Normal Metabolic Status Research Articles

Hematological indices as indicators of inflammation induced by exposure to pesticides.

Pesticide toxicity, both acute and chronic, is a global public health concern. Pesticides are involved in abnormal inflammatory responses by interfering with the normal physiology and metabolic status of cells. In this regard, inflammatory indices aggregate index of systemic inflammation (AISI), monocyte-to-high-density lipoprotein ratio, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte platelet ratio (NLPR), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index (SIRI) have been used as predictive markers of inflammatory status in several diseases and also in acute poisoning events. This study aimed to determine systemic inflammation indices and their relationship with pesticide exposure from urban sprayers in 302 individuals categorized into three groups (reference group and moderate and high exposure groups). The data suggest that the AISI, MLR, NLPR, and SIRI indices were significantly higher in the exposed groups compared with the reference group. In conclusion, this study proposes that inflammation indices warrant further attention in order to assess their value as early biomarkers of acute and chronic pesticide intoxication.

Stability and Transformation of Metabolic Syndrome in Adolescents: A Prospective Assessment in Relation to the Change of Cardiometabolic Risk Factors.

Underlying pathophysiological mechanisms drive excessive clustering of cardiometabolic risk factors, causing metabolic syndrome (MetS). MetS status may transform as adolescents transition to young adulthood. This study investigated the latent clustering structure and its stability for MetS during adolescence, and assessed the anthropometric and clinical metabolic determinants for MetS transformation. A community-based representative adolescent cohort (n = 1516) was evaluated for MetS using four diagnostic criteria, and was followed for 2.2 years to identify new-onset MetS. The clustering structure underlying cardiometabolic parameters was stable across adolescence; both comprised a fat—blood pressure (BP)—glucose three-factor structure (total variance explained: 68.8% and 69.7% at baseline and follow-up, respectively). Among adolescents with MetS-negative at baseline, 3.2–4.4% had incident MetS after 2.2 years. Among adolescents with MetS-positive at baseline, 52.0–61.9% experienced MetS remission, and 38.1–48.0% experienced MetS persistence. Increased systolic BP (SBP) was associated with a high MetS incidence risk, while decreased levels of SBP and glucose were associated with MetS remission. Compared with adolescents with a normal metabolic status at baseline, those with an initial abdominal obesity and increased triglycerides level had a 15.0- and 5.7-fold greater risk for persistent abnormality, respectively. Abdominal obesity and low high-density lipoprotein cholesterol are two abnormal MetS components that highly persist during adolescence, and are the intervention targets for reducing the future risk of cardiometabolic disorders.

Effects of an individualized nutritional intervention on the prognosis of patients with liver failure.

Patients with liver failure often have energy metabolism disorders and malnutrition, which lead to poor prognosis, rendering nutritional interventions essential. Individualized nutritional interventions were offered according to the resting energy expenditure (REE) of patients with liver failure, and the patients were followed up for 180 days. Sixty patients with liver failure were enrolled and grouped by their prognosis and energy intake. Model for end-stage liver disease (MELD) score and body fat mass of the nonsurvival group were significantly higher than those of the survival group (p<0.05), whereas the mean energy intake/REE (MEI/REE) and mean respiratory quotient (RQ) of the nonsurvival group were significantly lower than those of the survival group (p<0.01). Prediction REE (PredREE) was calculated using the Harris-Benedict formula. Most patients in the nonsurvival and survival groups had hypometabolic (REE/PredREE <0.9) and normal metabolic status (0.9<REE/PredREE<1.1; p=0.014), respectively. MEI/REE, MELD score, and REE/PredREE were independent predictors of survival in patients with liver failure. The optimal threshold for MEI/REE was 1.15 for predicting favorable prognosis, and the sensitivity and specificity of the threshold were 61.1% and 85.0%, respectively. The survival rates of patients in the <1.2-REE group and ≥1.2-REE group were 45.2% and 88.0%, respectively (p=0.001). Hypometabolism state and insufficient energy intake predict poor prognosis in patients with liver failure. Individualized nutritional interventions with energy intake ≥1.2 REE may improve the RQ and prognosis of such patients.

Baoyuan decoction alleviates myocardial infarction through the regulation of metabolic dysfunction and the mitochondria-dependent caspase-9/3 pathway

Abstract Objective: Baoyuan decoction (BYD) is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests. The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction (MI). Methods: Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation. Oxygen-glucose deprivation/recovery (OGD/R) model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD. Results: BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI. Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway. Conclusions: Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways. They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.

Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study

BackgroundParental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring.MethodsThis longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model.ResultsIn male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring.ConclusionExcept for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.

Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela.

Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called "healthy obese". Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional sub-analysis of The Maracaibo City Metabolic Syndrome Prevalence Study, with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster being predictive variables: HOMA2-IR, HOMA2-βcell, triglycerides. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 43.9% (n=538) were healthy normal weight, 5.2% (n=64) unhealthy normal weight, 17.4% (n=217) healthy obese and 33.5% (n=411) unhealthy obese subjects. Atypical phenotypes, Metabolically Unhealthy Normal-Weight (MUNW) was more frequent in males (56.3%), whereas Metabolically Unhealthy Obese (MUO) was more frequent in females (51.3%). This phenotypes had a higher coronary event risk, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes are common in Maracaibo city. Related factors may include insulin resistance, basal glucose, and triglycerides levels. Lastly, obese subjects show a higher coronary event risk even those with normal metabolic status.

Thyroid hormone resistance syndrome with P453T mutation in thyroid hormone receptor β gene: A pedigree report.

Rationale:Thyroid hormone resistance syndrome (THRS) is an inherited condition characterized by reduced responsiveness of target tissues to thyroid hormone. Due to their nonspecific symptomatic manifestations, these patients can be misdiagnosed. This study reports a pedigree with THRS caused by a mutation in the thyroid hormone receptor β (THRβ) gene.Patient concern:The proband, a 36-year-old woman at 19+4 weeks of gestation, was referred to our hospital because of abnormal thyroid function results. She was diagnosed with hyperthyroidism in October 2015, and had been treated with methimazole until her pregnancy.Diagnosis:The proband and 2 of her children were diagnosed with THRS based on genetic analysis. Sequence analysis of the THRβ gene showed a heterozygous mutation C>A located at exon 10. The mutation results in a change in proline for threonine at amino acid position 453, P453T.Interventions:No treatment will fully and specifically correct the defect. All 3 patients were in normal metabolic status, and thus treatment was not required.Outcomes:During a 2-year follow-up period, none of them had any complaints. The 20-year-old son (167 cm in height) and the 18-year-old daughter (150 cm in height) both had low academic performance.Lessons:Elevated serum thyroid hormone (TH) levels associated with nonsuppressed thyroid-stimulating hormone (TSH) levels usually leads to the diagnosis of THRS. Genetic analysis provides a short cut to diagnosis and the treatment should be based on the patient's clinical manifestations.

Spleen and thymus metabolomics strategy to explore the immunoregulatory mechanism of total withanolides from the leaves of Datura metel L. on imiquimod-induced psoriatic skin dermatitis in mice.

Our previous work demonstrated that total withanolides of Datura metel L. leaves (TWD) exhibited excellent therapeutic effects on psoriasis. However, current knowledge of its mechanisms is incomplete. In this study, integrated spleen and thymus untargeted metabolomics were used to analyze the changes in endogenous metabolites underlying the immunosuppressive activity of TWD on psoriasis animal models induced by imiquimod. The results suggested that TWD treatment markedly attenuated imiquimod-induced psoriasis and showed significant immunosuppressive activity as evidenced by decreased elevation index of spleen and thymus. Meanwhile, TWD significantly reversed the elevation of immunoregulatory factors, including IL-10, IL-17, IL-22 and IL-23. Multivariate trajectory analysis revealed that TWD treatment could restore the psoriasis-disturbed spleen and thymus metabolite profiles towards the normal metabolic status. A total of 25 and 27 metabolites associated with the immunomodulatory effects for which levels changed markedly upon treatment have been identified in spleen and thymus, respectively. These differential metabolites were mainly involved in amino acid metabolism, nucleotide metabolism, fatty acid metabolism and lipid metabolism. Our investigation provided a holistic view of TWD for intervention in psoriasis through immunoregulation and provided further scientific information in vivo about a clinical value of TWD for psoriasis.

Metabolic Dysfunction in Continuous-Flow Left Ventricular Assist Devices Patients and Outcomes.

BackgroundMetabolic impairment is common in heart failure patients. Continuous‐flow left ventricular assist devices (CF‐LVADs) improve hemodynamics and outcomes in patients with advanced heart failure; however, the effect of CF‐LVADs on metabolic status is unknown. This study aims to evaluate the changes in metabolic status following CF‐LVAD implantation and measure the correlation of metabolic status with outcomes.Methods and ResultsProspective data on CF‐LVAD patients were obtained. Metabolic evaluation, including hemoglobin A1C, free and total testosterone, thyroid‐stimulating hormone (TSH), and free T4, was obtained before and at multiple time points following implantation. Patients with nonelevated thyroid‐stimulating hormone and normal hemoglobin A1C and testosterone levels were defined as having normal metabolic status. Baseline characteristics, hemodynamics, and outcomes were collected. One hundred six patients were studied, of which 56 had paired data at baseline and 1‐ to 3‐month follow‐up. Before implantation, 75% of patients had insulin resistance, 86% of men and 39% of women had low free testosterone, and 44% of patients had abnormal thyroid function. There was a significant improvement in hemoglobin A1C, free testosterone, and thyroid‐stimulating hormone following implantation (P<0.001 for all). Patients with normal hemoglobin A1C (<5.7%) following implantation had higher 1‐year survival free of heart failure readmissions (78% versus 23%; P<0.001). Patients with normal metabolic status following implantation also had higher 1‐year survival free of heart failure readmissions (92% versus 54%; P=0.04).ConclusionsMetabolic dysfunction is highly prevalent in advanced heart failure patients and improves after CF‐LVAD implantation. Normal metabolic status is associated with a significantly higher rate of 1‐year survival free of heart failure readmissions.

Contrasting signals of cardiovascular health among natriuretic peptides in subjects without heart disease

Natriuretic Peptides (NP) are important in maintaining normal cardiac and metabolic status and have been used to predict cardiovascular events. Whether plasma concentrations of NP products within the normal range reflect cardio-metabolic health is unknown. Plasma NTproANP, NTproBNP and NTproCNP and their bioactive counterparts were measured in a random sample of 348 community dwellers aged 49–51 yr without heart disease and associations sought with established vascular risk factors, echocardiographic indices and a genetic variant previously linked with BNP. Stratified by sex, each of ten vascular risk factors were positively associated with NTproCNP whereas associations with NTproBNP and NTproANP were all negative. In both sexes, higher plasma NTproCNP was associated with higher arterial elastance, lower LV stroke volume and lower LV end diastolic volume. Exactly opposite associations were found with plasma NTproBNP or NTproANP. Sex specific differences were identified: positive association of NTproBNP with LV end systolic volume and the negative association with LV elastance were found only in males. The genetic variant rs198358 was independently associated with NTproBNP but not with NTproANP. In conclusion, higher NTproCNP is likely to be an adaptive response to impaired LV relaxation whereas genetic factors likely contribute to higher NTproBNP and improved cardio-metabolic health at midlife.

Normalization of Metabolic Status after LVAD Implantation is Associated with Heart Failure Free Survival

Purpose Metabolic abnormalities are common in advanced heart failure patients. It has previously been shown that after left ventricular assist device (LVAD) implantation, there is reversal of metabolic dysfunction. However, little is known if this reversal affects outcomes. This study investigates if normalization of metabolic dysfunction after LVAD implantation leads to improvement in outcomes including survival and hemocompatibility related adverse events (HRAEs). Methods Patients who received LVAD were consecutively enrolled in this prospective study. Metabolic labs, including thyroid function tests, total and free testosterone, and hemoglobin A1c (HgA1c) were drawn within 30 days before LVAD implantation and between 1-3 months after LVAD implantation. Normal metabolic status (NMS) was defined as HgA1c 90 pg/dL in males and > 3 pg/dL in females. Outcomes of patients who achieved NMS 1-3 months after implantation were compared to outcomes of patients who did not. Results 62 patients were enrolled in this study. At 1-3 months after LVAD implantation, 47 patients did not achieve NMS and 15 patients did. Overall, the percentage of patients with NMS improved from 2% before implantation to 24% after implantation (p Conclusion Advanced heart failure patients have metabolic derangements that improve after LVAD implantation. In patients who achieved NMS 1-3 months after LVAD implantation, there is a significant improvement in survival free from heart failure compared to those who did not.

Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela.

Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called "healthy obese". Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional sub-analysis of The Maracaibo City Metabolic Syndrome Prevalence Study, with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster being predictive variables: HOMA2-IR, HOMA2-βcell, triglycerides. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 43.9% (n=538) were healthy normal weight, 5.2% (n=64) unhealthy normal weight, 17.4% (n=217) healthy obese and 33.5% (n=411) unhealthy obese subjects. Atypical phenotypes, Metabolically Unhealthy Normal-Weight (MUNW) was more frequent in males (56.3%), whereas Metabolically Unhealthy Obese (MUO) was more frequent in females (51.3%). This phenotypes had a higher coronary event risk, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes are common in Maracaibo city. Related factors may include insulin resistance, basal glucose, and triglycerides levels. Lastly, obese subjects show a higher coronary event risk even those with normal metabolic status.

1H NMR-based dynamic metabolomics delineates the therapeutic effects of Baoyuan decoction on isoproterenol-induced cardiac hypertrophy

Cardiac hypertrophy (CH) is a major risk factor for many serious heart diseases. Sustained CH is catastrophic, resulting in cardiac dysfunction that eventually leads to heart failure (HF). Baoyuan decoction (BYD) is a famous traditional Chinese medicine (TCM) formula for supplementing and reinforcing Qi, clinically used for the treatment of cardiovascular diseases (CVDs). However, the therapeutic effects of BYD on CH remain unidentified. We herein investigated the effect of BYD on isoproterenol (ISO)-induced CH in rats and the underlying mechanisms by comprehensive pharmacodynamics and 1H NMR-based dynamic metabolomics analysis of the plasma and urine samples. Results showed that BYD treatment markedly attenuated ISO-induced CH as evidenced by decreasing the left ventricular wall thickness, pathological cardiomyocyte hypertrophy, myocardial collagen fiber deposition and apoptosis, and plasma natriuretic peptide levels. Multivariate trajectory analysis revealed that the BYD treatment could restore the CH-disturbed plasma and urinary metabolite profiles towards the normal metabolic status featuring with a time-dependent tendency. Moreover, the key metabolic alterations in CH rats at different BYD-treated time stages involved energy metabolism, oxidative stress responses, amino acid metabolism, and gut microbiota metabolism. Of particularly, the significant roles of BYD for treating CH lie in the improvement of cardiac energy generation and antioxidant capacity. Our investigation provides a holistic view of BYD for therapeutic intervention of CH through monitoring of the dynamic metabolic changes and the results indicate that BYD may be applied as a potential agent for treating CH.

Which obesity phenotypes predict poor health-related quality of life in adult men and women? Tehran Lipid and Glucose Study.

PurposeThis study aimed to explore the association between different obesity phenotypes and health-related quality of life (HRQoL) among Tehranian men and women.MethodsThe participants of this study were 2880 healthy adults (aged>19 years) who participated in Tehran Lipid and Glucose Study (TLGS). To obtain socio-demographic and HRQoL information, participants were interviewed by trained interviewers and were stratified by body mass index categories and metabolic status. Dysmetabolic status was defined as having either metabolic syndrome or diabetes according to the Joint Interim Statement definition and American Diabetes Association. Poor HRQoL was defined as the first quartile of HRQoL scores and logistic regression analysis was used to compare sex-specific odds ratios.ResultsMean age of participants was 47.7±15.6 and 47.8±14.2 years in men and women respectively. The most and the least common obesity phenotypes were overweight-normal metabolic status and normal weight-dysmetabolic status, respectively. Only mean scores for physical HRQoL were significantly different among obesity phenotypes in both men and women (p<0.05). In addition, after adjusting for age, marital status, level of education, job status and physical activity, the odds of reporting poor physical HRQoL was significantly higher in men (OR: 1.960, 95% CI: 1.037–3.704; p<0.05) and women (OR: 2.887, 95% CI: 1.674–4.977; p<0.001) with obese-dysmetabolic status, compared to their counterparts with normal weight-normal metabolic status. However, except for overweight-normal metabolic women, who were less likely to report poor mental HRQoL (OR: 0.638, 95% CI: 0.415–0.981; p<0.05), none of the phenotypes were associated with poor mental HRQoL in either gender.ConclusionsCompared to those with normal weight normal metabolic status, only obese dysmetabolic individuals were more likely to report poor physical HRQoL in both genders.

Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela

Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called “healthy obese”. Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional sub-analysis of The Maracaibo City Metabolic Syndrome Prevalence Study, with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster being predictive variables: HOMA2-IR, HOMA2-βcell, triglycerides. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 43.9% (n=538) were healthy normal weight, 5.2% (n=64) unhealthy normal weight, 17.4% (n=217) healthy obese and 33.5% (n=411) unhealthy obese subjects. Atypical phenotypes, Metabolically Unhealthy Normal-Weight (MUNW) was more frequent in males (56.3%), whereas Metabolically Unhealthy Obese (MUO) was more frequent in females (51.3%). This phenotypes had a higher coronary event risk, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes are common in Maracaibo city. Related factors may include insulin resistance, basal glucose, and triglycerides levels. Lastly, obese subjects show a higher coronary event risk even those with normal metabolic status.

Reference intervals for stone risk factors in 24-h urine among healthy adults of the Han population in China.

The aim of the study was to establish reference intervals for 24-h urinary stone risk factors in the healthy Chinese Han population. From May 2013 to July 2014, we collected and analyzed 24-h urine samples from healthy adult Han population during a cross-sectional study across China. The protocol for analysis of 24-h urine included volume, pH, oxalate, citrate, sodium, potassium, chloride, calcium, phosphorous, creatinine, urate, magnesium, the ion activity products of calcium oxalate (AP(CaOx) indexs) and calcium phosphate (AP(CaP) indexs). We calculated the reference intervals according to the Clinical and Laboratory Standards Institute (CLSI) 2008 guidelines and compared them with those recorded in other studies. A total of 132 male and 123 female healthy subjects with a mean (SD, range) age of 52.4 (15.2, 19-89) years were eligible in the final analysis. Men had higher 24-h excretion of creatinine, calcium, urate and phosphorus and lower levels of citrate, magnesium, chloride, sodium and potassium than women. AP(CaOx) indexs and AP(CaP) indexs were significantly higher among men than women. When urinary findings were compared with the reference intervals, most of our data showed a high abnormality rate, especially for creatinine, calcium, citrate, magnesium, chloride, sodium and potassium. The present study revealed the normal metabolic status for stone risk factors of the Chinese Han population. It is therefore necessary for each country or region to define their own reference intervals for comparison of stone risk factors between patients and healthy subjects.

Abstract 2508: Profiling the metabolic effects of AGI-5198 treatment on IDH1-mutated gliomas

Abstract Background: AGI-5198 (a specific IDH1mut inhibitor) inhibits the formation of D-2-hydroxyglutarate (D-2HG) typically produced in millimolar quantities by the R132H mutation of isocitrate dehydrogenase I (IDH1). AGI-5198 was found to delay growth, to promote differentiation in cells and to decrease tumor volume in IDH1-mutant (IDH1mut) mice xenographs, and as a result, has been advanced to clinical trials in humans with IDH1mut glioblastomas. However, no metabolic study of this drug has been reported to date. Here, we investigated the metabolic changes induced by AGI-5198 treatment in order to determine if the drug restores the normal metabolic status once D-2HG concentration is decreased. Methods: We treated glioma cells carrying an IDH1 mutation with 10 μM AGI-5198 for 72 h. Metabolic changes were explored using an untargeted metabolomics approach. Cell viability analysis verified that the concentration of drug does not lead to significant cell death. NMR and MS-linked metabolomics together with in vivo cell imaging using RAMAN were used. Principal component analysis was employed to explore the differences in the metabolic profiles comparing treated and untreated glioma cells. Results and Conclusions: We confirmed that AGI5198 treatment reduced D-2HG levels in the cell lines investigated, validating previous reports. Moreover, we observed a decrease in phospholipid levels upon AGI-5198 treatment, which suggests a decreased proliferative potential for these cells; of particular importance for clinical application. Our preliminary analysis also suggests that metabolites involved in one carbon metabolism are altered upon AGI-5198 treatment. This pathway provides the methyl group for the DNA methylation by DNA methylases producing a hypermethylated phenotype. Our findings suggest that combining the AGI-5198 treatment with a DNA methylase inhibitor may improve outcomes in IDH1-mutated gliomas. Citation Format: Victor Ruiz Rodado, Adrian Lita, Tyrone Dowdy, Mark R. Gilbert, Mioara Larion. Profiling the metabolic effects of AGI-5198 treatment on IDH1-mutated gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2508. doi:10.1158/1538-7445.AM2017-2508

The role of adipokines in chronic inflammation.

Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function.

Relationship between pancreatic beta cell function and liver function in hepatitis B cirrhosis

Objective To investigate the relationship between pancreatic beta cell function and liver function in hepatitis B cirrhosis with different glucose metabolism status. Methods A total of 247 patients with hepatitis B cirrhosis were included and divided into 3 groups according to measurement of fasting blood glucose(FBG),and 2h blood glucose in 75g oral glucose tolerance test(2h PG),normal glucose metabolic status group(group A,n= 47),glucose tolerance impairment group(group B,n= 103) and diabetes mellitus group(group C,n= 97).Data of fasting and 2h postprandial blood glucose,C-peptide,insulin and glycosylated hemoglobin(Hb A1c),pancreatic beta cell function index(HBCI),insulin sensitivity index(ISI), hepatitis B virus load were collected and analyzed.〛 Results Abnormal glucose metabolism was observed in 81% patients with hepatitis B cirrhosis,while hepatogenic diabetes accounted for 39.3%.2 hPG[(6.29±3.78)mmol/L,(10.56±4.26)mmol/L,(17.34±5.9)mmol/L],FBG[(4.72±2.15)mmol/L,(5.68±2.81) mmol/L,(9.82±5.1)mmol/L],Hb A1c[(4.5±1.2)%(10.56±4.26)%(9.5±3.0)%],HBV-DNA [(3.78±0.52),(4.82±0.61),(6.02±0.63)] were compared in group A,group B and C.2hPG,FBG, Hb A1c and HBV viral loads in group A were significantly lower than group B and group C(F= 93.23,41.35,84.93,237.2,P< 0.05).Fasting insulin[(15.65±4.17)m U/L,(26.53±7.22)m U/L,(30.18±3.23) m U/L],postprandial insulin[(45.28±10.22)m U/L,(106.8±20.74)m U/L,(141.68±20.25)m U/L], postprandial C peptide[(5.96±4.82)m U/L,(9.86±5.46)m U/L,(9.54±6.42)m U/L]and ISI[(-5.96± 0.61),(-4.92±0.42),(-5.03±0.51)]were compared in group C,group B and A,those values in group C were lower than group A and B,the defferences were stastistically significant(P< 0.05).HBCI in three groups were(5.66±0.64),(5.32±1.01),(4.30±1.53),respectively,the defferences were stastistically significant(F= 27.55,P< 0.05).Patients in group C with Child-Pugh C score was much more than group A and B,the defference was stastistically significant(χ2= 48.6,P< 0.01). Conclusion Hyperinsulinemia,increased insulin resistance and decreased insulin secretion exist in hepatitis B cirrhosis patients,and they are closely related to liver function. Key words: Hepatitis B; Liver cirrhosis; Liver function tests; Glucose metabolism disorders; Insulin resistance; Insulin-secreting cells

Association between γ-Glutamyl Transferase and Metabolic Syndrome: A Cross-Sectional Study of an Adult Population in Beijing

The relationship between liver enzymes and clustered components of metabolic syndrome (MetS) is explored and the predictive power of γ-glutamyl transferase (GGT) for the diagnosis of MetS in an adult population in Beijing is investigated. A total of 10,553 adults aged 20–65 years who underwent health examinations at Beijing Tongren Hospital in 2012 were enrolled in the study. Multivariate logistic regression analysis is conducted to determine the associations between the levels of various liver enzymes and clustered components of MetS. A receiver operating characteristic analysis is used to determine the optimal cut-off value of GGT for the diagnosis of MetS. A high level of GGT is found to be positively associated with clustered components of MetS in both men and women after adjusting for age, body mass index (BMI), history of alcoholic fatty liver, and the presence of taking anti-hypertensive, anti-dyslipidemic, and anti-diabetic drugs. Among all components of MetS, GGT is more predictive of triglyceride, and BMI. The area-under-the-curve values of GGT for discriminating MetS from normal metabolic status in men and women are 0.73 and 0.80, respectively. The optimal cut-off value of GGT for men is 31.50 U/L, demonstrating a sensitivity of 74.00% and specificity of 62.00%. For women, it is 19.50 U/L (sensitivity 76.00% and specificity 70.00%). GGT is therefore recommended as a useful diagnostic marker for MetS, because the test is inexpensive, highly sensitive, and frequently encountered in clinical practice.