title: Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationships with insulin and body composition.
abstract: Obesity is characterized by increased leptin levels and insulin resistance, whereas blunted GH secretion is paired with normal, low, or high plasma IGF-I levels. To investigate body composition in human obesity and the interactions among the GH-IGF-I axis, leptin, and insulin resistance [measured with the homeostasis model assessment (HOMA) score], we studied 15 obese females, aged 23-54 yr (mean age, 42.7 +/- 2.6), with a body mass index (BMI) of 44.02 +/- 1.45 kg/m(2), who underwent treatment by biliopancreatic diversion (BPD), before and after surgery (16-24 months; BMI, 28.29 +/- 0.89 kg/m(2)). Our controls were 15 normal females, aged 28-54 yr (mean age, 40.8 +/- 2.3 yr), with a BMI of 27.52 +/- 0.53 kg/m(2). Insulin and leptin levels and HOMA scores were higher pre-BPD than in the controls. The GH response to GHRH was blunted, with a GH peak and GH area under the curve (AUC) significantly lower than those in controls. IGF-I and IGF-binding protein-3 (IGFBP-3) were also lower than control values. After surgery, BMI, fat mass, lean body mass, HOMA, insulin, and leptin significantly decreased. Furthermore, the GH response to GHRH severely increased; IGF-I and IGFBP-3 levels did not significantly vary. Considering all subjects, correlation analysis showed a strong positive correlation between insulin and leptin, and a negative correlation between insulin and GH peak and between insulin and GH AUC. Regression analysis performed grouping pre- and post-BPD indicated that leptin and GH peak or AUC could best be predicted from insulin levels. The surgical treatment of severe obesity after stabilization of body weight decreases BMI and fat mass while preserving normal lean body mass as well as positively influencing insulin sensitivity and thus aiding the normalization of leptin levels. The insulin reduction may be mainly involved in the increase in the GH response to GHRH through various possible central and peripheral mechanisms while decreasing the peripheral sensitivity to GH itself, as shown by the stable nature of the IGF-I and IGFBP-3 values. Our findings suggest that the changes in insulin levels are the starting point for changes in both leptin levels and the somatotrope axis after BPD.
authors.affiliation: Institute of Endocrinology, Catholic University School of Medicine, 00168 Rome, Italy. laurademarinis@yahoo.it
authors.forename: L
authors.initials: L
authors.lastname: De Marinis
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.forename: A
authors.initials: A
authors.lastname: Mancini
authors.forename: R
authors.initials: R
authors.lastname: Gentilella
authors.forename: M
authors.initials: M
authors.lastname: Perrelli
authors.forename: A
authors.initials: A
authors.lastname: Giampietro
authors.forename: T
authors.initials: T
authors.lastname: Porcelli
authors.forename: L
authors.initials: L
authors.lastname: Tilaro
authors.forename: A
authors.initials: A
authors.lastname: Fusco
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: R M
authors.initials: RM
authors.lastname: Tacchino
mesh_terms: D000273:Adipose Tissue; D000328:Adult; D015904:Biliopancreatic Diversion; D001823:Body Composition; D015992:Body Mass Index; D005260:Female; D013007:Growth Hormone-Releasing Hormone; D006706:Homeostasis; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D009767:Obesity, Morbid / Q000503:physiopathology* / Q000601:surgery; D012044:Regression Analysis
chemical_list: D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D020738:Leptin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone