Background: Characterizing heterogeneity of type 2 diabetes (T2D) is essential for precision diabetes. We investigated phenotype clusters within T2D and their associations with mortality in South Asians.
Methods: In 2,639 individuals diagnosed with T2D from the CARRS cohort, we characterized T2D phenotypes by applying k-means clustering on age at diabetes diagnosis, BMI, HbA1c, HOMA-B, and HOMA-IR. All-cause mortality outcomes within these phenotypes were assessed over a median follow-up of 11-years using the Cox proportional hazard model.
Results: Three distinct phenotypes were identified: Mild Obesity-related Diabetes (MOD; 22.6%), characterized by high BMI but good HbA1c control; Mild Insulin Deficient Diabetes (MIDD; 54.5 %), observed in older individuals with lower BMI, lower HbA1c, and mild insulin deficiency; and Severe Insulin Deficient Diabetes (SIDD; 22.9 %) characterized by young age of onset of diabetes and severely impaired beta-cell function. Compared to individuals with normal glucose tolerance, SIDD exhibited the highest mortality rate followed by MIDD and MOD (Table).
Conclusion: Our data indicate that insulin deficiency phenotypes (MIDD and SIDD) are the primary drivers of T2D in South Asians and account for 82.5% of mortality.
P.K. Tiwari: None. R. Anjana: None. R. Jagannathan: None. D. Kondal: None. M. Deepa: None. U. Gujral: None. G.K. Walia: None. V. Radha: None. R. Pandey: None. S. Sengupta: None. Y. Sun: None. M.K. Ali: Advisory Panel; Eli Lilly and Company. D. Prabhakaran: None. V. Mohan: None. N. Tandon: None. K. Narayan: None.
National Institutes of Health (P01HL154996)
