Background: Current definitions of prediabetes fail to capture the heterogeneity of the type 2 diabetes (T2D) pathophysiology. We aim to identify clusters of prediabetes among South Asians and explore their associations with diabetes incidence and overall mortality.
Methods: Data from individuals with prediabetes based on the ADA criteria in the CARRS study were clustered using the k-means approach based on age, BMI, HbA1c, HOMA-B, and HOMA-IR. T2D incidence (based on the ADA criteria) and all-cause mortality were assessed using Cox proportional hazards models.
Results: Two distinct prediabetes phenotypes emerged: insulin resistant (35.8%) and insulin-deficient (64.2%). Among 5,794 individuals (normal glucose tolerance (NGT): 2,882; prediabetes: 2,912), over a median follow-up of 11 years, 487 individuals developed T2D, and 212 individuals died. Both insulin resistant and insulin deficient prediabetes phenotypes were associated with T2D incidence compared to NGT, but only insulin-deficient phenotype showed increased mortality risk (Table).
Conclusion: Two-thirds of South Asians with prediabetes exhibit insulin deficient phenotype, contributing to 74% of diabetes incidence and associated with increased mortality. This data could guide precision prevention interventions based on diabetes pathophysiology.
R. Jagannathan: None. D. Kondal: None. P.K. Tiwari: None. U. Gujral: None. R. Anjana: None. M. Deepa: None. G.K. Walia: None. S. Sengupta: None. R. Pandey: None. V. Radha: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. Y. Sun: None. D. Prabhakaran: None. N. Tandon: None. V. Mohan: None. K. Narayan: None.
The CARRS study has been funded with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health (HHSN2682009900026C, P01HL154996)
