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Clinical Context

Major clinical decisions regarding preventive strategies, including vaccination, and treatment for COVID-19 hinge on the patient’s baseline risk for severe illness. Multiple comorbid health conditions have been cited as major risk factors for complicated COVID-19, and this list has changed frequently, as data has emerged during the pandemic. Interesting highlights from the current list of conditions considered by the Centers for Disease Control and Prevention (CDC) to be most likely to promote a higher risk for COVID-19 include, but are not limited to, chronic kidney disease, nonalcoholic fatty liver disease, and physical inactivity.^[1]

There is only mixed evidence that asthma, hypertension, and chronic hepatitis infection increase the risk for severe COVID-19. Diabetes, both type 1 and 2, is entrenched on the list of high-risk conditions for severe COVID-19, but there might be geographic differences in this global disease. Moreover, there is controversy as to how much risk patients with diabetes have during infection with SARS-CoV-2. The current study by Kastora and colleagues explores these issues.

Study Synopsis and Perspective

An umbrella review of meta-analyses/systematic reviews of COVID-19 outcomes in patients with and without diabetes from around the world found overall worse outcomes in patients with COVID-19 who had diabetes -- with geographic differences.

Diabetes has been known to be a risk factor for poorer prognosis in COVID-19, but this is the first time a study has looked at the risks while factoring in the patients' location. In the study, diabetes almost doubled the rate of death from COVID-19, but good glucose control was a protective factor, and this seems to have differed across many of the countries studied, as well as within countries.

The review included 270,000 participants, with studies from North America, Europe, the Middle East, and the Far East. It was recently published in Endocrinology, Diabetes & Metabolism^[2]by Stavroula Kastora, MD, PhD, of the University of Aberdeen, United Kingdom, and colleagues.

In the pooled results, "people with diabetes were 1.87 times more likely to die with COVID, 1.59 times more likely to be admitted to [intensive care unit (ICU)], 1.44 times more likely to require ventilation, and 2.88 times more likely to be classed as severe or critical, when compared to patients without diabetes," Anne L. Peters, MD, who was not involved in this research, summarized in an email to Medscape Medical News.

Patients treated in the United States or Europe fared best, and patients in other areas, particularly China, Korea, and the Middle East, did the worst, said Peters, a professor of medicine at the University of Southern California (USC) Keck School of Medicine in Los Angeles. Older patients and patients treated with insulin also had worse outcomes, and people with better glycemic control did better, she noted.

"These findings are interesting because they reveal that worse outcomes due to COVID-19 in people with diabetes can be reduced in the right setting," Peters said.

She noted, however, that although the findings revealed differences in outcomes between countries, "within a country there is variation in outcomes."

For instance, within the United States and the United Kingdom, outcomes in the review differed according to whether people live in an area with higher or lower healthcare resources. 

"In light of the ongoing pandemic, strengthening outpatient diabetes clinics, ensuring consistent follow-up of patients with diabetes, and optimizing their glycemic control could significantly increase the chances of survival following a COVID-19 infection," she noted.

Francisco J. Pasquel, MD, MPH, who was not involved in the research, agreed.

"This is an alert to the global community about the importance of prioritizing care and research resources focused on people with diabetes and COVID-19 to reduce the gaps in outcomes compared to those without diabetes," he said in an email to Medscape Medical News.

Pasquel is associate professor, endocrinology, at Emory University School of Medicine, Atlanta, Georgia.

The researchers performed an umbrella review of other reviews -- according to 158 original articles (148 retrospective studies and 10 prospective studies, including 15 preprints) -- that were published up to August 30, 2021.

Twenty-two studies were conducted in the European Union (Denmark, France, Italy, Spain, Switzerland, and the United Kingdom), 90 were from the Far East (China and Korea), 16 were from the Middle East (Iran, Iraq, Israel, Kuwait, Oman, Qatar, and Turkey), and 30 were from North America (29 from the United States and 1 from Mexico). 

The total sample consisted of 270,212 patients, including 57,801 patients who were diagnosed with diabetes (488 with type 1 diabetes and 57,313 with type 2 diabetes).

Overall, 19% of the patients were admitted to an ICU, 12% were placed on a ventilator, and 13.5% died during follow-up.

In the 59 studies that looked at ICU admission, this outcome was more likely among patients with vs without diabetes (odds ratio [OR] 1.59; P = .005), driven primarily by the increased risk for ICU admission in patients with diabetes in the 29 studies from the Far East (OR 1.94; P < .0001).

There was no overall increased risk for ICU admission in patients with COVID-19 and diabetes (vs no diabetes) in the 8 studies from the Middle East (OR 1.32; P = .26), the 9 studies from the European Union (OR 1.2; P = .16), or the 13 studies from North America (OR 1.57; P = .36). 

In the 83 studies that looked at need for a ventilator, overall, there was a greater need in patients with vs without diabetes (OR 1.44; P < .0001).

Among patients with COVID-19, patients with diabetes had an overall increased need for a ventilator in the 10 studies from the Middle East (OR 2.02; P = .01), the 51 studies from the Far East (OR 1.61; P = .0001), and the 8 studies from Europe (OR 1.26; P < .0001), but not in the 14 studies from North America (OR 0.71; P = .19). 

Overall, in the 136 studies that looked at mortality, patients with diabetes and COVID-19 had an increased risk of dying during follow-up (OR 1.75; P < .0001). This was also true overall for patients with diabetes in the 77 studies from the Far East (OR 2.4), the 15 studies from the Middle East (OR 1.71; P < .0001), the 18 studies from Europe (OR 1.47; P = .04), and the 14 studies from North America (OR 1.42; P = .04) that looked at this outcome. 

The authors have reported no relevant financial relationships. Peters has reported receiving consulting fees from Abbott Laboratories; AstraZeneca Pharmaceuticals LP; Medscape; Novo Nordisk; Vertex Pharmaceuticals Incorporated; and Zealand Pharma and research funding from Abbott Laboratories; Dexcom, Inc.; and Insulet Corporation and having stock options with Omaha Health and Teladoc.

Clinical Implications

• Chronic diseases with the best evidence for promoting a higher risk for severe COVID-19 include coronary artery disease, nonalcoholic fatty liver disease, and mood disorders. Current and former smoking and physical inactivity are also associated with a higher risk for severe COVID-19; however, the evidence that hypertension, hepatitis B or C infection, or asthma promote a higher risk for severe COVID-19 is more mixed.
• The current study by Kastora and colleagues finds that diabetes is associated with higher risks for mortality, mechanical ventilation, and ICU admission among patients with COVID-19. These results were most pronounced in studies from the Far East and Middle East.
• Implications for the healthcare team: An interprofessional team approach should be used to provide education on COVID-19 prevention for patients with diabetes and use the results from the current study to help convince skeptical of the risks for COVID-19.

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