Enteroendocrine Connections in Congenital Isolated GH Deficiency Due to a GHRH Receptor Gene Mutation

GH and IGF-1 are crucial for attainment of normal body size and regulation of food intake, nutrient storage, and insulin sensitivity. Enteroendocrine connections exist between the GH-IGF-1 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. Design: In a cross-sectional study of 20 individuals with IGHD and 20 control subjects, we measured glucose, insulin, ghrelin, and GLP-1 before and 30, 60, 120, and 180 minutes after a standardized test meal. Homeostasis model assessment index of insulin resistance (HOMA-IR) and homeostasis model assessment (HOMA)-b were calculated. Participants scored feelings of hunger, fullness, and prospective food consumption on a visual analog scale. Main Outcome Measures: Area under the curve (AUC) values of glucose, insulin, ghrelin, GLP-1, hunger, fullness, and prospective food consumption. Results: Fasting HOMA-IR and HOMA-b were lower in individuals with IGHD than in control subjects (P 5 0.002 and P 5 0.023, respectively). AUC was higher for hunger (P , 0.0001), glucose (P 5 0.0157), ghrelin (P , 0.0001), and GLP-1 (P , 0.0001) and smaller for fullness (P , 0.0001) in individuals with IGHD compared with control subjects. There was no difference in AUC for prospective food consumption or insulin.