'The Story Unfolding Is Worrisome' for Diabetes and COVID-19

Miriam E. Tucker

May 26, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of "diabetes and COVID-19," publishing a range of articles with new data to help guide physicians in caring for patients.

"Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes," says an introductory commentary.

Entitled "COVID-19 in people with diabetes: Urgently needed lessons from early reports," the commentary is penned by the journal's editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.

Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) note it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor.

The ACE-2) receptor is known to be in the lungs and upper respiratory tract, "but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas," they say, as well as "in the kidney."

Hence, the emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.

"Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK," they state.

Although Rapidly Collected, Data "Offer Important Clues"

Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19;  a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.

Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes. 

"The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions," Riddle and colleagues caution. "Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients."

Even so, they say, some points are clear. "The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome."

Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19, who are also two to three times as likely to require intensive care, and to die, compared to those infected but without diabetes.  

"Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues," Riddle and colleagues say.

Existing Insulin Use Linked to COVID-19 Death Risk

One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.

Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio (OR), 1.09 per year increase; P = .001) elevated C-reactive protein (OR, 1.12; P = .043), and insulin use (OR, 3.58; P = .009).

"Attention needs to be paid to patients with diabetes and COVID-19 who use insulin," say the Chinese authors.

"Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear," Riddle and colleagues note.

Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker compared with those who did not, supporting existing recommendations to continue use of this type of medication.

Remote Glucose Monitoring a Novel Tool for COVID-19 Isolation

Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation, one had type 1 diabetes and the other had type 2 diabetes, treated with basal–bolus insulin.

Using Medtronic CGM systems, the hospital staff was able to view patients' real-time data uploaded to the web from computer terminals in virus-free areas outside the patients' rooms. The hospital's endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.  

"Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities," Shehav-Zaltzman and colleagues write.

"Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden," they observe.

Riddle and colleagues concur: "Newer methods of remotely monitoring glucose patterns could be uniquely helpful."

Key Question: Does Glycemic Management Make a Difference?

On the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues report on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.

They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness.

Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.

In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than those without diabetes and with normoglycemia.

Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than patients who didn't receive an insulin infusion.

And although they note limitations, the authors say: "Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status."

Riddle and colleagues say the findings of this unrandomized comparison were interpreted "as suggesting that insulin infusion may improve outcomes."

"If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential."

More on Obesity and COVID-19, This Time From China

As it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China — where this was less apparent initially — support observations in Europe and the United States.

An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index [BMI] ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared to the 203 patients classified as having normal weight (BMI, 18.5-23.9 kg/m2), with an odds ratio of 3.4.

A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou Medical University, China, and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 kg/m2 in this Asian population) to 75 patients without obesity matched by age and sex

After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.

Emerging from the Crisis: Protect Vulnerable, Increase Knowledge Base

As the research community emerges from the crisis, "there should be renewed efforts for multidisciplinary research...aimed at greatly increasing the knowledge base to understand how...the current COVID-19 threat" affects "both healthy people and people with chronic diseases and conditions," Cefalu and colleagues conclude in their commentary.

Riddle and coauthors agree: "We will enter a longer interval in which we must continue to support the most vulnerable populations — especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task."

Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Cefalu has reported no relevant financial relationships.

Diabetes Care. Published online May 14, 2020. Diabetes and COVID-19 section

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