Tumor necrosis factor alpha -238G>A genotype alters postprandial plasma levels of free fatty acids in obese individuals with type 2 diabetes mellitus.

Autor: Fontaine-Bisson B; Department of Nutritional Sciences, University of Toronto, Toronto, Canada., Wolever TM, Chiasson JL, Rabasa-Lhoret R, Maheux P, Josse RG, Leiter LA, Rodger NW, Ryan EA, El-Sohemy A
Jazyk: angličtina
Zdroj: Metabolism: clinical and experimental [Metabolism] 2007 May; Vol. 56 (5), pp. 649-55.
DOI: 10.1016/j.metabol.2006.12.013
Abstrakt: Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that impairs insulin action and alters lipid metabolism. We investigated the effects of genetic polymorphisms of TNF-alpha on circulating biomarkers of insulin resistance and lipid metabolism during an 8-hour metabolic profile test and a 2-hour oral glucose tolerance test in subjects with type 2 diabetes mellitus. Subjects (N = 123) recruited were type 2 diabetic men (n = 56) and women (n = 67) aged 36 to 75 years with a body mass index of at least 25 kg/m(2). Blood samples were collected to determine postprandial changes in circulating lipid levels and biomarkers of insulin resistance. Subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism for the TNF-alpha -238G>A, -308G>A, and -863C>A polymorphisms. Compared with subjects who were homozygous for the -238G allele, carriers of the -238A allele had an altered ability to suppress postprandial free fatty acids as shown by an increased net incremental area under the curve (0.26 +/- 2.44 vs -1.33 +/- 2.71 mEq h(-1) L(-1), P = .002) during the 8-hour metabolic profile test. This effect was observed in obese (1.04 +/- 2.42 vs -1.68 +/- 2.70 mEq h(-1) L(-1), P = .0004) but not in non-obese (-0.63 +/- 2.20 vs -0.95 +/- 2.71 mEq h(-1) L(-1), P = .6) individuals. Among obese subjects, carriers of the -308A allele had greater insulin resistance as estimated by the homeostasis model assessment of insulin resistance index (4.36 +/- 2.83 vs 2.85 +/- 1.75, P = .01), but no differences were observed among non-obese subjects (2.19 +/- 1.24 vs 1.97 +/- 0.90, P = .6). Our findings suggest that the -238G>A and -308G>A polymorphisms of TNF-alpha alter circulating free fatty acids and insulin resistance in obese subjects with type 2 diabetes mellitus.
Databáze: MEDLINE