Insomnia´s Impact on DNA Stability, Cardio-metabolic Health and Lifestyle Behaviors

Официальное название

Insomnia´s Impact on DNA Stability, Cardio-metabolic Health and Lifestyle Behaviors: A Case-control Study

Обзор

Insomnia is a highly prevalent sleep disorder worldwide, with an increasing incidence in athletes, older adults, university students, and individuals with metabolic syndrome. This disorder has been associated with metabolic dysfunction, cardiovascular diseases, and genetic instability. Recent evidence suggests that insomnia negatively impacts cardiorespiratory fitness, insulin sensitivity, and overall health through mechanisms involving neuroendocrine dysregulation, oxidative stress, and alterations in energy metabolism. However, the specific biological and environmental factors that contribute to its prevalence and health consequences remain poorly understood, particularly across different populations. Understanding these associations is crucial for developing effective prevention and intervention strategies to mitigate the long-term impact of insomnia. Therefore, this study aims to analyze the impact of insomnia on body composition, cardiorespiratory fitness, metabolic flexibility, and DNA integrity, across populations with high prevalence of insomnia, including athletes, older adults, university students, and individuals with metabolic syndrome. This study will also investigate which biological and lifestyle behaviors contribute to insomnia and its health consequences. By doing so, this work will provide critical insights into the physiological and molecular mechanisms that link insomnia with metabolic and cardiovascular dysfunction, contributing to the development of targeted interventions for at-risk populations

Подробное описание

Insomnia is a prevalent sleep disorder characterized by difficulty initiating or maintaining sleep despite adequate sleep opportunities and an appropriate sleep environment. It affects 10-50% of the adult population worldwide, with several biological, sociodemographic, and psychological-behavioral factors contributing to its occurrence. Notably, its prevalence is higher in women than in men (risk ratio: 1.58, p\<0.01) and increases with age, affecting 30-48% of older adults compared to 12-20% of young adults. Additionally, insomnia is more frequently reported among university students than in the general population (18.5% vs. 7.5%), and 13-70% of elite athletes experience persistent sleep disturbances indicative of insomnia.

Recent research has highlighted the long-term negative impact of insomnia on quality of life, as it induces chronic fatigue and excessive daytime sleepiness, which are strongly associated with reduced work productivity, academic performance, and athletic capabilities. Additionally, insomnia has been linked to an increased risk of cardiovascular and metabolic diseases, with a higher prevalence observed in individuals with obesity, type 2 diabetes, and hypertension.

Some studies have reported an inverse association between multiple indicators of insomnia and cardiorespiratory fitness in individuals without chronic diseases, further reinforcing the connection between insomnia and cardiovascular disease risk. This phenomenon may be driven by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system, both of which contribute to increased cardiac contractility and altered neuroendocrine function. Moreover, the observed negative correlation between insomnia and oxygen uptake capacity suggests that insomnia may compromise capillary and mitochondrial density as well as cardiovascular efficiency, which are key determinants of maximal oxygen consumption (VO₂max). Another plausible mechanism underlying this association is reduced heart rate variability (HRV) in individuals with chronic insomnia, likely resulting from elevated norepinephrine and cortisol levels, which are known to heighten sympathetic nervous system activity and impair cardiovascular function.

Beyond its cardiovascular implications, sleep deficiency disrupts metabolic homeostasis, promoting high-calorie food consumption through both hormonal (e.g., increased ghrelin secretion) and neurocognitive mechanisms (e.g., heightened hedonic drive for food intake). Over time, these physiological alterations contribute to body weight gain and insulin resistance, increasing the risk of metabolic disorders such as obesity and type 2 diabetes.

At the molecular level, chronic sleep deprivation has been shown to impair DNA repair cycles, which may contribute to the development of metabolic and cardiovascular diseases. Specifically, fragmentation of DNA strands has been observed following sleep restriction, leading to slower chromosomal dynamics and impaired cellular recovery. Additionally, sleep deprivation has demonstrated genotoxic effects in multiple organs and tissues, increasing oxidative DNA damage.

Despite the growing body of evidence linking insomnia to cardiovascular and metabolic dysfunction, most human studies have focused primarily on young adult males with low physical activity levels and without chronic diseases. Similarly, the genotoxic effects of sleep disorders have been assessed mainly in preclinical models, with limited investigation of their correlation with cardiovascular and metabolic biomarkers in humans.

Given these knowledge gaps, this study aims to examine the physiological and molecular consequences of insomnia across diverse populations, including athletes, older adults, university students, and individuals with metabolic syndrome. This research will provide valuable insights into the mechanisms underlying insomnia-related dysfunctions, ultimately contributing to the development of targeted interventions to mitigate its long-term health effects. The findings from this study will play a crucial role in guiding future clinical interventions aimed at improving sleep quality and metabolic health. Given that 27-40% of the Mexican adult population is affected by insomnia, addressing this disorder has become a public health priority. This research is aligned with the United Nations Sustainable Development Goals (SDGs), particularly in the areas of (i) health and well-being, (ii) quality education, and (iii) partnerships for achieving these objectives.

Additionally, the project will provide academic training opportunities for undergraduate and graduate students, reinforcing their competencies in research methodologies, data analysis, and clinical evaluations. Furthermore, collaboration with the National Institute of Public Health and the University of Granada will foster international research partnerships, enhancing the study's scientific impact.

By addressing the underlying insomnia and its multisystem effects, this project will contribute significantly to the prevention, diagnosis, and treatment of sleep disorders in vulnerable populations, ultimately improving overall public health and quality of life.

Вмешательства

• Другое Exercise
  A cardiopulmonary exercise test in a treadmill will be performed after an overnight fasting. Gas exchange, heart rate, and muscle oxygen saturation levels will be assessed continuously during the entire test. Blood pressure and rate of perceived exertion will be recorded prior the end of each stage whereas blood glucose concentration will be assessed before and after the test. All the hemodynamic parameters will be assessed at rest to standardize the cardio-metabolic condition of the participant
• Другое Bioelectrical Impedance
  Bioelectrical impedance analysis will be used to estimate body compartments through a mechanism of resistance and reactance (InBody 770, KOR) . The compartments measured include body cell mass, fat mass, extracellular tissue, lean mass, muscle mass, visceral adipose tissue area, phase angle, among others.
• Генная терапия Micronucleus Assay
  The frequency of micronuclei, nuclear buds, basal cells, binucleated cells, condensed chromatin cells, karyorrhexis, karyolysis, and pyknosis will be determined through microscopic examination of exfoliated oral mucosal cells from each participant.
• Поведенческое Physical activity and sedentary time
  Physical activity and sedentary time will be assessed through the Spanish version of the International Questionnaire of Physical activity. In half of the analyzed subjects a wearable device (Fitbit luxe, Fit bit Inc) will be also used to record daily steps, energy expenditure and heart rate patterns.
• Поведенческое Sleep
  Insomnia severity index, sleep quality, somnolence and chronotype will be subjectively assessed in all participants, using validated scales such as the Pittsburgh, Epworth and ISI questionnaires. In half of the participants, sleep quality will be tracked by wearing a Fit band luxe device in the wrist.
• Биопрепарат blood sampling
  The concentrations of glucose, glycated hemoglobin, and lipid profile will be determined through serum analysis using a blood chemistry analyzer (Spin120, Spinreact, ESP). Serum samples will be obtained by centrifuging peripheral venous blood samples (4-6 mL) collected in Vacutainer tubes at 2500 rpm for 10 minutes. From the same serum samples, circulating levels of insulin, ovarian hormones (estradiol and progesterone), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth facto
• Поведенческое psychometrics
  Perceived stress will be obtained from the Perceived Stress Scale adapted for Mexican population. Additionally, depression and anxiety scores will be obtained from the Becks Depression Inventory, validated in Mexican adults. Ruminative thinking will be assessed through the short version of the Ruminative Responses Scale and substance abuse will be examined through the 10-items Drug Abuse Screening Test. Social media disorder and screen time will be also investigated from the Social Media Disorde
• Поведенческое Nutritional Supplement
  A semi quantitative food frequency questionnaire will be applied to collect data about macronutrient intake and supplements consumption. Hierarchical consumption of each food groups will be also assessed. Last meal consumed prior to exercise testing will be also recorded in conjunction with fasting time.
• Генная терапия Genotyping
  The P10L polymorphism of the OPN4 gene, previously associated with chronic insomnia and severe daytime sleepiness in the Mexican population will be determined using RFLP-PCR assays. DNA will be extracted from previously collected blood samples (4 ml) using the Master Pure DNA purification kit from Epicentre (Illumina Inc., US).

Первичные конечные точки

• Insomnia severity index [Срок оценки: Day 1]
• Daytime sleepiness [Срок оценки: Day 1]
• Sleep quality Index [Срок оценки: Day 1]
• Body composition [Срок оценки: Day 1]
• DNA integrity [Срок оценки: Day 1]
• OPN4 Single nucleotide polymorphism [Срок оценки: Day 1]
• Cardiorespiratory fitness [Срок оценки: Day 1]
• Metabolic flexibility [Срок оценки: Day 1]
• Homeostatic Model Assessment of Insulin Resistance [Срок оценки: Day 1]
• Cholesterol [Срок оценки: Day 1]

Вторичные конечные точки (7)

• Nutrition [Срок оценки: Responding the food frequency questionnaire will take around 10 minutes and the questionnaire will be applied at the single visit the subjects will be requested to attend the laboratory.]
• Self-Reported Physical Activity Level [Срок оценки: Day 1]
• Perceived Stress [Срок оценки: Day 1]
• Depressive symptoms [Срок оценки: Day 1]
• Ruminative thinking [Срок оценки: Day 1]
• Substance abuse [Срок оценки: Day 1]
• Screen time [Срок оценки: Day 1]

Критерии участия

Критерии включения

Each population group will meet the following inclusion criteria:

• Healthy Individuals (18-35 years old, men and women)

• Waist circumference: <90 cm (men), <80 cm (women)
• Fasting glucose: 70-110 mg/dL
• Blood pressure: <120/80 mmHg
• Triglycerides: <150 mg/dL
• HDL-C: >40 mg/dL (men), >50 mg/dL (women)
• Physical activity level: 600-1500 MET-min/week
• Athletes (18-35 years old, men and women)

\*Engaged in structured sports training with a physical activity level >1500 MET-min/week

• Older Adults (65-75 years old, men and women)

\*Free of cognitive or mental health disorders. No specific cardiometabolic or body composition criteria due to the study's exploratory nature.

• University Students (18-35 years old, men and women)

\*No specific cardiometabolic or body composition criteria due to the study's exploratory nature.

• Individuals with Metabolic Syndrome (18-35 years old, men and women)

• Waist circumference: >90 cm (men), >80 cm (women)
• Fasting glucose: >110 mg/dL
• Blood pressure: >130/80 mmHg
• Triglycerides: >150 mg/dL
• HDL-C: <40 mg/dL (men), <50 mg/dL (women)
• Physical activity level: <600 MET-min/week

Критерии исключения

• Individuals with respiratory diseases or musculoskeletal injuries that prevent exercise, as determined by a clinical history review, a physical activity readiness questionnaire (PART-Q+), and pulmonary function tests (spirometry).

Individuals with rotating or night-shift work schedules (e.g., emergency personnel, security guards), as circadian rhythm disruptions significantly impact sleep quality

• Women diagnosed with polycystic ovary syndrome (PCOS) or showing high testosterone levels with a history of oligomenorrhea, as these conditions may influence metabolic and hormonal markers. However, women with menstrual irregularities related to premenstrual syndrome (PMS) or dysmenorrhea will not be excluded, given the established link between sleep disorders and menstrual cycle variations
• This study does not involve chronic dietary or exercise interventions, nor does it require long-term participant follow-up, so no additional exclusion criteria apply

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Мексика · 1 центр

• Laboratorio de Fisiologia Aplicada al Ejercicio — Ensenada

Публикации

• Gonzalez-Ramirez MT, Rodriguez-Ayan MN, Hernandez RL. The perceived stress scale (PSS): normative data and factor structure for a large-scale sample in Mexico. Span J Psychol. 2013;16:E47. doi: 10.1017/sjp.2013.35. PMID 23866243
• Chavez-Guevara IA. Assessment of metabolic flexibility by measuring maximal fat oxidation during submaximal intensity exercise: Can we improve the analytical procedures? Sports Med Health Sci. 2023 Feb 14;5(2):156-158. doi: 10.1016/j.smhs.2023.02.001. eCollection 2023 Jun. PMID 37424534
• Duan D, Kim LJ, Jun JC, Polotsky VY. Connecting insufficient sleep and insomnia with metabolic dysfunction. Ann N Y Acad Sci. 2023 Jan;1519(1):94-117. doi: 10.1111/nyas.14926. Epub 2022 Nov 13. PMID 36373239
• de Souza DV, Rosario BDA, Viana MB, Pisani LP, da Silva GN, Ribeiro DA. Sleep deprivation induces genetic damage in mammalian cells: a systematic review. Rev Assoc Med Bras (1992). 2024 Mar 15;70(1):e20231097. doi: 10.1590/1806-9282.20231097. eCollection 2024. No abstract available. PMID 38511758
• Serra Laborde, P. L., Torterolo Pizzuti, C., & Calvo Pesce, M. S. (2023). Calidad y cronotipo del sueño y su relación con la obesidad en población adulta. Revisión bibliográfica narrativa. Enfermería: Cuidados Humanizados, 12(2), e3213. https://doi.org/10.22235/ech.v12i2.3213
• Zada D, Bronshtein I, Lerer-Goldshtein T, Garini Y, Appelbaum L. Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons. Nat Commun. 2019 Mar 5;10(1):895. doi: 10.1038/s41467-019-08806-w. PMID 30837464
• Strand LB, Laugsand LE, Wisloff U, Nes BM, Vatten L, Janszky I. Insomnia symptoms and cardiorespiratory fitness in healthy individuals: the Nord-Trondelag Health Study (HUNT). Sleep. 2013 Jan 1;36(1):99-108. doi: 10.5665/sleep.2310. PMID 23288976
• Knutson KL, Van Cauter E, Zee P, Liu K, Lauderdale DS. Cross-sectional associations between measures of sleep and markers of glucose metabolism among subjects with and without diabetes: the Coronary Artery Risk Development in Young Adults (CARDIA) Sleep Study. Diabetes Care. 2011 May;34(5):1171-6. doi: 10.2337/dc10-1962. Epub 2011 Mar 16. PMID 21411507

Идентификаторы

NCT: NCT06869486 · CEEIP0004-FDE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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