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

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 1 ) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR; 2 ) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance; and 3 ) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NMR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS.