Current diagnostic classifications for type 2 diabetes mellitus (T2DM) and prediabetes do not fully reflect the heterogeneity of the underlying metabolic abnormalities. Findings from an observational cohort analysis published in Diabetes Care identified distinct data-driven subtypes of T2D and prediabetes in a South Asian population and evaluated their associations with all-cause and cardiovascular disease (CVD) mortality.

The analysis included 14,036 participants from the CArdiometabolic Risk Reduction cohort and applied unsupervised k-means clustering using age, body mass index (BMI), glycated hemoglobin (HbA1c), insulin resistance, and β-cell dysfunction. The analysis identified three T2DM subtypes among 2,639 participants: severe insulin-deficient diabetes (SIDD), mild insulin-deficient diabetes (MIDD), and severe insulin-resistant diabetes (SIRD). Among 4,992 participants with prediabetes, insulin-deficient prediabetes (IDPD) and insulin-resistant prediabetes (IRPD) subtypes were identified.

During a median follow-up of 10.6 years, 1,076 deaths occurred, including 405 attributed to CVD. Compared with individuals with normal glucose tolerance, SIDD was associated with the highest all-cause mortality hazard (HR 3.34; 95% CI, 2.39-4.68), followed by MIDD (HR 1.39; 95% CI, 1.05-1.84) and SIRD (HR 1.67; 95% CI, 1.15-2.41). Within the prediabetes cohort, IDPD was associated with increased all-cause mortality (HR 1.32; 95% CI, 1.03-1.68) and CVD mortality (HR 1.53; 95% CI, 1.00-2.34), whereas IRPD was not associated with increased mortality.

Excess years of life lost were greatest in SIDD at 17.7 years, followed by 12.8 years in MIDD and 12.0 years in SIRD. Overall, insulin-deficient subtypes of T2DM and prediabetes were associated with higher mortality hazards and greater loss of life expectancy in this cohort.