Aims To investigate the effects of glutamate on insulin secretion and glucose tolerance in humans. Methods Monosodium (L)-glutamate (10 g) was given orally in a double-blind placebo-controlled cross-over study to 18 healthy volunteers, aged 19-28 years, with an oral (75 g) glucose load. Results The 75 min insulin response (AUC(0,75 min)), up to t max of glutamate kinetics, was significantly correlated with the AUC(0,75 min) of glutamate concentrations (r=0.485, P=0.049). Glucose tolerance was not affected. Conclusions Oral (L)-glutamate enhances glucose-induced insulin secretion in healthy volunteers in a concentration-dependent manner.

BackgroundThe present study aimed at investigating in healthy volunteers the effects of diazepam and clonazepam on beta-cell function, insulin sensitivity and glucose effectiveness based on the frequently sampled intravenous (0.5 gkg-1) glucose tolerance test with minimal-model analysis.MethodsThe 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: 20–29), 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.ResultsBoth 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 ± 0.3 versus 2.84 ± 0.60 × 10-2min-1 (P = 0.028) for the coefficient of glucose tolerance (Kg), 2.18 ± 0.29 versus 3.71 ± 0.89 × 10-4μUml-1min-1 (P = 0.018) for insulin sensitivity (Si) and 1.80 ± 0.39 versus 3.59 ± 0.71 × 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.ConclusionThe present results suggest that a benzodiazepine, in particular clonazepam, may alter insulin secretion and insulin sensitivity after a single administration in healthy volunteers.

SUMMARYRufinamide (RUF) is a novel antiepileptic drug considered as second-line therapy in the treatment of Lennox-Gastaut syndrome. Treatment-emergent adverse events (AEs) have consisted mainly of drowsiness, irritability, vomiting, and loss of appetite. RUF is considered as a ''weight-neutral'' drug. We found clinically significant weight loss in 7 of 15 consecutive adult patients (47%; 3 male, 4 female, aged 18-31 years) treated with RUF as add-on therapy (800-2,400 mg/day: 23.5-57.1 mg/kg/day). The body mass index (BMI) decreased by 7.3-18.7%. Two patients were obese class I before RUF. Five patients (71%) were underweight before RUF (mild in one case, moderate in two cases, and severe in two cases). Four of these patients stopped RUF because of this adverse effect. RUF was recommenced in two patients using a lower and slower dosing strategy; one patient showed improvement in seizure control and no weight loss but RUF was re-stopped in the second patient because of continued weight loss. Despite of weight loss, RUF was continued in two other patients because it reduced seizure activity. We primarily related weight loss to reduced food intake, that is, loss of appetite and nausea, although in two patients no obvious loss of appetite was reported. RUF can cause clinically significant weight loss in adult patients, even at low dose. This AE can affect patients who are already underweight. There is a possibility that lower starting doses and slower escalation might minimize weight loss, but further information is required to determine whether this is the case.

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