The Atherogenic Lipoprotein Profile Associated With Obesity and Insulin Resistance Is Largely Attributable to Intra-Abdominal Fat
- Delma J. Nieves,
- Miriam Cnop,
- Barbara Retzlaff,
- Carolyn E. Walden,
- John D. Brunzell,
- Robert H. Knopp and
- Steven E. Kahn
- From the Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System and Harborview Medical Center, University of Washington, Seattle, Washington
Obesity and insulin resistance are both associated with an atherogenic lipoprotein profile. We examined the effect of insulin sensitivity and central adiposity on lipoproteins in 196 individuals (75 men and 121 women) with an average age of 52.7 years. Subjects were subdivided into three groups based on BMI and their insulin sensitivity index (SI): lean insulin sensitive (n = 65), lean insulin resistant (n = 73), and obese insulin resistant (n = 58). This categorization revealed that both obesity and insulin resistance determined the lipoprotein profile. In addition, the insulin-resistant groups had increased central adiposity. Increasing intra-abdominal fat (IAF) area, quantified by computed tomography scan and decreasing SI, were important determinants of an atherogenic profile, marked by increased triglycerides, LDL cholesterol, and apolipoprotein B and decreased HDL cholesterol and LDL buoyancy (Rf). Density gradient ultracentrifugation (DGUC) revealed that in subjects who had more IAF and were more insulin resistant, the cholesterol content was increased in VLDL, intermediate-density lipoprotein (IDL), and dense LDL fractions whereas it was reduced in HDL fractions. Multiple linear regression analysis of the relation between the cholesterol content of each DGUC fraction as the dependent variable and IAF and SI as independent variables revealed that the cholesterol concentration in the fractions corresponding to VLDL, IDL, dense LDL, and HDL was associated with IAF, and that SI additionally contributed independently to VLDL, but not to IDL, LDL, or HDL. Thus an atherogenic lipoprotein profile appears to be the result primarily of an increase in IAF, perhaps via insulin resistance.
Address correspondence and reprint requests to Steven E. Kahn, ChB, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108. E-mail:.
Received for publication 10 May 2002 and accepted in revised form 2 October 2002.
D.J.N. and M.C. contributed equally to this work
Current address for C.E.W. is College of Medicine Research Office, University of Arizona, Tucson, AZ.
CT, computed tomography; DGUC, density gradient ultracentrifugation; IAF, intra-abdominal fat; IDL, intermediate-density lipoprotein; LIR, lean insulin resistant; LIS, lean insulin sensitive; OIR, obese insulin resistant; Rf, LDL relative flotation; SCF, subcutaneous fat; SI, insulin sensitivity index; WHR, waist-to-hip ratio.