TY - JOUR
T1 - Impaired plasma nonesterified fatty acid tolerance is an early defect in the natural history of type 2 diabetes
AU - Brassard, P.
AU - Frisch, F.
AU - Lavoie, F.
AU - Cyr, D.
AU - Bourbonnais, A.
AU - Cunnane, S. C.
AU - Patterson, B. W.
AU - Drouin, R.
AU - Baillargeon, J. P.
AU - Carpentier, André C.
N1 - Funding Information:
Disclosure Summary: A.C.C. was a new investigator of the Canadian Institutes of Health Research and is currently the recipient of a Fonds de recherche en santé du Québec Junior 2 Scholarship Award. P.B. is the recipient of the Schering-Université de Sherbrooke Department of Medicine Fellowship Award and a Fellowship from the Canadian Diabetes Association. S.C.C. holds the Canada Research Chair in Brain Metabolism and Aging, and his component of this project was supported by Natural Sciences and Engineering Research Council of Canada and the Canadian Foundation for Innovation. R.D. holds the Canada Research Chair in Genetics, Mutagenesis and Cancer. J-P.B. currently holds a Fonds de recherche en santé du Québec Junior 2 Scholarship Award.
Funding Information:
This work was supported by a grant from the Canadian Institutes of Health Research (MOP 53094). Institutions involved in the present studies were supported by grants from the National Institutes of Health at the Biomedical Mass Spectrometry Resource (NIH NCRR-00954) and the Clinical Nutrition Research Unit (NIH P30-DK56341) of the Washington University School of Medicine, the Fonds de recherche en santé du Québec, and an institutional grant of the Centre de Recherche Clinique Étienne-Le Bel.
PY - 2008/3
Y1 - 2008/3
N2 - 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 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. Design: These are cross-sectional studies. Setting: The studies were performed at an academic clinical research center. Participants: 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. Interventions: Pancreatic clamps and iv infusion of stable isotopic tracers ([1,1,2,3,3-2H 5]-glycerol and [U-13C]-palmitate or [1,2- 13C]-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. Main Outcome Measures: 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 μmol/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.
AB - 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 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. Design: These are cross-sectional studies. Setting: The studies were performed at an academic clinical research center. Participants: 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. Interventions: Pancreatic clamps and iv infusion of stable isotopic tracers ([1,1,2,3,3-2H 5]-glycerol and [U-13C]-palmitate or [1,2- 13C]-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. Main Outcome Measures: 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 μmol/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.
UR - http://www.scopus.com/inward/record.url?scp=40849086208&partnerID=8YFLogxK
U2 - 10.1210/jc.2007-1670
DO - 10.1210/jc.2007-1670
M3 - Article
C2 - 18182453
AN - SCOPUS:40849086208
VL - 93
SP - 837
EP - 844
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 3
ER -