Abstract MP31: Incident Type 2 Diabetes Onset Age and Duration, Mortality Risk, and Loss in Life Expectancy

Introduction: Evidence on the relationship between type 2 diabetes onset age, duration, and mortality risk has been influenced by limited follow-up, inadequate control for confounding, and inability to cover the full range of onset age, duration, and the full spectrum of major causes of death. Moreover, there are scarce data dissecting how type 2 diabetes onset age and duration shape life expectancy. Hypothesis We assessed the hypothesis that early onset of type 2 diabetes and longer disease duration may be associated with higher risk of all-cause and cause-specific mortality and greater loss in life expectancy. Methods: We prospectively followed 270,075 eligible participants in the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study longitudinal cohorts for up to 40 years. The exposures include type 2 diabetes onset age (<40, ≥40 to <50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 years) and duration (<10, ≥10 to <20, ≥20 to <30, and ≥30 years). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age and a wide spectrum of potential confounders. Results: We documented 73,076 deaths during 8,166,216 person-years of follow-up. In fully-adjusted analyses, incident early-onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), kidney disease (8.55, 1.98-36.9), and suggestively increased mortality from diabetes-related cancer (1.63, 0.94-2.83) and obesity-related cancer (1.63, 0.92-2.88). The relative risk elevations declined dramatically with each higher decade of age at type 2 diabetes diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Comparing individuals with early-onset type 2 diabetes to those without type 2 diabetes, their estimated multivariable-adjusted cumulative incidence of all-cause mortality at age 80 was 0.43 vs. 0.20, and the estimated life expectancy loss at age 40 was 2.5 years. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Conclusions: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy. The effect of early-onset type 2 diabetes on mortality risk is stronger than that of later-onset type 2 diabetes.