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 (SI). 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 'supraphy-siological' ('high' dose: 0.010 mg/kg/day; 'highest' dose: 0.025 mg/kg/day) GH doses on SI, beta-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 SI and beta-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 beta-cell function (P < 0.001), but decreased SI (P < 0.001). The high and low doses did not modify fasting glucose and insulin, SI or beta-cell function, whereas the lowest dose enhanced beta-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 negative correlation with final SI (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 beta-cell function without compromising SI. It is, however, yet to be determined whether the positive effects of the lowest GH dose on beta-cell function can be demonstrated over a longer period of time.