title: Acute hyperinsulinemia and very-low-density and low-density lipoprotein subfractions in obese subjects.
abstract: BACKGROUND
  The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified.
  
  
  OBJECTIVE
  We analyzed VLDL and LDL subfractions before and after a euglycemic, hyperinsulinemic clamp.
  
  
  METHODS
  Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obese patients, obese patients with type 2 diabetes, and nonobese control subjects.
  
  
  RESULTS
  Hyperinsulinemia tended to reduce concentrations (&xmacr;: 20%) of large, triacylglycerol-rich VLDL(1) in obese patients but had a minor effect on VLDL(2) and VLDL(3). Placing obese patients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL(1) concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (&xmacr;: 62%; P < 0.01). VLDL(1) concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL(3) concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes.
  
  
  CONCLUSIONS
  Insulin resistance appears to be the primary determinant of the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obese patients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia.
authors.affiliation: Clinical Diabetes Unit, Division of Endocrinology and Diabetology, and the Division for Treatment of Chronic Diseases, University Hospital, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Bioletto
authors.forename: A
authors.initials: A
authors.lastname: Golay
authors.forename: R
authors.initials: R
authors.lastname: Munger
authors.forename: B
authors.initials: B
authors.lastname: Kalix
authors.forename: R W
authors.initials: RW
authors.lastname: James
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL