The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.
BACKGROUND
The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, 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 patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA.


METHODS
We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects.


RESULTS
The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 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 recombinant 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. controls). 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-alpha do not reflect the degree of insulin resistance in obesity and GHDA. They, however, do not exclude that TNF-alpha may induce insulin resistance at tissue level.
Pincelli
A I
AI
Chair of Endocrinology, University of Milan, IRCCS Ospedale San Luca, Istituto Auxologico Italiano, Milan, Italy.
Brunani
A
A
Scacchi
M
M
Dubini
A
A
Borsotti
R
R
Tibaldi
A
A
Pasqualinotto
L
L
Maestri
E
E
Cavagnini
F
F
D000273:Adipose Tissue; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D001824:Body Constitution; D015992:Body Mass Index; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D019382:Human Growth Hormone / Q000172:deficiency* / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007700:Kinetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha