Association of small dense LDL-cholesterol with incident type II diabetes mellitus and metabolic syndrome: The atheroscleosis risk in communities (aric) study

Background -- Elevated small dense low density lipid protein cholesterol (sdLDL-C) levels are highly correlated with increased triglycerides and decreased High-density lipoprotein-cholesterol (HDL-C) and therefore are believed to be part of an atherogenic lipid profile that confers an increased risk for cardiometabolic disease.;Objective -- To assess the association of sdLDL-C levels with the prevalence of the Metabolic Syndrome (MetS) and risk of incident type II diabetes mellitus (T2DM) in Atherosclerosis Risk in Communities (ARIC) study participants.;Methods -- Plasma sdLDL-C was measured using a newly developed automated homogeneous assay in 11,419 individuals at the baseline visit. Cox proportional hazard model was applied to the incident T2DM analysis. The association of sdLDL-C and risk of incident T2DM was also investigated by diabetes risk categories (i.e. non-diabetics (fasting glucose (FG) <100 mg/dl) and pre-diabetics (FG≥100mg/dl)).;Results -- After an average of 12.8 years of follow-up, among 9,447 individuals without prevalent diabetes, 1,960 people developed type II diabetes. The means of sdLDL-C were 46.8 and 41.4 mg/dL (p<0.001) in those with and without incident diabetes respectively. Compared to non-diabetics, people who developed type II diabetes tended to have higher BMI, triglycerides, and lower HDL-C. sdLDL-C was associated with incident diabetes in a model adjusted for established risk factors with a hazard ratio of the highest vs the lowest quartile of 1.27; 95% confidence interval (CI), 1.10--1.47; p trend of linearity across four quartiles was 0.0091. For people with baseline fasting glucose less than 100 mg/dL, if their sdLDL-C levels in the highest quartile, they would have 59% increased risk to develop incident diabetes than those with sdLDL-C levels in the lowest quartile. sdLDL-C was also associated with prevalent MetS in the fully adjusted model with a odds ratio of the highest vs the lowest quartile of 8.57, 95% CI 7.30--10.07, p trend of linearity across quartiles less than 0.0001.;Conclusion -- Elevated plasma sdLDL-C levels were associated with prevalence of MetS and increased risk of incident diabetes in the biracial cohort of the ARIC study. Additional studies are needed to investigate whether sdLDL-C is a useful biomarker for monitoring efficacy of pharmacologic interventions or lifestyle modifiable risk factors for type II diabetes.