RESUMEN
AIM: In the last years there has been a progressive reduction of the average duration of sleep and an increase in the incidence of sleep disturbances. At the same time, an increase of the incidence of the metabolic syndrome has been described, partly attributable to the progressive worsening of dietary habits and the increase in sedentary lifestyle. Recent studies suggest that adequate sleep is essential to maintain good glucose metabolism and sleep disturbances may contribute to the manifestation of the metabolic syndrome. Benzodiazepines (BZ), such as brotizolam, and imidazopyridines, such as zolpidem, are frequently used as hypnotics but their potential impact on glucose metabolism has never been evaluated so far. METHODS: In 12 healthy volunteers [age (mean ± SEM) 38.3 ± 8.1 years; body mass index (BMI) 21.9 ± 0.8 kg/m²] we studied glucose and insulin responses to oral glucose tolerance test (OGTT, 75 g) before and after 15 days treatment with brotizolam 0.25 mg/day or zolpidem 10 mg/day. RESULTS: Brotizolam increased glucose delta area under curve response to the OGTT by 122 % (p < 0.01) and zolpidem by 86 % (p < 0.01) without significant variations of insulin levels, suggesting an impact on insulin sensitivity and/or insulin secretion. CONCLUSIONS: This study suggests that BZ and imidazopyridines have a rapid glucometabolic effect that is detectable as early as after 15 days treatment.
Asunto(s)
Benzodiazepinas/administración & dosificación , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Piridinas/administración & dosificación , Adulto , Azepinas/administración & dosificación , Azepinas/efectos adversos , Benzodiazepinas/efectos adversos , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Esquema de Medicación , Femenino , Prueba de Tolerancia a la Glucosa , Salud , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Piridinas/efectos adversos , Factores de Tiempo , ZolpidemRESUMEN
BACKGROUND: It is well recognized that beta-adrenergic receptors mediate important endocrine and metabolic actions. In fact, beta-adrenergic receptor activation negatively influences GH secretion while exerting relevant metabolic actions such as the stimulation of insulin secretion, glycogenolysis, and lipolysis. AIM: We have already shown that the activation of the GH secretagogue receptor (GHS-R)-1a by acylated ghrelin (AG) counteracts the inhibitory effect of salbutamol (SALB), a beta2-adrenergic agonist, on GH release. The aim of the present study in humans was to clarify whether the metabolic response to SALB is affected by the infusion of AG, also known to exert significant metabolic actions. METHODS: Six healthy young male volunteers underwent the following testing sessions in random order at least 5 days apart: a) SALB (0.06 microg/kg/min iv from 0 to 60 min) alone; b) SALB in combination with AG (1.0 microg/kg/min iv from -60 to 60 min); c) isotonic saline. Insulin, glucose, and free fatty acids (FFA) levels were evaluated every 15 min. RESULTS: As expected, with respect to saline, SALB administration tended to increase both insulin secretion [Delta area under the curve (DeltaAUC): 0.16+/-0.09 vs 0.003+/-0.077 x 10(3) microU/ml/min; p>0.05] and FFA levels (DeltaAUC: 8.0+/-7.3 vs -4.0+/-4.0 mEq/l/min; p>0.05), while glucose levels did not change. The metabolic response to SALB was significantly modified under the exposure of AG. In fact, under AG infusion, SALB elicited a more marked increase of FFA (DeltaAUC: 22.3+/-3.2 vs 8.0+/-7.3 mEq/l/min; p<0.05) as well as a slight elevation in insulin (DeltaAUC: 0.37+/-0.11 vs 0.16+/-0.09 x 10(3) microU/ml/min; p>0.05). Under AG, the baseline glucose levels were more elevated but, again, in combination with AG, SALB did not significantly modify glucose levels. CONCLUSIONS: Beta-adrenergic receptors and AG are likely to interact at the metabolic level. In humans, the lypolitic response to a beta2-adrenergic agonist such as SALB is amplified by AG. Meanwhile, during the co-treatment, the marginal insulinotropic effect was not associated with an increase in glycemia.