2318-P: Heterogeneity in Rates of Mortality among Subtypes of Prediabetes

Introduction and Objective: Prediabetes is a clinically heterogeneous and an independent risk factor for mortality. Identifying subtypes of prediabetes at elevated risk for mortality can improve targeted enrollment in preventive interventions. Methods: Adults (≥18 years; n = 14,568) with prediabetes (HbA1c 5.6-6.4% or fasting glucose 100-125 mg/dL) from pooled cohort studies were followed until death or administrative censoring at 15 years. Prediabetes was classified into seven subtypes using data-driven clustering of ten variables (Panel A). Cox proportional hazards was used to estimate covariate-adjusted relative hazards (HR) by subtype. Validation was conducted among prediabetes cases in the nationally representative NHANES 1999-2018 sample with linked mortality data (n = 11,284). Results: Among the analytic sample (57 years [SD: 10]; 51% female), 2,198 died. Prediabetes subtypes were similar in their 15-year hazards of mortality. In the validation sample (52 years [SD: 18.1]; 46% female), relative to the overweight and normotensive group, obesity with severe insulin resistance and older age with severe insulin resistance were associated with highest rates of mortality. Conclusion: Prediabetes subtypes may differ in mortality risk, with higher hazard ratios observed among insulin-resistant (IR) subtypes in NHANES but not in the Pooled Cohorts. Further research should disentangle the heterogeneity in the period before diabetes for further risk stratification. Disclosure T. Hung: None. D. Hua: None. Z. Li: None. R.N. Ekanayake: None. J. Guo: None. J. Varghese: None.