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

Abstract Tumor necrosis factor α (TNF- α ) is a proinflammatory cytokine that impairs insulin action and alters lipid metabolism. We investigated the effects of genetic polymorphisms of TNF- α on circulating biomarkers of insulin resistance and lipid metabolism during an 8-hour metabolic profile tes...

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Published in:Metabolism, clinical and experimental clinical and experimental, 2007, Vol.56 (5), p.649-655
Main Authors: Fontaine-Bisson, Bénédicte, Wolever, Thomas M.S, Chiasson, Jean-Louis, Rabasa-Lhoret, Rémi, Maheux, Pierre, Josse, Robert G, Leiter, Lawrence A, Rodger, N. Wilson, Ryan, Edmond A, El-Sohemy, Ahmed
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Language:English
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Summary:Abstract Tumor necrosis factor α (TNF- α ) is a proinflammatory cytokine that impairs insulin action and alters lipid metabolism. We investigated the effects of genetic polymorphisms of TNF- α 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/m2 . 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- α −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- α alter circulating free fatty acids and insulin resistance in obese subjects with type 2 diabetes mellitus.
ISSN:0026-0495
1532-8600
DOI:10.1016/j.metabol.2006.12.013