Nuclear Magnetic Resonance Lipoprotein Abnormalities in Prediabetic Subjects in the Insulin Resistance Atherosclerosis Study

BACKGROUND: Subjects with type 2 diabetes have smaller LDL and HDL particles in addition to higher levels of triglycerides and lower HDL cholesterol. Elevated insulin resistance, blood pressure, and dyslipidemia (including small dense LDL) predicted incident diabetes. In the Insulin Resistance Atherosclerosis Study (IRAS) we studied nuclear magnetic resonance (NMR) lipoprotein particle measures in prediabetic individuals, considering potentially modifying covariates, including insulin resistance, as directly measured using a frequently sampled intravenous glucose tolerance test. METHODS AND RESULTS: Of 830 subjects who were nondiabetic at baseline, 130 (15.7%) developed diabetes after a mean follow-up of 5.2 years. Various lipoprotein abnormalities were found in prediabetic subjects compared with subjects who stayed nondiabetic at follow-up. In logistic regression analyses (demographically adjusted), VLDL particles, large VLDL, LDL particles, small LDL, large HDL, small HDL, VLDL size, LDL size, and HDL size were related to incident diabetes. The relation of VLDL size and small HDL to incident diabetes was independent of waist (odds ratio OR 95% CI, 1.43 1.18 to 1.73 and 1.23 1.01 to 1.51 for VLDL size and small HDL, respectively) and independent of conventionally (chemically) measured triglycerides and HDL cholesterol (OR 95% CI, 1.45 1.18 to 1.78 and 1.30 1.06 to 1.60, respectively). Insulin sensitivity attenuated the relation to incident diabetes of VLDL size (OR 95% CI, 1.25 1.01 to 1.53) but not of small HDL particles (OR 95% CI, 1.25 1.02 to 1.54). CONCLUSIONS: We have shown a range of lipoprotein abnormalities in prediabetic individuals, including compositional changes in HDL and VLDL. These findings extend previous work indicating a proatherogenic state in healthy, nondiabetic subjects who subsequently develop diabetes.