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The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus.

Abstract：

AIMS/HYPOTHESIS: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. CONCLUSION/INTERPRETATION: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.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Williams RM,Amin R,Shojaee-Moradie F,Umpleby AM,Acerini CL,Dunger DB

doi

10.1007/s00125-003-1175-8

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

1203-10

issue

eissn

0012-186X

issn

1432-0428

journal_volume

pub_type

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The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus.