COVID-19 and Diabetes: Understanding the Interrelationship and Risks for a Severe Course

Abstract

The relationship between COVID-19 and diabetes mellitus is complicated and bidirectional. On the one hand, diabetes mellitus is considered one of the most important risk factors for a severe course of COVID-19. Several factors that are often present in diabetes mellitus are likely to contribute to this risk, such as older age, a proinflammatory and hypercoagulable state, hyperglycemia and underlying comorbidities (hypertension, cardiovascular disease, chronic kidney disease and obesity). On the other hand, a severe COVID-19 infection, and its treatment with steroids, can have a specific negative impact on diabetes itself, leading to worsening of hyperglycemia through increased insulin resistance and reduced β-cell secretory function. Worsening hyperglycemia can, in turn, adversely affect the course of COVID-19. Although more knowledge gradually surfaces as the pandemic progresses, challenges in understanding the interrelationship between COVID-19 and diabetes remain.

Keywords: COVID-19; SARS-CoV-2; comorbidities; coronavirus; diabetes; mortality; severity; treatment.

Figure 1

Illustration of the interrelationship between SARS-CoV-2, COVID-19 and diabetes. The relationship between COVID-19 and diabetes is complicated and bidirectional. Diabetes mellitus is one of the most important risk factors for severe COVID-19. In a patient with diabetes, the associated comorbidities and diabetes-related complications as well as certain demographic features can further contribute to this higher risk of a severe course of COVID-19. Another key factor is glycemic control. On the one hand, hyperglycemia is a strong risk factor for a more severe course of COVID-19. On the other hand, the hyperinflammation associated with severe COVID-19 as well as its treatment with steroids can cause or worsen hyperglycemia through an effect on insulin target tissues (predominantly liver, muscle and fat cells) reducing insulin sensitivity (insulin resistance), as well as on pancreatic β-cells causing insufficient insulin secretion. There may even be a direct effect of SARS-CoV-2 on the β-cell through the ACE-2 receptor, but this is controversial. Hyperglycemia itself can lead to glucose toxicity, thus further decreasing insulin sensitivity and insulin secretory function. Hereby, the risk of severe COVID-19 in patients with diabetes is increased even further. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; ACE-2, angiotensin converting enzyme 2.