MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. METHODS: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. RESULTS: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). CONCLUSIONS: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS: We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.

Baseline urinary osteopontin levels are associated with the improvement of metabolic syndrome.

BACKGROUND AND AIMS: While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we propose its potential predictive role over a 12-month period of standard care, with the ability to complement anthropometric measures. METHODS AND RESULTS: Hierarchical clustering revealed a notable association of urinary OPN (uOPN) with MetS criteria and overcame anthropometric measures in predicting the improvement at 12 months (OR of 2.74 [95% CI 1.32 to 6.29]). uOPN significantly contributed to the homogeneity of the nodes in the random forest and ultimately enhanced the performance of anthropometric measures when assessed for accuracy and area under the curve (AUC). CONCLUSION: Our findings offer insights into potential applications in cardiometabolic medicine for uOPN, which is easily detectable in non-invasive biological samples through an affordable assay.

Increased nocturnal urinary cortisol levels in the elderly patients with depression, coexisting major geriatric syndromes and combined pathogenetic mechanisms.

BACKGROUND: The mechanisms at the basis of depression are still matter of debate, but several studies in the literature suggest common pathways with dementia (genetic predispositions, metabolic and inflammatory mechanisms, neuropathological changes) and other geriatric syndromes. AIMS: To evaluate the role of cortisol (as marker of the HPA, hypothalamus-pituitary-adrenal axis hyperactivity) in elderly subjects with depressive symptoms (by the means of the AGICO, AGIng and COrtisol, study), in relationship to the presence of the major geriatric syndromes. METHODS: The AGICO study enrolled patients from ten Geriatric Units in Italy. Every subject received a comprehensive geriatric assessment or CGA (including the Mini Mental State Examination or MMSE, Geriatric Depression Scale or GDS and Cornell Scale for Depression in Dementia or CSDD), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal), a CGA-derived frailty index (FI) and a modified measure of allostatic load (AL). RESULTS: The MMSE scores were significantly and inversely related to the values of GDS (p < 0.001) and CSDD (p < 0.05), respectively. The patients with depressive symptoms (GDS/CSDD > 8) showed significantly increased disability, MetS, inflammation, FI and AL and significantly reduced MMSE and renal function. The diurnal and nocturnal urinary cortisol levels in the patients with depressive symptoms (GDS/CSDD > 8) were higher with respects to controls (p < 0.05 for nocturnal difference). DISCUSSION: The AGICO study showed that the stress response is activated in the patients with depression. CONCLUSION: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome.

Spot urinary microalbumin concentration, metabolic syndrome and type 2 diabetes: Tehran lipid and glucose study.

AIM: This study aimed to determine the association of urinary microalbumin concentrations with type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), and its phenotypes. The optimum cut-off values of urinary microalbumin and microalbumin-to-creatinine ratio (MCR) for predicting the chance of having T2DM and MetS were also defined. METHODS: Adult men and women (n = 1192) participated in the sixth phase (2014-2017) of the Tehran Lipid and Glucose Study (TLGS), with completed data, were included in the analyses. Odds ratios (ORs) (and 95% confidence intervals (CIs)) of T2DM, MetS, and its components across tertile categories of urinary microalbumin concentrations were estimated using multivariable logistic regressions. The optimal cut-off points of urinary microalbumin and MCR were determined using the receiver operator characteristic (ROC) curve analysis. RESULTS: Participants' mean (±SD) age was 44.9 (±14.0) years, and 44.6% of the participants were men. The prevalence of microalbuminuria was 14.4%. Chance of having T2DM was significantly higher in the highest tertile of urinary microalbumin concentration (OR = 2.29, 95% CI = 1.43-3.67) and MCR (OR = 1.82, 95% CI = 1.15-2.89). Subjects with the highest urinary microalbumin concentration were more likely to have MetS (OR = 1.66, 95% CI = 1.17-2.35), hypertension (OR = 1.63, 95% CI = 1.16-2.30) and hyperglycemia (OR = 1.78, 95% CI = 1.24-2.56). No significant association was observed between urinary microalbumin concentrations and other components of MetS. The optimal cut-off points of urinary microalbumin for predicting the chance of having T2DM and MetS were 14.0 and 13.6 mg/L, respectively. CONCLUSIONS: Elevated spot urinary microalbumin, below the values defined as microalbuminuria, was associated with the chance of having T2DM and MetS.

A molecular signature for the metabolic syndrome by urine metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine. METHODS: We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18-75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4-5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS. RESULTS: MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (17 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.83 and 0.87). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome. CONCLUSIONS: Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.

The impact of metabolic syndrome components on urinary parameters and risk of stone formation.

PURPOSE: To investigate the relationship between metabolic syndrome (MS) and urinary abnormalities in stone-forming patients. Additionally, to delineate whether severity of urinary derangements is impacted by the number of co-occurring MS components. METHODS: Stone-forming patients who underwent initial metabolic workup prior to medical intervention at a comprehensive stone clinic were retrospectively reviewed and included in the study. Patients were given a six point (0-5) Metabolic Syndrome Severity Score (MSSS) based on the number of co-occurring MS components and split into six respective groups. Baseline clinical characteristics and metabolic profiles were compared between groups. RESULTS: Four-hundred-ninety-five patients were included in the study. Median age and median BMI was 58 years and 27.26 kg/m2, respectively. Several significant metabolic differences were noted, most notably a downward trend in median urinary pH (p < 0.001) and an upward trend in median urinary supersaturation uric acid (p < 0.001) across groups as MSSS increased. Multivariate analysis demonstrated an independent association between higher MSSS and increasing number of urinary abnormalities. A second multivariate analysis revealed that all MS components except hyperlipidemia were independently associated with low urinary pH. Additionally, obesity was independently associated with the greatest number of urinary abnormalities and had the strongest association with hyperuricosuria. CONCLUSIONS: Prior research has attributed the strong association of nephrolithiasis and MS to high prevalence of UA nephrolithiasis and low urinary pH. Our findings indicate that all MS components with the exception of hyperlipidemia were independently associated with low urinary pH suggesting a mechanism independent from insulin resistance.

Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats.

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)-regular diet with a FR < 3%; F10 (n = 6)-regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)-60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.

Multivariate Statistical Approach for Nephrines in Women with Obesity.

Catecholamines are physiological regulators of carbohydrate and lipid metabolism during stress, but their chronic influence on metabolic changes in obese patients is still not clarified. The present study aimed to establish the associations between the catecholamine metabolites and metabolic syndrome (MS) components in obese women as well as to reveal the possible hidden subgroups of patients through hierarchical cluster analysis and principal component analysis. The 24-h urine excretion of metanephrine and normetanephrine was investigated in 150 obese women (54 non diabetic without MS, 70 non-diabetic with MS and 26 with type 2 diabetes). The interrelations between carbohydrate disturbances, metabolic syndrome components and stress response hormones were studied. Exploratory data analysis was used to determine different patterns of similarities among the patients. Normetanephrine concentrations were significantly increased in postmenopausal patients and in women with morbid obesity, type 2 diabetes, and hypertension but not with prediabetes. Both metanephrine and normetanephrine levels were positively associated with glucose concentrations one hour after glucose load irrespectively of the insulin levels. The exploratory data analysis showed different risk subgroups among the investigated obese women. The development of predictive tools that include not only traditional metabolic risk factors, but also markers of stress response systems might help for specific risk estimation in obesity patients.

Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: A potential pitfall for the diagnosis.

Infantile onset cardiomyopathies are highly heterogeneous with several phenocopies compared with adult cardiomyopathies. Multidisciplinary management is essential in determining the underlying etiology in children's cardiomyopathy. Elevated urinary excretion of 3-methylglutaconic acid (3-MGA) is a useful tool in identifying the etiology in some metabolic cardiomyopathy. Here, we report the delayed appearance of 3-MGA-uria, between 6 and 18 months in three patients (out of 100 childhood onset cardiomyopathy) with neonatal onset cardiomyopathy, secondary to TMEM70 mutations and TAZ mutations (Barth syndrome), in whom extensive metabolic investigations, performed in the first weeks of life, did not display 3-MGA-uria. Serial retrospective evaluations showed full characteristic features of TMEM70 and TAZ mutations (Barth syndrome) in these three patients, including a clearly abnormal monolysocardiolipin/cardiolipin ratio in the two Barth syndrome patients. Serially repeated metabolic investigations finally discovered the 3-MGA-uria biomarker in all three patients between the age of 6 and 18 months. Our observation provides novel insights into the temporal appearance of 3-MGA-uria in TMEM70 and TAZ mutations (Barth syndrome) and focus the importance of multidisciplinary management and careful evaluation of family history and red flag signs for phenocopies in infantile onset cardiomyopathies.

Urinary Resveratrol Metabolites Output: Differential Associations with Cardiometabolic Markers and Liver Enzymes in House-Dwelling Subjects Featuring Metabolic Syndrome.

Metabolic syndrome (MetS) components are strongly associated with increased risk of non-alcoholic fatty liver disease (NAFLD) development. Several studies have supported that resveratrol is associated with anti-inflammatory and antioxidant effects on health status. The main objective of this study was to assess the putative associations between some urinary resveratrol phase II metabolites, cardiometabolic, and liver markers in individuals diagnosed with MetS. In this cross-sectional study, 266 participants from PREDIMED Plus study (PREvención con DIeta MEDiterránea) were divided into tertiles of total urinary resveratrol phase II metabolites (sum of five resveratrol conjugation metabolites). Urinary resveratrol metabolites were analyzed by ultra- performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS), followed by micro-solid phase extraction (µ-SPE) method. Liver function markers were assessed using serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Moreover, lipid profile was measured by triglycerides, very-low-density lipoprotein cholesterol (VLDL-c), and total cholesterol/high-density lipoprotein ratio (total cholesterol/HDL). Linear regression adjusted models showed that participants with higher total urine resveratrol concentrations exhibited improved lipid and liver markers compared to the lowest tertile. For lipid determinations: log triglycerides (ßT3= -0.15, 95% CI; -0.28, -0.02, p-trend = 0.030), VLDL-c, (ßT3= -4.21, 95% CI; -7.97, -0.46, p-trend = 0.039), total cholesterol/HDL ratio Moreover, (ßT3= -0.35, 95% CI; -0.66, -0.03, p-trend = 0.241). For liver enzymes: log AST (ßT3= -0.12, 95% CI; -0.22, -0.02, p-trend = 0.011, and log GGT (ßT3= -0.24, 95% CI; -0.42, -0.06, p-trend = 0.002). However, there is no difference found on glucose variables between groups. To investigate the risk of elevated serum liver markers, flexible regression models indicated that total urine resveratrol metabolites were associated with a lower risk of higher ALT (169.2 to 1314.3 nmol/g creatinine), AST (599.9 to 893.8 nmol/g creatinine), and GGT levels (169.2 to 893.8 nmol/g creatinine). These results suggested that higher urinary concentrations of some resveratrol metabolites might be associated with better lipid profile and hepatic serum enzymes. Moreover, urinary resveratrol excreted showed a reduced odds ratio for higher liver enzymes, which are linked to NAFLD.

Sodium status and the metabolic syndrome: A systematic review and meta-analysis of observational studies.

The prevalence of metabolic syndrome (MetS) has been greatly increased, worldwide. In recent years, investigators have proposed that sodium might contribute to the development of metabolic syndrome; however, the published data were conflicting. The present systematic review aimed to summarize the evidence from observational studies in this regard. We conducted a systematic search for relevant observational studies investigating the association between sodium status and MetS, published until June 2017 in electronic databases including PubMed, EMBASE, Scopus and Google Scholar. Summary effects were derived using random effects model. After screening the records, seventeen publications with 66,274 participants were eligible to be included in the systematic review and meta-analysis. The analysis revealed that subjects with MetS have significantly higher levels of sodium compared to healthy controls (Hedges' g = 0.21, 95% CI: 0.12, 0.29, I2 = 68.6). Subgroup analyses revealed that the difference was significant when the sodium status was assessed using urinary sodium levels. The random effects meta-regression analysis also revealed that body sodium level increases with the number of MetS components. Furthermore, participants with highest dietary/urinary or serum sodium levels had 37% higher chance of developing MetS when compared with participants with the lowest sodium levels (OR = 1.37 95%CI: 1.31, 1.42, I2 = 86.9). The current meta-analysis revealed that higher sodium input into the body is directly associated with the likelihood of MetS. Prospective cohort studies and well-designed randomized clinical trials considering the effect of sodium restricted diets on the risk of MetS as an outcome are necessary to represent the causal association.

High-fat simple carbohydrate (HFSC) diet impairs hypothalamic and corpus striatal serotonergic metabolic pathway in metabolic syndrome (MetS) induced C57BL/6J mice.

OBJECTIVES: To study the effect of specially formulated high-fat simple carbohydrate diet (HFSC) on the serotonin metabolic pathway in male C57BL/6J mice. METHODS: Previous studies from our laboratory have shown that specially formulated HFSC induces metabolic syndrome in C57BL/6J mice. In the present investigation, 5-hydroxytryptophan, serotonin and 5-hydroxyindoleacetic acid were analyzed in two brain regions (hypothalamus, corpus striatum), urine and plasma of HFSC-fed mice on a monthly basis up to 5 months using high-performance liquid chromatography fitted with electrochemical detector. The data were analyzed using Graph pad Prism v7.3 by two-way ANOVA and post hoc Tukey's test (to assess the effect of time on the serotonergic metabolic pathway). RESULTS: HFSC feed was observed to lower the hypothalamic serotonergic tone as compared to the age-matched control-fed C57BL/6J mice. Although the hypothalamic serotonergic tone was unaltered over time due to consumption of diet per se, hypothalamic 5-HTP levels were observed to be lower on consumption of HFSC feed over duration of 5 months as compared to 1st month of consumption of HFSC feed. The striatal 5-HTP levels were lowered in the HFSC-fed mice after 4 months of feeding as compared to the age-matched control-fed mice. The striatal 5-HTP levels were also lower in both control and HFSC-fed mice due to consumption of the respective diet over a duration of 5 months. Increased plasma 5-HTP levels were observed due to consumption of HFSC feed over duration of 5 months in the HFSC-fed group. However, higher breakdown of serotonin was observed in both the plasma and urine of HFSC-fed C57BL/6J mice as per the turnover studies. DISCUSSION: The central and peripheral serotonergic pathway is affected differentially by both the type of diet consumed and the duration for which the diet is consumed. The hypothalamic, striatal and plasma serotonergic pathway were altered both by the type of feed consumed and the duration of feeding. The urine serotonergic pathway was affected by mainly the duration for which a particular diet was consumed. These findings may have implications in the feeding behavior, cognitive decline and depression associated with metabolic syndrome patients.

Fructose increases risk for kidney stones: potential role in metabolic syndrome and heat stress.

BACKGROUND: Fructose intake, mainly as table sugar or high fructose corn syrup, has increased in recent decades and is associated with increased risk for kidney stones. We hypothesized that fructose intake alters serum and urinary components involved in stone formation. METHODS: We analyzed a previously published randomized controlled study that included 33 healthy male adults (40-65 years of age) who ingested 200 g of fructose (supplied in a 2-L volume of 10% fructose in water) daily for 2 weeks. Participants were evaluated at the Unit of Nephrology of the Mateo Orfila Hospital in Menorca. Changes in serum levels of magnesium, calcium, uric acid, phosphorus, vitamin D, and intact PTH levels were evaluated. Urine magnesium, calcium, uric acid, phosphorus, citrate, oxalate, sodium, potassium, as well as urinary pH, were measured. RESULTS: Ingestion of fructose was associated with an increased serum level of uric acid (p < 0.001), a decrease in serum ionized calcium (p = 0.003) with a mild increase in PTH (p < 0.05) and a drop in urinary pH (p = 0.02), an increase in urine oxalate (p = 0.016) and decrease in urinary magnesium (p = 0.003). CONCLUSIONS: Fructose appears to increase urinary stone formation in part via effects on urate metabolism and urinary pH, and also via effects on oxalate. Fructose may be a contributing factor for the development of kidney stones in subjects with metabolic syndrome and those suffering from heat stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT00639756 March 20, 2008.

Urinary profiling of tryptophan and its related metabolites in patients with metabolic syndrome by liquid chromatography-electrospray ionization/mass spectrometry.

Tryptophan (Trp) is an essential amino acid that plays an important role in protein synthesis and is a precursor of various substances related to diverse biological functions. An imbalance in Trp metabolites is associated with inflammatory diseases. The accurate and precise measurement of these compounds in biological specimens would provide meaningful information for understanding the biochemical states of various metabolic syndrome-related diseases, such as hyperlipidemia, hypertension, diabetes, and obesity. In this study, we developed a rapid, accurate, and sensitive liquid chromatography-tandem mass spectrometry-based method for the simultaneous targeted analysis of Trp and its related metabolites of the kynurenine (Kyn), serotonin, and tryptamine pathways in urine. The application of the developed method was tested using urine samples after protein precipitation. The detection limits of Trp and its metabolites were in the range of 0.01 to 0.1 µg/mL. The method was successfully validated and applied to urine samples from controls and patients with metabolic syndrome. Our results revealed high concentrations of Kyn, kynurenic acid, xanthurenic acid, and quinolinic acid as well as a high Kyn-to-Trp ratio (KTR) in patients with metabolic syndromes. The levels of urine Kyn and KTR were significantly increased in patients under 60 years old. The profiling of urinary Trp metabolites could be a useful indicator for age-related diseases including metabolic syndrome. ᅟ.

The Association Between the Metabolic Syndrome and Metabolic Syndrome Score and Urine Microalbumin/Urine Creatinine Ratio and Glomerular Filtration Rate in Korean Adults With Obesity.

OBJECTIVE: This study assessed the association between metabolic syndrome (MetS) and metabolic syndrome score (MSS) and the levels of urine microalbumin-urine creatinine ratio (uACR) and glomerular filtration rate (GFR) in Korean adults with obesity. METHODS: Analyses of data obtained during the 2012 Korean National Health and Nutrition Examination Survey were restricted to that obtained from 1,612 adults aged ≥20 years with obesity. RESULTS: After adjusting for relevant variables (excluding age), uACR levels were positively associated with MetS (P < .001) and MSS (P < .001), and GFR levels were inversely associated with MetS (P < .001) and MSS (P < .001). However, when further adjusting for age, uACR levels were positively associated with MetS (P < .001) and MSS (P < .001) levels, but GFR levels were not associated with MetS (P = .632) and MSS (P = .275) levels. CONCLUSION: MetS and MSS were positively associated with uACR levels in Korean adults with obesity, but were not associated with GFR levels.

Comprehensive Metabolomic Analysis in Blood, Urine, Fat, and Muscle in Men with Metabolic Syndrome: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Resveratrol after Four Months' Treatment.

Resveratrol possesses several beneficial metabolic effects in rodents, while the effects of resveratrol in humans remain unclear. Therefore, we performed a non-targeted comprehensive metabolomic analysis on blood, urine, adipose tissue, and skeletal muscle tissue in middle-aged men with metabolic syndrome randomized to either resveratrol or placebo treatment for four months. Changes in steroid hormones across all four matrices were the most pronounced changes observed. Resveratrol treatment reduced sulfated androgen precursors in blood, adipose tissue, and muscle tissue, and increased these metabolites in urine. Furthermore, markers of muscle turnover were increased and lipid metabolism was affected, with increased intracellular glycerol and accumulation of long-chain saturated, monounsaturated, and polyunsaturated (n3 and n6) free fatty acids in resveratrol-treated men. Finally, urinary derivatives of aromatic amino acids, which mainly reflect the composition of the gut microbiota, were altered upon resveratrol treatment. In conclusion, the non-targeted metabolomics approach applied to four different matrices provided evidence of subtle but robust effects on several metabolic pathways following resveratrol treatment for four months in men with metabolic syndrome-effects that, for the most part, would not have been detected by routine analyses. The affected pathways should be the focus of future clinical trials on resveratrol's effects, and perhaps particularly the areas of steroid metabolism and the gut microbiome.

Fasting Single-Spot Urine pH Is Associated with Metabolic Syndrome in the Japanese Population.

OBJECTIVE: To investigate the relationship between urine pH and metabolic syndrome (MetS) and its components, while controlling for covariates. SUBJECTS AND METHODS: This cross-sectional study was conducted on 5,430 Japanese subjects (4,691 without MetS; 739 with MetS) undergoing health assessments. Partial correlation analysis and analysis of covariance were used for controlling confounding parameters (age, gender, levels of serum uric acid and high-sensitivity C-reactive protein, estimated glomerular filtration rate, and smoking and drinking status). Using multiple logistic regression analyses, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for MetS incidence were calculated across urine pH categories. Path analysis was used to determine the relationship between MetS and urine pH. RESULTS: Subjects with MetS had significantly lower urine pH (5.9 ± 0.7) than those without MetS (6.0 ± 0.7) (p < 0.001). Partial correlation analysis showed that systolic and diastolic blood pressure, and triglyceride and fasting plasma glucose levels were negatively correlated with urine pH, while high-density lipoprotein cholesterol was positively correlated with urine pH. Analysis of covariance indicated that urine pH decreased with an increasing number of metabolic abnormalities. Adjusted ORs (95% CI) for the presence of MetS in subjects with urine pH 5.5-6.0 and pH <5.5 were 1.34 (1.04-1.73) and 1.52 (1.09-2.13), respectively (reference: subjects with a urine pH >6.0). CONCLUSION: The MetS and its components were independently associated with lower urine pH.

Exercise-induced albuminuria is related to metabolic syndrome.

Microalbuminuria (MA) is a known marker for endothelial dysfunction and future cardiovascular events. Exercise-induced albuminuria (EiA) may precede the appearance of MA. Associations between EiA and metabolic syndrome (MS) have not been assessed so far. Our aim was to investigate this association in a large sample of apparently healthy individuals with no baseline albuminuria. This was a cross-sectional study of 2,027 adults with no overt cardiovascular diseases who took part in a health survey program and had no baseline MA. Diagnosis of MS was based on harmonized criteria. All patients underwent an exercise test (Bruce protocol), and urinary albumin was measured before and after the examination. Urinary albumin-to-creatinine ratio (ACR) values before and after exercise were 0.40 (0.21-0.89) and 1.06 (0.43-2.69) mg/g for median (interquartile range) respectively. A total of 394 (20%) subjects had EiA; ACR rose from normal rest values (0.79 mg/g) to 52.28 mg/g after exercise (P < 0.001); this effect was not shown for the rest of the study population. EiA was related to higher prevalence of MS (13.8% vs. 27.1%, P < 0.001), higher metabolic equivalents (P < 0.001), higher baseline blood pressure (P < 0.001), and higher levels of fasting plasma glucose, triglycerides, and body mass index (P < 0.001). Multivariate binary logistic regression model showed that subjects with MS were 98% more likely to have EiA (95% confidence interval: 1.13-3.46, P = 0.016). In conclusion, EiA in the absence of baseline MA is independently related to MS.

The association between phthalates and metabolic syndrome: the National Health and Nutrition Examination Survey 2001-2010.

BACKGROUND: Higher exposure to certain phthalates is associated with a diabetes and insulin resistance, with sex differences seen. Yet, little is known about the association between phthalates and metabolic syndrome (MetS), particularly with consideration for differences by sex and menopausal status. METHODS: We analyzed data from 2719 participants in the National Health and Nutrition Examination Survey (NHANES) 2001-2010 aged 20-80 years. Five urinary phthalate metabolites (MEP, MnBP, MiBP, MBzP, and MCPP) and DEHP metabolites were analyzed by the Centers for Disease Control and Prevention and were evaluated as population-specific quartiles. MetS was defined by National Cholesterol Education Program's Adult Treatment Panel III report criteria. Prevalence odds ratios (POR) and 95 % confidence intervals (CI) were calculated using multivariable logistic regression, adjusting for potential confounders and stratifying by sex and menopausal status. RESULTS: Participants with MetS (32 % of the study population) had higher concentrations for all urinary phthalate metabolites. After full adjustment, higher DEHP metabolite concentrations were associated with an increased odds of MetS in men, but not women (adj. POR for men Q4 versus Q1: 2.20; 95 % CI: 1.32, 3.68 and adj. POR for women Q4 versus Q1: 1.50; 95 % CI: 0.89, 2.52). When evaluating by menopausal status, pre-menopausal women with higher concentrations of MBzP had close to a 4-fold increased odds of MetS compared to pre-menopausal women with the lowest concentrations of MBzP (adj POR: Q4 versus Q1: 3.88; 95 % CI: 1.59, 9.49). CONCLUSIONS: Higher concentrations of certain phthalate metabolites were associated with an increased odds of MetS. Higher DEHP metabolite concentrations were associated with an increased odds of MetS for men. In women, the strongest association was between higher concentrations of MBzP and MetS, but only among pre-menopausal women.