Elsevier

Metabolism

Volume 54, Issue 2, February 2005, Pages 264-270
Metabolism

Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study

https://doi.org/10.1016/j.metabol.2004.09.002Get rights and content

Abstract

Background

Insulin resistance and obesity are associated with a dyslipidemia composed of high levels of triglycerides (TG), low levels of high-density lipoprotein cholesterol (HDL-C), and no change in level of low-density lipoprotein cholesterol (LDL-C). We examined the association of insulin resistance and adiposity with lipoprotein particle size, concentration, and subclass concentrations.

Methods

The Insulin Resistance Atherosclerosis Study is a multicenter cohort study of middle-aged men and women. Lipoprotein lipid concentrations were determined using standard methods. Lipoprotein size, particle concentration, and subclass concentrations were determined using nuclear magnetic resonance technology. Insulin resistance (SI) was determined based on the frequently sampled intravenous glucose tolerance test and the MINMOD program. A higher SI represents less insulin resistance. Fasting insulin, body mass index, waist circumference, and waist/hip ratio were assessed.

Results

Among the 1371 participants were 754 women and 617 men; 459 Hispanics, 383 African Americans, and 529 non-Hispanic whites; 437 with type 2 diabetes, 301 with impaired glucose tolerance, and 633 with normal glucose tolerance. The mean (SD) age was 55.5 (8.5) years, body mass index was 29.3 (5.8) kg/m2, and SI was 1.6 (1.8) units. Adjusted for age, sex, and ethnicity, SI was not associated with LDL-C (r = 0.01); however, SI was associated with LDL size (r = 0.34, P < .001), LDL particle concentration (r = −0.28, P < .001), small LDL (r = −0.34, P < .001), intermediate LDL (r = −0.37, P < .001), and large LDL (r = 0.21, P < .001). In addition, SI was associated with TG (r = −0.36, P < .001), VLDL particles (r = −0.08, P < .01), large VLDL (r = −0.32, P < .001), VLDL size (r = −0.38, P < .001), HDL-C (r = 0.37, P < .001), HDL particles (r = 0.09, P < .001), large HDL (r = 0.31, P < .001), and HDL size (r = 0.33, P < .001). A factor analysis revealed a factor that accounted for 41.4% of the variance across the lipoprotein measures and that was correlated with SI (r = −0.33, P < .001). Similar results of opposing direction were observed for analyses of lipoprotein measures with fasting insulin and adiposity.

Conclusions

The dyslipidemia associated with insulin resistance and obesity includes effects on lipoprotein metabolism that are missed when traditional lipoprotein cholesterol and total TG are examined. Lipoprotein size and subclasses should be examined in studies investigating the roles of insulin resistance and obesity in the pathogenesis and prevention of atherosclerosis.

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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