The insulinotropic effect of pulsatile compared with continuous intravenous delivery of GLP-1.
Diabetologia
; 59(5): 966-9, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26831299
ABSTRACT
AIMS/HYPOTHESIS:
In healthy individuals, both insulin and glucagon-like peptide 1 (GLP-1) are secreted in a pulsatile fashion. Insulin has greater glucose-lowering properties when administered in pulses compared with a constant i.v. infusion. The primary aim of this randomised double-dummy cross-over study was to compare the insulinotropic response to pulsatile and continuous i.v. infusions of equivalent doses of GLP-1.METHODS:
Twelve healthy participants aged 18-35 years were randomised to three different treatments on separate days a continuous infusion day (GLP-1 at 0.6 pmol kg(-1) min(-1) [1 ml/min] and a 1 ml placebo bolus every 6 min); a pulsatile infusion day (placebo at 1 ml/min and a 3.6 pmol/kg GLP-1 bolus every 6 min); and a placebo day (placebo at 1 ml/min and a 1 ml placebo bolus every 6 min). Between 45 and 120 min, a hyperglycaemic clamp was used to maintain blood glucose at 9 mmol/l. Venous blood glucose and plasma insulin concentrations were measured every 5 min from 0 to 45 min and every 1 min from 45 to 120 min; plasma glucagon was measured every 15 min. The order of treatment was randomised by the Pharmacy Department and both study investigators and participants were blinded to the treatment arm. The dextrose requirement and glucagon data were analysed using repeated measures ANOVA and insulin data were analysed with a linear mixed effects maximum likelihood model.RESULTS:
Continuous and pulsatile infusions of GLP-1 increased the dextrose requirement by ~threefold (p < 0.001) and increased insulin secretion by ~ninefold (p < 0.001). There was no difference in the effect of both treatments. Although hyperglycaemia reduced plasma glucagon concentrations, there was no difference between the treatment days. CONCLUSIONS/INTERPRETATION:
In healthy individuals, pulsatile and continuous administration of i.v. GLP-1 appears to have comparable insulinotropic effects. TRIAL REGISTRATION ACTRN12612001040853FUNDING:
This study was supported by the National Health and Medical Research Council (NHMRC) of Australia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infusões Intravenosas
/
Peptídeo 1 Semelhante ao Glucagon
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
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Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article