Blunted GH Response to Growth Hormone-Releasing Hormone (GHRH) Alone or Combined with Arginine in Non-Insulin-Dependent Diabetes Mellitus

Abstract

An increased spontaneous and stimulated growth hormone (GH) secretion is well documented in insulin-dependent diabetes mellitus. On the contrary, in non-insulin-dependent diabetes mellitus (NIDDM) conflicting results arise from literature. In 14 patients with NIDDM, 7 normal weight (NWD) and 7 obese (OD), we investigated the somatotrope responsiveness to GHRH (1 µg/kg) alone or combined with arginine (ARG, 0.5 g/kg), which is able to enhance the GH response to GHRH, probably by inhibiting somatostatin release from hypothalamus. Baseline IGF-I, IRI, FFA and glucose levels were also determined. Twelve healthy normal subjects (NS) and 12 obese patients (OP) were evaluated as control groups. GH but not IGF-I levels were higher (p < 0.05) in NS than in OP (1.5 ± 0.5 vs 0.5 ± 0.2 µg/l). Insulin levels were higher (p < 0.05) in OP than in NS, NWD and OD (18.7 ± 1.8 vs 8.7 ± 0.5, 6.4 ± 1.9 and 11.8 ± 1.2 µU/l). FFA were higher (p < 0.05) in NWD, OD and OP than in NS (0.69 ± 0.04, 0.70 ± 0.04 and 0.65 ± 0.06 vs 0.39 ± 0.03 mmol/l). Plasma glucose was higher (p < 0.05) in diabetic patients than in normal and obese subjects. GH responses to GHRH in NWD, OD and OP were similar (AUC: 221.6 ± 33.3, 206.0 ± 35.9 and 177.2 ± 57.3 µg/l/min, respectively) and all lower (p < 0.05) than that in NS (776.7 ± 206.5 µg/l/min). ARG determined a significant increase of GHRH-induced GH release in all groups (p < 0.01). Again the GH responses to ARG + GHRH in NWD, OD and OP were lower (p < 0.05) than that observed in NS. In conclusion, our results demonstrate that, irrespective of body weight, patients with non-insulin-dependent diabetes mellitus had an impairment of GH responses to GHRH alone or combined with arginine. This finding may be explained by the presence of high FFA levels which are known to inhibit GH secretion.

Key words

GH - FFA - NIDDM - Obesity