Abstract 076: Risk of Atherosclerotic Cardiovascular Disease and Heart Failure by Type 2 Diabetes Subtypes

Introduction: Type 2 diabetes (T2D) appears to have subtypes with different trajectories of health. Compared to the mild obesity-related (MOD) and mild age-related (MARD) subtypes, the severe insulin-deficient (SIDD) subtype has higher HbA1c, reduced beta-cell function, younger age at diagnosis, and is consistently associated with a higher risk of diabetic retinopathy and neuropathy. However, little is known about the heterogeneity in risk for types of atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) by T2D subtype ( Figure 1 ). Methods: To describe the risks of ASCVD and HF by T2D subtypes, we analyzed electronic health records (EHRs) of newly diagnosed T2D from USA (2012-2023), defined using the SUPREME-DM phenotype, in the Epic Cosmos Research Platform (n = 727,076; 64.4 years [SD:13.3] and 52% female). Using previously validated models to identify subtypes in EHRs (AUC: 0.81-0.99, F1 score: 0.87-0.90), we classified T2D cases as SIDD (21.6%), MOD (23.8%), MARD (40.9%), and Mixed (13.7%). Six outcomes were defined using ICD-10-CM codes within five years after T2D diagnosis and included: severe ASCVD (non-ST [NSTEMI] and ST [STEMI] elevation myocardial infarction, unstable angina, stroke) and Heart Failure (preserved [HFpEF] and reduced [HFrEF] ejection fraction). We reported hazard ratios [HR] from Cox Proportional Hazards models adjusting for age, sex, and medications (statin, ACE/ARB, beta blockers). Results: Compared to MOD, SIDD was associated with higher hazards of NSTEMI (HR,1.68 [95%CI,1.61-1.75]), STEMI (HR, 1.48 [95%CI,1.40-1.56]), unstable angina (HR,1.41 [95%CI,1.34-1.48]), stroke (HR, 1.62 [95%CI,1.57-1.68]), HFrEF (HR, 1.36 [95%CI,1.32-1.41]) and HFpEF (HR, 1.10 [95%CI,1.07-1.13]) ( Figure 2 ). MARD had elevated hazards for NSTEMI (HR, 1.16 [95%CI,1.11-1.21]), STEMI (HR, 1.13 [95%CI,1.07-1.21]), stroke (HR, 1.20 [95%CI,1.16-1.25]) and angina [HR,1.07 [95%CI,1.01-1.13]), but lower hazards of HFpEF (HR, 0.72 [95%CI, 0.70-0.74]) and HFrEF (HR, 0.94 [95%CI, 0.91-0.97]) relative to MOD. The Mixed subtype had hazards similar to MARD for all outcomes. Conclusions: SIDD was associated with the highest risk of cardiovascular complications, relative to milder subtypes. These findings highlight the need to evaluate targeted prevention and treatment strategies tailored to this high-risk T2D subtype to reduce the burden of cardiovascular disease.