1307-P: To What Extent Are the Risks in Prediabetes Explained by Progression to Diabetes?

Introduction: Prediabetes is associated with elevated risks of microvascular and macrovascular complications but it is unknown to what extent progression from prediabetes to diabetes explains these associations. Methods: In 11536 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46-70, ~55% women, ~20% Black) without diabetes at baseline (1990-2), we used Cox regression to characterize associations of prediabetes (A1C 5.7-6.4%) with incident atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), non-traumatic amputation, and all-cause mortality before and after accounting for time-varying diabetes. We calculated the excess risk in prediabetes explained by progression to diabetes. Results: Of the ~20% of adults with prediabetes at baseline, ~40% progressed to diabetes (median time to diabetes, ~15 years). Over ~25 years of follow-up, there were 2195 ASCVD and 2307 HF events, 100 amputations, and 5556 deaths. Prediabetes was associated with modestly elevated risks of all outcomes (Figure). Incident diabetes accounted for 15% of CVD risk, 19% of HF risk, 24% of amputation risk, and 29% of mortality risk in persons with baseline prediabetes. Conclusion: Progression to diabetes explained an important fraction of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to risk of clinical outcomes even when persons do not progress to overt diabetes. Disclosure M.R.Rooney: None. J.Echouffo tcheugui: None. P.Lutsey: None. M.Fang: None. J.Hu: None. M.Grams: None. J.Coresh: Consultant; Healthy.io Ltd, SomaLogic. E.Selvin: None.