Conexões enteroendócrinas na deficiência isolada de GH devido a uma mutação no gene do receptor do GHRH

Abstract

CONTEXT: GH and IGF-I are crucial for attainment of normal body size and regulation of food intake, nutrients storage, and insulin sensitivity. Enteroendocrine connections exist between the GH/IGF-I axis and insulin, ghrelin, and glucagon-like peptide 1 (GLP-1). The status of these connections in GH deficiency (GHD) is unknown. OBJECTIVE: To study the enteroendocrine connections before and after a standard meal test in a homogeneous population of adults with congenital untreated isolated GHD (IGHD) due to a mutation in the GHRH receptor gene. MATERIALS AND METHODS: In a cross-sectional study of 20 IGHD and 20 controls, we measured glucose, insulin, ghrelin, and GLP-1 before and 30, 60, 120 and 180 min after a standardized test meal. HOMA-IR and HOMA-β were calculated. Participants scored on a visual analogue scale the feelings of hunger, fullness, and prospective food consumption. Main outcome measures: areas under the curves (AUC) of glucose, insulin, ghrelin, GLP-1, hunger, fullness and prospective food consumption. RESULTS: Fasting HOMA-IR and HOMA-β were lower in IGHD than controls (p=0.002 and p=0.023 respectively). AUC were higher for hunger (p<0.0001), glucose (p=0.0157), ghrelin (p<0.0001) and GLP-1 (p<0.0001), and smaller for fullness (p<0.0001) in IGHD compared to controls. There was no difference in AUC for prospective food consumption or insulin. CONCLUSIONS: Untreated IGHD is associated to increased GLP-1 secretion and reduced post-prandial ghrelin and hunger attenuation in response to a mixed meal. These enteroendocrine connections can result into a favourable outcome in terms of environmental adaptation, guaranteeing appropriate food intake, and can confer metabolic benefits.