METABOLIC EFFECTS OF BIOSYNTHETIC GROWTH-HORMONE TREATMENT IN SEVERELY ENERGY-RESTRICTED OBESE WOMEN

OBJECTIVE: Severe energy restriction in the treatment of obesity is li mited by catabolism of body protein stores and, consequently, loss of lean as well as fat tissue. Growth hormone (GH), whose secretion is ma rkedly impaired in obesity, is endowed with both lipolytic and protein anabolic properties. The aim of this study was to verify the effects of GH administration on body composition, plasma leptin levels and ene rgy metabolism in obese patients undergoing severe dietary restriction . DESIGN: Single-blind placebo-controlled study. Twenty obese women we re fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks : 10 of them were randomly assigned to a 4 week treatment with biosynt hetic GH (rhGH, Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections; the other 10 patients, matched for age and B MI, received vehicle only. SUBJECTS: Twenty women with simple obesity (age: 25.4 +/- 1.07 y, BMI: 35.9 +/- 0.35 kg/m(2)). MEASUREMENTS: Plas ma IGF-I and leptin, serum markers of bone turnover (serum bone isoenz yme of alkaline phosphatase, osteocalcin and urinary hydroxyproline), nitrogen balance, body composition (by DEXA), and resting energy expen diture (REE, by indirect calorimetry) were evaluated at baseline and a fter 4 weeks. RESULTS: Mean IGF-I plasma levels, not influenced by ene rgy restriction in patients receiving placebo, displayed a significant increase in the group treated with rhGH. The mean weight reduction an d fat mass loss were not significantly different in the two groups (6. 0 +/- 0.51 vs 7.2 +/- 0.30 kg, NS, and 5.36 +/- 0.460 vs 4.28 +/- 0.57 2 kg, NS, with rhGH and placebo, respectively). Likewise, plasma lepti n levels decreased significantly in weight-reduced subjects receiving either rhGH (from 16.2 +/- 2.37 to 6.4 +/- 0.39 ng/ml, P < 0.05) or pl acebo (from 14.3 +/- 2.55 to 7.7 +/- 3.77 ng/ml, P < 0.05). On the con trary, the mean decrease of lean body mass (LBM) was significantly low er in the GH-treated patients than in those receiving vehicle (1.52 +/ - 0.60 vs 3.79 +/- 0.45 kg, P < 0.05). In keeping with these findings, the mean daily nitrogen balance was significantly less negative in th e GH-treated subjects than in the vehicle-injected patients (mean of t he 4 week daily urine collections - 185.7 +/- 40.33 vs - 363.9 +/- 55. 47 mmol/d, P < 0.05, respectively). Further, a significant reduction o f mean REE was recorded in the energy-restricted placebo-treated patie nts (from 8807 +/- 498 to 7580 +/- 321 kJ/24 h, P < 0.05), but not in the patients receiving rhGH (from 8367 +/- 580 to 8903 +/- 478 kJ/24h, NS). Actually, when corrected for LBM, REE was even increased by GH a dministration (from 197.9 +/- 11.76 to 219.3 +/- 9.87 kJ/kg LBM/24h, P < 0.05), whereas it was unchanged in the placebo group (from 201.7 +/ - 13.85 to 190.0 +/- 9.87 kJ/kg LBM/24 h, NS). A tendency of serum mar kers of bone turnover to increase was observed in the patients treated with rhGH, however with no changes in bone mineral content and densit y. CONCLUSION: rhGH treatment, though unable to enhance diet-induced w eight and fat mass reduction, was effective in stimulating IGF-I produ ction and conserving LBM and increasing its energy metabolism even in the presence of severe energy restriction.