title: The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus.
abstract: OBJECTIVE
  Growth hormone hypersecretion in Type 1 diabetes could exacerbate insulin resistance and contribute to declining glycaemic control. Our aim was to determine the effects of specific growth hormone blockade on insulin sensitivity and lipolysis in young adults with Type 1 diabetes.
  
  
  METHODS
  We studied the effects of two doses of a specific growth hormone antagonist (B2036-PEG; Somavert, Pharmacia Corporation, Milton Keynes, UK) on insulin sensitivity in seven young adults (17-22 yrs, 3M) with Type 1 diabetes. Subjects received 5 and 10 mg B2036-PEG, in random order for 3 weeks, with a 3-week washout. At baseline and following each treatment block, an overnight (03:00 to 08:00 h) insulin infusion for euglycaemia (5 mmol/l), followed by two-step hyperinsulinaemic euglycaemic clamp, using [6,6 2H2] glucose and 2H5 glycerol to measure glucose and glycerol turnover was performed.
  
  
  RESULTS
  Compared to baseline, overnight insulin requirements decreased with both doses: (means+/-SEM) 0.34+/-0.02 mU/Kg/min vs 0.25+/-0.01 (5 mg) (p=0.04), and 0.24+/-0.01 (10 mg) (p=0.004). IGF-I (ng/ml) decreased following 10 mg [223.5+/-23.9 vs 154.6+/-28.1 (p=0.005], but not 5 mg. Mean overnight non esterified fatty acid concentrations (mmol/l) decreased with 10 mg [0.51+/-0.04 vs 0.38+/-0.04 (p=0.03)], as did beta-hydroxybutyrate (mmol/l); [0.31+/-0.04 vs 0.15+/-0.02 (p=0.004)]. Glycerol production rate, an index of lipolysis, was lower following 10 mg (p=0.04), but insulin sensitivity during the clamp did not change with either dose.
  
  
  CONCLUSIONS
  Treatment with both doses of B2036-PEG reduced overnight insulin requirements. The 10 mg dose suppressed lipolysis and reduced IGF-I. Failure to show enhanced insulin sensitivity during the clamp with the 10 mg dose could reflect opposing actions of growth hormone and IGF-I.
authors.affiliation: University of Cambridge, Department of Paediatrics, Addenbrooke's Hospital, Hills Rd, Cambridge, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Amin
authors.forename: F
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: C L
authors.initials: CL
authors.lastname: Acerini
authors.forename: D B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male
chemical_list: C422172:B 2036; D001786:Blood Glucose; D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I