Hyperuricemia and metabolic syndrome in children with overweight and obesity

ObjectiveTo study the prevalence of hyperuricemia in children with overweight or obesity and analyze the relation with metabolic syndrome and the diseases that define it.Materials and methodsThis is a cross-sectional prevalence study in 148 children recruited from pediatric endocrinology consultation, with overweight or obesity (12 ± 3 years, 48% boys, BMI 31.8 ± 6.1). We measured BMI, waist-height, waist circumference, blood pressure with standard instrumentation and glucose (fasting and after overload with 75 g), insulin resistance, cholesterol HDL, triglycerides and uric acid.ResultsThe prevalence of hyperuricemia was 53%. Patients with hyperuricemia had greater BMI (33.9 vs 30.6, p = 0.003), plus waist circumference (101.4 vs 91.1 cm, p < 0.001), higher blood pressure: systolic (123.4 vs 111.9 mm Hg, p < 0.001), diastolic (78.2 vs 68.7 mm Hg, p < 0.001). They presented greater blood glucose after overload oral glucose (107.5 vs 100.7 mg/dl, p = 0.03), insulin was higher (29.2 vs 20.7 mg/dl, p = 0.001) as well as HOMA IR (6.5 vs 4.4, p < 0.001) and HDL levels were lower (49.5 vs 54.4 mg/dl, p = 0.02).Uric acid's level which most is the likely diagnosis of metabolic syndrome corresponds to 5.4 mg/dl in our sample (sensitivity: 64% and specificity 62%).ConclusionThe prevalence of hyperuricemia in children with overweight and obesity is high. In the group of patients with obesity and hyperuricemia, we found out that the parameters measured to diagnose with metabolic syndrome were less favorable. Uric acid's level from where there is a higher possibility to see metabolic syndrome is 5.4 mg/dl.     

Effects of Successful Parathyroidectomy on Metabolic Cardiovascular Risk Factors In Patients With Severe Primary Hyperparathyroidism

ObjectiveTo evaluate the effect of parathyroidectomy on metabolic abnormalities associated with cardiovascular disease in patients with primary hyperparathyroidism (PHPT).MethodsThirty-four patients with PHPT (aged 51.0 ± 11.8 years, mean ± standard deviation) underwent assessment before and 1 year after successful parathyroidectomy. A control group of 42 normocalcemic healthy subjects, matched for age and body mass index, was also examined at baseline. We measured serum lipids, glucose, insulin, uric acid, calcium, parathyroid hormone, C-reactive protein, and bone density. Insulin resistance index was evaluated by homeostasis model assessment, and the presence of metabolic syndrome was determined. Because of multiple tests, the level of statistical significance was set at .01.ResultsAfter parathyroidectomy, there was a decrease in diastolic blood pressure (P < .02) and in serum concentrations of uric acid (P < .04) and insulin (P < .009). No difference was observed in rates of metabolic syndrome in patients before and 1 year after parathyroidectomy (23.5% versus 17.6%; P > .46). Insulin resistance index values were also unchanged from before to after parathyroidectomy (1.3 ± 0.9 and 1.1 ± 0.9, respectively; P > .68). A substantial increase in spine bone density (5%; P < .05) was notedpostoperatively. Multivariate logistic regression analysis, after adjustment for age and body mass index, revealed that parathyroidectomy did not lead to a significant decrease in likelihood of cardiovascular risk—odds ratio (OR), 1.82; 95% confidence interval (CI), 0.53 to 6.21 (P > .34) for the metabolic syndrome and OR, 0.82; 95% CI, 0.17 to 3.88 (P > .8) for the insulin resistance index.ConclusionIn this study, surgical treatment had no beneficial effect on cardiovascular risk, as assessed by the metabolic syndrome and insulin resistance markers in patients with PHPT 1 year after parathyroidectomy.(Endocr Pract. 2011;17:584-590)     

Particular characteristics of the metabolic syndrome in patients with morbid obesity

BackgroundCriteria for the diagnosis of the metabolic syndrome are currently being reconsidered, as their usefulness is not the same for all phenotypes in relation to the risk of cardiovascular disease.AimWe analyzed the changes in metabolic parameters after a fat overload in different groups of patients.Materials and methodsThe study included 20 healthy persons, 30 metabolic syndrome patients without morbid obesity, 80 metabolic syndrome patients with morbid obesity and 16 patients with morbid obesity without the metabolic syndrome. All the participants received a fat overload of 60 g. Measurements were made before the overload and 3 h afterwards of triglycerides, free fatty acids, insulin and uric acid.ResultsMetabolic syndrome patients with morbid obesity had a lower waist-to-hip ratio, and lower plasma free fatty acid and triglycerides levels at baseline and after the overload than patients without morbid obesity. Plasma uric acid levels rose after the fat overload in the metabolic syndrome patients who had morbid obesity but not in the patients without morbid obesity. A positive relation was found between plasma triglycerides and free fatty acid levels in all the patients but not in the controls after the fat overload. A positive relation was also found between uric acid and insulin levels in the metabolic syndrome patients with morbid obesity.ConclusionsMetabolic syndrome patients with and without morbid obesity presented different metabolic characteristics. This suggests that there are 2 different clinical phenotypes, both grouped under the metabolic syndrome umbrella.     

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity

Background and aimPrevious evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity.MethodsPlasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n = 78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group.ResultsIn the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r = 0.390, P < 0.05) and with fatty acid binding protein-4 (FABP4) (r = 0.474, P < 0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r = ?467, P < 0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r = 0.413, P < 0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r = ?0.429, P < 0.05).ConclusionsThese results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.     

Exenatide Use in the Management of Metabolic Syndrome: A Retrospective Database Study

ObjectiveTo evaluate the effect of exenatide therapy on cardiometabolic risk factors and anthropometric parameters in patients with metabolic syndrome.MethodsFrom June 2005 to June 2007, we performed a retrospective analysis of data extracted from the records of adult patients with metabolic syndrome being treated with exenatide. Diagnosis of any type of diabetes mellitus was exclusionary. Patients were initiated on exenatide therapy, 5 mcg, 1 hour before their morning and evening meals for the first month and were instructed to titrate up to 10 mcg. Cardiometabolic risk factors (total cholesterol, high-denssity lipoprotein cholesterol, triglycerides, calculated low- density lipoprotein cholesterol, and blood pressure) and anthropometric parameters (absolute body weight, body mass index, and abdominal girth) were measured at baseline and at 16 ± 4 weeks after initiating exenatide therapy. Data collected also included age, sex, metabolic syndrome diagnosis, and other concomitant medication used in the management of endocrine disorders.ResultsThe study population consisted of 299 patients (259 women, 40 men) with an age range of 18 to 74 years. Exenatide treatment was associated with significant reductions in mean body weight (P < .001) and body mass index (P < .001). Weight loss in 76.6% of patients was concomitant with a significant reduction in mean abdominal girth (P < .001). Further analysis revealed significant decreases in mean triglycerides (P < .001), total cholesterol (P < .01), and both systolic (P < .01) and diastolic blood pressure (P < .03). Approximately 60.2% of patients used metformin concomitantly, and half either decreased or discontinued metformin therapy.ConclusionsThis is the first report examining the effect of exenatide on patients with metabolic syndrome. We observed a significant improvement in cardiometabolic risk factors and anthropometric parameters as a result of exenatide over the treatment interval. (Endocr Pract. 2008;14:993-999)     

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation

BackgroundA high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified.MethodsWe used male Wistar rats, which were orally administered fructose (5 g/kg). Those rats were used in each experiment at 12 h after administration.ResultsSingle administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose.ConclusionsSingle administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia.     

Correlation of IL-12, IL-22, and IL-23 in patients with psoriasis and metabolic syndrome. Preliminary report

BackgroundPsoriasis is an autoimmune skin disease characterised by proliferation of keratinocytes, primarily due to cytokines Th1 and Th17. This profile is involved in pathogenesis of metabolic syndrome, a frequently found comorbidity in patients with psoriasis.ObjectiveIn this study we determine the correlation of levels of pro-inflammatory cytokines TNF-α, IL-23, IL-12, and IL-22 in patients with psoriasis with and without metabolic syndrome and clinically healthy controls.MethodsWe included 55 patients with plaque psoriasis: 30 with metabolic syndrome (PPMS), 25 without metabolic syndrome (PP), 15 healthy subjects (HS) and 15 with metabolic syndrome (MS). Quantification of serum levels of IL-12, TNF-α, IL-22, and IL-23 was done by ELISA.ResultsWe observed that serum levels of IL-12 were more elevated in PP group, while the lowest levels of TNF-α were seen in HS group. IL-22 was found to be higher in PP than in PPMS (p < 0.05). PP patients with PASI scores rating as severe showed higher levels of IL-12. TNF-α level analysis showed significant differences in HS group compared with the others; levels of this cytokine were lower in patients with PP and moderate PASI scores than in MS group (p < 0.05). We found no correlation between cytokine levels and psoriasis or between cytokines and PASI scores. In PP group, a positive correlation was observed between IL-23 and fasting glucose (r = 0.432, p < 0.05), as well as a negative correlation between IL-23, IL-22, and IL-12 versus waist circumference (r = −0.504, r = −0.556 and r = −0.511, respectively; p < 0.05).ConclusionsPsoriasis is not just a skin disorder, but rather a condition with systemic implications, with intervention of pro-inflammatory cytokines that contribute to metabolic syndrome and other comorbidities, which in turn increases the risk of developing cardiovascular disease.     

Gender-dependent impacts of body mass index and moderate alcohol consumption on serum uric acid—an index of oxidant stress status?

Uric acid seems to be causally involved in a variety of medical disorders involving oxidative stress. Although alcohol abuse and obesity are known to increase serum uric acid, the interactions between moderate drinking, adiposity, and uric acid metabolism have remained poorly understood. We examined serum uric acid concentrations from 2062 apparently healthy volunteers (970 men, 1092 women) reporting either no alcohol (abstainers) or < 40 g of ethanol consumption per day (moderate drinkers). The study population was further classified according to BMI as follows: < 19 (underweight), 19–25 (normal weight), 25–30 (overweight), and > 30 (obese). Serum uric acid concentrations in male moderate drinkers were significantly higher, and in females they were lower, than in the corresponding groups of abstainers. In the BMI-based subgroups, the highest concentrations were found in those who were overweight or obese. Significant two-factor interactions occurred between gender and drinking status (p < 0.001) and between gender and BMI (p < 0.02). Serum uric acid also correlated with indices of hepatocellular health (GGT, ALT, AST). The data indicate distinct gender-dependent impacts of alcohol consumption and BMI on serum uric acid. These findings should be applicable to the assessment of oxidative stress status and associated morbidity in alcohol consumers and individuals with excess body weight.     

Evaluation of Para- and Perirenal Fat Thickness and its Association with Metabolic Disorders in Polycystic Ovary Syndrome

Objective: The aim of this study was to compare para- and perirenal fat (PFT) and subcutaneous abdominal fat (SFT) measurements between patients with polycystic ovary syndrome (PCOS) and control subjects and to assess the possible relation with metabolic disorders.Methods: This study included 68 patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls. We evaluated anthropometric, hormonal, and metabolic parameters, and abdominal ultrasonography was performed to measure PFT and SFT.Results: The mean PFT values were 6.1 ± 2.9 mm in patients with PCOS and 4.3 ± 2.3 mm in healthy controls (P = .002). SFT values were also higher in the patient group (9.6 ± 5 mm) compared to healthy subjects (3.5 ± 0.5 mm) (P = .017). A significant positive correlation was found between PFT and BMI (r = 0.368), waist circumference (WC) (r = 0.441), Ferriman-Gallwey (FG) score (r = 0.313), blood pressure (systolic, SBP, r = 0.213; diastolic, DBP, r = 0.215), plasma glucose (r = 0.195), homeostasis model assessment-insulin resistance (HOMA-IR, r = 0.273), SFT (r = 0.555). Conversely, negative correlations were found between PFT and estradiol (r = -0.218) and sex hormone-binding globulin (SHBG, r = -0.304). Nonobese PCOS patients (6.1 ± 3.07 mm) had higher PFT values than nonobese controls (3.47 ± 1.5 mm); however, SFT measurements did not differ (P = .086). In multiple linear regression analysis, SFT (P = .006) was a significant and independent predictor for PFT, along with WC (P = .023). In a stepwise model, SFT was the predictor of PFT (P = .001).Conclusion: PFT values were higher particularly in nonobese PCOS patients compared to nonobese control subjects. There was a significant interaction between PCOS and obesity on PFT.Abbreviations: BMI = body mass index; CT = computed tomography; DBP = diastolic blood pressure; FPG = fasting plasma glucose;; HDL-cholesterol = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment-insulin resistance; hsCRP = high-sensitivity C-reactive protein; LDL-cholesterol = low-density lipoprotein cholesterol; LH = luteinizing hormone; NCAH = nonclassic congenital adrenal hyperplasia; 17-OHP = 17-hydroxyprogesterone; PCOS = polycystic ovary syndrome; PFT = para- and perirenal fat; SAT = subcutaneous abdominal adipose tissue; SBP = systolic blood pressure; SFT = abdominal subcutaneous fat thickness; TG = triglyceride; US = ultrasound; VAT = visceral abdominal adipose tissue; WC = waist circumference     

Relationship Between the Environmental Endocrine Disruptor Bisphenol a and Dyslipidemia: A Five-Year Prospective Study

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia.Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively.Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (β= 0.13, P = .002) and negatively associated with HDL cholesterol (β= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29).Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia.Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A     

High levels of plasma selenium are associated with metabolic syndrome and elevated fasting plasma glucose in a Chinese population: A case-control study

BackgroundSelenium is important for human health and involved in various metabolic processes. Deficiency of selenium associates with increased risk for cancer and cardiovascular diseases. There has been an increase use of selenium supplements for the treatment of autoimmune thyroid conditions. However, the potential biological effects of selenium overload arouse the public concern. The aim of this study was to investigate the associations of plasma selenium concentrations of adults with metabolic syndrome (MS) in Chinese population.MethodsA matched case-control study including 204 metabolic syndrome patients and 204 healthy controls was conducted in 2012. The MS cases were defined according to the criteria of Chinese Diabetes Society (CDS). Healthy controls without abnormality of metabolic components were matched with cases in age, gender and region. Plasma concentrations of selenium were determined by graphite furnace atomic absorption spectrometry (GFAAS). Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were detected by automatic biochemical analyzer.ResultsThe median levels of plasma selenium in MS group were 146.3 (107.3–199.4) μg/L, which were significantly higher than that in the control group (127.4: 95.7–176.0) μg/L; Plasma levels of selenium were related to the risk of MS in dose-response manner. Risk of MS was significantly higher in subjects with plasma selenium in the highest tertile (T3: ≥176.0 μg/L) compared to those in the lowest tertile (T1: <95.7 μg/L) [odds ratio (OR) = 2.416 (95% CI: 1.289–4.526)]. The plasma levels of selenium were positively correlated with fasting plasma glucose (FPG) (r_s = 0.268, P < 0.001). Plasma selenium at the median (T2: 95.7–176.0 μg/L) or upper tertile (T3: ≥176.0 μg/L) was associated with increased risk of elevated FPG (defined by FPG ≥ 6.1 mmol/L) as compared with the lowest tertile (T1: ≤95.7 μg/L) [T2 vs. T1, OR = 3.487 (1.738–6.996); T3 vs. T1, OR = 6.245 (3.005–12.981)].ConclusionsHigher levels of plasma selenium might increase the risk of metabolic syndrome and elevated fasting plasma glucose. Selenium supplements should be used with prudence for CVD and cancer prevention.     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Marcadores bioquímicos,nutricionales y actividad antioxidante en el síndrome metabólico

Background and objectives1) Nutritional assessment of the diet followed by patients with metabolic syndrome, and 2) biochemical analysis of the oxidation-reduction level in patients with metabolic syndrome.Material and methodsA cross-sectional study was conducted in patients with metabolic syndrome in Murcia. Fifty-three patients, 33 with and 20 without (control group) metabolic syndrome, were selected. The intervention consisted of completion of a recall survey and a test to nutritionally assess dietary intake. Anthropometric and laboratory variables, including those related to antioxidant activity, were also tested.ResultsAntioxidant activity was within normal limits in both groups (1.7 ± 0.2 mmol/L in the control group and 1.8 ± 0.1 mmol/L in the metabolic syndrome group) (NS). Superoxide dismutase levels were not significantly different between the groups. Mean glutathione reductase levels (U/L) were higher in the control group as compared to patients with metabolic syndrome (P < .05). As regards oxidative stress biomarkers, mean isoprostane levels were higher in the control group (4.9 ± 6.2 ng/mL) than in metabolic syndrome patients (3.5 ± 3.9 ng/mL) (P < .05). Oxidized LDL values tended to be higher in metabolic syndrome patients (96 ± 23.2 U/L) as compared to the control group (86.2 ± 17.3  U/L), but differences were not significant.ConclusionsThere is a trend to a poorer nutritional and biochemical profile in patients with metabolic syndrome, who also tend to have a greater degree of oxidative stress.     

Hyperuricemia influences tryptophan metabolism via inhibition of multidrug resistance protein 4 (MRP4) and breast cancer resistance protein (BCRP)

Hyperuricemia is related to a variety of pathologies, including chronic kidney disease (CKD). However, the pathophysiological mechanisms underlying disease development are not yet fully elucidated. Here, we studied the effect of hyperuricemia on tryptophan metabolism and the potential role herein of two important uric acid efflux transporters, multidrug resistance protein 4 (MRP4) and breast cancer resistance protein (BCRP). Hyperuricemia was induced in mice by treatment with the uricase inhibitor oxonic acid, confirmed by the presence of urate crystals in the urine of treated animals. A transport assay, using membrane vesicles of cells overexpressing the transporters, revealed that uric acid inhibited substrate-specific transport by BCRP at clinically relevant concentrations (calculated IC₅₀ value: 365 ± 13 μM), as was previously reported for MRP4. Moreover, we identified kynurenic acid as a novel substrate for MRP4 and BCRP. This finding was corroborated by increased plasma levels of kynurenic acid observed in Mrp4^?/? (107 ± 19 nM; P = 0.145) and Bcrp^?/? mice (133 ± 10 nM; P = 0.0007) compared to wild type animals (71 ± 11 nM). Hyperuricemia was associated with > 1.5 fold increase in plasma kynurenine levels in all strains. Moreover, hyperuricemia led to elevated plasma kynurenic acid levels (128 ± 13 nM, P = 0.005) in wild type mice but did not further increase kynurenic acid levels in knockout mice. Based on our results, we postulate that elevated uric acid levels hamper MRP4 and BCRP functioning, thereby promoting the retention of other potentially toxic substrates, including kynurenic acid, which could contribute to the development of CKD.     

The Association of Thyroid Hormones and Tsh with the Metabolic Syndrome in Euthyroid Taiwanese Individuals

Objective: There are conflicting studies in euthyroid males and females regarding associations between thyroidrelated hormones and parameters of the metabolic syndrome (MetS). We investigated the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations and MetS in euthyroid men and women.Methods: Taiwanese subjects aged 20 to 65 years who had undergone a voluntary health examination at a preventive examination agency in Taipei were enrolled in this cross-sectional study. The definition of MetS was suggested by the Bureau of Health Promotion, Department of Health, Taiwan. Euthyroidism was defined as TSH and free thyroxine (FT4) levels within the normal reference ranges while not taking any thyroid medication. We conducted multiple logistic regression to identify the ability of serum triiodothyronine (T3), FT4, and TSH concentrations to identify the relative risk for the presence of MetS and components of the MetS in euthyroid Taiwanese individuals.Results: A total of 8,207 Taiwanese subjects (mean age: men, 45.3 ± 9.9 years; women, 43.5 ± 9.3 years) were enrolled in this study. A total of 1,672 subjects (20.4%) were defined as having MetS; these subjects had significantly higher (P<.0001) mean age (48.4 ± 9.1 years vs. 43.6 ± 10.7 years), prevalence of men (78.7% vs. 53.4%), and smoking (16.8% vs. 11.6%) than those without MetS. The median TSH, FT4, and T3 levels in all subjects were 1.70 mIU/L, 1.41 ng/dL, and 1.20 ng/mL, respectively. Higher T3 and lower FT4 values rather than TSH increased the odds ratio for MetS in men and women after adjusting for smoking and age, particularly for the association of T3 and MetS in women (uppermost quartile versus lowermost quartile: odds ratio, 2.4; 95% confidence interval, 1.6 to 3.5; P for trend <.0001).Conclusion: In euthyroid Taiwanese men and women, relatively high serum T3 concentrations was most strongly associated with the presence of the MetS; relatively low serum T4 was less strongly related, and serum TSH levels were not associated with the MetS. It is not known if the relationship of serum T3 and T4 to the MetS is causal.Abbreviations:BMI = body mass indexFT4 = free thyroxineMetS = metabolic syndromeOR = odds ratioT3 = triiodothyronineTSH = thyroid-stimulating hormoneWC = waist circumference     

Zinc and glycemic control: A meta-analysis of randomised placebo controlled supplementation trials in humans

BackgroundImpaired zinc metabolism is prominent in chronic disorders including cardiovascular disease and diabetes. Zinc has the potential to affect glucose homeostasis in animals and humans and hence impact the risk of type 2 diabetes mellitus.MethodsA systematic review and meta-analysis of randomised placebo controlled trials was conducted to determine the effect of zinc supplementation on fasting blood glucose, HbA1c, serum insulin and serum zinc concentrations. Relevant studies for inclusion were identified from a literature search of electronic databases up to July 2011.ResultsFourteen reports (n = 3978 subjects) were included in the meta-analysis. In the overall analysis, a small but statistically significant reduction in fasting glucose concentrations was observed (?0.19 ± 0.08 mmol/L, P = 0.013) after zinc supplementation. HbA1c tended to decrease in zinc-supplemented individuals (?0.64 ± 0.36%, P = 0.072). No significant effect was observed for serum insulin concentrations. Plasma zinc concentrations increased significantly following supplementation (+4.03 ± 0.81 μmol/L, P = 0.001). In secondary analyses of participants with chronic metabolic disease (types 1 and 2 diabetes mellitus, metabolic syndrome and obesity), zinc supplementation produced a greater reduction in glucose concentrations (?0.49 ± 0.11 mmol/L, P = 0.001) compared to the effect that was observed in healthy participants.ConclusionThe significant albeit modest reduction in glucose concentrations and tendency for a decrease in HbA1c following zinc supplementation suggest that zinc may contribute to the management of hyperglycemia in individuals with chronic metabolic disease.     

The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

BackgroundAdipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine.Material and methodsPref-1 was quantified in patients with PE (n = 51) and healthy pregnant controls (n = 51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2).ResultsIn study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 μg/l) as compared to healthy pregnant controls (0.7 μg/l) (p < 0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue.ConclusionMaternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.     

Serum and urinary selenium levels in obese children: A cross-sectional study

ObjectiveTo determine serum and urinary selenium (Se) levels in children with and without obesity, and to assess if Se influences the risk of obesity.Subjects and methodsHigh-resolution-continuum source-atomic absorption spectrometry (HR-CS-AAS) was used to determine the content of Se in 80 children (age 6–17; 40 boys, 40 girls). Correlations between variables were tested with the use of Spearman's correlation coefficient. U Mann–Whitney test was applied to assess the difference of Se contents in samples. Measured metabolic risk factors (blood pressure, glucose level, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol), age, gender, and BMI were correlated. Logistic regression models were fitted to identify predictors of obesity interacting with selenium content in serum and urine, separately.ResultsObese children, regardless of gender, had lower Se content. Se level in serum (p = 0.001, OR 0.74, 95%CI 0.62–0.88) and total cholesterol (p = 0.001, OR 1.19, 95%CI 1.08–1.31) were the independent factors significantly influencing the risk of obesity in children. Two separate models were observed for Se in urine: (i) Se level (p < 0. 0001, OR 0.70, 95%CI 0.58–0.84) and glucose level (p < 0.0001, OR 1.22, 95%CI 1.10–1.35), and (ii) Se level (p = 0.002, OR 0.60 95%CI 0.43–0.83) and total cholesterol level (p = 0.003, OR 1.16, 95%CI 1.05–1.28).ConclusionThe current study suggests a possible role of Se in obesity. Further research needs to be performed to check if obese children are an at-risk group for Se deficiency.     

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds

ObjectivesWomen with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity.MethodsPCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA_1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]).ResultsIn 2006, ≤ 25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile < 20%; ALT/AST ≤ 25%. By 2011, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P < .0001; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P < .0001). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P < .05).ConclusionDespite the publication of recommendations in 2005, screening rates for metabolic disease in women with PCOS remained low across all race-ethnicities in 2011. (Endocr Pract. 2014;20:855-863)     

Vitamin D-Binding Protein in Healthy Pre- and Postmenopausal Women: Relationship with Estradiol Concentrations

Objective: To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women.Methods: In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels.Results: Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in prethan postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05).Conclusion: Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.Abbreviations: 25OHD = 25-hydroxyvitamin D BMI = body mass index CV = coefficient of variation DBP = vitamin D–binding protein PTH = parathyroid hormone SHBG = sex hormone–binding globulin