Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study
Introduction
Insulin resistance, adiposity, and diabetes are associated with a dyslipidemia composed of high concentrations of triglycerides (TG), low concentrations of high-density lipoprotein cholesterol (HDL-C), and no change in concentration of low-density lipoprotein cholesterol (LDL-C) [1], [2], [3], [4], [5], [6], [7]. Although LDL-C concentrations are unaffected, insulin resistance, adiposity, and diabetes influence LDL size [1], [8], [9]. Previous investigations of these relationships have been based most often on results regarding lipoprotein size and subclass quantification from gradient gel electrophoresis [1], [8], [9]. Recently, nuclear magnetic resonance (NMR) techniques have been developed that enable the high volume assessment of lipoprotein size, concentration, and subclass concentration [10], [11]. The automated nature of this NMR method may lead to increased clinical use of this information. Garvey and colleagues [12] reported the association of insulin resistance and diabetes with lipoprotein subclass, particle size, and concentration from a small group (n = 148) of patients examined using the hyperinsulinemic clamp. In this report, we examined the association of insulin resistance, measured directly using the frequently sampled intravenous glucose tolerance test [13], and adiposity with lipoprotein size, particle concentration, and subclass concentrations measured using NMR technology in a large and ethnically diverse cohort.
Section snippets
Design and population
The objectives, design, and methods of the Insulin Resistance Atherosclerosis Study (IRAS) have been published previously [14]. Briefly, the major objective of IRAS was to assess the relationship between insulin resistance and atherosclerosis. This cross-sectional epidemiologic study was conducted at 4 clinical centers. African Americans and non-Hispanic whites were studied in center in Oakland and Los Angeles, Calif, and Hispanics and non-Hispanic whites were studied in centers in San Luis
Results
The IRAS cohort included 1625 participants. Data were available for the present analyses for 1371 participants with mean (SD) age of 55.5 (8.5) years. Other characteristics are shown in Table 1. The study population was slightly more than half women and approximately one third each were African Americans, Hispanic Americans, and non-Hispanic whites. Almost half had NGT, approximately one fifth had IGT, and three tenths had diabetes. There were no substantive differences between persons with and
Discussion
Nuclear magnetic resonance technology reveals a complex array of relationships between lipoprotein particles (including size, concentration, and subfraction concentration), glucose tolerance status, insulin sensitivity, and adiposity.
The dyslipidemia associated with insulin resistance and obesity includes a derangement of LDL metabolism that is missed when only total LDL-C concentration is examined. The lack of association between LDL-C concentration and measures of insulin sensitivity and
Acknowledgment
This study was supported by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health, Bethesda, Md (NHLBI grants no. HL47887, HL47889, HL47890, HL47892, and HL47902) and by the General Clinical Research Centers Program of the National Center for Research Resources (M01 RR431 and M01 RR01346).
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