2351-P: Assessment of Phenotypic Clustering of Incident and Prevalent Type 2 Diabetes: A MESA Pilot Study in the Definition, Etiology, Function: Integration to Enhance Type 2 Diabetes Treatment (DEFINE-Type 2 Diabetes) Consortium

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Introduction and Objective: Phenotypic clustering of T2D into aging-related (MARD), obesity-related (MOD), insulin-deficient (SIDD), and insulin-resistant (SIRD) subgroups may capture heterogeneity, but performance and stability in diverse populations are uncertain.Methods: We performed established k-means clustering models in 871 prevalent and 462 incident T2D cases with data for age at onset, BMI, HbA1c, HOMA2-IR, and HOMA2-β in the Multiethnic Study of Atherosclerosis across four exams (2000-2007). We assessed subgroup distribution, transitions, and mortality between exams. In 869 prevalent cases with long-term follow-up, we evaluated discrimination for mortality, CVD, and CKD using three models: discrete subgroup membership, continuous subgroup probabilities, or the original variables.Results: MARD was the most common subgroup (50% of prevalent; 64% of incident), while SIDD was rare among incident T2D (0.6%). Incident cases had higher BMI and HOMA2-β and lower HbA1c than prevalent T2D. Silhouette indices were modest (0.22-0.23). Across exams, MARD and SIRD increased in prevalence, and SIDD showed the greatest instability (only 21-42% remaining SIDD) and higher between exam mortality (4-10%). Over 18 years, cumulative incidence of mortality, CVD, and CKD were 38%, 32%, and 50%. Discrimination of these outcomes was similar across the three models (C-indices: mortality 0.696-0.700; CVD 0.642-0.647; CKD 0.669-0.677).Conclusion: In a multiethnic cohort, established T2D clustering shows limited separation, substantial subgroup transitions—especially for SIDD—and similar prognostic performance compared with clinical variables. Accounting for diabetes duration and progression may improve future clustering approaches.

Disclosure

L. Olson: None. F. Hsu: None. K. Smith: None. R. Dagostino Jr: Other – I am on a DSMB for this company; Current; Daiichi Sankyo. Consultant; Ended; Merck & Co., Inc. Other – I am on several DSMBs for this company; Current; AstraZeneca. M. Bancks: None. M. Udler: Advisory Panel; Ended; Novo Nordisk. Research Support; Current; Novo Nordisk.

Funding

National Institutes of Health (1U01DK140778 and 1U01DK140757)



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