title: Growth hormone (GH) effects on central fat accumulation in adult Japanese GH deficient patients: 6-month fixed-dose effects persist during second 6-month individualized-dose phase.
abstract: Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.
authors.affiliation: Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohno
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kazue
authors.initials: K
authors.lastname: Takano
authors.forename: Minoru
authors.initials: M
authors.lastname: Irie
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects*; D000328:Adult; D001823:Body Composition; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004393:Dwarfism, Pituitary / Q000188:drug therapy*; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013995:Time
chemical_list: D008055:Lipids; D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I