Features of melatonin cyrcadian secretion in patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome

Abstract

Aim. To evaluate the features of melatonin cyrcadian production in patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome.

Methods. We examines 29 patients with gastroesophageal reflux disease were examined (group 1), 29 patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome (group 2), and 22 patients with obstructive sleep apnea/hypopnea syndrome (group 3). The comparison group included 21 people without gastroesophageal reflux disease and obstructive sleep apnea/hypopnea syndrome (group 4). The content of 6-sulfatoxymelatonin was determined in 24-hour urine and separately in its daytime and night portions by enzyme immune assay. The night/day index was calculated. The compared groups were comparable by gender but the patients with obstructive sleep apnea/hypopnea syndrome and gastroesophageal reflux disease associated with this syndrome differed from the patients from comparison group by older age, which is consistent with epidemiology of sleep apnea. The analysis of the data obtained was performed using the program Statistica 10.0. When comparing quantitative indicators between four independent samples, Kruskel–Wallis test was used. In order to study the relationship between the phenomena, the Spearman rank correlation coefficient was calculated.

Results. A significantly increased level of 6-sulfatoxymelatonin in 24-hour urine was determined in group 2 (p=0.0000), as well as in day (0.0000) and night portions (0.015) compared to group 1, in 24-hour urine (p=0.0007) and its day portion (p=0.0001) compared to group 3, in day portion of urine compared to group 4 (p=0.029). In group 2 compared to group 4 a significant shift in melatonin synthesis peak during daytime hours was observed, which is expressed in a statistically significant decrease in the night/day index (p=0.0003). Correlation analysis revealed statistically significant relations between the level of 6-sulfatoxymelatonin in urine and the severity of sleep apnea (in 24-hour urine: r=0.64, p=0.0000; in daytime portion: r=0.62, p=0.0000; in night portion: r=0.40, p=0.003), as well as respiratory monitoring indicators indicating sleep fragmentation due to apnea (the number of awakenings associated with respiratory events: r=0.58; p=0.00001; activation of the central nervous system associated with respiratory efforts: (r=0.50; p=0.0002).

Conclusion. The patients with gastroesophageal reflux disease associated with obstructive sleep apnea/hypopnea syndrome have an increased level of 6-sulfatoxymelatonin in urine associated with the shift of its peak synthesis to daytime hours; the identified changes correlate with apnea/hypopnea index reflecting the severity of apnea and sleep disturbance.

Keywords

6-sulfatoxymelatonin / gastroesophageal reflux disease / obstructive sleep apnea/hypopnea syndrome / sleep disorder / sleep fragmentation

References

[1] Amaral F.G.D., Cipolla-Neto J. A brief review about melatonin, a pineal hormone. Arch. Endocrinol. Metabol. One. 2018; 62 (4): 472–479. DOI: 10.20945/2359-3997000000066.

[2] Tsfasman A.Z., Gorokhov V.D., Alpaev D.V. Circadian rhythms of melatonin secretion during nocturnal sleep deprivation. Problemy ehndokrinologii. 2013; (2): 40–44. (In Russ.)

[3] Цфасман А.З., Горохов В.Д., Алпаев Д.В. Суточный ритм мелатонина при депривации ночного сна. Пробл. эндокринол. 2013; (2): 40–44.

[4] Lindam A. Symptoms of obstructive sleep apnea, gastroesophageal reflux and the risk of Barrett's esophagus in a population-based case — control study. PLoS One. 2015; 10 (6): 831–836. DOI: 10.1371/journal.pone.0129836.

[5] Pourhoseingholi M.A., Vahedi M., Moghimi-Dehkordi B. et al. Burden of hospitalization for gastrointestinal tract cancer patients-Results from a cross-sectional study in Tehran. Asian Pac. J. Cancer Prev. 2009; 10 (1): 107–110. PMID: 19469635.

[6] Peppard P.E., Young T., Barnet J.H. et al. Increased pre­valence of sleep-disordered breathing in adults. Am. J. Epi­demiol. 2013; 177 (9): 1006–1014. DOI: 10.1093/aje/kws342.

[7] Jansson C., Nordenstedt H., Wallander M. et al. A population-based study showing an association between gastroesophageal reflux disease and sleep problems. Clin. Gastroenterol. Hepatol. 2009; 7 (9): 960–965. DOI: 10.1016/j.cgh.2009.03.007.

[8] Raykhlin N.T. Melatonin: yesterday, today, tomorrow. Klinicheskaya meditsina. 2002; (5): 72–77. (In Russ.)

[9] Райхлин Н.Т. Мелатонин: вчера, сегодня, завтра. Клин. мед. 2002; (5): 72–77.

[10] Zirlik S., Hildner K.M., Targosz A. et al. Melatonin and omentin: influence factors in the obstructive sleep apnea syndrome? J. Physiol. Pharmacol. 2013; 64 (3): 353–360. PMID: 23959732.

[11] Kaybysheva V.O., Kucheryavyy Yu.A., Trukhmanov A.S. et al. Results of multicenter observation study on application of international questionnaire GerdQ for diagnostics of gastroesophageal reflux disease. RZhGGK. 2013; (5): 15–23. (In Russ.)

[12] Кайбышева В.О., Кучерявый Ю.А., Трухманов А.С. и др. Результаты многоцентрового наблюдательного исследования по применению международного опросника GerdQ для диагностики ГЭРБ. РЖГГК. 2013; (5): 15–23.

[13] Kim B. The utility of three screening questionnaires for obstructive sleep apnea in a sleep clinic setting. Yonsei. Med. J. 2015; 6 (3): 684–690. DOI: 10.3349/ymj.2015.56.3.684.

[14] Glants S. Mediko-biologicheskaya statistika. (Medical and biological statistics.) Moscow: Praktika. 1999; 459 p. (In Russ.)

[15] Гланц С. Медико-биологическая статистика. Пер. с англ. М.: Практика. 1999; 459 с.

[16] Barnaś M., Maskey-Warzęchowska M., Bielicki P. et al. Diurnal and nocturnal serum melatonin concentrations after treatment with continuous positive airway pressure in patients with obstructive sleep apnea. Polish Arch. Intern. Med. 2017; 127 (9): 589–596. DOI: 10.20452/pamw.4062.

[17] Karpovich O.A., Shishko V.I. The protective action of me­latonin in gastroesophageal reflux disease. Gepatologiya i gastroehnterologiya. 2019; 3 (1): 61–65. (In Russ.)

[18] Карпович О.А., Шишко В.И. Протективная роль мелатонина при гастроэзофагеальной рефлюксной болезни. Гепатол. и гастроэнтерол. 2019; 3 (1): 61–65. DOI: 10.25298/2616-5546-2019-3-1-61-65.

[19] Datieva V.K., Lyashenko E.A., Levin O.S. Use of melatonin in sleep disorders. Sovremennaya terapiya v psikhiatrii i nevrologii. 2015; (1): 36–38.

[20] Датиева В.К., Ляшенко Е.А., Левин О.С. Применение мелатонина при нарушении сна. Соврем. терап. в психиатрии и неврол. 2015; (1): 36–38.

[21] Bubenik G.A., Konturek S.J. Melatonin and ­aging: prospects for human treatment. J. Physiol. Pharmacol. 2011; 62 (1): 13–19. PMID: 21451205.

[22] Loloei S., Sepidarkish M., Heydarian A. et al. The effect of melatonin supplementation on lipid profile and anthropometric indices: A systematic review and meta-ana­lysis of clinical trials. Diabetes Metab. Syndr. 2019; 13 (3): 1901–1910. DOI: 10.1016/j.dsx.2019.04.043.

RIGHTS & PERMISSIONS

Karpovich O.A., Shishko V.I., Shulika V.R.