Cardiometabolic Disorders Research Articles

Tissue-specific mitochondrial toxicity of cigarette smoke concentrate: consequence to oxidative phosphorylation.

Cigarette smoke exposure is a well-known risk factor for developing numerous chronic health conditions, including pulmonary disease and cardiometabolic disorders. However, the cellular mechanisms mediating the toxicity of cigarette smoke in extrapulmonary tissues are still poorly understood. Therefore, the purpose of this study was to characterize the acute dose-dependent toxicity of cigarette smoke on mitochondrial metabolism by determining the susceptibility and sensitivity of mitochondrial respiration from murine skeletal (gastrocnemius and soleus) and cardiac muscles, as well as the aorta to cigarette smoke concentrate (CSC). In all tissues, exposure to CSC inhibited tissue-specific respiration capacity, measured by high-resolution respirometry, according to a biphasic pattern. With a break point of 451 ± 235 μg/mL, the aorta was the least susceptible to CSC-induced mitochondrial respiration inhibition compared with the gastrocnemius (151 ± 109 μg/mL; P = 0.008, d = 2.3), soleus (211 ± 107 μg/mL; P = 0.112; d = 1.7), and heart (94 ± 51 μg/mL; P < 0.001; d = 2.6) suggesting an intrinsic resistance of the vascular smooth muscle mitochondria to cigarette smoke toxicity. In contrast, the cardiac muscle was the most susceptible and sensitive to the effects of CSC, demonstrating the greatest decline in tissue-specific respiration with increasing CSC concentration (P < 0.001, except the soleus). However, when normalized to citrate synthase activity to account for differences in mitochondrial content, cardiac fibers' sensitivity to cigarette smoke inhibition was no longer significantly different from both fast-twitch gastrocnemius and slow-twitch soleus muscle fibers, thus suggesting similar mitochondrial phenotypes. Collectively, these findings established the acute dose-dependent toxicity of cigarette smoke on oxidative phosphorylation in permeabilized tissues involved in the development of smoke-related cardiometabolic diseases.NEW & NOTEWORTHY Despite numerous investigations into the mechanisms underlying cigarette smoke-induced mitochondrial dysfunction, no studies have investigated the tissue-specific mitochondrial toxicity to cigarette smoke. We demonstrate that, while aorta is least sensitive and susceptible to cigarette smoke-induced toxicity, the degree of cigarette smoke-induced toxicity in striated muscle depends on the tissue-specific mitochondrial content. We conclude that while the mitochondrial content influences cigarette smoke-induced toxicity in striated muscles, aorta is intrinsically protected against cigarette smoke-induced mitochondrial toxicity.

Hyperuricemia remodels the serum proteome toward a higher inflammatory state

Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia never develop gout but have an increased risk of developing cardiometabolic disorders. Current management of gout aims at MSU crystal dissolution by lowering serum urate. We apply a targeted proteomic analysis, using Olink inflammation panel, to a large group of individuals with gout, asymptomatic hyperuricemia, and normouricemic controls, and we show a urate-driven inflammatory signature. We add invivo evidence of persistent immune activation linked to urate exposure and describe immune pathways involved in the pathogenesis of gout. Our results support a pro-inflammatory effect of asymptomatic hyperuricemia and pave the way for new research into targetable mechanisms in gout and cardiometabolic complications of asymptomatic hyperuricemia.

Exploring Patient Beliefs and Medication Adherence in the Mediterranean Context: A Cross-Sectional Study in Patients with Cardiovascular Diseases and Cardiometabolic Disorders in Greece-The IACT-Study.

Evidence has shown that poor adherence to vascular medications contributes to a considerable proportion of all cardiovascular disease (CVD) events and mortality. The aim of the present work was to examine patients' beliefs/views that affect their level of adherence to the assigned medical treatment in the context of a multi-center study in Greece. Between July 2022 and April 2023, 1988 patients (1180 females) with established cardiovascular disease or relevant cardiometabolic disorders were chosen from seven medical centers in Greece. The 4-item Morisky Medication Adherence Questionnaire gauged medication adherence and investigated patients' beliefs/views regarding treatment. Among participants, 51.2% showed perfect medication adherence, contrasting with 48.8% displaying poor adherence. Patients with negative medication beliefs were around three times more likely to be non-adherent (OR = 2.73; 95% CI = 2.28-3.28). Non-adherers held concerns about drug efficacy (OR = 2.34; 95% CI = 1.10-4.97) and favored alternative therapies (OR = 2.25; 95% CI = 1.75-2.91). The findings highlight the significance of addressing patient beliefs/views to improve medication adherence. The distinct Mediterranean context, influenced by cultural, socioeconomic, and clinical factors, emphasizes the need for tailored interventions. This underscores the call for contextually sensitive strategies to boost medication adherence and improve health outcomes in this unique region.

A systematic review and meta-analysis of the SIRT1 response to exercise

Sirtuin 1 (SIRT1) is a key physiological regulator of metabolism and a target of therapeutic interventions for cardiometabolic and ageing-related disorders. Determining the factors and possible mechanisms of acute and adaptive SIRT1 response to exercise is essential for optimising exercise interventions aligned to the prevention and onset of disease. Exercise-induced SIRT1 upregulation has been reported in animals, but, to date, data in humans have been inconsistent. This exploratory systematic review and meta-analysis aims to assess various exercise interventions measuring SIRT1 in healthy participants. A total of 34 studies were included in the meta-analysis (13 single bout exercise, 21 training interventions). Studies were grouped according to tissue sample type (blood, muscle), biomarkers (gene expression, protein content, enzyme level, enzyme activity), and exercise protocols. A single bout of high-intensity or fasted exercise per se increases skeletal muscle SIRT1 gene expression as measured by qPCR or RT-PCR, while repeated resistance training alone increases blood SIRT1 levels measured by ELISA. A limited number of studies also show a propensity for an increase in muscle SIRT1 activity as measured by fluorometric or sirtuin activity assay. In conclusion, exercise acutely upregulates muscle SIRT1 gene expression and chronically increases SIRT1 blood enzyme levels.

Genetic architecture of adiposity measures among Asians: Findings from GWAS.

Adiposity has gradually become a global public threat over the years with drastic increase in the attributable deaths and disability adjusted life years (DALYs). Given an increased metabolic risk among Asians as compared to Europeans for any given body mass index (BMI) and considering the differences in genetic architecture between them, the present review aims to summarize the findings from genome-wide scans for various adiposity indices and related anthropometric measures from Asian populations. The search for related studies, published till February 2022, were made on PubMed and GWAS Catalog using search strategy built with relevant keywords joined by Boolean operators. It was recorded that out of a total of 47 identified studies, maximum studies are from Korean population (n=14), followed by Chinese (n=7), and Japanese (n=6). Nearly 200 loci have been identified for BMI, 660 for height, 16 for weight, 28 for circumferences (waist and hip), 32 for ratios (waist hip ratio [WHR] and thoracic hip ratio [THR]), 5 for body fat, 16 for obesity, and 28 for adiposity-related blood markers among Asians. It was observed that though, most of the loci were unique for each trait, there were 3 loci in common to BMI and WHR. Apart from validation of variants identified in European setting, there were many novel loci discovered in Asian populations. Notably, 125 novel loci form Asian studies have been reported for BMI, 47 for height, 5 for waist circumference, and 2 for adiponectin level to the existing knowledge of the genetic framework of adiposity and related measures. It is necessary to examine more advanced adiposity measures, specifically of relevance to abdominal adiposity, a major risk factor for cardiometabolic disorders among Asians. Moreover, in spite of being one continent, there is diversity among different ethnicities across Asia in terms of lifestyle, climate, geography, genetic structure and consequently the phenotypic manifestations. Hence, it is also important to consider ethnic specific studies for identifying and validating reliable genetic variants of adiposity measures among Asians.

Cardiovascular disease and all-cause mortality associated with individual and combined cardiometabolic risk factors

BackgroundPrevious studies have investigated the association between cardiometabolic risk factors and cardiovascular disease (CVD), but evidence of the attributable burden of individual and combined cardiometabolic risk factors for CVD and mortality is limited. We aimed to investigate and quantify the associations and population attributable fraction (PAF) of cardiometabolic risk factors on CVD and all-cause mortality, and calculate the loss of CVD-free years and years of life lost in relation to the presence of cardiometabolic risk factors.MethodsTwenty-two thousand five hundred ninety-six participants aged ≥ 35 without CVD at baseline were included between October 2012 and December 2015. The outcomes were the composite of fatal and nonfatal CVD events and all-cause mortality, which were followed up in 2018 and 2019 and ascertained by hospital records and death certificates. Cox regression was applied to evaluate the association of individual and combined cardiometabolic risk factors (including hypertension, diabetes and high low-density lipoprotein cholesterol (LDL-C)) with CVD risk and all-cause mortality. We also described the PAF for CVD and reductions in CVD-free years and life expectancy associated with different combination of cardiometabolic conditions.ResultsDuring the 4.92 years of follow-up, we detected 991 CVD events and 1126 deaths. Hazard ratio were 1.59 (95% confidential interval (CI) 1.37–1.85), 1.82 (95%CI 1.49–2.24) and 2.97 (95%CI 1.85–4.75) for CVD and 1.38 (95%CI 1.20–1.58), 1.66 (95%CI 1.37–2.02) and 2.97 (95%CI 1.88–4.69) for all-cause mortality, respectively, in participants with one, two or three cardiometabolic risk factors compared with participants without diabetes, hypertension, and high LDL-C. 21.48% of CVD and 15.38% of all-cause mortality were attributable to the combined effect of diabetes and hypertension. Participants aged between 40 and 60 years old, with three cardiometabolic disorders, had approximately 4.3-year reductions life expectancy compared with participants without any abnormalities of cardiometabolic disorders.ConclusionsCardiometabolic risk factors were associated with a multiplicative risk of CVD incidence and all-cause mortality, highlighting the importance of comprehensive management for hypertension, diabetes and dyslipidemia in the prevention of CVD.

The Impact of Metabolic Syndrome Risk Factors on Lung Function Impairment: Cross-Sectional Study.

Metabolic syndrome (MetS) is a constellation of risk factors increasingly present in the world's population. People with this syndrome are at an increased risk of cardiovascular disease and type 2 diabetes mellitus. Moreover, evidence has shown that it affects different organs. MetS and its risk factors are independently associated with impaired lung function, which can be quantified through spirometric variables. This study aims to determine whether a high number of MetS criteria is associated with increased lung function decline. We conducted a descriptive cross-sectional study with a random sample of 1980 workers. Workers with acute respiratory pathology (eg, influenza), chronic respiratory pathology (eg, chronic bronchitis), or exposure to substances harmful to the lungs (eg, organic and inorganic dust) were not included. MetS was established based on harmonized criteria, and lung function was assessed according to spirometric variables. On the basis of these, classification into restrictive lung disease (RLD), obstructive lung disease, and mixed lung disease (MLD) was performed. In addition, the association between MetS and lung function was established based on analysis of covariance, linear trend analysis, and multiple linear regression. MetS was associated with worse lung function according to all the spirometric parameters analyzed (percentage of predicted forced expiratory volume in 1 second: mean 83, SD 13.8 vs mean 89.2, SD 12.8; P<.001 and percentage of predicted forced vital capacity: mean 85.9, SD 11.6 vs mean 92, SD 11.3; P<.001). Moreover, those diagnosed with MetS had a higher prevalence of lung dysfunction (41% vs 21.9%; P<.001), RLD (23.4% vs 11.2%; P<.001), and MLD (7.3% vs 2.2%; P<.001). Furthermore, an increasing number of MetS criteria was associated with a greater impairment of pulmonary mechanics (P<.001). Similarly, with an increasing number of MetS criteria, there was a significant linear trend (P<.001) in the growth of the prevalence ratio of RLD (0 criteria: 1, 1: 1.46, 2: 1.52, 3: 2.53, 4: 2.97, and 5: 5.34) and MLD (0 criteria: 1, 1: 2.68, 2: 6.18, 3: 9.69, and 4: 11.37). Regression analysis showed that the alteration of all MetS risk factors, adjusted for various explanatory variables, was significantly associated with a worsening of spirometric parameters, except for forced expiratory volume in 1 second/forced vital capacity. The findings have shown that an increase in cardiometabolic risk factors is associated with a more significant worsening of spirometric variables and a higher prevalence of RLD and MLD. As spirometry could be a crucial tool for monitoring patients at risk of developing chronic pathologies, we conclude that this inexpensive and easily accessible test could help detect changes in lung function in patients with cardiometabolic disorders. This highlights the need to consider the importance of cardiometabolic health in lung function when formulating public health policies.

Pharmacological and Nutritional Modulation of Metabolome and Metagenome in Cardiometabolic Disorders.

Cardiometabolic disorders are major causes of morbidity and mortality worldwide. A growing body of research indicates that the gut microbiota, whether it interacts favorably or not, plays an important role in host metabolism. Elucidating metabolic pathways may be crucial in preventing and treating cardiometabolic diseases, and omics methods are key to studying the interaction between the fecal microbiota and host metabolism. This review summarizes available studies that combine metabolomic and metagenomic approaches to describe the effects of drugs, diet, nutrients, and specific foods on cardiometabolic health and to identify potential targets for future research.

Abstract P400: Effects Of Time Restricted Feeding On Blood Pressure And Urine Output

Americans consume ~48% more salt than the recommended daily intake, increasing the sodium load placed on the kidneys. Normally, the kidneys excrete this excess sodium, however salt-sensitive (SS) individuals are unable to do so and develop hypertension. Time-restricted feeding (TRF), in which food is consumed in &lt;10 hours, has been shown to improve various cardiometabolic disorders, however there is limited research on its effect in SS hypertension. The goal of this study was to determine if intermittent salt consumption via TRF can improve SS hypertension in the Dahl SS rat model. Male (n=7-9/group) and female (n=4/group) SS rats were randomly divided into the following groups: low salt ad libitum (LS ad lib), low salt TRF (LS TRF), high salt ad libitum (HS ad lib), or high salt TRF (HS TRF) and underwent a two-week protocol. During the first week, all rats had ad libitum access to their respective diet to establish hypertension in the HS groups. During the second week, some animals began TRF, in which food was provided for 8 hours during the active period (2200-0600 hrs), and metabolic phenotypes were assessed in all rats using the Promethion (Sable Systems). Urine was collected for 8-9 hrs after the feeding period. Prior to endpoint, anesthetized blood pressure was measured at the end of the fasting period. We found that the HS TRF group had reduced systolic blood pressure in both males (138.69 ± 4.29 mmHg vs 143.33 ± 7.43 mmHg; mean ± SEM) and females (129.19 ± 6.29 mmHg vs 135.85 ± 10.88 mmHg; mean ± SEM) compared to the HS ad lib group, however this was not significant. Urine excretion was significantly higher in the HS TRF group compared to the HS ad lib group in both males (8.89 ± 1.06 mL vs 4.06 ± 0.42 mL; mean ± SEM; p&lt;0.05) and females (7.5 ± 0.20 mL vs 4.88 ± 0.43 mL; mean ± SEM; p&lt;0.05). Furthermore, while the rats were in the Promethion, there was a higher amount of water loss (VH 2 O; which can include evaporated urine) in the HS TRF group compared to the HS ad lib group during the fasting period in both males (1.52 ± 0.03 g/hr vs 1.40 ± 0.03 g/hr; mean ± SEM; p&lt;0.05) and females (1.18 ± 0.03 g/hr vs 0.96 ± 0.01 g/hr; mean ± SEM; p&lt;0.05). Overall, these results may suggest that TRF produces a diuretic effect in the Dahl SS rat model, however further studies are required to confirm this.

A small, polyphyletic group of Firmicutes synthesizes trimethylamine froml-carnitine.

Gut microbiota-derived trimethylamine (TMA) is associated with cardiometabolic disorders and exemplifies a microbial involvement in the etiology of emerging, noncommunicable diseases, the leading causes of death worldwide. Three biochemical pathways taking dietary compounds as intake have been described with distinct taxa involved that are all present at low relative abundances. A recently discovered pathway is now considered to be the main route for TMA synthesis from l-carnitine involving γ-butyrobetaine as an intermediate product. By comprehensive (meta) genomic screening of publicly available data, namely, genomes of the UHGG catalog (n > 200,000) and 10 metagenomic (transcriptomic) data sets, we revealed bacteria synthesizing TMA via this pathway and specified their ecophysiology. Results will contribute to stratification of individuals based on their gut microbiota's potential to synthesize TMA and might aid in the development of strategies restricting TMA formation.

Abstract P340: Codonopsis Lanceolata Extract Prevents Metabolic And Cardiovascular Alterations In Short-term High-fat/high-fructose Diet-fed Adolescent Rats

Fast food consumption, which has increased among adolescents, has been associated with the risk of cardio-metabolic disorders. However, the effects of short-term high-fat/high-fructose diet (HFFD) on cardiovascular and metabolic parameters in adolescent rats has not yet been evaluated. Also, preventive effects of codonopsis lanceolata (CL) in these rats are unknown. Therefore, we investigated the effects of short-term HFFD consumption on cardiovascular and metabolic factors in adolescent rats, as well as the preventive effects of CL extract. Adolescent rats were fed a 60% high-fat diet plus 10% fructose water for 2 weeks. During this time, CL extract (200 or 400 mg/kg) was administered once daily. Short-term HFFD increased visceral white adipose tissue (WAT) weight, fasting blood sugar (FBS) concentration and water intake in adolescent rats. This diet also significantly increased systolic blood pressure (SBP), heart rate, and phenylephrine-induced vasocontraction. CL extract, however, effectively reduced visceral WAT weight, FBS, SBP and heart rate in short-term HFFD-fed adolescent rats. These findings indicate that exposure to HFFD for only 2 weeks induced cardiovascular and metabolic alterations in adolescent rats and that CL extract is effective in preventing these harmful effects of short-term HFFD in adolescent rats. This work was by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1A2C2004118). * Corresponding author. Keywords: high-fat/high-fructose diet; adolescent; codonopsis lanceolata ; prevention; visceral white adipose tissue; fasting blood sugar; systolic blood pressure

To Investigate the Correlation Between the Socioeconomic Status and Cardiometabolic Associated Risk Indicator Among Middle Aged Adults in Selected Sub-Counties in Kisumu County in Nyanza Region in Kenya

The prevalence of Cardio- metabolic associated risk indicators are known to vary significantly across the world (Huh et al., 2019). Study design. This was a cross-sectional quantitative study on correlation between socioeconomic and cardio metabolic associated risk indicators among Residents in selected sub counties in Kisumu county Nyanza region in Kenya. It involved the determination of five indicators of cardio metabolic disorders, which included; general obesity (BMI), central obesity (waist: hip ratio), blood pressure (SBP and DBP), dyslipidemia (Lipid profile) among the residents. Results. Our study showed a strong association between BMI, WC and hypertension in the study population. These findings are in agreement with other studies that also reported an association between hypertension and prehypertension, BMI and WC as well as diabetes (hypertension 19.4%, obesity 44%, hyperglycemia 21.8% and dyslipidemia 14.9%)

Sugar and Dyslipidemia: A Double-Hit, Perfect Storm.

The availability of sugar has expanded over the past 50 years, due to improved industrial processes and corn subsidies, particularly in the form of sweetened beverages. This correlates with a surge in the prevalence of cardiometabolic disorders, which has brought this issue back into the spotlight for public health. In this narrative review, we focus on the role of fructose in the genesis of cardiometabolic dyslipidemia (an increase in serum triglyceride-rich lipoproteins (TRL): VLDL, chylomicrons (CM), and their remnants) bringing together the most recent data on humans, which demonstrates the crucial interaction between glucose and fructose, increasing the synthesis while decreasing the catabolism of these particles in a synergistic downward spiral. After reviewing TRL metabolism, we discuss the fundamental principles governing the metabolism of fructose in the intestine and liver and the effects of dysregulated fructolysis, in conjunction with the activation of carbohydrate-responsive element-binding protein (ChREBP) by glucose and the resulting crosstalk. The first byproduct of fructose catabolism, fructose-1-P, is highlighted for its function as a signaling molecule that promotes fat synthesis. We emphasize the role of fructose/glucose interaction in the liver, which enhances de novo lipogenesis, triglyceride (TG) synthesis, and VLDL production. In addition, we draw attention to current research that demonstrates how fructose affects the activity of lipoprotein lipase by increasing the concentration of inhibitors such as apolipoprotein CIII (apoCIII) and angiopoietin-like protein 3 (ANGPTL3), which reduce the catabolism of VLDL and chylomicrons and cause the building up of their atherogenic remnants. The end outcome is a dual, synergistic, and harmful action that encourages atherogenesis. Thus, considering the growing concerns regarding the connection between sugar consumption and cardiometabolic disease, current research strongly supports the actions of public health organizations aimed at reducing sugar intake, including dietary guidance addressing "safe" limits for sugar consumption.

Using Mendelian Randomization to Study the Role of Iron in Health and Disease.

Iron has been shown to play a dual role in health and disease, with either a protective or harmful effect. Some of the contradictory findings from observational studies may be due to reverse causation, residual confounding, or small sample size. One approach that may overcome these limitations without the high cost of randomized control trials is the use of Mendelian randomization to examine the long-term role of iron in a variety of health outcomes. As there is emerging evidence employing Mendelian randomization as a method of assessing the role of micronutrients in health and disease, this narrative review will highlight recent Mendelian randomization findings examining the role of iron in cardiometabolic disorders, inflammation, neurological disorders, different cancers, and a number of other health-related outcomes.

Associations between nutrients in one-carbon metabolism and fetal DNA methylation in pregnancies with or without gestational diabetes mellitus

BackgroundGestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B12, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM.ResultsIn this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25–33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = − 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = − 0.13, p = 0.049 and r = − 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = − 0.28, p = 0.015).ConclusionsIn conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.

Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents

IntroductionThe onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation.ResultsThe gene-wide analysis indicated differential methylation within or around 1818 unique genes across the sleep initiation measurements using self-report, actigraphy (ACT), and polysomnography (PSG), while GWAS-informed analysis yielded 67 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG). DNA methylation within 12 genes was associated with both subjective and PSG-measured SOL, 31 with both ACT- and PSG-measured SOL, 19 with both subjective and ACT-measured SOL, and one gene (SMG1P2) had methylation sites associated with subjective, ACT- and PSG-measured SOL.ConclusionsObjective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Additionally, our data provide evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNA methylation in and around genes involved in circadian regulation (i.e., RASD1, RAI1), cardiometabolic disorders (i.e., FADS1, WNK1, SLC5A6), and neuropsychiatric disorders (i.e., PRR7, SDK1, FAM172A). If validated, these sites may provide valuable targets for early detection and prevention of disorders involving prolonged or delayed SOT, such as insomnia, delayed sleep phase, and their comorbidity.

Cardiometabolic Disorders Are Important Correlates of Vulnerability in Hospitalized Older Adults.

With an increasingly aging population worldwide, the concept of multimorbidity has attracted growing interest over recent years, especially in terms of frailty, which leads to progressive multisystem decline and increased adverse clinical outcomes. The relative contribution of multiple disorders to overall frailty index in older populations has not been established so far. This study aimed to assess the association between the vulnerable elders survey-13 (VES-13) score, which is acknowledged to be one of the most widely used measures of frailty, and the most common accompanying diseases amongst hospitalized adults aged 60 years old and more. A total of 2860 participants with an average age of 83 years were included in this study. Multiple logistic regression with adjustment for age and nutritional status was used to assess the independent impact of every particular disease on vulnerability. Diabetes mellitus type 2, coronary artery disease, atrial fibrillation, heart failure, chronic kidney disease, osteoarthritis, fractures, eyes disorders, depression, dementia, pressure ulcers, and urinary incontinence were associated with higher scores of VES-13. Hospital admission of older subjects with those conditions should primarily draw attention to the risk of functional decline, especially while qualifying older patients for further treatment in surgery and oncology. At the same time, lipid disorders, gastrointestinal diseases, higher body mass index, and albumins level were related to a lower risk of being vulnerable, which may be attributed to a younger age and better nutritional status of those patients.

Assessment of Serum Fibroblast Growth Factor 21 as a Risk Factor for the Occurrence of Cardiometabolic Disorders among Psoriatic Patients

Abstract Background Fibroblast growth factors 21 is a new marker of cardiometabolic disorders which are common comorbidities in psoriasis. Fibroblast growth factor 21 could be useful in predicting the risk of cardiometabolic disorders in psoriatic patients as well as assessment of the impact of phototherapy on serum level of FGF-21 will be done. Aim of the Work The aim of the present work was to evaluate the serum level of FGF-21 in psoriatic patients versus healthy controls and to correlate it with the disease severity (PASI Score), BMI, metabolic parameters and phototherapy. Patients and Methods Assays to measure the level of FGF-21 in serum of 30 Psoriatic patients and 30 healthy adults matched to age, sex and BMI and compare the FGF-21 level between the two groups and after 3 months of treatment the psoriatic patients with NB-UVB sessions. Laboratory investigations including CRP, FBG, Total Cholesterol and serum triglycerides. Results Significantly higher serum levels of FGF-21 in Psoriatic patients compared to the controls. Statistically significant positive correlation between FGF-21 level and severity indices (p &amp;lt; 0.001) denoting its role as severity marker. Statistically positive correlation with CRP (p &amp;lt; 0.001) denoting its role as an activity marker. Conclusion Fibroblast Growth Factor 21 has been described as Psoriatic severity and activity biomarker with prognostic and therapy monitoring applications.

Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.

The role of sex in the relationship between fasting adipokines levels, maximal fat oxidation during exercise, and insulin resistance in young adults with excess adiposity

AimPrevious evidence suggest that a sexual dimorphism in exercise fat oxidation and adipokines levels may explain a lower risk of cardio-metabolic disorders in women. Therefore, we investigated the role of sex in the relationship between adipokines levels, maximal fat oxidation (MFO) during exercise and insulin resistance. MethodsFifty young adults with excess adiposity (31 women; body fat: 38.7 ± 5.3%) were included in this study. The fasting levels of leptin, adiponectin, glucose and insulin were determined from blood samples and the homeostatic model assessment of insulin resistance index (HOMA-IR) subsequently calculated. Body fat percentage and visceral adipose tissue (VAT) were assessed through dual-energy X-ray absorptiometry whereas MFO was estimated during an incremental-load exercise test after an overnight fasting through indirect calorimetry. ResultsMen had lower levels of body fat (d = 1.80), adiponectin (d = 1.35), leptin (d = 0.43) and MFO (d = 1.25) than women. Conversely, men showed higher VAT (d = 0.85) and fasting glucose levels (d = 0.89). No sex differences were observed in HOMA-IR (d = 0.34). Adipokines levels were not associated with MFO in both sexes (r < 0.30), whereas adiponectin levels were inversely related with HOMA-IR in both men (r = −0.58) and women (r = −0.50). Leptin concentration was associated to HOMA-IR only in men (r = 0.41), while no statistically significant relationships were observed between MFO and HOMA-IR in both sexes (r < 0.44). ConclusionInsulin resistance was similar between sexes regardless of superior levels of adipokines and MFO during exercise in women. Therefore, adiponectin and leptin may regulate glucose homeostasis without altering whole body fat oxidation rate during exercise.