Introduction:
Studies evaluating the relationship of severe hypoglycemia (SH) with the risk of atherosclerotic cardiovascular disease (ASCVD) events are limited by size, confounding and inconsistent outcome definitions. The aim of this study was to assess the association of SH, as defined by hypoglycemia-related hospital utilization, with risk of ASCVD.
Methods:
We conducted an observational cohort study of adults with diabetes with or without established ASCVD (as of 1/1/2014). All subjects were members of Kaiser Permanente Northern California, an integrated health care delivery system. Baseline was determined by the date of the first hypoglycemia-related utilization (primary diagnosis of hypoglycemia in the emergency department or principal diagnosis in the hospital) during 1/1/2013 - 12/31/2013. Baseline for those without SH, was a randomly assigned date in 2013. Multivariate Cox proportional hazard models were specified to estimate hazard ratios (HRs) for SH in adjusted models of time to incident ASCVD events. This outcome was defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through 12/31/2017.
Results:
Among 233,696 eligible individuals, mean age was 63.6 years, 47.6% were women, and mean follow-up was 3.8 years. There were 2,179 episodes of SH. Age-sex-race adjusted risk of ASCVD among those with SH versus those without was HR 2.59 (95% CI 2.3-2.9). When additionally adjusted for prior ASCVD, the HR was still more than double, HR 2.32 (95% CI 2.1-2.6). In a fully saturated model with additional adjustments for diabetes type, diabetes duration, HbA1c, GFR, Charlson score, insulin use, sulfonylureas, and quartiles of neighborhood deprivation, SH was associated with a 30% increased risk (HR 1.31, 95% CI 1.16-1.5). The substantial attenuation in risk after more comprehensive adjustment suggests that patients at higher risk of SH are likely at higher risk of ASCVD.
Conclusions:
In a large, diverse and contemporary cohort of patients with diabetes, SH as defined by hypoglycemia-related hospital utilization is associated with greater risk of ASCVD. Increased awareness in recognizing this risk and vigilance in care for this higher risk population is warranted.
Severe Hypoglycemia and Risk of Atherosclerotic Cardiovascular Disease in Patients With Diabetes
