SLOW RELEASE MELATONINE IN METABOLIC SYNDROME SYMPTHOMATICS CORRECTION

Aim. To compare effectiveness of metformin monotherapy (Mf) and combination of metformin with slow release melatonine (MfM) from the perspective of correction of anthropometric, hemodynamical parameters, premature vascular ageing and somnological status in patients with metabolic syndrome (MS).

Material and methods. An open label prospective comparative study conducted, in 3 parallel groups: 238 MS patients (IDF, 2005) having, at the moment of prescreening, sleep disorders (less than 19 points in Questionnaire of self sleep evaluation), were randomized to 3 groups. During 12 weeks all patients underwent life style correction that included regimen of meal intake, normalization of “sleepwakefulness” rhythm, physical activity. In addition to this, first group patients (n=80) received Mf, and second (n=78) — combination MfM (Circadin 2 mg). Controls (n=80) were patients without pharmaceutical interventions. Groups were comparable by the baseline clinical and demographic characteristics. Sleep quality, anthropometric and metabolic parameters, adipocytokine level and vascular elasticity parameters were assessed at baseline and in 12 weeks after treatment.

Results. The results of the study performed have proved the feasibility of melatonine slow release addition to standard MS therapy in circadian disorders (CD). MfM no only normalizes the rhythm “sleep-wakefulness”, but also retards vascular ageing, has positive profile of cardiovasular and metabolic effects, acting on insulin resistance as trigger of MS development. Serious adverse events were not marked during the study.

 Conclusion. Combination therapy by MfM is more effective than monotherapy by Mf in correction of body overweight, carbohydrate and lipid metabolism disorders in MS with CD.

1. Knutson KL, Spiegel K, Penev P, et al. The metabolic consequences of sleep deprivation. Sleep medicine reviews. 2007: 11(3), 163-78.

2. National Center for Health Statistics. Quick-Stats: percentage of adults who reported an average of ≤6 hours of sleep per 24-hour period, by sex and age group — United States, 1985 and 2004. MMWR Morb. Mortal. Wkly. Rep. 2005: 54, 933.

3. Knutson KL, Van Cauter E. Associations between sleep loss and increased risk of obesity and diabetes. Annals of the New York Academy of Sciences. 2008: 1129(1), 287-304.

4. Spiegel K, Tasali E, Leproult R, et al. Effects of poor and short sleep on glucose metabolism and obesity risk. Nature Reviews Endocrinology. 2009: 5(5), 253-61.

5. Fitzpatrick A. Melatonin in health and disease. Alternative & Complementary Therapies. 2006: 12(6), 282-91.

6. Cuende JI, Cuende N, Calaveras-Lagartos J. How to calculate vascular age with the SCORE project scales: a new method of cardiovascular risk evaluation. European heart journal. 2010: 31(19), 2351-8.

7. Zisapel N. Drugs for insomnia. Expert opinion on emerging drugs. 2012: 17(3), 299317.

8. Jiménez-Aranda A, Fernández-Vázquez G, Campos D, et al. Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats. Journal of pineal research. 2013: 55(4), 416-23.

9. Rapoport SI. Melatonin: prospects of application in the clinic. 2014. M.: IMA-PRESS, 2012. 176 s.

10. Lemoine P, Garfinkel D, Laudon M, et al. Prolonged-release melatonin for insomnia–an open-label long-term study of efficacy, safety, and withdrawal. Therapeutics and clinical risk management. 2011: 7, 301.

11. Laudon GE, Zisapel N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc. Health Risk Manag. 2011: 7, 577-84.

12. Mayo KE, Godfrey PA, Suhr ST. Growth hormone-releasing hormone: synthesis and signal ing. Recent Progress in Hormone Research-Volume 50: Proceedings of the 1993 Laurentian Hormone Conference. Academic Press, 2013: 35.

13. Leger D, Laudon M, Zisapel N. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med. 2004; 116(2): 91-5.

14. Lemoine P, Garfinkel D, Laudon M, et al. Prolonged release melatonin for insomnia — an open label long term study of efficacy, safety and withdrawal symptoms Therapeutics and Clinical Risk Management. 2011; 7301–11.

15. Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007; 16: 372-80.

16. Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007; 23(10): 2597-605.

17. Wade AG, Ford I, Crawford G, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010; 8(1): 51.