Background: Ghrelin and its endogenous antagonist liver-expressed antimicrobial peptide-2 (LEAP-2) are involved in GH secretion, both acting on GSH-r1α, and regulation of glucose and lipids metabolism. Metabolic impairments are often accompanied by an upregulation of LEAP-2 expression, with a usual concomitant reduction in ghrelin secretion. Adult growth hormone deficiency (aGHD), characterized by weight gain, increased fat mass and insulin resistance, represent a condition of metabolic derangement.
Objectives: The primary objective of this cross-sectional observational pilot study was to compare circulating LEAP-2 and ghrelin serum levels in aGHD and healthy controls.
Methods: 30 patients were included in the study. Group A included adult GHD: 15 patients, 8 females and 7 males. Median and interquartile range age of the group was 53 (4157) years, while BMI was 27.1 (2535) kg/m2. Group B was formed by 15 healthy controls (10 females and 5 males). Median and interquartile range age was 47 (3657) years, while BMI 22.9 (20.8-33.1) kg/m2. They were evaluated for serum glucose and insulin, HOMA-index, QUICKI-index, total/lDL/HDL cholesterol, triglycerides, IGF-1, ghrelin and LEAP-2.
Results: Ghrelin levels in the aGHD group were significantly lower than in healthy controls. In contrast, LEAP-2 showed a trend toward higher levels, although the differences were not significant. However, LEAP-2/Ghrelin molar ratio, an index of receptor affinity, was significantly higher in aGHD. No significant correlations between ghrelin and LEAP-2 with BMI, HOMA index and other parameters were found in aGHD population. However, a significant inverse correlation (r2=0.15, P=0.047) between BMI and ghrelin was evidenced when considering the whole population.
Conclusions: These results may suggest a body adaptation to a metabolic scenario typical of aGHD. The decrease in ghrelin production could prevent further weight gain and fat mass increase, although losing its secretagogue effect.