Relationship between Diabetes and infection-related hospitalizations

Diabetes is linked with an increased risk of common and rare infections…

Diabetes increases the likelihood of infection by damaging neutrophil performance, antioxidant systems, and humoral immune response. Diabetes Guidelines focus on preventing microvascular and macrovascular complications. There is less emphasis on the role of Diabetes as it pertains to infections which can lead to hospitalization. In the past 15 years, the general rate of hospitalizations from infections in the United States has remarkably increased, particularly in individuals with Diabetes. Recently, Diabetes has emerged as a considerable risk factor for adverse events in Covid-19 infection and hospitalization. Thus, the goal is to examine the relationship between diabetes and infection leading to hospitalization risk in the atherosclerosis risk in communities (ARIC) study.

 The ARIC is a continuing community-based cohort to analyze the etiology of atherosclerotic disease. The study participants consisted of 15,792 adults 45-64 years of age from Forsyth County, NC; Jackson, MS; suburban Minneapolis, MN and Washington County, MD. All participants provided written informed authorization and approval of the study by institutional review boards at all research facilities. Due to the small sample size, participants who were not black or white were not a part of the study. Black participants in Minneapolis, MN, or Washington County, MD, were not a part of the study yielding 12,379 participants.

The definition of Diabetes at baseline is fasting glucose less than or equal to 7 mmol/1 and non-fasting baseline less than or equal 11.1 mmol/1. Diabetes status was confirmed through participants’ self-reporting diagnosis of Diabetes by a physician. Due to antibody testing not being performed, the researchers could not distinguish between type 1 and type 2 diabetes in the analyses. The ARIC study conducted ongoing active surveillance of hospitalizations for all participants. Prior hospitalization is hospitalization for infection of ICD-9-CM/ICD-10-CM code such as mortality. Linking the national death index, telephone interviews with participants representatives, and review of state records all played a role in determining the vital status of the participants. Questionnaires were utilized at baseline to gather information on participant’s demographic characteristics and lifestyle behaviors. From the demographic characteristics, race and study center were merged into a single measure to account for the unequal amount of black and white participants across research sites.

The Cox proportional hazard design examined the relationship between Diabetes and risk of hospitalization due to infection and infection mortality. The Cox proportional hazard evaluated three methods. Design 1 included age, sex, and race center. Design 2 consisted of design one and SES score, health insurance status, smoking, and alcohol consumption. Design 3 consisted of design two and BMI, hypertension, CKD, CHD status, HDL-cholesterol and triacylglycerols, and LDL-cholesterol. The risk for hospitalization due to infection with Diabetes was computed as a time-varying exposure in sensitivity analyses. The Poisson model roughly calculated the rate of total hospitalization for infections and repeating events. The study utilized Stata 16.0 to perform calculations with a two side P-value less than 0.05 being statistically significant.

The general rate of hospitalization for infection was 15.9 per 1000 person-years. Participants with Diabetes had a higher likelihood of hospitalization due to infection, with their rate being 25.4 per 1000 person-years. The higher probability of hospitalization due to infection associated with Diabetes was evaluated for all subgroups and was more significant for black and younger participants. Diabetes is associated with an increased risk of almost every kind of infection, particularly foot infections.

The study presented many limitations, such as determining whether participants presented with type 1 or type 2 diabetes and HBA1C not evaluated at baseline. Other restrictions included the study’s interpretation of hospitalization for infection remaining unverified from medical record review, missed milder cases of infections, and physicians being more inclined to refer patients with Diabetes to hospitals instead of outpatient settings when infections arise. Ultimately, Diabetes is associated with a higher risk of hospitalization due to infection. Raising prevention and early treatment of infections in individuals with Diabetes is necessary to lessen infection-related morbidity and mortality.

Practice pearls:

Diabetes increases the likelihood of infection.

Diabetes is associated with a greater risk of hospitalization due to infection.

Hospitalization rates due to infections associated with Diabetes were higher in black participants and younger participants.

References

Fang, M., Ishigami, J., Echouffo-Tcheugui, J. B., Lutsey, P. L., Pankow, J. S., & Selvin, E. (2021, August 4). Diabetes and the risk of hospitalization for infection: The atherosclerosis risk in communities (ARIC) study. Diabetologia. https://link.springer.com/article/10.1007/s00125-021-05522-3#ref-CR14.

Bertoni, A. G., Saydah, S., & Brancati, F. L. (2001, June 1). Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care. https://care.diabetesjournals.org/content/24/6/1044.

Emmanuella Louissaint, PharmD candidate, LECOM College of Pharmacy