What is the contribution of differences in three measures of tumor necrosis factor-alpha activity to insulin resistance in healthy volunteers?

To address the potential role that tumor necrosis factor-alpha (TNF-α) might play in modulation of insulin resistance in healthy, nondiabetic individuals, we compared plasma TNF-α and soluble TNF-α receptor 2 (sTNF-R2) concentrations, as well as TNF-α 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 μU/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-α 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-α 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-α and sTNF-R2 concentrations, as well as TNF-α 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-α activity contribute to the marked variations in insulin action that occur in healthy individuals.