“Diabetes is widely thought to increase susceptibility to infection by impairing neutrophil functioning, antioxidant systems, and humoral immune response,” explains Michael Fang, Ph.D. “Consistent with this hypothesis, diabetes is associated with an increased risk of common and rare infections. However, most studies on this association have examined small clinical populations and were cross-sectional or had short follow-up periods. Few large, prospective studies have investigated the link between diabetes and future risk of infection-related outcomes in the general population.”

For a paper published on Diabetologia, Dr. Fang and colleagues assessed the association between diabetes and risk for infection-related hospitalization and mortality. They conducted a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study, which included more than 12,000 participants (mean age, 54.5; 24.7% Black; 54.3% female). Hospitalization for infection was ascertained from hospital discharge records. Participants were followed from 1987-1989 to 2019.

A Growing Public Health Issue

“There are at least two important reasons why studying the link between diabetes and infection-related outcomes is important,” Dr. Fang says. “First, there’s an ongoing pandemic caused by an infectious disease. We found that persons with diabetes are especially susceptible to some of the most serious adverse outcomes related to infections. This is consistent with the emerging research on diabetes and serious COVID-19 outcomes (eg, hospitalization and mortality). These findings indicate that people with diabetes may need to be especially cautious. Second, even prior to the COVID-19 pandemic, recent studies have shown an increase in the rate of hospitalization for infection among adults in the United States with diabetes. This is a growing public health issue, and we wanted to continue raising awareness around the link between diabetes and infection.”

The study team found that serious infection-related complications are an underappreciated issue among patients with diabetes. “When clinicians consider diabetic complications, they traditionally focus on microvascular issues or cardiovascular disease,” Dr. Fang says. “Accordingly, clinical guidelines have largely focused on preventing and managing these conditions. However, our study shows that people with diabetes are also at higher risk for serious infection-related complications, including hospitalization and death. This suggests that diabetes guidelines should provide more comprehensive guidance on infection prevention and management, as current guidelines focus mostly on foot care and routine vaccinations (eg, for influenza). These are undoubtedly important, but there is a pressing need to more broadly understand how to prevent and manage infections effectively in people with diabetes, especially given the ongoing COVID-19 pandemic.”

 Significantly Higher Risk of Mortality

The researchers found that increased risk for infection-related hospitalization among patients with diabetes exists regardless of age, sex, race, income, and other factors. This risk was stronger for Black versus White individuals and younger versus older adults (Figure). When compared with patients without diabetes, those with the condition had a significantly higher risk for dying from an infection, even after accounting for other comorbidities. “Taken together, these findings suggest that diabetes may confer risk for the most serious infection-related outcomes,” Dr. Fang says.

Dr. Fang and colleagues note the need to address two important questions in future researcher. “First, why is diabetes associated with an increased risk of infection-related complications?” asks Dr. Fang, rhetorically. “One likely factor is glycemic control. Emerging research suggests that patients with diabetes with better glycemic control may be at a significantly lower risk of infection-related complications. Second, why is diabetes more strongly associated with certain populations, including younger people and Blacks?  With respect to younger patients, emerging literature suggests that diabetes tends to be more aggressive when it emerges early in life. These studies generally focus on cardiovascular disease and microvascular issues, but our results suggest that infection-related complications may be another condition associated with earlier diabetes onset. With respect to Black patients, new research highlights racial differences in glycemic control, access to care, and beliefs surrounding vaccines. Further understanding the role of these different mechanisms will be important to developing effective guidance for clinicians.”