%0 Journal Article
%T Assessment of single-dose benzodiazepines on insulin secretion, insulin sensitivity and glucose effectiveness in healthy volunteers: a double-blind, placebo-controlled, randomized cross-over trial [ISRCTN08745124]
%A Hugues Chevassus
%A Isabelle Mourand
%A Nathalie Molinier
%A Bruno Lacarelle
%A Jean-Fr¨¦d¨¦ric Brun
%A Pierre Petit
%J BMC Pharmacology and Toxicology
%D 2004
%I BioMed Central
%R 10.1186/1472-6904-4-3
%X The study was designed as a double-blind, placebo-controlled, cross-over clinical trial. Diazepam (10 mg) and clonazepam (1 mg) were infused during 30 min to 15 male subjects with a mean age of 22 years (range: 20¨C29), after informed consent was given. Benzodiazepines were assayed by capillary gas chromatography with electron capture, insulin by radioimmunoassay and glucose by the enzymatic glucose oxidase method.Both benzodiazepines induced significant psychotropic effects. The acute insulin responses (AIR) were significantly and negatively correlated with the clonazepam plasma concentrations (r = -0.609, P < 0.05, n = 14). However, the mean AIR was not significantly different between the benzodiazepine-treated subjects and the controls. In addition, the parameters of glucose assimilation were significantly decreased as compared with placebo in the subgroup of 7 subjects with plasma clonazepam concentrations higher than 6.0 ng ml-1 (median and lower limit of effective therapeutic concentrations): 1.37 ¡À 0.3 versus 2.84 ¡À 0.60 ¡Á 10-2min-1 (P = 0.028) for the coefficient of glucose tolerance (Kg), 2.18 ¡À 0.29 versus 3.71 ¡À 0.89 ¡Á 10-4¦ÌUml-1min-1 (P = 0.018) for insulin sensitivity (Si) and 1.80 ¡À 0.39 versus 3.59 ¡À 0.71 ¡Á 10-2min-1 (P = 0.028) for glucose effectiveness at basal insulin (Sg). These parameters were not significantly modified when diazepam was administered; plasma levels of this drug however, were below the effective therapeutic concentrations (300 ng ml-1) from min 15 after the end of the perfusion.The present results suggest that a benzodiazepine, in particular clonazepam, may alter insulin secretion and insulin sensitivity after a single administration in healthy volunteers.Benzodiazepine drugs are widely prescribed, mainly for their anxiolytic and sedative properties. In addition to these psychotropic actions, different metabolic effects have also been reported but few clinical trials on that topic are available.A trend to increased glycemia without
%K benzodiazepine
%K clinical investigation
%K insulin secretion
%K insulin sensitivity
%K glucose tolerance
%K diabetes
%U http://www.biomedcentral.com/1472-6904/4/3