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Background: African-Americans (AA) and South Asians (SA) are known to have higher risk for T2D and cardiovascular disease (CVD) compared to Caucasians (CA). Advanced analysis of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into CVD risk and lipid metabolism beyond a standard lipid panel. Insulin resistance (IR) is known to be associated with atherogenic lipoprotein profile. Objective: To characterize the lipoprotein profile in AA, CA, and SA men and women. Design: A cross-sectional study of 182 healthy, non-diabetic SA, AA and CA patients was conducted at NIH. Subjects underwent an intravenous glucose tolerance test from which insulin sensitivity (Si) was derived using the Minimal Model. Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). For group comparisons, Si was adjusted for age and fat free mass. Lipoprotein parameters were adjusted for age and body fat %. Results: Fifty-nine non-diabetic SA (33 males, 26 females), 49 AA (26 males, 23 females), and 74 CA (29 males, 45 females) were included in the study. Ethnic differences in Si were observed in men (p=0.002) but not in women (p=0.43). SA men had a significantly lower Si than both AA and CA men (p=0.02). TG concentrations and TRL particle number were significantly higher in CA men and women when compared with AA. TRLP size was not different between the ethnic groups in either sex. LDL particle number and ApoB concentration was significantly higher in SA men and women compared to AA and CA. There were no ethnic or sex differences in LDL size. HDL concentration, HDL particle number, and ApoA-I levels were not different between the groups in both sexes. However, in SA, large HDL particle number and HDL particle size was significantly lower than CA. Cholesteryl ester transfer protein (CETP) activity was significantly higher in SA men, but not women, when compared with AA and CA. Ethnic differences in LDLP and L-HDLP number remained even after adjusting for Si. Conclusions: In SA men and women, the lipoprotein phenotype (higher LDLP and lower L-HDLP) is independent of insulin sensitivity. Increased CETP activity may contribute to the lower large HDL particle number in this group. In AA, TG and TRLP number were lower as previously reported. Further investigation is needed to determine the factors mediating the atherogenic profile in SA.

OR08-05 Sex and Ethnic Differences in Advanced Lipoprotein Profiles in South Asians, African-Americans, and Caucasians