Effects of Insulin Resistance and Type 2 Diabetes on Lipoprotein Subclass Particle Size and Concentration Determined by Nuclear Magnetic Resonance

Effects of Insulin Resistance and Type 2 Diabetes on Lipoprotein Subclass Particle Size and Concentration Determined by Nuclear Magnetic Resonance W. Timothy Garvey 1 2 , Soonho Kwon 1 , Deyi Zheng 3 , Sara Shaughnessy 1 , Penny Wallace 1 , Amy Hutto 1 , Kimberly Pugh 1 , Alicia J. Jenkins 1 , Richard L. Klein 1 2 and Youlian Liao 3 1 Division of Endocrinology and Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 2 Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina 3 Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, South Carolina Abstract The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic clamps in 56 insulin sensitive (IS; mean ± SD: GDR 15.8 ± 2.0 mg · kg −1 · min −1 , fasting blood glucose [FBG] 4.7 ± 0.3 mmol/l, BMI 26 ± 5), 46 insulin resistant (IR; GDR 10.2 ± 1.9, FBG 4.9 ± 0.5, BMI 29 ± 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 ± 2.8, FBG 10.8 ± 3.7, BMI 30 ± 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size ( r = −0.40) and an increase in large VLDL particle concentrations ( r = −0.42), a decrease in LDL size ( r = 0.42) as a result of a marked increase in small LDL particles ( r = −0.34) and reduced large LDL ( r = 0.34), an overall increase in the number of LDL particles ( r = −0.44), and a decrease in HDL size ( r = 0.41) as a result of depletion of large HDL particles ( r = 0.38) and a modest increase in small HDL ( r = −0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL),