Growth hormone (GH) response to GH-releasing peptide-6 and GH-releasing hormone in normal-weight and overweight patients with non-insulin-dependent diabetes mellitus

The growth hormone (GH) response to GH-releasing hormone (GHRH) in patients with non-insulin-dependent diabetes mellitus (NIDDM) was found to be eithe r decreased or normal. The recent introduction of a new and potent GH stimu lus, GH-releasing peptide-6 (GHRP-6), allowed further investigation of the functional properties of somatotropes in a variety of metabolic diseases. T he aim of the present study was to investigate the response of GH to GHRP-6 , GHRH, and GHRP-6 + GHRH in NIDDM patients. Twenty-one patients with NIDDM were divided into two groups: group A, normal weight (body mass index [BMI ], 23.31 +/- 0.62 kg/m(2)); and group B, overweight (BMI, 27.62 +/- 0.72 kg /m(2)). Eight normal-weight control subjects (group C) were studied. Each s ubject received GHRP-6 (90 mu g intravenously [IV]), GHRH (100 mu g IV), an d GHRP-6 + GHRH on three separate occasions. There was no difference betwee n the GH response after GHRP-6 in groups A, B, and C in terms of the GH pea k (50.95 +/- 11.55, 51.96 +/- 7.71, and 70.07 + 15.59 mU/L, P > .05) and th e area under the curve (AUC) for GH (2,340.06 +/- 617.36, 2,684.54 +/- 560. 57, 3,462.78 +/- 1,223.53 mU/L/120 min, P > .05). A decreased GH response t o GHRH was found in group B in comparison to group A (B v A: peak GH respon se, 8.25 +/- 1.90 v 22.19 +/- 8.81, P < .05; AUC GH, 479.62 +/- 84.0 v 1,44 3.21 +/- 743.76, P < .05). There was no difference in the GH response betwe en group A and group C (peak GH response, 22.19 +/- 8.81 v 26.42 +/- 6.71, P > .05; AUG, 1,443.21 +/- 743.76 v 1,476.51 +/- 386.56, P > .05). There wa s a significant difference between the same parameters in group B versus gr oup C (8.25 +/- 1.90 v 26.42 +/- 6.71, P < .05; AUG, 479.62 +/- 84.0 v 1,47 6.51 +/- 386.56, P < .05). The combined administration of GHRP-6 + GHRH eli cited a synergistic GH response in NIDDM patients and controls. There was a significant difference between groups A and B for the GH peak (96.49 +/- 9 .80 v 68.38 +/- 8.25, P < .05), whereas there was no difference for the AUC (5,111.13 +/- 703.77 v 3,425.95 +/- 459.67, P > .05). There was no differe nce in the peak GH after the combined test between group A and group C (96. 49 +/- 9.80 v 139.82 +/- 24.16, P > .05), whereas the peak GH in the same t est was significantly decreased in group B in comparison to group C (68.38 +/- 8.25 v 139.82 +/- 24.16, P < .05). The AUC for GH after combined GHRP-6 + GHRH in group A versus group C was not significantly different (5,111.13 +/- 703.77 v 9,274.71 +/- 1,541.46, P > .05), whereas there was a signific ant difference for the same test between group B and group C (3,425.95 +/- 459.67 v 9.274.71 +/- 1,541.46, P < .05). Our results demonstrate that norm al-weight NIDDM patients have a preserved GH response to GHRP-6, GHRH, and GHRP-6 + GHRH, and overweight NIDDM patients have a blunted response to GHR H and GHRP-6 + GHRH. The preserved GH response to GHRP-6 in both diabetic g roups suggests that the secretory potential of somatotropes is preserved in NIDDM patients. The impairment of the GH response to GHRH in overweight NI DDM patients could be a functional defect due to the obesity, since it coul d be overridden by administration of GHRP-6. Copyright (C) 1999 by W.B. Sau nders Company.