Impact of 2 weeks high dose growth hormone treatment on basal and insulin stimulated substrate metabolism in humans.

OBJECTIVE

Short-term, high dose growth hormone (GH) treatment has been advocated in many catabolic disease states. It is likely that some of the anabolic effects of GH are mediated through activation of lipolysis, but the metabolic impact of therapeutically relevant GH exposure is not known in detail. The present study was accordingly designed to assess the effects of such GH exposure on basal and insulin stimulated intermediary metabolism.

DESIGN, PATIENTS AND MEASUREMENTS: Six healthy young females were examined following daily injections of GH (12 IU/day) or saline for 2 weeks in a placebo controlled design. Each study consisted of a 3 hour basal period and a 2 hour hyperinsulinaemic euglycaemic clamp.

RESULTS

GH treatment caused (1) increased levels of IGF-I (382 +/- 46 vs 294 +/- 22 micrograms/l, P < 0.05) and (2) increased basal values of free fatty acids (714 +/- 40 (GH) vs 634 +/- 64 (placebo) mumol/l, P < 0.05), 3-hydroxybutyrate (118.3 +/- 42.8 (GH) vs 57.7 +/- 21.6 (placebo) mumol/l, P < 0.05), glycerol (54.3 +/- 8.2 (GH) vs 41.4 +/- 8.4 (placebo) mumol/l, P < 0.05) and forearm uptake of 3-hydroxybutyrate, together with increments of plasma glucose (5.28 +/- 0.11 (GH) vs 4.87 +/- 0.16 (placebo) mmol/l, P < 0.05). Basal forearm uptake of glucose, isotopically determined glucose turnover and serum levels of GH, insulin and C-peptide were unaltered. During the clamp GH treatment was associated with (1) a 40% decrease in the administered amount of glucose (M-value) (P < 0.05) and (2) a 70% decrease in forearm glucose uptake (P < 0.05). Indirect calorimetry revealed a 15% increase in resting energy expenditure (P < 0.05) and a decreased basal respiratory exchange ratio (0.75 (GH) vs 0.80 (placebo), P < 0.05), presumably reflecting increased lipid oxidation.

CONCLUSIONS

Administration of GH in a therapeutic dose for 2 weeks, despite apparently normal daytime levels of major metabolic hormones, induces significant increases in circulating lipid fuel substrates, increased energy expenditure and lipid oxidation, together with insulin resistance. Such effects should be considered when applying GH treatment schedules clinically.