The Links Between COVID-19 and Diabetes, Known and Unknown

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The story of COVID-19 and the science behind the pandemic is evolving rapidly every day, with a flurry of publications in various clinical and preclinical journals.

Here, I summarize the known and unknown links between diabetes and COVID-19, focusing on three pertinent clinical questions.

How does diabetes affect the risk for COVID-19 infection?

Just as with other respiratory illnesses, such as influenza A, it appears that diabetes increases the risk for COVID-19 infection, although no prevalence studies comparing people with and without diabetes for COVID-19 have been published to support this presumption.

Several studies from China, Italy, and the United States suggest that diabetes increases risks for severe COVID-19 complications and mortality. In one Chinese study, people with diabetes had the second highest fatality rate (7.3%) after cardiovascular disease (CVD; 10.5%) among those with comorbid conditions.

Although several questions regarding mechanisms responsible for increased severity of COVID-19 with diabetes need to be investigated (immune dysfunction, link to comorbidities such as hypertension or obesity, link to complications such as CVD or nephropathy), the single most important outstanding clinical question in my mind is: What is the role of achieving euglycemia in COVID-19 infection and its severity? That is, does improving glucose control (chronically in an outpatient setting or acutely in an inpatient setting) result in primary prevention of COVID-19 infection or reduce its complications and fatality?

Notably, a recent data analysis for hospitalized patients with COVID-19 suggested a much higher mortality rate and increased length of stay among those who developed hyperglycemia during their hospital stay but had no evidence of diabetes before being admitted. Similarly, a previous publication had found an independent association between fasting glucose at hospital admission and severity of H1N1.

The question that needs to be explored further in both type 1 and type 2 diabetes, however, is whether acute hyperglycemia is truly an independent causal factor or simply a marker for increased severity and mortality from COVID-19.

Additional investigations into the efficacy (or at least safety) of common diabetes medications in relation to COVID-19 infection would be of clinical interest. Specifically, ACE2 and DPP-4 have been identified as receptors for the coronavirus and a related virus. Some reassurance on the safety of ACE inhibitors and angiotensin receptor blockers with COVID-19 hospitalizations is provided by recent retrospective study publications.

Clinical pearls: Healthcare providers should continue to follow routine diabetes management guidelines and encourage their patients to follow lifestyle modifications within the bounds of lockdown, along with medication adherence. In addition, it behooves us to counsel people with diabetes about the potentially higher risk for COVID-19 severity and re-emphasize public health prevention measures such as hand hygiene, physical distancing, wearing masks, etc.

How might this pandemic affect diabetes management?

Lockdowns across the globe pose serious challenges for acute non-COVID care, with many elective procedures and surgeries being postponed.

Several newspaper reports suggest that people may be averse to seeking emergency hospital care because of worries about COVID-19 infection or about hospital capacity. Timeliness of acute care by community clinics may be affected, leading to people presenting to emergency departments later in the course of disease (eg, heart attack, stroke, diabetic ketoacidosis, hyperglycemic coma, cellulitis, gangrene).

This acute care interruption in diabetes, as depicted in the figure below (which was designed by my daughter), may recur like a shadow after each subsequent wave of COVID-19 infection anticipated over the next year.

In addition to acute care interruption, COVID-related changes in care patterns will invariably have a negative impact on the comprehensive management of diabetes, including metabolic control, self-care behaviors, and self-management (depicted in the figure as morbidity and mortality related to chronic care interruption).

The extent of these COVID-19 infection waves and their effect on acute or chronic care may vary among countries and will need to be monitored carefully by analyses of national health systems.

Clinical pearls: Mitigation strategies to lesson the damaging impact of chronic care interruption involves health systems and healthcare providers adapting to the "new normal" of reduced or nonexistent face-to-face diabetes visits by adopting virtual technologies and innovative team-based approaches for diabetes management.

Should patients with diabetes be prioritized for COVID-19 vaccine research and rollout?

Many believe that a COVID-19 vaccine is the light at the end of a long tunnel. On the basis of the possible links between COVID-19 and diabetes, perhaps people with diabetes should be among the torchbearers.

With safety trials already underway in many countries, efficacy trials should prioritize people who are at risk for severe infection—those who are older or who have conditions such as diabetes and CVD—so as to potentially expedite vaccine development timelines and to prove efficacious immunity in these highest-risk groups. When an approved vaccine is available, it might also make sense to prioritize vaccinating high-risk groups first, including essential workers.

Harpreet S. Bajaj, MD, MPH, is a community endocrinologist in Brampton, Ontario, and vice chair of the Diabetes Canada Guidelines. His clinical and research interests are the prevention and management of diabetes and its related complications. He is the founder of STOP Diabetes Foundation and volunteers with numerous community public health organizations to raise awareness of diabetes prevention and treatment.

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