The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes

Abstract

Objective: There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality.

Research design and methods: We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996-1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure.

Results: There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27-3.20), all-cause mortality (HR 1.73, 95% CI 1.38-2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15-2.34), and cancer mortality (HR 2.49, 95% CI 1.46-4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk.

Conclusions: Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.

Figure 1

Severe hypoglycemia HRs and 95% CIs for all-cause mortality by subgroups of the study population. CHD, coronary heart disease. *Cardiovascular risk defined by inclusion criteria for the ACCORD trial.

Figure 2

Hypoglycemia HRs and 95% CIs for cardiovascular disease and mortality outcomes by time since severe hypoglycemic event. All HRs are adjusted for covariates in model 3.