GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis

Abstract

Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P < 0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P < 0.005; r = 0.572, P < 0.005; r = 0.453, P < 0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = ¹0.432, P < 0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r 2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance; (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP; and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity.

Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects

“…In adults low levels are also found in type 1 diabetes [277,278] and in pregnant females with type 1 diabetes as well [170], whereas GHBP levels are increased in type 2 diabetics with hyperinsulinaemia [278,279], and in females with gestational diabetes [169]. In type 1 diabetes, portal insulin levels as well as peripheral GHBP levels are low; in type 2 diabetes, portal insulin levels and GHBP levels are high, and a positive correlation has been found between insulin levels and GHBP in type 2 diabetes [278,280]. The underlying mechanisms are incompletely understood, but there are data to suggest that portal insulin is essential for the regulation of GH receptors, GHBP and IGF-I production [281,282].…”

GH/IGF-I Regulation in Obesity – Mechanisms and Practical Consequences in Children and Adults

“…They are associated with an increased GH clearance leading to a lower GH half-life, suggesting a defect both in secretion and clearance [3,5]. Alterations in GH receptors and circulating GH-binding proteins support these changes [6,7]. …”

Growth Hormone and Adipocyte Function in Obesity

“…Increased circulating GHBP levels have been observed in obese subjects with positive correlation between GHBP levels and body mass index and amount of body fat [66, 67, 68, 69]. Considering that the GHBP is mainly generated from proteolysis of the extracellular domain of the GH receptor, changes in circulating GHBP levels may reflect changes in GH receptor levels in target tissues [70, 71].…”