Differential Association Between HDL Subclasses and the Development of Type 2 Diabetes in a Prospective Study of Japanese Americans

OBJECTIVE: Recent studies have suggested that HDL cholesterol is inversely associated with the development of type 2 diabetes. However, little is known about the association between different HDL subclasses and the risk for future type 2 diabetes. RESEARCH DESIGN AND METHODS: The study enrolled 406 Japanese Americans (51% male) without diabetes, aged 34–75 years. Oral glucose tolerance tests were performed to determine type 2 diabetes status at baseline, 2.5 years, 5 years, and 10 years after enrollment. HDL2, HDL3, total HDL cholesterol, and visceral adipose tissue (VAT) area by computed tomography were measured at baseline. RESULTS: In univariate analysis, total HDL and HDL2 cholesterol were inversely associated with the incidence of type 2 diabetes, but HDL3 cholesterol was not. In multivariate analysis, total HDL cholesterol (odds ratio per 1-SD increment, 0.72 [95% CI 0.52–0.995], P = 0.047) and HDL2 cholesterol (odds ratio per 1-SD increment, 0.64 [95% CI 0.44–0.93], P = 0.018) were inversely associated with the risk for type 2 diabetes independent of age, sex, BMI, waist circumference, family history of diabetes, lifestyle factors, systolic blood pressure, lipid-lowering medication use, triglyceride level, HOMA-insulin resistance, and 2-h glucose; however, HDL3 cholesterol was not associated with diabetes risk. The association between diabetes risk and total HDL and HDL2 cholesterol became insignificant after adjustment for VAT area. CONCLUSIONS: Subjects with higher HDL2 cholesterol were at lower risk for incident type 2 diabetes, but this association was confounded by and not independent of VAT. Higher HDL3 cholesterol was not associated with diabetes risk.