Impaired Plasma Nonesterified Fatty Acid Tolerance Is an Early Defect in the Natural History of Type 2 Diabetes

• DOI: 10.1210/jc.2007-1670
• Publication Date: 2008-01-09T03:34:08Z
• Authors: P. Brassard; F. Frisch; F. Lavoie; D. Cyr; A. Bourbonnais; S. C. Cunnane; B. W. Patterson; R. Drouin; J.-P. Baillargeon; A. C. Carpentier
• Keywords: NEFA

Abstract Context: Abnormal plasma nonesterified fatty acid (NEFA) metabolism may play a role in the development of type 2 diabetes. Objectives: Our objectives were to demonstrate whether there is defect insulin-mediated suppression NEFA appearance (RaNEFA) and oxidation (OxNEFA) during enhanced intravascular triacylglycerol lipolysis early natural history diabetes, if so, determine other mechanisms than reduced intracellular are involved. Design: These cross-sectional studies. Setting: The studies performed at an academic clinical research center. Participants: Nine healthy subjects with both parents diabetes (FH+) nine no first-degree relatives (FH−) similar anthropometric features included Interventions: Pancreatic clamps iv infusion stable isotopic tracers ([1,1,2,3,3-2H5]-glycerol [U-13C]-palmitate or [1,2-13C]-acetate) while was simultaneously clamped by heparin plus Intralipid low (fasting) high insulin levels. Oral nicotinic (NA) used inhibit lipolysis. Main Outcome Measures: RaNEFA OxNEFA determined. Results: During levels, despite lipolytic rates, FH+ had higher FH− (RaNEFA: 17.4 ± 6.3 vs. 9.2 4.2; OxNEFA: 4.5 1.8 2.3 1.5 μmol/kg lean body mass/min), independent NA intake, gender, age, composition. In presence NA, still observed FH−, but not FH+. Conclusions: Increased levels occur