Diabetes Mellitus-Related All-Cause and Cardiovascular Mortality in a National Cohort of Adults

Background-Diabetes mellitus is a risk factor for cardiovascular disease (CVD) and has been associated with 2- to 4-fold higher mortality. Diabetes mellitus-related mortality has not been reassessed in individuals receiving routine care in the United States in the contemporary era of CVD risk reduction. Methods and Results-We retrospectively studied 963 648 adults receiving care in the US Veterans Affairs Healthcare System from 2002 to 2014; mean follow-up was 8 years. We estimated associations of diabetes mellitus status and hemoglobin A1c (HbA1c) with all-cause and CVD mortality using covariate-adjusted incidence rates and multivariable Cox proportional hazards regression. Of participants, 34% had diabetes mellitus. Compared with nondiabetic individuals, patients with diabetes mellitus had 7.0 (95% CI, 6.7-7.4) and 3.5 (95% CI, 3.3-3.7) deaths/1000-person-years higher all-cause and CVD mortality, respectively. The age-, sex-, race-, and ethnicity-adjusted hazard ratio for diabetes mellitus-related mortality was 1.29 (95% CI, 1.28-1.31), and declined with adjustment for CVD risk factors (hazard ratio, 1.18 [95% CI, 1.16-1.19]) and glycemia (hazard ratio, 1.03 [95% CI, 1.02-1.05]). Among individuals with diabetes mellitus, CVD mortality increased as HbA1c exceeded 7% (hazard ratios, 1.11 [95% CI, 1.08-1.14], 1.25 [95% CI, 1.22-1.29], and 1.52 [95% CI, 1.48-1.56] for HbA1c 7%-7.9%, 8%-8.9%, and >= 9%, respectively, relative to HbA1c 6%-6.9%). HbA1c 6% to 6.9% was associated with the lowest mortality risk irrespective of CVD history or age. Conclusions-Diabetes mellitus remains significantly associated with all-cause and CVD mortality, although diabetes mellitusrelated excess mortality is lower in the contemporary era than previously. We observed a gradient of mortality risk with increasing HbA1c > 6% to 6.9%, suggesting HbA1c remains an informative predictor of outcomes even if causality cannot be inferred.