title: What is the contribution of differences in three measures of tumor necrosis factor-alpha activity to insulin resistance in healthy volunteers?
abstract: To address the potential role that tumor necrosis factor-alpha (TNF-alpha) might play in modulation of insulin resistance in healthy, nondiabetic individuals, we compared plasma TNF-alpha and soluble TNF-alpha receptor 2 (sTNF-R2) concentrations, as well as TNF-alpha polymorphisms, in 94 healthy individuals, stratified into insulin-resistant (IR) and insulin-sensitive (IS) groups based on their plasma insulin concentrations 120 minutes after oral glucose on 2 occasions (1993 and 2000). The IR group (n = 50; 29 men and 21 women) was in the upper quartile and the IS group (n = 44; 24 men and 20 women) in the lowest quartile of the distribution of post-glucose challenge insulin concentrations in a large unselected population (>50 v <23 microU/mL). The IR group had significantly higher values for body mass index, waist-to-hip girth, fasting and post-glucose challenge insulin concentrations, and fasting triglyceride concentrations, and lower high-density lipoprotein cholesterol concentrations as compared to the IS group. Despite the fact that they were relatively more obese, and insulin-resistant, plasma concentrations of TNF-alpha were similar in the IR (1.6 +/- 0.6 pg/mL) and IS (1.7 +/- 0.6 pg/mL) groups, as were the concentrations (5.4 +/- 1.4 v 5.8 +/- 2.0 pg/mL) of sTNF-R2. Furthermore, TNF-alpha polymorphisms (detected by polymerase chain reaction [PCR]) were similar in the 2 groups, with essentially identical allelic frequencies of the 238 (10.3% v 9.4%) and 308 polymorphisms (17.9% v 18.7%). In conclusion, plasma TNF-alpha and sTNF-R2 concentrations, as well as TNF-alpha gene polymorphisms, were not different in healthy volunteers stratified into IR and IS groups on the basis of their plasma insulin response to an oral glucose challenge. Given these data, it does not appear that differences in TNF-alpha activity contribute to the marked variations in insulin action that occur in healthy individuals.
authors.affiliation: Department of Internal Medicine and Biomedical Sciences, Parma University, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Zavaroni
authors.forename: F
authors.initials: F
authors.lastname: Numeroso
authors.forename: P
authors.initials: P
authors.lastname: Dongiovanni
authors.forename: D
authors.initials: D
authors.lastname: Ardigò
authors.forename: L
authors.initials: L
authors.lastname: Valenti
authors.forename: A l
authors.initials: Al
authors.lastname: Fracanzani
authors.forename: S
authors.initials: S
authors.lastname: Valtuena
authors.forename: R
authors.initials: R
authors.lastname: Delsignore
authors.forename: S
authors.initials: S
authors.lastname: Fargion
authors.forename: G M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D005215:Fasting / Q000502:physiology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D005947:Glucose