Growth hormone administration in addition to a very low calorie diet and an exercise program in obese subjects

Drent ML, Wever LDV, Adèr HJ, van der Veen EA. Growth hormone administration in addition to a very low calorie diet and an exercise program in obese subjects. Eur J Endocrinol 1995;132:565–72. ISSN 0804–4643 A major problem of weight reduction in obesity is the undesirable loss of lean body mass that accompanies fat loss, particularly in severe calorie restriction. In order to achieve maximal fat loss, but without great loss of lean tissue, growth hormone (GH) in a dose of 6 U/day subcutaneously was added to a very low calorie diet and an exercise program for moderately obese subjects. Body weight, body composition and hormonal status were studied during an eight-week period. The results of seven patients using GH (seven females; mean age 39.1 ± 7.9 years; mean body weight 94.2 ± 10.7 kg; mean body mass index 35.1 ± 2.3 kg/m2) were compared to the results of eight patients using placebo (two males, six females; mean age 38.9 ± 10.4 years; 100.0 ± 11.0 kg; mean body mass index 32.9 ± 1.9 kg/m2). The groups were comparable for demographic data. Both serum insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) levels became significantly higher in the GH group (p = 0.001 and p = 0.014, respectively). Mean serum IGF-I levels increased from 29.0 ± 8.19 nmol/l at randomization to 50.14 ± 14.66 nmol/l after 2 weeks in the GH group, whereas the levels decreased from 34.25 ± 10.26 nmol/l to 27.63 ± 8.14 nmol/l in the placebo group. After two weeks, IGF-I and IGFBP-3 levels stabilized. In the first half of the study serum free triiodothyronine (T3) levels remained stable in the GH group, whereas a decrease was found in the placebo group. Mean serum free T3 level in the GH group was 5.59 ± 0.74 pmol/l at randomization and 5.69 ± 0.76 pmol/l after 2 weeks of treatment, whereas in the placebo group mean serum free T3 level decreased from 5.89 ± 1.04 pmol/l at randomization to 4.61 ± 0.78 pmol/l after two weeks (p = 0.033). In the same period, serum insulin levels increased in the GH group but remained unchanged in the placebo group. In the second half of the study these differences between both groups disappeared. However, in this period serum norepinephrine levels increased in the GH group and a trend in the same direction was seen for serum epinephrine levels. These changes were accompanied by an increase in both systolic and diastolic blood pressure following a consistent decrease in the previous weeks. Total weight loss was similar in both groups: 12.8 ± 5.0 kg in the GH group versus 13.8 ± 4.0 kg in the placebo group. The decreases in fat mass, lean body mass and body water as measured by means of bioelectrical impedance analysis also were not different between the groups. The nitrogen balance tended to be less negative in the GH group (mean nitrogen loss 3.37± 1.23 g/day) compared to the placebo group (4.41 ± 1.58 g/day) (p = 0.18), indicating a clinically relevant reduction in loss of muscle mass over the 8-week period. It can be concluded that the addition of GH in a low, but effective, dose to a very low calorie diet and exercise program in moderately obese patients induces significant changes in the hormonal status. Although these effects do not result in a greater weight loss or significant changes in body composition as measured by means of bioelectrical impedance analysis, a relevant reduction in muscle mass loss seems to be achieved. ML Drent, Department of Endocrinology, Free University Hospital, Boelelaan 1117, 1081 HV Amsterdam, The Netherlands