title: Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity.
abstract: Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal IGFBP-1 levels and a decrease in basal insulin levels occurred in the normal controls, whereas no such changes were observed in the obese subjects. After caloric restriction 24-hr GH release, IGFBP-1 levels and insulin levels were similar in control subjects and obese subjects after weight loss. This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat and perpetuate the obese state.
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark.
authors.forename: M H
authors.initials: MH
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Juul
authors.forename: L L
authors.initials: LL
authors.lastname: Kjems
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: J
authors.initials: J
authors.lastname: Hilsted
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D004038:Diet, Reducing; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009765:Obesity / Q000378:metabolism*; D011384:Proinsulin / Q000097:blood; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D011384:Proinsulin