title: Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency.
abstract: OBJECTIVE
  Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore the hypothesis that LGH, in contrast to the standard GH dose titrated to normalize serum IGF-I levels (SGH), may have differing effects on insulin sensitivity, body composition, and cardiovascular risk markers [lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and adiponectin] in adults with severe GH deficiency.
  
  
  METHODS
  In this 12-month open, prospective study, 25 GH-deficient adults were randomized to receive either a fixed LGH (0.10 mg/day, n = 13) or SGH (mean dose 0.48 mg/day, n = 12), and eight age- and body mass index (BMI)-matched GH-deficient adults acted as untreated controls. Fasting blood samples were collected at baseline and at months 1, 3, 6, 9 and 12. Assessments of insulin sensitivity, using the hyperinsulinaemic euglycaemic clamp technique, and body composition, using dual-energy X-ray absorptiometry, were performed at baseline and at month 12.
  
  
  RESULTS
  The LGH decreased fasting glucose levels (P < 0.01) and enhanced insulin sensitivity (P < 0.02), but body composition, nonesterified fatty acid (NEFA) levels and cardiovascular risk markers were unchanged. The SGH did not modify insulin sensitivity, decreased truncal fat mass (P < 0.05), CRP (P < 0.05) and IL-6 (P < 0.05) levels, and increased NEFA levels (P < 0.05). No changes were observed with the untreated controls.
  
  
  CONCLUSIONS
  Our data indicate that, in contrast to the SGH, fixed administration of the LGH enhances insulin sensitivity with no apparent effects on body composition, lipolysis and other surrogate cardiovascular risk markers in adults with severe GH deficiency. Thus, the LGH may potentially be a beneficial replacement dose in reducing type 2 diabetes risk in adults with severe GH deficiency.
authors.affiliation: Department of Endocrinology and Paediatrics, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Kevin C J
authors.initials: KC
authors.lastname: Yuen
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Deborah K
authors.initials: DK
authors.lastname: White
authors.forename: Th B
authors.initials: TB
authors.lastname: Twickler
authors.forename: Hans P F
authors.initials: HP
authors.lastname: Koppeschaar
authors.forename: Philip E
authors.initials: PE
authors.lastname: Harris
authors.forename: Linda
authors.initials: L
authors.lastname: Fryklund
authors.forename: Peter R
authors.initials: PR
authors.lastname: Murgatroyd
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D004334:Drug Administration Schedule; D005260:Female; D013006:Growth Hormone / Q000172:deficiency*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone