740-P: Six Subclasses with Glucose and Insulin Curves during OGTTs Capture Distinct Metabolic Characteristics and the Most Common Pathway to T2D in a Cohort of Koreans

Abstract

Heterogeneity of glucose abnormalities makes prevention and treatment of diabetes challenging. Subclasses of people at high risk have been identified based on glucose profiles during OGTTs. However, previous work on subclasses lacks longitudinal confirmation. Here, we used glucose and insulin during OGTTs and k-means clustering to classify subclasses of people without diabetes and then determined the model-derived beta-cell function (BCF) and insulin sensitivity (IS) within each subclass. We identified metabolic risk and the most common pathway to T2D by tracking transitions of subclasses over the 16-year Korean Genome Epi. Study. Participants underwent OGTTs every 2 years for up to 16 years or until diabetes (N=2682, BMI=24.4±2.9 kg/m2, age 49.8±7.6 y). 1) 6 subclasses: Cluster A: Normal BCF, Normal IS, B: Mildly impaired BCF and IS, C: Impaired BCF, mildly impaired IS, D: Strong BCF, impaired IS, E: Mildly impaired BCF, impaired IS, F: Strong BCF, severely impaired IS; 2) Cluster C had the highest risk for T2D, HR: 10.7 (8.0, 14.1), compared to cluster A, followed by Clusters E, B, F, and D; Transition from A to B and C was the most common pathway; A, B, and C together comprised 86% of the cohort. Clustering using glucose and insulin classified 6 subgroups showing distinct metabolic parameters and identified the most common pathway to T2D in Koreans. Disclosure J.Kim: None. H.Kang: None. S.T.Chung: None. A.Sherman: None. S.Kim: None. J.Ha: None. W.Yi: None. D.Kim: None. M.Im: None. S.Ryang: None. M.Kim: None. Y.Kim: None. I.Kim: None. Y.Kim: None. Funding Busan Economic Promotion Agency; National Research Foundation of Korea (2022H1D3A2A01063552); Korea Health Industry Development Institute (HI18C2383); dkNET New Investigator Pilot Program in Bioinformatics; National Institute of Diabetes and Digestive and Kidney Diseases