Causes of Excess Mortality in Diabetes Patients Without Coronary Artery Disease: A Cohort Study Revealing Endocrinologic Contributions

BACKGROUND: Diabetes mellitus (DM) patients without coronary artery disease (CAD) have a higher all-cause mortality rate than patients with neither DM nor CAD. We examined cause-specific death of DM patients with and without CAD. METHODS: We conducted a cohort study of all patients who underwent CAG in Western Denmark between 2003 and 2016. Using Danish health registries, patients were followed for a maximum of 10 years and stratified according to their DM and CAD status. Outcomes included all-cause-, cancer-, circulatory-, and endocrinologic death. Ten-year cumulative risks were computed as well as adjusted and unadjusted hazard ratios (aHR and HR). RESULTS: A total of 132,432 patients (28,524 deaths, median follow-up of 6.2 years) were included. Compared to patients with neither DM nor CAD, DM patients without CAD had a higher 10-year risk of all-cause death (27.9% versus 19.7%, aHR 1.43 [95% CI 1.35-1.52]), cancer death (7.2% versus 5.4%, aHR 1.29 [95% CI 1.15-1.46]), circulatory death (9.1% versus 6.9%, aHR 1.35 [95% CI 1.22-1.49]), and endocrinologic death (3.9% versus 0.3%, aHR 14.02 [95% CI 10.95-17.95]). Among endocrinologic deaths, 87% were due to classical complications of DM, such as diabetic nephropathy and ketoacidosis, in DM patients without CAD. CONCLUSION: Diabetes patients without CAD exhibit a higher risk of all-cause mortality, driven primarily by elevated rates of cancer, circulatory, and endocrinologic deaths, particularly related to diabetic microvascular complications.