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

RM Williams, R Amin, F Shojaee-Moradie… - Diabetologia, 2003 - Springer
RM Williams, R Amin, F Shojaee-Moradie, AM Umpleby, CL Acerini, DB Dunger
Diabetologia, 2003Springer
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 …
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 recieved 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 β-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.
Springer