Advancing age and insulin resistance: role of plasma tumor necrosis factor-alpha.
In 70 healthy subjects with a large age range, the relationships between plasma tumor necrosis factor-alpha (TNF-alpha) and body composition, insulin action, and substrate oxidation were investigated. In the cross-sectional study (n = 70), advancing age correlated with plasma TNF-alpha concentration (r = 0.64, P < 0.001) and whole body glucose disposal (WBGD; r= -0.38, P < 0.01). The correlation between plasma TNF-alpha 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 plasma 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), plasma TNF-alpha was still correlated with WBGD (r = -0.33, P < 0.007). Further correction for plasma free fatty acid (FFA) concentration made the latter correlation no more significant. In a multivariate analysis, a model made by age, sex, BF, fat- free mass, WHR, and plasma TNF-alpha 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 the longitudinal study, made with subjects at the highest tertiles of plasma 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 further adjustment for plasma fasting FFA concentration, the predictive role 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 with advancing age.
Department of Geriatric Medicine and Metabolic Diseases, University of Napoli, 80138 Naples, Italy.
G
G
Paolisso
M R
MR
Rizzo
G
G
Mazziotti
M R
MR
Tagliamonte
A
A
Gambardella
M
M
Rotondi
C
C
Carella
D
D
Giugliano
M
M
Varricchio
F
F
D'Onofrio
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D011506:Proteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha