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

Abstract

The growth hormone (GH) response to GH-releasing hormone (GHRH) in patients with non-insulin-dependent diabetes mellitus (NIDDM) was found to be either decreased or normal. The recent introduction of a new and potent GH stimulus, GH-releasing peptide-6 (GHRP-6), allowed further investigation of the functional properties of somatotropes in a variety of metabolic diseases. The 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 subject received GHRP-6 (90 μg intravenously [IV]), GHRH (100 μg IV), and GHRP-6 + GHRH on three separate occasions. There was no difference between the GH response after GHRP-6 in groups A, B, and C in terms of the GH peak (50.95 ± 11.55, 51.96 ± 7.71, and 70.07 ± 15.59 mU/L, P > .05) and the 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 to GHRH was found in group B in comparison to group A (B v A: peak GH response, 8.25 ± 1.90 v 22.19 ± 8.81, P < .05; AUC GH, 479.62 ± 84.0 v 1,443.21 ± 743.76, P < .05). There was no difference in the GH response between group A and group C (peak GH response, 22.19 ± 8.81 v 26.42 ± 6.71, P > .05; AUC, 1,443.21 ± 743.76 v 1,476.51 ± 386.56, P > .05). There was a significant difference between the same parameters in group B versus group C (8.25 ± 1.90 v 26.42 ± 6.71, P < .05; AUC, 479.62 ± 84.0 v 1,476.51 ± 386.56, P < .05). The combined administration of GHRP-6 + GHRH elicited 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 difference 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 test 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 significant 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 normal-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 GHRH and GHRP-6 + GHRH. The preserved GH response to GHRP-6 in both diabetic groups suggests that the secretory potential of somatotropes is preserved in NIDDM patients. The impairment of the GH response to GHRH in overweight NIDDM patients could be a functional defect due to the obesity, since it could be overridden by administration of GHRP-6.