The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance

Backgound: The tumor necrosis factor alpha (TNF-a) might play a central rol e in insulin resistance, a frequent correlate of obesity likely contributin g to some obesity-associated complications. Adult growth hormone (GH) defic iency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemi a, increased cardiovascular risk, and insulin resistance. On the other hand , GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA pati ents. No information is presently available on the relationship between ser um TNF-alpha levels and insulin sensitivity in GHDA. Methods: We compared t he serum TNF-a levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone p opulation of 16 obese (OB) patients and in 38 normal-weight healthy blood d onors (controls). The insulin sensitivity was assessed by a euglycemic-hype rinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 c ontrol subjects. Results: The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at basel ine (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A sligh t decrease of TNF-a values was noted in GHDA patients after 6 months of rec ombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The in sulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.3 0 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recomb inant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. control s). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. Conclusions: These data indicate that circulating concentrations of TNF-a do not reflect the degree of insu lin resistance in obesity and GHDA. They, however, do not exclude that TNF- a may induce insulin resistance at tissue level. Copyright (C) 2001 S. Karg er AG, Basel.