title: Tumor necrosis factor alpha -238G>A genotype alters postprandial plasma levels of free fatty acids in obese individuals with type 2 diabetes mellitus.
abstract: 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.
authors: Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
authors: Bénédicte
authors: B
authors: Fontaine-Bisson
authors: Thomas M S
authors: TM
authors: Wolever
authors: Jean-Louis
authors: JL
authors: Chiasson
authors: Rémi
authors: R
authors: Rabasa-Lhoret
authors: Pierre
authors: P
authors: Maheux
authors: Robert G
authors: RG
authors: Josse
authors: Lawrence A
authors: LA
authors: Leiter
authors: N Wilson
authors: NW
authors: Rodger
authors: Edmond A
authors: EA
authors: Ryan
authors: Ahmed
authors: A
authors: El-Sohemy
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002784:Cholesterol / Q000097:blood; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D002784:Cholesterol