The metabolic effects of short-term administration of physiological versus high doses of GH therapy in GH deficient adults

OBJECTIVE: GH treatment has demonstrated favourable effects on most features of GH deficiency in hypopituitary adults. However, most studies employed supraphysiological GH doses, resulting in deterioration in insulin sensitivity (S_I). The short-term metabolic effects of physiological doses of GH therapy in GH deficient (GHD) adults are largely unknown. We therefore compared the effects of short-term administration of two 'physiological' ('lowest' dose: 0.0017 mg/kg/day; 'low' dose: 0.0033 mg/kg/day) with two 'supraphysiological' ('high' dose: 0.010 mg/kg/day; 'highest' dose: 0.025 mg/kg/day) GH doses on S_I, β-cell function, IGF-1 and IGFBPs -1 and -3 in a group of GHD adults. PATIENTS AND METHODS: Thirteen GHD adults were recruited (seven men, aged 23-63 years). For each of the four doses, six patients (three men) were allocated randomly to undergo a 7-day treatment phase. Fasting blood samples were collected daily (days 1-8), and S_I and β-cell function were calculated using the homeostasis model assessment (HOMA). RESULTS: All four GH doses increased IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio, and decreased IGFBP-1 from day 3 onwards (P < 0.05). The highest dose increased fasting glucose (P < 0.001), insulin (P < 0.001) and β-cell function (P(P < 0.001). < 0.001), but decreased S_I The high and low doses did not modify fasting glucose or β-cell function, whereas the lowest and insulin, S_I β dose enhanced ?-cell function (P < 0.05). The overall increase in the GH dose increased IGF-1, IGFBP-3, fasting glucose and insulin (P < 0.001), demonstrated a positive correlation with the final change in fasting glucose (r = 0.5,P < 0.05) and insulin (r = 0.8,P < 0.001) and a (r = 0.5,P < 0.05). negative correlation with final S_I (r=-0.5, P < 0.05. CONCLUSIONS: Our results suggest that short-term administration of the highest GH dose induced insulin resistance, whereas the lowest dose (0.0017 mg/kg/day) could represent the optimal starting dose in GHD adults due to its beneficial effects on β-cell function without compromising S_I. It is, however, yet to be determined whether the positive effects of the lowest GH dose on β-cell function can be demonstrated over a longer period of time.