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 lipolys is, but the metabolic impact of therapeutically relevant GH exposure i s not known in detail. The present study was accordingly designed to a ssess 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/d ay) or saline for 2 weeks in a placebo controlled design. Each study c onsisted of a 3 hour basal period and a 2 hour hyperinsulinaemic eugly caemic clamp. RESULTS GH treatment caused (1) increased levels of IGF- I (382 +/- 46 vs 294 +/- 22 mug/l, P < 0.05) and (2) increased basal v alues of free fatty acids (714 +/- 40 (GH) vs 634 +/- 64 (placebo) mum ol/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-hydroxybut yrate, 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 treatmen t 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 glucos e uptake (P < 0.05). Indirect calorimetry revealed a 15% increase in r esting energy expenditure (P < 0.05) and a decreased basal respiratory exchange ratio (0.75 (GH) vs 0.80 (placebo), P < 0.05), presumably re flecting increased lipid oxidation. CONCLUSIONS Administration of GH i n a therapeutic dose for 2 weeks, despite apparently normal daytime le vels of major metabolic hormones, induces significant increases in cir culating lipid fuel substrates, increased energy expenditure and lipid oxidation, together with insulin resistance. Such effects should be c onsidered when applying GH treatment schedules clinically.