Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels

• Published in: Clinical endocrinology (Oxford) 2012-10, Vol.77 (4), p.531-536
• Main Authors: Fusco, Alessandra, Miele, Luca, D'Uonnolo, Annalisa, Forgione, Alessandra, Riccardi, Laura, Cefalo, Consuelo, Barini, Angela, Bianchi, Antonio, Giampietro, Antonella, Cimino, Vincenzo, Landolfi, Raffaele, Grieco, Antonio, De Marinis, Laura
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blood Glucose - metabolism; Carrier Proteins - blood; Cross-Sectional Studies; Endocrinopathies; Fatty Liver - blood; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Glycoproteins - blood; Growth Hormone - blood; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - metabolism; Liver cirrhosis; Liver diseases; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Multivariate analysis; Non-alcoholic Fatty Liver Disease; Obesity - blood; Other diseases. Semiology; Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2011.04291.x

Summary Introduction  Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF‐I, GH‐binding protein (GHBP), IGF‐binding proteins (IGFBPs) and acid‐labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. Aim of the study  To explore whether GH secretion and/or levels of IGF‐I, IGFBP‐3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. Materials and methods  A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age‐ and BMI‐matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF‐I, GHBP, IGFBP‐3, ALS and GH after GHRH and arginine stimulation test. Results  As expected, patients with NAFLD had blood glucose, insulin, HOMA‐R significantly higher than controls, indicating a more severe insulin‐resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP‐3 and lower GH peak and IGF‐I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF‐1 was negatively associated with hepatic steatosis. Conclusions  This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF‐I axis is significantly altered probably leading to reduced IGF‐I bioavailability at tissue level.