Introduction and Objective: Subtypes of type 2 diabetes (T2D) identified at diagnosis differ in risks of diabetes complications. We modeled their metabolic trajectories preceding diagnosis to inform subtype membership and pathophysiology.Methods: From cohort studies (ARIC, CARDIA, DPP/OS, JHS, MESA), we subtyped individuals with newly diagnosed T2D (n = 2,691; age = 63 years [SD: 12], 60% female) and identified those without T2D (n = 20,233; age = 63 years [SD: 13]; 56% female). We estimated adjusted trajectories of BMI, HbA1c, homeostasis model estimates of β-cell function [HOMA2-%B] and insulin resistance [HOMA2-IR] in the 15 years before diagnosis or last follow-up using linear mixed models and natural splines.Results: Severe Insulin Deficient Diabetes (SIDD), Mild Obesity-related Diabetes, and Severe Insulin Resistant Diabetes (SIRD) had increasing BMI in the 15 years before diagnosis, relative to the Mild Age-related Diabetes and those without T2D (Figure). Relative to those without T2D, in the five years before diagnosis, SIDD displayed sharp increases in HbA1c (4.6% points, 95%CI: 4.5, 4.8) and decreases in HOMA2-%B (-84.5, 95%CI: -84.6, -84.3), while SIRD displayed sharp increases in HOMA2-IR (2.2, 95%CI: 2.0, 2.3) and HOMA2-%B (42.2, 95%CI: 42.1, 42.3).Conclusion: Distinct metabolic trajectories suggest early separation of T2D subtypes from each other and those without T2D.
J. Varghese: None. J. Guo: None. Z. Li: None. Q. Xue: None. H. Shao: None. H.H. Chang: None. S.A. Patel: None. M.K. Ali: Advisory Panel; Eli Lilly and Company.
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