title: Impaired plasma nonesterified fatty acid tolerance is an early defect in the natural history of type 2 diabetes.
abstract: BACKGROUND
  Abnormal plasma nonesterified fatty acid (NEFA) metabolism may play a role in the development of type 2 diabetes.
  
  
  OBJECTIVE
  Our objectives were to demonstrate whether there is a defect in insulin-mediated suppression of plasma NEFA appearance (RaNEFA) and oxidation (OxNEFA) during enhanced intravascular triacylglycerol lipolysis early in the natural history of type 2 diabetes, and if so, to determine whether other mechanisms than reduced insulin-mediated suppression of intracellular lipolysis are involved.
  
  
  METHODS
  These are cross-sectional studies.
  
  
  METHODS
  The studies were performed at an academic clinical research center.
  
  
  METHODS
  Nine healthy subjects with both parents with type 2 diabetes (FH+) and nine healthy subjects with no first-degree relatives with type 2 diabetes (FH-) with similar anthropometric features were included in the studies.
  
  
  METHODS
  Pancreatic clamps and iv infusion of stable isotopic tracers ([1,1,2,3,3-(2)H5]-glycerol and [U-(13)C]-palmitate or [1,2-(13)C]-acetate) were performed while intravascular triacylglycerol lipolysis was simultaneously clamped by iv infusion of heparin plus Intralipid at low (fasting) and high insulin levels. Oral nicotinic acid (NA) was used to inhibit intracellular lipolysis.
  
  
  METHODS
  RaNEFA and OxNEFA were determined.
  
  
  RESULTS
  During heparin plus Intralipid infusion at high plasma insulin levels, and despite similar intravascular lipolytic rates, FH+ had higher RaNEFA and OxNEFA than FH- (RaNEFA: 17.4+/-6.3 vs. 9.2+/-4.2; OxNEFA: 4.5+/-1.8 vs. 2.3+/-1.5 micromol/kg lean body mass/min), independent of NA intake, gender, age, and body composition. In the presence of NA, insulin-mediated suppression of RaNEFA was still observed in FH-, but not in FH+.
  
  
  CONCLUSIONS
  Increased RaNEFA and OxNEFA during intravascular lipolysis at high insulin levels occur early in the natural history of type 2 diabetes.
authors.affiliation: Department of Medicine, Division of Endocrinology, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: P
authors.initials: P
authors.lastname: Brassard
authors.forename: F
authors.initials: F
authors.lastname: Frisch
authors.forename: F
authors.initials: F
authors.lastname: Lavoie
authors.forename: D
authors.initials: D
authors.lastname: Cyr
authors.forename: A
authors.initials: A
authors.lastname: Bourbonnais
authors.forename: S C
authors.initials: SC
authors.lastname: Cunnane
authors.forename: B W
authors.initials: BW
authors.lastname: Patterson
authors.forename: R
authors.initials: R
authors.lastname: Drouin
authors.forename: J-P
authors.initials: JP
authors.lastname: Baillargeon
authors.forename: A C
authors.initials: AC
authors.lastname: Carpentier
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005260:Female; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D005990:Glycerol