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

• Published in: Metabolism, clinical and experimental clinical and experimental, 2007-05, 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Cholesterol - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; DNA - chemistry; DNA - genetics; Fatty Acids, Nonesterified - blood; Female; Genotype; Glucose Tolerance Test; Humans; Insulin Resistance; Lipid Metabolism; Male; Middle Aged; Obesity - blood; Obesity - genetics; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Postprandial Period; Triglycerides - blood; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0026-0495
• DOI: 10.1016/j.metabol.2006.12.013

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.