title: Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study.
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, S I 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, S I 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.
authors.affiliation: Public Health Sciences and Internal Medicine, Wake Forest University School of Meicine, Winston-Salem, NC 27157-1063, USA. dgoff@wfubmc.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000886:Anthropometry; D001161:Arteriosclerosis / Q000097:blood*; D001823:Body Composition / Q000502:physiology*; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D049629:Waist-Hip Ratio
chemical_list: D007328:Insulin; D008055:Lipids; D008074:Lipoproteins