title: Insulin Sensitivity and β-Cell Function in SGA Children Treated With GH and GnRHa: Results of a Long-Term Trial.
abstract: BACKGROUND
  Pubertal children born small for gestational age with a poor adult height (AH) expectation can benefit from treatment with GH 1 mg/m(2)/d (∼0.033 mg/kg/d) in combination with 2 years of GnRH analog (GnRHa) and even more so with GH 2 mg/m(2)/d. Because both GH and GnRHa can negatively influence insulin sensitivity, combining these treatments has raised concerns. The long-term GH dose effects on insulin sensitivity in children treated with combined GH/GnRHa are unknown.
  
  
  OBJECTIVE
  The purpose of this study was to investigate insulin sensitivity and β-cell function by a very precise method during long-term GH treatment, either with or without 2 years of additional GnRHa and to study differences in insulin sensitivity during treatment until AH between GH at 1 or 2 mg/m(2)/d.
  
  
  METHODS
  This was a randomized, dose-response GH trial involving 110 short small for gestational age children (59 girls) treated with GH until AH (GH randomized to 1 or 2 mg/m(2)/d). Sixty-seven children received additional GnRHa treatment. Frequently sampled intravenous glucose tolerance tests were performed and insulin sensitivity (Si), acute insulin response (AIR), and disposition index (DI) were calculated using Bergman's MINMOD. The GH dose effect was evaluated in a subgroup of 48 children who started GH treatment in early puberty (randomized to 1 or 2 mg/m(2)/d) combined with 2 years of GnRHa.
  
  
  RESULTS
  At AH, after 5.9 years of GH treatment, Si, AIR, and DI were similar between children treated with combined GH/GnRHa and those treated with GH only. In the subgroup of children who started GH treatment in early puberty (randomized to 1 or 2 mg/m(2)/d) together with 2 years of GnRHa treatment, there were no significant differences in Si, AIR, or DI between the GH dose groups during the treatment.
  
  
  CONCLUSIONS
  Combined GH/GnRHa treatment has no long-term negative effects on insulin sensitivity and β-cell function compared with GH only. Started in early puberty, a GH dose of 2 mg/m(2)/d results in a similar insulin sensitivity at AH as a GH dose of 1 mg/m(2)/d.
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.-K.), 3001 KB Rotterdam, The Netherlands; and Erasmus University Medical Center/Sophia Children's Hospital ((M.v.d.S., A.C.S.H.-K.), 3000 CA Rotterdam, The Netherlands.
authors.forename: Manouk
authors.initials: M
authors.lastname: van der Steen
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.-K.), 3001 KB Rotterdam, The Netherlands; and Erasmus University Medical Center/Sophia Children's Hospital ((M.v.d.S., A.C.S.H.-K.), 3000 CA Rotterdam, The Netherlands.
authors.forename: Annemieke J
authors.initials: AJ
authors.lastname: Lem
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.-K.), 3001 KB Rotterdam, The Netherlands; and Erasmus University Medical Center/Sophia Children's Hospital ((M.v.d.S., A.C.S.H.-K.), 3000 CA Rotterdam, The Netherlands.
authors.forename: Daniëlle C M
authors.initials: DC
authors.lastname: van der Kaay
authors.affiliation: Dutch Growth Research Foundation (M.v.d.S., A.J.L., D.C.M.v.d.K., A.C.S.H.-K.), 3001 KB Rotterdam, The Netherlands; and Erasmus University Medical Center/Sophia Children's Hospital ((M.v.d.S., A.C.S.H.-K.), 3000 CA Rotterdam, The Netherlands.
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D001823:Body Composition; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005951:Glucose Tolerance Test; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007236:Infant, Small for Gestational Age / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D010186:Pancreatic Function Tests; D011627:Puberty
chemical_list: D007328:Insulin; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone