Abstract
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.
Abbreviations
- BMI:
-
Body mass index
- OGTT:
-
Oral glucose tolerance test
- GABA:
-
γ-Aminobutyric acid A
- REM:
-
Rapid eyes movements
- BZ:
-
Benzodiazepines
- CV:
-
Coefficient of variation
- AUC:
-
Area under curve
- IGT:
-
Impaired glucose tolerance
References
Spiegel K, Tasali E, Leproult R, Van Cauter E (2009) Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol 5:253
Lam JC, Ip MS (2010) Sleep and metabolic syndrome. Indian J Med Res 131:206
Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR et al (2008) The metabolic syndrome. Endocr Rev 29:777–822
Ashton H (1994) Guidelines for the rational use of benzodiazepines. When and what to use. Drugs 48:25–40
Holbrook A, Crowther R, Lotter A, Endeshaw Y (2001) The role of benzodiazepines in the treatment of insomnia: meta-analysis of benzodiazepine use in the treatment of insomnia. J Am Geriatr Soc 49:824–826
Dang A, Garg A, Rataboli PV (2011) Role of zolpidem in the management of insomnia. CNS Neurosci Ther 17:387–397
Peterson BT, Chiao P, Pickering E, Freeman J, Zammit GK, Ding Y et al (2012) Comparison of actigraphy and polysomnography to assess effects of zolpidem in a clinical research unit. Sleep Med 13:419–424
Huang Y, Mai W, Cai X, Hu Y, Song Y, Qiu R et al (2011) The effect of zolpidem on sleep quality, stress status, and nondipping hypertension. Sleep Med 13:263–268
Cavagnini F, Pinto M, Dubini A, Invitti C, Cappelletti G, Polli EE (1982) Effects of gamma aminobutyric acid (GABA) and muscimol on endocrine pancreatic function in man. Metabolism 31:73–77
Gilon P, Bertrand G, Loubatières-Mariani MM, Remacle C, Henquin JC (1991) The influence of gamma-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas. Endocrinology 129:2521–2529
Gu XH, Kurose T, Kato S, Masuda K, Tsuda K, Ishida H et al (1993) Suppressive effect of GABA on insulin secretion from the pancreatic beta-cells in the rat. Life Sci 52:687–694
Passariello N, Giugliano D, Torella R, Sgambato S, Coppola L, Frascolla N (1982) A possible role of gamma-aminobutyric acid in the control of the endocrine pancreas. J Clin Endocrinol Metab 54:1145–1149
Dong H, Kumar M, Zhang Y, Gyulkhandanyan A, Xiang YY, Ye B et al (2006) Gamma-aminobutyric acid up- and down regulates insulin secretion from beta cells in concert with changes in glucose concentration. Diabetologia 49:697–705
Brice NL, Varadi A, Ashcroft SJ, Molnar E (2002) Metabotropic glutamate and GABA (B) receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells. Diabetologia 45:242–252
Faraji F, Ghasemi A, Motamedi F, Zahediasl S (2011) Time-dependent effect of GABA on glucose-stimulated insulin secretion from isolated islets in rat. Scand J Clin Lab Invest 71:462–466
Chevassus H, Mourand I, Molinier N, Lacarell B, Brun JF, Petit P (2004) 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. BMC Clin Pharmacol 4(4):3
Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470
Borai A, Livingstone C, Kaddam I, Ferns G (2011) Selection of the appropriate method for the assessment of insulin resistance. BMC Med Res Methodol 11:158
Hedrington MS, Farmerie S, Ertl AC, Wang Z, Tate DB, Davis SN (2010) Effects of antecedent GABAA activation with alprazolam on counterregulatory responses to hypoglycemia in healthy humans. Diabetes 59:1074–1081
Acknowledgments
The study protocol has been funded by University of Turin (grants year 2007) and Fondazione per la Ricerca delle Malattie Endocrino Metaboliche (FSMEM).
Conflict of interest
The authors E. Gramaglia, V. Ramella Gigliardi, I. Olivetti, M. Tomelini, S. Belcastro, E. Calvi, A. Dotta, E. Ghigo, A. Benso, and F. Broglio declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gramaglia, E., Ramella Gigliardi, V., Olivetti, I. et al. Impact of short-term treatment with benzodiazepines and imidazopyridines on glucose metabolism in healthy subjects. J Endocrinol Invest 37, 203–206 (2014). https://doi.org/10.1007/s40618-013-0016-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-013-0016-y