Authors: E Y H Khoo J Wallis K Tsintzas I A Macdonald P Mansell
Publish Date: 2009/11/07
Volume: 53, Issue: 1, Pages: 139-143
Abstract
Exenatide a glucagon like peptide1 agonist is a treatment for type 2 diabetes mellitus that stimulates insulin and suppresses glucagon secretion in a glucosedependent manner By contrast during aerobic exercise the serum insulin concentration normally falls with a rise in plasma glucagon We therefore assessed whether exenatide might predispose to hypoglycaemia during exerciseWe studied eight nondiabetic men who were 353 ± 63 years of age with BMI of 247 ± 17 kg/m2 mean ± SD using a randomised crossover doubleblind design investigation After an overnight fast participants received 5 μg of subcutaneous exenatide or placebo and rested for 105 min before cycling at 60 of their maximal oxygen uptake dot VtextO text2max for 75 min and then recovering for a further 60 minThe insulin/glucagon molar ratio rose with exenatide at rest p 001 then fell during exercise with placebo and with exenatide At rest fasting blood glucose fell by approximately 1 mmol/l with exenatide to a nadir of 34 ± 01 mmol/l p 001 During exercise blood glucose fell with placebo but unexpectedly rose with exenatide Plasma adrenaline epinephrine and noradrenaline norepinephrine but not cortisol concentrations increased to a greater extent during exercise after exenatide No participant developed symptomatic hypoglycaemia and the lowest individual blood glucose recorded was 28 mmol/l with exenatide at 50 min in the preexercise periodExenatide a glucagonlike peptide1 mimetic has several beneficial modes of action for patients with type 2 diabetes 1 Exenatide increases satiety delays gastric emptying increases insulin and decreases glucagon concentrations The endocrine responses are glucosedependent 1 although there is still a pronounced insulinotropic effect at glucose concentrations of 50 and 54 mmol/l 2 with a modest fall in fasting blood glucose concentration in nondiabetic volunteers 3 The glucosedependence of the endocrine effects explains the low risk of hypoglycaemia with exenatide in clinical studies 4
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