ADVANCING AGE AND INSULIN-RESISTANCE - ROLE OF PLASMA TUMOR-NECROSIS-FACTOR-ALPHA

In 70 healthy subjects with a large age range, the relationships betwe en plasma tumor necrosis factor-alpha (TNF-alpha) and body composition , insulin action, and substrate oxidation were investigated. In the cr oss-sectional study (n = 70), advancing age correlated with plasma TNF -alpha concentration (r = 0.64, P < 0.001) and whole body glucose disp osal (WBGD; r = -0.38, P < 0.01). The correlation between plasma TNF-a lpha and age was independent of sex and body fat (BF; r = 0.31, P < 0. 01). Independent of age and sex, a significant relationship between pl asma TNF-alpha and leptin concentration (r = 0.29, P < 0.02) was also found. After control for age, sex, BF, and waist-to-hip ratio (WHR), p lasma TNF-alpha was still correlated with WBGD (r = -0.33, P < 0.007). Further correction for plasma free fatty acid (FFA) concentration mad e the latter correlation no more significant. In a multivariate analys is, a model made by age, sex, BF, fat-free mass, WHR, and plasma TNF-a lpha concentrations explained 69% of WBGD variability with age (P < 0. 009), BF (P < 0.006), fat-free mass (P < 0.005), and plasma TNF-alpha (P < 0.05) significantly and independently associated with WBGD. In th e longitudinal study, made with subjects at the highest tertiles of pl asma TNF-alpha concentration (n = 50), plasma TNF-alpha concentration predicted a decline in WBGD independent of age, sex, BF, WHR [relative risk (RR) = 2.0; 95% confidence intervals (CI) = 1.2-2.4]. After furt her adjustment for plasma fasting FFA concentration, the predictive ro le of fasting plasma TNF-alpha concentration on WBGD (RR = 1.2; CI = 0 .8-1.5) was no more significant. In conclusion, our study demonstrates that plasma TNF-alpha concentration is significantly associated with advancing age and that it predicts the impairment in insulin action wi th advancing age.