Phenotyping lipid profiles in type 2 diabetes: Risk association and outcomes from the Cardiovascular Health Study

To determine whether discrete lipid profiles (refer to as lipid phenotyping) can be used to stratify cardiovascular risk in individuals with type 2 diabetes.

Cardiovascular Health Study participants with diabetes and fasting lipid profiles at baseline (n = 866) were categorized separately by level of LDL cholesterol and HDL-C/Triglyceride (Tg) profiles (low Tg/high HDL-C; high Tg/low HDL-C; high Tg only or low HDL-C only). We performed Cox multivariate regression analysis to assess the risk of CVD mortality, incident myocardial infarction (MI), heart failure (HF), stroke, and composite MACE (MI, HF, stroke, and CVD mortality) associated with each lipid category. We also calculated risk estimates for MACE using lipid measures as continuous variables. In the fully adjusted model, the high triglyceride plus low HDL-C cholesterol phenotype demonstrated risk that was at least as high as the highest LDL-C sub-group phenotype for CVD mortality (Hazard ratio {HR} 1.58 vs 1.48), MI (HR 1.53 vs 1.58), HF (HR 1.47 vs 1.20), stroke (HR 2.02 vs 1.43), and MACE (HR 1.58 vs 1.38). When modeled continuously, the HR per SD for MACE was 1.12 (p = 0.03) for LDL-C and 1.19-1.20 (p < 0.001) for triglycerides or remnant cholesterol.

Participants with the high triglyceride/low HDL-C phenotype had equivalent or higher CVD risk than those with the high LDL-C phenotype. Further studies are necessary to determine whether lipid phenotyping accounts for the substantial CVD risk not explained by LDL cholesterol among individuals with type 2 diabetes.