and avoid the potentially lethal ''cytokine storm."

Study Details: Chinese Study

The Chinese researchers conducted a multi-centered evaluation of 7,337 cases of COVID-19 in Hubei Province, China, including 952 with pe-existing type 2 diabetes. Those with diabetes had higher mortality rates (7.8% versus 2.7%, adjusted HR, 1.49). However, well-controlled blood glucose (glycemic variability within 3.9 to 10.0 mmol/L) was linked with lower mortality compared to those with poorly controlled (upper limit of glycemic variability exceeding 10. Mmol/L), adjusted HR, 0.14.

Study Details: U.S. Studies

University of Miami researchers retrospectively collected data from 85 patients with lab-confirmed COVID-19 infection admitted to the University of Miami Hospital from March 4 to April 4. Of the 85, 27 had a past history of diabetes. They were on a variety of medications, from oral agents to insulin or a combination. Ages ranged from 31 to 95. 

Average blood glucose on day 1 was 166 and median A1C was 7%. The day 1 average blood glucose was the strongest independent variable predicting the SARS-CoV2 finding on the chest X-rays. The researchers speculate that ''acute hyperglycemia may lead to an abnormal inflammatory and immune response contributing to the development and progression of the radiographic findings of ARDS in patients with COVID-19." They recommend that admission hyperglycemia should not be overlooked, regardless of if the patent has diabetes or not.

In a third study, researchers evaluated the records of 1122 patients in 88 U.S. hospitals, including 451 with diabetes and/or uncontrolled hyperglycemia. They focused on 570 patients who died or were discharged, finding that the mortality rate was 28.8% in the 184 with either diabetes or uncontrolled hyperglycemia or both, but 6.2% in the 386 patients without hyperglycemia or diabetes. The conclusion: "We recommend health systems ensure that patient hyperglycemia is safely and effectively treated."

Expert analysis

J. Michael Gonzalez-Campoy, MD, PhD, FACE, medical director and CEO of the Minnesota Center for Obesity, Metabolism and Endocrinology, commented on the Chinese study, saying it confirms what endocrinologists would expect. The research, he said, ''also highlights another aspect unique to diabetes care. The stress hormones that we all make during a serious illness antagonize insulin. The sicker a person with diabetes is, the higher the level these stress hormones are, including cortisol and adrenalin. Therefore, the sicker a person is, the higher their insulin needs are, and the more difficult it is to achieve a tighter control of their blood sugar. Poor blood sugar control becomes a reflection of the severity of the underlying illness, and therefore a marker of poor prognosis—or higher mortality."

In an editorial, Antonio Ceriello, MD, head of the diabetes department at IRCCS MultiMedica, Milan, wrote there are at least two reasons why hyperglycemia, particularly an acute episode, can be dangerous during a COVID-19 infection. One, he says, is that an acute increase is accompanied by a huge rise of inflammatory mediators. A second is that the glycosylation, ''a reaction that can be induced by the hyperglycemia of the ACE2 is needed'' for the virus to link to this cellular receptor, perhaps easing the intrusion of the virus into the cells and leading to a more severe illness.

Dr. Ceriello wrote that the hyperglycemia-related process of glycosylation ''is at the beginning a reversible process," explaining his caution that hyperglycemia in the very early stage of the disease may play an important role in determining how serious the infection will be, and predicting the outcome.

Scott  Isaacs, MD, FACP, FACE, an Atlanta endocrinologist and a member of the EndocrineWeb editorial board, offers further perspective about patients with type 2 diabetes and COVID-19. "Patients with diabetes are at extra risk for COVID-19 complications and death. Having poorly-controlled diabetes and blood sugar levels further magnifies this risk. "

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