Levels Of Metabolic Biomarkers Research Articles

Human immune and metabolic biomarker levels, and stress-biomarker associations, differ by season: Implications for biomedical health research

Although seasonal changes in physiology are well documented, little is known about how human immune and metabolic markers vary across seasons, and no studies have examined how stress → health biomarker associations differ across the year. To investigate these issues, we analyzed data from 2118 participants of the Midlife in the United States (MIDUS) study to determine whether there were differences in (a) levels of 19 immune and metabolic markers, and (b) the association between perceived stress and each biomarker across the year. Results of component-wide boosted generalized additive models revealed seasonal patterning for most biomarkers, with immune proteins generally peaking when days were shorter. Moreover, whereas levels of hemoglobin A1C rose from late fall to spring, triglycerides were elevated in the summer and fall, and high-density lipoprotein decreased steadily from January to December. Urinary cortisol and cortisone exhibited opposite patterns, peaking at the beginning and end of the year, respectively. Most critically, we found that the effects of perceived stress on 18 of the 19 health biomarkers assessed varied by month of measurement. In some cases, these differences involved the magnitude of the stress → biomarker association but, in other cases, it was the direction of the effect that changed. Studies that do not account for month of biomarker assessment may thus yield misleading or unreproducible results.

Patterns of Sleep Duration and Metabolic Biomarkers Across the Menstrual Cycle.

Along the menstrual cycle, associations between inconsistent sleep duration and levels of metabolic biomarkers are uncertain and could involve fluctuations in estrogen concentrations. To examine associations between patterns of sleep duration and metabolic biomarkers across two menstrual cycles within a cohort of premenopausal women. The BioCycle Study was conducted in New York between 2005-2007, enrolling 259 premenopausal women over two menstrual cycles. This micro-longitudinal cohort study involved intensive data collection including daily sleep diaries and biomarker assessments of leptin, insulin, and glucose at 16 key points timed to menstrual cycle phases. We considered dynamic sleep duration, as hours slept one night or as mean hours slept during the two nights prior to each biomarker assessment. Variability in habitual sleep duration, i.e., reported daily sleep duration, summarized across both menstrual cycles. Variation in habitual sleep duration was computed using L-moments, a robust version of dispersion, skewness, and kurtosis. To examine associations between patterns of sleep duration and metabolic biomarkers, we fitted a series of linear mixed models with random intercepts and inverse probability weighting. These models were adjusted for potential demographic, lifestyle, health confounders, and menstrual cycle phase. Sleep duration one night or two nights prior to clinic visits were not associated with metabolic biomarker measures we assessed. However, overall variability (dispersion) in habitual sleep duration was associated with lower mean insulin HOMA-IR levels, but not glucose. Moreover, extreme short or long bouts of sleep duration was associated with higher mean levels of leptin, insulin, and HOMA-IR. These data suggest that variation in habitual sleep duration along the menstrual cycle may be associated with metabolic function.

Differences in metabolic biomarkers in people with schizophrenia who are of Mexican descent compared to non-Hispanic whites

Metabolic dysfunction is highly prevalent and contributes to premature mortality among people with schizophrenia (PwS), especially in Hispanic/Latino/a/x/e PwS, compared to non-Hispanic White (NHW) PwS. This study evaluated the relative contributions of Mexican descent and schizophrenia diagnosis to metabolic biomarker levels. This cross-sectional study included 115 PwS and 102 non-psychiatric comparison (NC) participants – English-speakers aged 26–66 years, 27% Mexican descent, and 52% women across both groups. Assessments included evaluations of BMI, psychopathology, and fasting metabolic biomarkers. We used ANOVA analyses to compare metabolic outcomes between diagnostic and ethnic subgroups, linear regression models to examine associations between Mexican descent and metabolic outcomes, and Spearman's correlations to examine relationships between metabolic outcomes and illness-related variables in PwS. Mexican PwS had higher hemoglobin A1c levels, insulin resistance, and body mass index than NHW PwS. Mexican descent was associated with higher hemoglobin A1c levels, insulin resistance, body mass index, and leptin levels, controlling for age, sex, depression, education, and smoking. Among Mexican PwS, worse negative symptoms were associated with greater insulin resistance. These findings support the possibility of ethnicity-based differences in metabolic dysregulation, though further investigation is warranted to create targeted health interventions for Hispanic PwS.

Linking biomarkers with healthy lifestyle outcomes after stroke: Supplementary results of a 12-month randomized controlled trial

Background and aimsParticipation in a healthy lifestyle intervention such as the Diabetes Prevention Program Group Lifestyle Balance–adapted for stroke (GLB-CVA) may reduce stroke burden. Identifying biomarkers associated with lifestyle changes may enhance an individualized approach to stroke recovery. We investigated metabolic biomarkers related to cardiovascular and neurological function in individuals with stroke in the GLB-CVA study and healthy (non-stroke) individuals. Methods and resultsParticipants with chronic (>12 months) stroke were recruited to this wait-list randomized controlled trial if they were overweight (BMI ≥25 kg/m2). Participants were randomized to (1) the GLB-CVA program to complete 22 educational sessions addressing behavioral principals of dietary and physical activity or (2) a 6 month wait-list control (WLC). Biomarkers [Plasma irisin, vascular endothelial growth factor, lipoprotein-associated phospholipase A2 (Lp-PLA2), insulin-like growth factor 1 and brain-derived neurotrophic factor (BDNF)] were collected at baseline, 3, and 6 months. Age-matched healthy individuals were recruited for biomarker assessment. Compared to healthy adults (n = 19), participants with stroke (GLB-CVA = 24; WLC = 24) at baseline had higher tHcy levels (p < 0.001) and lower PLA2 levels (p = 0.016). No statistically significant interactions were observed for any biomarkers between the GLB-CVA and WLC or between people who achieved 5% weight loss and those who did not. ConclusionParticipation in a 6-month healthy lifestyle program did not result in statistically significant changes to select metabolic biomarker levels for our participants with chronic stroke. However, participants with stroke demonstrated a unique biomarker profile compared to age-matched healthy individuals.

Relationship between longitudinal changes in neuropsychological outcome and disease biomarkers in urea cycle disorders.

Urea cycle disorders (UCDs) cause impaired conversion of waste nitrogen to urea leading to rise in glutamine and ammonia. Elevated ammonia and glutamine have been implicated in brain injury. This study assessed relationships between biomarkers of metabolic control and long-term changes in neuropsychological test scores in participants of the longitudinal study of UCDs. The hypothesis was that elevated ammonia and glutamine are associated with neuropsychological impairment. Data from 146 participants who completed 2 neuropsychological assessments were analyzed. Neuropsychological tests that showed significant changes in scores over time were identified and associations between score change and interim metabolic biomarker levels were investigated. Participants showed a significant decrease in performance on visual motor integration (VMI) and verbal learning immediate-recall. A decrease in scores was associated with experiencing interim hyperammonemic events (HAE) and frequency of HAE. Outside of HAE there was a significant association between median ammonia levels ≥50µmol/L and impaired VMI. VMI and memory encoding are specifically affected in UCDs longitudinally, indicating that patients experience difficulties when required to integrate motor and visual functions and learn new information. Only ammonia biomarkers showed a significant association with impairment. Preventing HAE and controlling ammonia levels is key in UCD management. The Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) and List A Trial 5 of the California Verbal Learning Test (CVLT) may be good longitudinal biomarkers of treatment outcome in urea cycle disorders (UCD). This is the first report of longitudinal biomarkers for treatment outcome in UCD. These two biomarkers of outcome may be useful for clinical trials assessing new treatments for UCD. These results will also inform educators how to design interventions directed at improving learning in individuals with UCDs.

Impact of Innate Immunity, Endothelial Damage, and Metabolic Biomarkers on COVID-19 Severity and Mortality.

In this study, abnormal levels of myeloid activation, endothelial damage, and innate immune markers were associated with severe coronavirus disease 2019 (COVID-19), while higher levels of metabolic biomarkers (irisin, leptin) demonstrated a protective effect. These data support a model for COVID-19 immunopathogenesis linking robust inflammation and endothelial damage in metabolically predisposed individuals.

Association between metabolic body composition status and vitamin D deficiency: A cross-sectional study.

This study aimed to investigate the risk of vitamin D deficiency in a relatively healthy Asian population, with (i) metabolically healthy normal weight (MHNW) (homeostasis model assessment-insulin resistance [HOMA-IR] < 2. 5 without metabolic syndrome [MS], body mass index [BMI] < 25), (ii) metabolically healthy obesity (MHO) (HOMA-IR < 2.5, without MS, BMI ≥ 25), (iii) metabolically unhealthy normal weight (MUNW) (HOMA-IR ≥ 2.5, or with MS, BMI < 25), and (iv) metabolically unhealthy obesity (MUO) (HOMA-IR ≥ 2.5, or with MS, BMI ≥ 25) stratified by age and sex. This cross-sectional study involved 6,655 participants aged ≥ 18 years who underwent health checkups between 2013 and 2016 at the Chang Gung Memorial Hospital. Cardiometabolic and inflammatory markers including anthropometric variables, glycemic indices, lipid profiles, high-sensitivity C-reactive protein (hs-CRP), and serum 25-hydroxy vitamin D levels, were retrospectively investigated. Compared to the MHNW group, the MHO group showed a higher odds ratio (OR) [1.35, 95% confidence interval (CI) 1.05–1.73] for vitamin D deficiency in men aged < 50 years. By contrast, in men aged > 50 years, the risk of vitamin D deficiency was higher in the MUO group (OR 1.44, 95% CI 1.05–1.97). Among women aged < and ≥ 50 years, the MUO group demonstrated the highest risk for vitamin D deficiency, OR 2.33 vs. 1.54, respectively. Our study revealed that in women of all ages and men aged > 50 years, MUO is associated with vitamin D deficiency and elevated levels of metabolic biomarkers. Among men aged < 50 years, MHO had the highest OR for vitamin D deficiency.

The obesity paradox: Retinopathy, obesity, and circulating risk markers in youth with type 2 diabetes in the TODAY Study

AimTo understand the relationship of obesity and 27 circulating inflammatory biomarkers to the prevalence of non-proliferative diabetic retinopathy (NPDR) in youth with type 2 diabetes. MethodsYouth with type 2 diabetes who participated in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study were followed for 2–6.5 years. Digital fundus photographs were obtained in the last year of the study. Blood samples during the study were processed for inflammatory biomarkers, and these were correlated with obesity tertiles and presence of retinopathy. ResultsHigher BMI was associated with an increase in circulating levels of metabolic biomarkers including high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, LDL-cholesterol (LDL-C) and Apolipoprotein B (ApoB), tumor necrosis factor receptors 1 and 2 (TNFR-1 and -2), interleukin 6 (IL-6), E-selectin, and homocysteine, as well as a decrease in the metabolic risk markers HDL-cholesterol (HDLC), and insulin-like growth factor binding protein 1 (IGFBP-1). Although NPDR risk decreased with increasing obesity, it was not associated with any of the measured biomarkers. ConclusionsCirculating levels of measured biomarkers did not elucidate the “obesity paradox” of decreased NPDR in the most obese participants in the TODAY study.Trial Registration: clinicaltrials.govNCT00081328.

Metabolomics-Based Pharmacodynamic Analysis of Zhuang Yao Shuang Lu Tong Nao Granules in a Rat Model of Ischemic Cerebral Infarction.

This study used a metabolomic approach to reveal changes in the levels of metabolic biomarkers and related metabolic pathways before and after Zhuang Yao Shuang Lu Tong Nao granule (YHT) treatment in rats with cerebral ischemia. The neurological deficit scores were significantly higher in the MCAO_R group than in the NC group, indicating that the mice had significantly impaired motor functions. The YHT group had significantly lower scores than the MCAO_R group, suggesting that YHT significantly improved motor function in rats. TTC staining of the brain tissue revealed that YHT significantly reduced the area of cerebral infarction in the treated rats. The MCAO_R group was better separated from the NC rent, sham, and YHT groups via metabolomic PCA. Moreover, there were significant differences in the differential metabolites between the MACO_R and YHT groups. Eighteen common differential metabolites were detected between the MACO_R and NC groups, MACO_R and sham groups, and MACO_R and YHT groups, indicating that YHT significantly increased the levels of various metabolites in the serum of cerebral ischemic stroke (CIS) rats. Moreover, a total of 23 metabolic pathways were obtained. We identified 11 metabolic pathways with the most significant effects in the bubble plots. In conclusion, from a systems biology perspective, this metabolomics-based study showed that YHT could be used to treat ischemic stroke by modulating changes in endogenous metabolites.

Induction of P-glycoprotein expression by dandelion in tumor and heart tissues: Impact on the anti-tumor activity and cardiotoxicity of doxorubicin

BackgroundPreviously, we have investigated the anti-tumor activity and mechanism through which dandelion acts against triple-negative breast cancer (TNBC). However, traditional Chinese medicine is mostly accepted as an adjunct therapy during chemotherapy in clinical practice. So far, little is known about the effects of dandelion in conjunction with chemotherapeutic drugs. PurposeTo investigate the effects of dandelion on the anti-tumor activity and cardiotoxicity of doxorubicin (DOX), and to further explore the molecular mechanisms through which these effects occur. Study designAt the beginning of this study, dandelion was observed to alleviate DOX-induced cardiotoxicity and reduce the anti-tumor activity of DOX. Subsequently, we investigated whether the resistance to DOX mediated by P-glycoprotein was involved in the above effects. MethodsThe cardioprotective effect of dandelion was investigated on DOX-treated mice by histological analysis, myocardial enzyme assays, and an untargeted metabolomics study based on LC-Q-TOF/MS. TNBC cell lines and 4T1 tumor-bearing mice were employed to investigate the combined anti-tumor activity. Laser scanning confocal microscope and a flow cytometry analysis were employed to measure the intracellular accumulation of DOX. A specific, sensitive, and rapid LC–MS/MS method was developed to detect the efflux of DOX from cells. Expression of P-glycoprotein in mouse tumor and heart tissues was detected via Western blotting analysis. ResultsDandelion was found to significantly alleviate DOX-induced cardiotoxicity, as was evidenced by improved cardiomyocyte morphology, decreased LDH and CK-MB release, and adjusted metabolic biomarker levels. However, in vitro and in vivo studies showed that dandelion could reduce the anti-tumor activity of DOX. This counteraction was achieved by activating of the drug efflux transporter P-glycoprotein, thereby promoting the efflux of DOX from cells and reducing the intracellular accumulation of DOX. Moreover, the activation of P-glycoprotein by dandelion in mouse heart tissue was also observed, thus suggesting that the decrease of cardiac DOX accumulation plays an important role in the cardioprotective effect of dandelion. ConclusionDandelion can activate the P-glycoprotein in heart and tumor tissues, which ameliorates DOX-induced cardiotoxicity but attenuates DOX cytotoxicity toward TNBC. Our findings have important implications for the correct clinical use of dandelion.

Alterations in metabolic biomarkers and their potential role in amyotrophic lateral sclerosis.

BackgroundMetabolic dysfunction has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the potential role of metabolic biomarkers in the progression of ALS and understand the possible metabolic mechanisms.MethodsFifty‐two patients with ALS and 24 normal controls were included, and blood samples were collected for analysis of metabolic biomarkers. Basal anthropometric measures, including body composition and clinical features, were measured in ALS patients. The disease progression rate was calculated using the revised ALS functional rating scale (ALSFRS‐R) during the 6‐month follow‐up.ResultsALS patients had higher levels of adipokines (adiponectin, adipsin, resistin, and visfatin) and other metabolic biomarkers [C‐peptide, glucagon, glucagon‐like peptide 1 (GLP‐1), gastric inhibitory peptide, and plasminogen activator inhibitor type 1] than controls. Leptin levels in serum were positively correlated with body mass index, body fat, and visceral fat index (VFI). Adiponectin was positively correlated with the VFI and showed a positive correlation with the ALSFRS‐R and a negative correlation with baseline disease progression. Patients with lower body fat, VFI, and fat in limbs showed faster disease progression during follow‐ups. Lower leptin and adiponectin levels were correlated with faster disease progression. After adjusting for confounders, lower adiponectin levels and higher visfatin levels were independently correlated with faster disease progression.InterpretationThe current study found altered levels of metabolic biomarkers in ALS patients, which may play a role in ALS pathogenesis. Adiponectin and visfatin represent potential biomarkers for prediction of disease progression in ALS.

Differences in metabolic biomarkers in people with schizophrenia who are of Mexican descent compared to non-Hispanic Whites

<h3>Introduction</h3> Metabolic syndrome, a significant risk factor for cardiovascular-related mortality, is highly prevalent in people with schizophrenia (PwS). It is a leading contributor to the growing mortality gap between PwS and the general population. Hispanics/Latinos/as/x (henceforth Hispanics) with schizophrenia, are more likely to have metabolic dysregulation (e.g.,insulin resistance and abdominal obesity) compared to non-Hispanic Whites (NHW). Yet, little is known about the prevalence of metabolic risk factors in PwS of Mexican descent (Mex) and whether they differ from NHW PwS. Further, metabolic biomarkers such as leptin and adiponectin have not been explored in Hispanic PwS. This study compares metabolic biomarkers between Mex PWS that self-report as Mexican, Mexican-American, or Chicano and NHW PwS. We hypothesized that Mex PwS will have worse biomarker levels compared to NHW PwS. We explored the relative contributions of Mex descent and schizophrenia diagnosis to metabolic biomarker levels. Within PwS, we explored whether biomarker differences observed were related to illness-related group differences (e.g.,antipsychotic doses). <h3>Methods</h3> This cross-sectional study included 95 PwS (37% Mex, 46% women) and 88 non-psychiatric comparison participants (NC; 24% Mex, 56% women), ages 26-68 years. Standardized assessments were administered to evaluate body mass index (BMI) and psychopathology (Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms). Fasting levels of leptin, adiponectin, lipids, hemoglobin A1c, insulin, glucose, and insulin resistance (HOMA) were measured. Antipsychotic defined daily dosage (DDD) was determined using the WHO guidelines. Independent sample <i>t</i>-tests were used to assess sociodemographic and clinical differences between Mex and NHW PwS. Linear regression models were conducted to examine the relative contribution of Mex heritage to biomarker levels, including the interaction of Mex heritage and schizophrenia diagnosis as well as controlling for age and sex. Follow-up linear regression models within PwS examined whether biomarker differences were associated with antipsychotic DDD. <h3>Results</h3> Mex and NHW PwS had comparable severity of positive and negative symptoms. Mex PwS reported higher antipsychotic DDD compared to NHW PwS (M=2.42,SD=1.7 and M=1.66,SD=1.6, respectively). Mex NCs had higher mean BMI compared to NHW NCs, but Mex PwS and NHW PwS had similar mean BMI. In the whole sample, there were no significant Mex descent by schizophrenia diagnosis interactions for any of the biomarkers. Mexican descent and having schizophrenia were associated with higher insulin resistance (B=0.16, SE=.05, <i>p</i>=.003, η_p²=0.05 and B=0.24,SE=0.05, <i>p</i><.001, η_p²=0.13, respectively). Mexican descent, female sex, and having schizophrenia were associated with higher leptin levels (B=0.20, SE=0.08, p=0.007, η_p²=0.04; B=0.57, SE=.07, <i>p</i><.001, η_p²=0.29 and B=0.33,SE=0.07, <i>p</i><.001, η_p²=0.12, respectively). The remaining metabolic biomarkers (adiponectin, lipids, hemoglobin, A1c, insulin, and glucose) were not significantly associated with Mexican descent. In the PwS group alone, higher insulin resistance was associated with Mexican descent (B=0.22,SE=0.08,p=.009,η_p²=0.08), but not with antipsychotic DDD (B=-0.02,SE=0.02,p=0.42,η_p²=0.008). Among the PwS group, higher leptin levels were associated with female gender (B=0.62,SE=0.09,p=<.001,η_p²=0.35), but not with Mexican descent or antipsychotic DDD. <h3>Conclusions</h3> PwS of Mexican origin reported higher antipsychotic doses than NHW PwS. Consistent with other studies, we found worse insulin resistance in Mex PwS compared to NHW PwS, despite similar mean BMI. These findings highlight the importance of examining biomarker differences in Hispanic subgroups with schizophrenia, as they may illuminate specific underlying mechanisms in the development of metabolic dysregulation. The current study strengths include its focus on Mexico as the country origin and examining multiple metabolic biomarkers, though limitations include lack of statistical control of dietary intake and acculturation. Future studies of Hispanic PwS should examine antipsychotic dosing, which can be influenced by systemic prescribing practices and symptom severity, as well as the impact of culturally focused interventions to improve metabolic health. In order to improve health outcomes for Hispanic PwS, a deeper understanding of biological, cultural, and medical influences is warranted. <h3>This research was funded by</h3> This work was supported, in part, by the Veterans Affairs Pala Pilot Grant(PI: Ellen E. Lee, MD), NARSAD Young Investigator grant from the Brain & Behavior Research Foundation(PI: Ellen E. Lee, MD), National Institute of Mental Health grants T32 Geriatric Mental Health Program MH019934(PI: Dilip V. Jeste), R01MH094151(PI: Dilip V. Jeste), K23 MH119375(PI: Ellen E. Lee), National Institutes of Health CTSA grant UL1TR001442 (PI: Gary Firestein, MD), and Stein Institute for Research on Aging at the University of California San Diego.

MicroRNA profiling and the effect on metabolic biomarkers and weight loss after laparoscopic sleeve gastrectomy: A prospective cohort study

Background: Epigenetic changes after bariatric surgery are of increasing interest; we evaluated the levels of two circulating microRNAs (miRNA-222 and miRNA-146a) before and after the laparoscopic sleeve gastrectomy (LSG) and the effect of weight loss on the levels of metabolic biomarkers. Materials and Methods: We prospectively evaluated patients pre- and 12 months post-LSG for percent excess weight loss (%EWL), miRNAs levels, metabolic biomarkers (leptin, ghrelin, peptide YY, and glucagon peptide-1 [GLP-1]) levels from August 2019 to September 2021. Results: Significant differences were observed in the miRNA146a-3p (median: 0.64 (0.012-2.68) vs. 1.07 (0.1-3.6); P = 0.019) and miRNA222-5p (median 1.80 (0.1–3.61) vs. 1.19 (0.1-3.68); P = 0.003) levels before and after (12 months) LSG; fasting leptin, ghrelin, insulin, total cholesterol, high- and low-density lipoproteins, fasting blood sugar (FBS), and triglyceride levels also showed significant differences. Significant changes were observed in postprandial values of glucagon-like peptide l (GLP-1) (P = 0.0001) and peptide YY (P = 0.0006) 12 months after LSG. Homeostatic model assessment of insulin resistance (IR) was significantly correlated with %EWL, miRNA146a, and miRNA222-5p (P = 0.002). Postoperatively measured miR146a-39 and miRNA222-5p showed significant coefficient of determination R2 of 0.184 (P = 0.008) and 0.259, P = 0.0007 toward %EWL, respectively. Furthermore, significant correlations of miRNA146a were observed with FBS and IR. Conclusions: LSG-mediated weight loss affected the plasma levels of miR146a and miR222-5p. Due to the simultaneous decrease of ghrelin and increase of postprandial hormones (peptide YY and GLP-1), medical problems in patients with obesity were reduced. This study identified miRNAs as the new markers in the treatment, diagnosis, and therapeutic direction of patients with obesity.

Prevalence, clinical correlates and risk factors associated with Tardive Dyskinesia in Chinese patients with schizophrenia.

Tardive Dyskinesia (TD) is a serious, nonrhythmic and iatrogenic movement disorder, and is a common comorbidity in patients with schizophrenia (SZ). The main goal of this study was to investigate the prevalence, clinical correlates, and risk factors of TD in Chinese patients with chronic SZ, which has not been fully studied. This study adopted a cross-sectional design. A total of 901 Chinese inpatients with SZ were recruited between 2008 and 2011. We used the Abnormal Involuntary Movement Scale (AIMS) to measure the severity of TD, and the Positive and Negative Syndrome Scale (PANSS) was used to measure the psychopathological symptoms of SZ. Blood samples were also collected for routine blood tests, including the levels of triglyceride (TG), cholesterol (CHO), HDL-cholesterol (HDL-CHO), LDL-cholesterol (LDL-CHO), Apolipoprotein A1 (ApoA1), and Apolipoprotein B (ApoB). Overall, 36% of patients with SZ had TD. Compared with the non-TD patients, the TD patients were more likely to be men, had older age, lower education level, higher smoking rate, higher hospitalization frequency, and longer duration of illness (DOI). Further, compared with the non-TD patients, the TD patients had higher PANSS total, PANSS negative subscale, and cognitive subscale scores, but had lower depressive subscale scores and lower mean levels of metabolic biomarkers, including TG, CHO, HDL-CHO, LDL-CHO, ApoA1 and ApoB. Moreover, binary regression analysis showed that antipsychotic type, BMI, gender, age, HDL-CHO, and ApoB were associated with TD. Our findings indicate that TD is a common movement disorder in patients with chronic SZ, with certain demographic and clinical variables being risk factors for the development of TD.

Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology.

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet

As an active interface between the host and their diet, the gut microbiota influences host metabolic adaptation; however, the contributions of fungi have been overlooked. Here, we investigate whether variations in gut mycobiome abundance and composition correlate with key features of host metabolism. We obtained animals from four commercial sources in parallel to test if differing starting mycobiomes can shape host adaptation in response to processed diets. We show that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic outcomes. We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet. Fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels are linked with alterations in fungal community diversity and composition. Specifically, variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with metabolic disturbance and weight gain. These data suggest that host–microbe metabolic interactions may be influenced by variability in the mycobiome. This work highlights the potential significance of the gut mycobiome in health and has implications for human and experimental metabolic studies.

Circulating levels of metabolic biomarkers of site-specific and sex-specific arterial calcification in the multi-cohort BBMRI setting

Abstract Background/Introduction Increasing evidence shows that greater arterial calcification leads to an elevated risk of atherosclerotic cardiovascular disease. Risk factors and prognosis of arterial calcification seems to vary per site and between women and men. However, the underlying biological mechanisms of site-specific calcification and the associated sex differences are largely unknown. Within the BBMRI framework, we performed a multi-cohort study on the associations of the circulating levels of metabolic biomarkers with arterial calcification at various sites among women and men. Purpose To examine the associations of the circulating levels of metabolic biomarkers with coronary artery (CAC), aortic arch (AAC) and the aortic valve (AVC) calcifications among women and men. Methods We included a total of 1,114 participants from the population-based Rotterdam Study and 390 from the Leiden Longevity Study. Study populations were comparable concerning study characteristics. Blood samples were used to determine a wide range of plasma metabolic biomarkers by proton nuclear magnetic resonance (NMR). Participants underwent non-contrast computed tomography to quantify the volume of CAC, AAC, and AVC. Linear regression modelling adjusted for relevant covariates was used to assess the associations of 166 metabolic biomarkers with CAC, AAC, and AVC. Correction for multiple testing was based on 33 independent metabolic biomarkers (p-value 0.05/33 = 1.5 x 10–3). Results Mean (standard deviation - SD) age was 69.5 (6.8) and 780 (52.0%) of the study population were women. One SD increase in concentration of a1-acid glycoprotein, was associated with a 0.10 SD (standard error (SE) = 0.03) increase in AAC (p-value = 9.5x10–4) in the overall population (Figure 1). When we stratified our analyses based on sex, this association was mainly driven by men [beta (SE) per SD: 0.12 (0.05), p-value = 0.007]. Moreover, an SD increase in acetate was associated with a 0.14 SD (SE = 0.04) decrease in CAC (p-value 1.7x10–4) in women but not in men [beta (SE) per SD: −0.04 (0.03), p-value = 0.22] (Figure 1). Conclusion(s) Higher levels of circulating glycoproteins were associated with increased AAC in men. Moreover, lower levels of circulating acetate were associated with increased CAC in women. These results provide evidence for location-specific differences and sex-specific effects in the underlying biological mechanisms of atherosclerosis. Our findings carry the potential to contribute to the early detection of individuals at increased risk for developing atherosclerotic cardiovascular disease and to a better understanding of disease etiology. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was performed within the framework of the BBMRI Metabolomics Consortium funded by BBMRI-NL, a research infrastructure financed by the Dutch government through Netherlands Organisation for Scientific Research (NWO) (Grant Nos. 184.021.007 and 184033111). MK was supported by VENI grant (91616079) from The Netherlands Organization for Health Research and Development (ZonMw).

Association of upper airway surgery and improved cardiovascular biomarkers and risk in OSA.

To evaluate the association between upper airway surgery and changes of cardiological metabolic biomarkers and the overall cardiovascular risk in obstructive sleep apnea (OSA), and to define factors associated with better cardiovascular outcomes. A total of 161 patients with newly diagnosed OSA who underwent classical or modified uvulopalatopharyngoplasty with or without genioglossus advancement and hyoid suspension were included. The pre- and postoperative (at least 6 months later) assessments, including polysomnography, measurement of glucose and lipids, blood pressure, and overall cardiovascular risk (as estimated by Framingham Risk Scores), were compared. We accounted for multiple comparisons with the use of the Benjamini-Hochberg correction. The mean follow-up time was 2.5 ± 1.9 years. The apnea hypopnea index decreased significantly in the entire cohort (mean changes with 95% confidence intervals were [-25.3 (-29.5, -21.0) events/hour, P < 0.001]. We also noted decreases in the age-adjusted Framingham Risk Scores [-2.5% (-4.0%, -1.0%), P < 0.001] as well as single cardiometabolic biomarkers, including glucose [-0.50 (-0.70, -0.30) mmol/L, P < 0.001], total cholesterol [-0.46 (-0.65, -0.28) mmol/L, P < 0.001], triglycerides [-0.56, (-0.99, -0.14) mmol/L, P = 0.014], low-density lipoprotein cholesterol [-0.27, (-0.43, -0.11) mmol/L, P = 0.002], apolipoprotein B [-0.10 (-0.14, -0.07) g/L, P < 0.001], systolic blood pressure [-3.58 (-6.02, -1.14) mmHg, P = 0.007], and diastolic blood pressure [-3.25 (-5.47, -1.02) mmHg, P = 0.008] after surgery. Patients with preoperative metabolic abnormalities exhibited better postoperative risk profiles changes (P < 0.001). In addition, associations were found between Δapolipoprotein B, Δsystolic blood pressure, and improvements in nocturnal oxygen level after surgery. OSA-related upper airway surgery was associated with improvements in cardiological metabolic biomarker levels and the overall cardiovascular risk, especially in patients with both OSA and metabolic disorders. The changes in biomarker levels may be associated with improved oxygen saturation after surgery. 4 Laryngoscope, 130:818-824, 2020.

Childhood Adversity and Schizophrenia: The Protective Role of Resilience in Mental and Physical Health and Metabolic Markers.

To determine the impact of childhood adversity and current (adulthood) resilience on mental and physical health and markers of metabolic function among adults with schizophrenia and nonpsychiatric comparison participants (NCs). We conducted a cross-sectional study of 114 participants with schizophrenia (DSM-IV-TR criteria) and 101 NCs aged 26-65 years during 2012-2017. Sociodemographic, clinical, and laboratory measures were examined. Childhood Trauma Questionnaire was used to retrospectively assess emotional abuse/neglect, physical abuse/neglect, and sexual abuse experienced during childhood. Connor-Davidson Resilience Scale was employed to measure resilience. Persons with schizophrenia reported more severe childhood trauma, lower resilience, and worse mental and physical health and had worse metabolic biomarker levels than NCs. Trauma severity correlated with worse depression in the NCs (r = 0.34), but not in the schizophrenia group (r = 0.02). In both groups, trauma severity was associated with worse physical well-being, higher fasting insulin levels, and greater insulin resistance (P ≤ .02). Notably, resilience appeared to counteract effects of trauma and diagnosis on mental and physical health. The schizophrenia subgroup with high resilience and severe trauma reported mental and physical well-being and had glycosylated hemoglobin levels and insulin resistance scores that were comparable to those of NCs with low resilience and severe trauma. To our knowledge, this is the first study to quantitatively assess effects of both childhood trauma and resilience in schizophrenia on health, notably metabolic function. Interventions to bolster resilience in the general population and in people with schizophrenia may improve outcomes for those with a history of childhood adversity.

Toenail Chromium Concentration and Metabolic Syndrome among Korean Adults.

Although in vivo and in vitro studies have shown that chromium has protective effects against metabolic diseases, few studies have examined this association in humans. The present study examined chronic chromium (Cr) exposure among Koreans based on the measurement of toenail Cr concentrations, and analyzed the associations between toenail Cr concentrations and metabolic syndrome (MetS) and its components. We conducted a cross-sectional analysis using baseline data from the prospective cohort study in the Yeungnam area of South Korea that included 232 men and 268 women. Toenail Cr concentration was quantified by neutron activation analysis, and metabolic biomarker levels were obtained through medical examinations. The odd ratios (OR) of prevalent MetS and its components in correlation with Cr concentrations were calculated using multivariable logistic regression. After multiple confounding variables were adjusted for, participants with higher concentrations of Cr had a prevalence rate of MetS similar to those with lower concentrations (OR, 1.84; 95% confidence interval, 0.65–5.23). Our results do not support an association between long-term exposure to Cr and a lower prevalence of MetS in Koreans, whose Cr concentrations are relatively low compared to those of populations in Europe and the United States.