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THE RELATIONSHIP BETWEEN SLEEP AND SALIVARY AND SERUM IMMUNOMETABOLIC BIOMARKERS

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2024-04-29

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Abdullah, Abeer M. 2022. THE RELATIONSHIP BETWEEN SLEEP AND SALIVARY AND SERUM IMMUNOMETABOLIC BIOMARKERS. Doctoral dissertation, Harvard University School of Dental Medicine.

Abstract

Background and Objectives: Sleep plays a vital role in maintaining health and well-being. Poor sleep contributes to several adverse health outcomes due to hormonal and metabolic disorders that alters molecular processes that drive cellular immune activation and induce the secretion of immunometabolic biomarkers. Most studies use blood samples for their investigations, in this study we tested both salivary and serum samples to study the effect of sleep variables on immunometabolic biomarkers. There is established evidence on the relationship between poor sleep behavior and inflammatory and metabolic biomarkers. In this study, our aims were to determine the relationship between sleep timing (bedtime), sleep debt and social jetlag with levels of nine salivary and serum immunometabolic biomarkers (C-Reactive Protein (CRP), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleuken-10 (IL-10), Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein-1 (MCP-1), adiponectin, leptin, and insulin). Materials and Methodology: Data were collected from 352 adolescents, 16-18 years old and enrolled in Kuwait’s public high schools. Nine biomarkers were measured in saliva and serum supernatants using multiplex magnetic bead panels on a Luminex 200™ system. For statistical analyses, we conducted mixed effect linear regression models to account for school variable as a random effect to study the association between biomarkers as our outcome variables and sleep variables as our exposure variables, controlling for confounders (age, sex, medical history, nap, screen time, negative dietary habits). We also investigated the role of Nap, BMI and Waist circumference (WC) in these associations. Results: After controlling for confounding variables in all our models we found that (bedtime) sleep timing was statistically significantly associated with an overall elevation for salivary IL-6 and serum (CRP, IL-6, IL-10, MCP-1 and insulin) and reduction in serum IL-8 biomarkers. BMI and WC played a major rule in attenuating some of these associations as confounding variables, for example, leptin biomarker with bedtime. In addition, we displayed a mediation effect of BMI for the associations between bedtime and serum (CRP, IL-6, and insulin). Adolescents who exhibited catch-up sleep on free days (weekends) showed a statistically significant positive association with salivary IL-6 and serum (CRP and IL-6) and negative association with serum IL-8 biomarkers. For students with social jetlag (SJL), only salivary biomarkers (IL-6, VEGF and leptin) showed a statistically significant reduction with increase in SJL. Conclusion: This change of biomarker levels and directions with sleep timing behaviors support the hypothesis that late bedtime and disrupted circadian rhythm promote local and systemic inflammation that can trigger chronic metabolic diseases. Our findings highlight the importance of late bedtime as a strong predictor of oral and systemic inflammation, indexed by salivary and serum biomarkers.

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Biomarkers, BMI, chronic diseases, Circadian rhythms, inflammation, Sleep, Public health, Immunology, Middle Eastern studies

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