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Treatment of Obese, Diet-Restricted Subjects with Growth Hormone for 11 Weeks: Effects on Anabolism, Lipolysis, and Body Composition^*

Departments of Medicine and Pediatrics, University of North Carolina Chapel Hill, North Carolina 27599

Address requests for reprints to: Dr. David Snyder, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.

We found in a previous study that injections of GH for 3 weeks caused nitrogen conservation despite restriction of intake to 24 Cal (100 kJ)/kg ideal BW (IBW). To determine the effects of longer periods of treatment and further caloric restriction on nitrogen balance, lipolysis, and body composition, 20 obese (30–67% over IBW) subjects (16 women and 4 men; 20–54 yr old) were fed a diet of 18 Cal (75 kJ)/kg IBW with 1.2 g protein/kg IBW daily for 13 weeks. During weeks 2–12, 10 subjects received injections of recombinant methionyl GH (0.1 mg/kg IBW every other day), and the other 10 sex-, age-, and weight-matched subjects were given injections of saline.

There were no significant differences between the two groups in total weight lost [GH, 13.9 ± 3.0 (±SD) kg; saline, 15.2 ± 3.8 kg] or the percentage of body fat lost (GH, 8.1 ± 2.4%; saline, 7.5 ± 1.5%), although GH injection caused a significant acute increment in serum FFA concentrations (GH, 0.53 ± 0.37 mmol/L; saline, 0.08 ± 0.22 mmol/L; P < 0.001) throughout the study. This acute lipolytic response to GH decreased significantly, from 0.86 ± 0.32 mmol/L on day 1 of GH treatment to 0.35 ± 0.41 mmol/L by day 35 of GH injection (P < 0.01). Nitrogen balance was significantly more positive in the group receiving GH during the first 33 days of the GH injection period [GH, +0.07 ± 1.82 g/day (+5.0 ± 130.0 mmol/day); saline, –1.91 ± 1.10 g/day (–136.3 ± 78.5 mmol/day); P < 0.001]. During the last 44 days of GH injection, however, the nitrogen balance in the two groups was similar [GH, –0.90 ± 1.65 g/day (–64.2 ± 117.8 mmol/day); saline, –1.08 ± 0.95 g/day (–77.1 ± 67.8 mmol/day); P = NS]. Mean plasma insulin-like growth factor I (IGF-I) concentrations rose from a basal value of 1.6 ± 0.8 to 2.9 ± 1.2 U/mL by 48 h after the first GH injection and ranged subsequently from 3.2 ± 1.3 to 4.9 ± 3.3 U/mL during GH injection (P < 0.001). In contrast, the mean IGF-I concentration did not change in the group that received saline. Dietary restriction during the first week of study caused serum T₃ concentrations to decline in both groups. With GH injection, T₃ values increased to basal levels, but after 38 days of GH injections T₃ concentrations declined again and thereafter were not significantly different from the saline group. GH injections did not produce glucose intolerance. There were no significant differences between the two groups in fasting or postprandial serum insulin concentrations, 24-h urinary C-peptide excretion, or serum protein glycosylation.

We conclude that GH promotes nitrogen retention and increases plasma IGF-I concentrations in obese subjects despite caloric restriction. GH produced no significant acceleration of fat loss. Of major importance is the observation that after 5 weeks of therapy the anabolic effects were lost, but plasma IGFI concentrations remained elevated. We speculate that this loss of anabolic effect might result from the development of resistance to IGF-I.

^* This work was supported by NIH Research Grants AG-02331, AM-01022, and HD-08299; NIH Training Grant AM-07129; and a grant from Genentech, Inc. The Clinical Research Unit of the University of North Carolina is supported by Grant RR-00046 from the General Clinical Research Centers Program of the Division of Research Resources, NIH

Received October 12, 1987.

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