Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin

Abstract

Context: Metabolic substrates and nutritional status play a major role in growth hormone (GH) secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG) administration in normal and obese patients is a pending issue.

Objective: The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity.

Participants and methods: We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC) were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed.

Results: The AUC of GH (μg/L•min) was lower in obese (249.8±41.8) than in healthy women (490.4±74.6), P=0.001. The AUC of total ghrelin (pg/mL•min) was lower in obese (240995.5±11094.2) than in healthy women (340797.5±37757.5), P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.

Fig 1. Mean±SE plasma glucose (a; mg/dL), insulin (b; μU/mL) GH (c; μg/L) and total ghrelin levels (d; pg/mL) in normal (grey) and obese women (black) during the prolongued oral glucose tolerance test.

* p<0.05 between normal and obese women at that time point. Insulin was higher in the obese women than in the healthy control women after the 300 min OG (Fig. 1b). GH was lower in the the obese women than in the healthy control women after OG (Fig. 1c). The AUC of GH (μg/L·min) between 0 and 300 min was lower in the obese patients than in the controls; 249.8±41.8 vs 490.4±74.6, P = 0.001, for the obese patients and controls respectively. Peak GH (μg/L) levels were lower in the obese than in the healthy women, 3.3±0.5 vs 6.6±0.8 p<0.001, for the obese and healthy women respectively. Total ghrelin was lower in the obese women than in the healthy women after OG (Fig. 1d). The AUC of total ghrelin (pg/mL·min) between 0 and 300 min was lower in the obese patients than in the controls; 240995.5±11094.2 vs 340797.5±37757.5, P = 0.042, for the obese and healthy women respectively (Fig. 2).

Fig 2. Mean±SE plasma GH AUC_0–300 (pg/mL·min) and Ghrelin AUC_0–300 (pg/mL·min) in normal (grey) and obese women (black) during the prolongued oral glucose tolerance test.

* p<0.05 between normal and obese women.

Fig 3. Relationship between GH secretion indices (log-transformed) and IGF-I, waist circumference, Matsuda index and Ghrelin AUC_0–300 data.

Univariate generalized additive regression (GAM) models. A clear linear association between ghrelin AUC and the different indices of GH secretion (log-transformed) was found (Fig. 3).