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Lower plasma choline levels are associated with sleepiness symptoms.

ABSTRACT: Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk. METHODS:An exploratory case-control sample of 36 subjects, categorized based on the Epworth Sleepiness Scale (ESS) questionnaire as sleepy (ESS ? 10) or non-sleepy (ESS < 10), was recruited among subjects undergoing an overnight sleep study for suspected sleep apnea at the University of Pennsylvania Sleep Center. The average age was 42.4 ± 10.5 years, the mean body mass index (BMI) was 40.0 ± 9.36 kg/m2, median Apnea Hypopnea Index (AHI) was 8.2 (IQR: 2.5-26.5), and 52% were male. Fasting morning blood plasma samples were collected after an overnight sleep study. Biomarkers were explored in subjects with sleepiness versus those without using the multiple linear regression adjusting for age, BMI, smoking, Apnea Hypopnea Index (sleep apnea severity), study cohort, and hypertension. RESULTS:The level of choline is significantly lower (P = 0.003) in sleepy subjects (N = 18; mean plasma choline concentration of 8.19 ± 2.62 ?mol/L) compared with non-sleepy subjects (N = 18; mean plasma choline concentration of 9.14 ± 2.25 ?mol/L). Other markers with suggestive differences (P < 0.1) include isovalerylcarnitine, Alpha-Amino apidipic acid, Spingosine 1 Phosphate, Aspartic Acid, Propionylcarnitine, and Ceramides (fatty acids; C14-C16 and C-18). CONCLUSION:This pilot study is the first to show that lower levels of plasma choline metabolites are associated with sleepiness. Further exploration of choline and other noted metabolites and their associations with sleepiness will guide targeted symptom management.

SUBMITTER: Pak VM

PROVIDER: S-EPMC6531048 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Lower plasma choline levels are associated with sleepiness symptoms.

Pak Victoria M VM Dai Feng F Keenan Brendan T BT Gooneratne Nalaka S NS Pack Allan I AI

Sleep medicine 20171026

Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness ...[more]

PMID: 29530375

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Project description:Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targeted metabolomics approach to identify novel metabolites associated with insulin dysregulation.Oral glucose testing triggered alterations in serum insulin (26.28?±?4.20 vs. 422.84?±?88.86 ?IU/mL, p?<?0.001) and plasma glucose concentrations (5.00?±?0.08 vs. 9.43?±?0.44 mmol/L, p?<?0.001) comparing basal and stimulated conditions after 180 min. Metabolome analyses indicated OGT-induced changes in short-chain acylcarnitines (6.00?±?0.53 vs. 3.99?±?0.23 ?mol/L, p?<?0.001), long-chain acylcarnitines (0.13?±?0.004 vs. 0.11?±?0.002 ?mol/L, p?<?0.001) and amino acids (2.18?±?0.11 vs. 1.87?±?0.08 ?mol/L, p?<?0.05). Kynurenine concentrations increased (2.88?±?0.18 vs. 3.50?±?0.19 ?mol/L, p?<?0.01), whereas spermidine concentrations decreased during OGT (0.09?±?0.004 vs. 0.08?±?0.002 ?mol/L, p?<?0.01), indicating proinflammatory conditions after oral glucose load. Insulin dysregulation was associated with lower concentrations of trans-4-hydroxyproline (4.41?±?0.29 vs. 6.37?±?0.71 ?mol/L, p?<?0.05) and methionine sulfoxide (0.40?±?0.06 vs. 0.87?±?0.13 ?mol/L, p?<?0.01; mean?±?SEM in insulin-dysregulated vs. insulin-sensitive basal samples, respectively), two metabolites which are related to antioxidant defense mechanisms.Oral glucose application during OGT resulted in profound metabolic and proinflammatory changes in horses. Furthermore, insulin dysregulation was predicted in basal samples (without OGT) by pathways associated with trans-4-hydroxyproline and methionine sulfoxide, suggesting that oxidative stress and oxidant-antioxidant disequilibrium are contributing factors to insulin dysregulation. The present findings provide new hypotheses for future research to better understand the underlying pathophysiology of insulin dysregulation in horses.

Project description:ObjectiveThis study examined the prevalence, sociodemographic features, patterns of comorbidity, and impact on functional impairment of excessive sleepiness (Ex.S) and associated symptoms in a nationally representative sample of adults using the National Comorbidity Survey Replication (NCS-R) dataset.MethodsParticipants ≥18 years (n = 5,962) were queried about their sleep using the Composite International Diagnostic Interview (CIDI). Specifically, respondents were questioned about feeling sleepy during the day and falling asleep in permissive situations, feelings of insufficient sleep despite adequate time in bed, and/or difficulty waking up. Those endorsing daytime sleepiness and at least one additional symptom were considered to have Ex.S plus associated symptoms. Associations between Ex.S plus associated symptoms and sociodemographics, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) mental disorders, chronic physical conditions, and functional impairment were examined.ResultsThe prevalence of Ex.S plus associated symptoms in U.S. adults was 23.34% (standard error [SE] = 0.88) and significantly co-occurred with insomnia-related symptoms after adjusting for confounders (Odds ratio [OR] = 5.65; 95% confidence interval [CI] = 4.55-7.02). The presence of Ex.S and associated symptoms was more common in women, particularly younger women, those with lower family income, and the unemployed (all P<.001). After controlling for demographic characteristics and other confounders, Ex.S plus associated symptoms was associated with having a DSM-IV mental disorder (OR = 4.25; 95% CI = 3.53-5.10), a chronic physical condition (OR = 2.57; 95% CI = 1.94-3.42) and greater disability (P<.001).ConclusionEx. S with associated symptoms was common, frequently co-occurred with other mental and physical conditions, and was associated with substantial disability. Dissipation of some associations after controlling for insomnia-related symptoms indicated that physical-mental comorbidity and disability were greater among individuals with more pervasive sleep disturbances.

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Lower plasma choline levels are associated with sleepiness symptoms.

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Lower plasma choline levels are associated with sleepiness symptoms.

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