Uric Acid In Subjects Research Articles

Uric Acid and P-Wave Dispersion in Subjects with Heart Failure

Uric acid used as a marker of cardiovascular risk, which is associated with oxidative stress and inflammation. P-wave dispersion (PWD) is an electrocardiographic measure, which shows heterogeneity of atrial depolarization. It has demonstrated that there is an association of increased PWD with atrial fibrillation. This article's goal was to investigate the relationship between PWD and uric acid in subjects with heart failure (HF). Methods This descriptive, cross-sectional study included a total of 315 stable HF outpatients. The subjects were classified into two groups by their PWD: the normal PWD group consisted of subjects with a PWD lower than 40 ms (n = 201), and the increased PWD group consisted of subjects with a PWD higher than or equal to 40 ms (increased PWD) (n = 114). Results Significantly higher uric acid levels determined in the increased PWD group, in comparison with the normal PWD group (7.4 ± 1.6 mg/dL, vs. 6.5 ± 1.6 mg/dL p < 0.001). Univariate analyses revealed an association between uric acid, blood urea nitrogen, systolic pulmonary artery pressure, left atrial diameter, and increased PWD. In multivariate logistic regression analysis, there was an association of uric acid level (OR: 1.293; 95% CI: 1.106-1.511, p: 0.001), systolic pulmonary artery pressure (OR: 1.027; 95% CI: 1.011-1.044, p: 0.001), and left atrial diameter (OR: 1.754; 95% CI: 1.028-2.992, p: 0.039) with PWD. The receiver operating characteristics (ROC) curve analysis demonstrated that the optimal cut-off level of uric acid for predicting increased PWD was ≥ 7.1 mg/dL with a specificity of 77 percent and a sensitivity of 81 percent. Conclusion Our study results suggest that serum uric acid levels independently correlated with PWD in subjects with HF.

Urine Glucose Excretion Attenuates the Association Between Lipid Accumulation Product and Serum Uric Acid in Subjects with Prediabetes.

PurposeObesity is known to be strongly associated with hyperuricemia. Moreover, the impact of urine glucose excretion (UGE) on serum uric acid (UA) levels has gained much more attention in recent years. Yet concern is raised about whether UGE influences the relationship between obesity and hyperuricemia. The aim of this study was to assess the effect of UGE on the association between lipid accumulation product (LAP), a novel marker of visceral adipose accumulation, and UA in subjects with prediabetes.Materials and MethodsData were obtained from a cross-sectional study. A total of 3645 subjects with prediabetes were included in the present study. The separate and joint associations of LAP and UGE with hyperuricemia were examined using logistic regression analyses.ResultsLAP was positively associated with UA in both genders. Subgroup analysis based on UGE revealed that the association was strongest in subjects with low UGE (r = 0.328, p < 0.001), whereas the positive association was weakened, but still remained significant in subjects with moderate and high UGE. High LAP was significantly associated with an increased odds ratio for hyperuricemia after adjustment for potential confounders in the overall population (OR = 2.07, 95% CI: 1.66–2.58, p < 0.001). However, a downward trend in odds ratios for hyperuricemia was observed across UGE categories. In addition, the joint association analysis confirmed that the relationship between LAP and hyperuricemia was attenuated by UGE.ConclusionThe positive association between LAP and UA appears to be attenuated by UGE, indicating that promoting UGE may be an effective strategy for controlling UA levels, especially for people with obesity who are at increased risk for hyperuricemia.

Effects of Aster glehni Extract on Serum Uric Acid in Subjects with Mild Hyperuricemia: A Randomized, Placebo-Controlled Trial.

Aster glehni extracts (AGE) reduced serum uric acid levels in hyperuricemia rats in several previous studies. However, its efficacy in human has not been yet explored. This study aimed at investigating the efficacy and safety of AGE on the anti-hyperuricemia effect in subjects with slightly high serum uric acid. A randomized, double-blinded, placebo-controlled clinical trial was conducted for 12 weeks. Eligible subjects were randomly assigned to either AGE (480 mg/day) or placebo. The primary endpoint was the change in serum uric acid concentrations from baseline to follow-up time points. The secondary endpoints were the change of serum xanthine oxidase activity, and the levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) in the blood from baseline to follow-up time points. Safety was assessed by clinical laboratory parameters and adverse events reported by subjects. Six weeks of AGE supplementation significantly reduced serum uric acid level from baseline (P = .0468) but at the end of the intervention the participants did not show the beneficial effect of AGE supplementation. Also, the serum uric acid level in the AGE group was not significantly different at the follow-up time points, when compared with placebo. The mean changes of secondary endpoints from baseline to each time point did not show significant differences within and between the two groups. There were no adverse events reported by subjects or changes in safety parameters after intervention. In conclusion, AGE supplementation for 12 weeks did not show significant benefits for reducing serum uric acid concentrations in subjects with mild hyperuricemia.

Relationship between carotid-femoral pulse wave velocity and uric acid in subjects with hypertension and hyperuricemia.

Increasing of arterial stiffness is the pathophysiological characteristic of hypertension. Carotid-femoral pulse wave velocity (CF-PWV) is an index of arterial stiffness. Serum uric acid has been found to be involved the development of hypertension. We investigated the relationship between CF-PWV and serum uric acid in subjects with hypertension and hyperuricemia. 651 subjects (M/F 271/380) were divided into four groups, group 1: subjects without hypertension and hyperuricemia; group 2: hypertension subjects without hyperuricemia; group 3: hyperuricemia subjects without hypertension; group 4: subjects with hypertension and hyperuricemia. CF-PWV was measured by Complior apparatus. Results showed that levels of CF-PWV (10.75 ± 2.03 vs. 10.06 ± 1.98 m/s, p < 0.001) and serum uric acid (319.33 ± 80.12 vs. 298.78 ± 74.88 umol/L, p = 0.001) were significantly higher in hypertensive (groups 2 + 4) group than in normotensive (groups 1 + 3) group. CF-PWV was significantly higher in group 4 than group 1, group 2 and group 3 (ANOVA analysis: F = 13.348, p < 0.001; 11.78 ± 2.10 vs. 9.98 ± 1.98, 10.52 ± 1.93, 10.56 ± 1.99 m/s, all p < 0.05, respectively). There was positive correlation between CF-PWV and serum uric acid in entire study group (r = 0.187, p < 0.001), even after adjusting for gender, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (r = 0.100, p = 0.015). Multiple linear regressions showed that SBP, age, benzbromarone, statin and serum uric acid were independent associating factors of CFPWV in all subjects (β = 0.310, p < 0.001; β = 0.330, p < 0.001; β = 0.172, p = 0.002; β = -0.143, p = 0.006; β = 0.126, p = 0.027; respectively). In conclusions, CF-PWV was significantly higher in hypertension subjects with hyperuricemia compared to hypertension without hyperuricemia subjects, and serum uric acid was an independent associating factor of CF-PWV.

Cardiovascular Autonomic Neuropathy and Uric Acid in Subjects with Type 1 Diabetes—Preventing Early Renal Loss (PERL) in Type 1 Diabetes Trial

Elevated serum uric acid (SUA), an established risk factor for diabetic nephropathy (DN) may also be a risk factor for cardiovascular autonomic neuropathy (CAN). We evaluated the cross-sectional association between CAN and SUA levels in subjects with type 1 diabetes (T1D), mild to moderate chronic kidney disease (CKD) and a SUA ≥4.5 mg/dl enrolled in the ongoing PERL trial that is evaluating the effect of SUA lowering by allopurinol on kidney function decline, specifically iohexol plasma disappearance glomerular filtration rate (iGFR). Also measured are estimated GFR (eGFR) and albumin excretion rates (AER). Measures of baseline CAN included resting heart rate, standard deviation of normal RR interval (SDNN), and QTi (Bazzett formula) derived from resting ECG recordings (RR interval extracted from digital ECG images by ECGSCAN software). Four hundred ninety seven PERL participants had valid baseline CAN and renal function data (age 51 ± 11 years, 68% male, T1D duration 35 ± 12 years, HbA1c 8±1%). Subjects in the highest tertile of serum UA levels had worse measures of renal function (iGFR 60 ± 16 vs. 74 ± 60 ml/min/1.73 m2, eGFR 65.7 ± 18.1 vs. 82.7 ± 17.2 ml/min/1.73 m2, AER 370 ± 783 vs. 1181 ± 475 mcg/mg creatinine) compared to those in the lowest tertile. SDNN correlated negatively with SUA levels (r = -0.11, P = 0.0093). In a multiple linear regression model, lower SDNN was associated with higher SUA levels independent of age, gender, BMI, blood pressure, and HbA1c (β = -0.061, SE= 0.021, P = 0.0049), but this association was no longer significant when adjusted for iGFR (β = -0.0184, SE= 0.024, P = 0.46). In summary, elevated SUA was significantly associated with CAN in subjects with T1D independent of some traditional cardiovascular risk factors. This relationship operated, at least in part, through the inverse association of SUA levels with renal function. Disclosure M. Jaiswal: None. A. Doria: Research Support; Self; Sanofi-Aventis. M. Mauer: None. R. Pop-Busui: Research Support; Self; AstraZeneca.

Prevalence of diabetes mellitus and prediabetes: Changes during past 10 years in Shandong coastal area

Objective To determine the changes in the prevalence of type 2 diabetes mellitus and prediabetes in residents aged over 20 years in Shandong coastal areas during years 2004-2014. Methods A random stratified cluster sampling was conducted, and 3 944 inhabitants were investigated in Qingdao, Yantai, Weihai, and Rizhao regions. Results (1)The standardized rate of diabetes mellitus prevalence was 10.36% in 2014, increased by 2.38% as compared with 2004 and 0.85% as compared with 2009 (P<0.05). There were 341 newly diagnosed diabetes mellitus patients, accounting for 57.4% of the diabetes mellitus patients, increased by 6.09% as compared with 2004 and decreased by 4.11% as compared with 2009 (P<0.05). The standardized rate of prediabetes was 12.47% in 2014, increased by 2.63% as compared with 2004 and 0.61% as compared with 2009 (P<0.05). (2) The prevalence of diabetes mellitus and impaired glucose regulation in individuals aged under 50 years in 2014 was significantly higher than that in 2004, but lower than that in 2009 (P<0.05). (3) Compared with 2004 and 2009, the levels of diastolic blood pressure, total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol in subjects with prediabetes and diabetes mellitus increased significantly in 2014 (all P<0.05). The levels of serum uric acid in subjects with prediabetes and diabetes mellitus decreased significantly in 2014 (P<0.05). (4) The logistic regression analysis showed that the age, body mass index, waist-hip ratio, triglyceride, LDL-C, systolic blood pressure, and diabetic family history were the risk factors for abnormal glucose regulation, while total cholesterol was the protective factor. Conclusions The prevalence of diabetes mellitus and prediabetes increased during 10 years (2004-2014), but the growth rate dropped precipitously during last five years as compared with the first five years. The age of diabetes mellitus onset is getting older in residents of Shandong coastal area, especially in females. Aging, overweight, hypertension, lipid disorders, and diabetic family history were the risk factors of diabetes mellitus. (Chin J Endocrinol Metab, 2017, 33: 473-478) Key words: Diabetes mellitus; Prediabetes; Epidemiology; Shandong coastal area

Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common hepatic diseases in the general adult population. Dyslipidemia, hyperuricemia, and insulin resistance are common risk factors and accompanying features of NAFLD. Curcumin is a dietary natural product with beneficial metabolic effects relevant to the treatment of NAFLD. To assess the effects of curcumin on metabolic profile in subjects with NAFLD. Patients diagnosed with NAFLD (grades 1-3; according to liver sonography) were randomly assigned to curcumin (1000 mg/d in 2 divided doses) (n = 50) or control (n = 52) group for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, lipid profile, glucose, insulin, glycated hemoglobin, and uric acid concentrations were measured at baseline and after 8 weeks of follow-up. Eighty-seven subjects (n = 44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in serum levels of total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), non-high-density lipoprotein cholesterol (P < 0.001), and uric acid (P < 0.001), whereas serum levels of high-density lipoprotein cholesterol and glucose control parameters remained unaltered. Curcumin was safe and well tolerated during this study. Results of the present trial suggest that curcumin supplementation reduces serum lipids and uric acid concentrations in patients with NAFLD.

Alterations in Urinary Microalbumin and Serum Antioxidants in Sickle Cell Disease

ABSTRACT Changes in the level of various biochemical parameters play a significant role in the physiopathology of sickle cell disease (SCD). The aim of this study is to determine the level of urinary micoalbumin and plasma level of ascorbic acid and uric acid in subjects suffering from sickle cell anemia. A total of 30 subjects consisting of both males and females whose age range varied from 10 to 30 years were included in the study. The urinary albumin/creatinine ratio invariably increased in all studied subjects as compared with the control subjects. The level of ascorbic acid in the plasma significantly declined in SCD subjects when compared with that of control subjects (p &lt; 0.05). Also, the decrease in level of uric acid in plasma of SCD patients was significant as compared with the control subjects. Significant changes in these biochemical parameters thus could be used as reliable markers in nephropathy in sickle cell patients and thus in the management of the disease. How to cite this article Patra PK, Khodiar PK, Sahu D, Sahu GK. Alterations in Urinary Microalbumin and Serum Antioxidants in Sickle Cell Disease. Indian J Med Biochem 2016;20(1):1-5.

Change in prevalence of diabetes mellitus and prediabetes during 5 years in Shandong coastal area

Objective To determine the changes in prevalence of type 2 diabetes mellitus (DM) and prediabetes in residents aged over 20 years in Shandong coastal areas during 2004-2009 years.Methods A random stratified cluster sampling was conducted,and 5191 inhabitants were investigated in Qingdao,Yantai,Weihai,Rizhao,and Dongying.Results (1) According to the uniform population standardization,the standardized rate of DM prevalence was 9.51％ in 2009,increased by 1.53％ (P＜0.05) as compared with 2004.The standardized rates were 9.86％ in males and 9.26％ in females,increased by 2.11％ and 0.94 ％ (P＜0.05) respectively compared with 2004.In this epidemiological study,there were 374 newly diagnosed DM patients,accounting for 61.51％ of the DM patients,increased by 10.2％ (P＜0.05) as compared with 2004.(2) the standardized rate of prediabetes was 11.86％ in 2009,increased by 2.02％ (P＜0.05) compared with 2004.The standardized rate was 14.19％ in males and 9.79％ in females.(3) The prevalence of DM in individuals aged under 50 years in 2009 was significantly higher than that in 2004 (P＜0.05).The prevalence of prediabetes in individuals aged under 60 years was also significantly higher than that in 2004 (P ＜ 0.05).(4) Compared with 2004,the levels of diastolic blood pressure,serum triglyceride (TG),total cholesterol (TC),low density lipoprotein-cholesterol (LDL-C),and uric acid in subjects with prediabetes and DM increased obviously in 2009 (P＜0.05).TG level in DM patients was higher than that in prediabetic patients (P＜0.01),while the serum uric acid level was lower (P＜0.01).(5) Logistic regression analysis showed that age,body mass index,systolic blood pressure,TG,LDL-C were the risk factors for abnormal glucose regulation,while high density lipoprotein-cholesterol and daily intake of sea-food were the protective factors.Conclusion The prevalence of DM and prediabetes increased during 5 years (2004-2009),especially in males.Aging,overweight,hypertension,and lipid disorders were the risk factors of DM.The quantitative intake of sea-food was helpful for controlling blood glucose.Uric acid plays an important role in the onset of DM. Key words: Diabetes mellitus ; Prediabetes; Prevalence ; Shandong coastal area

A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function

Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers. Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at baseline and at 4 months. Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at baseline. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with baseline. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = -0.55) and after (beta = -0.40) treatment. Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia.

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase

PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 ± 2.1 mg/dl (mean ± SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 ± 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use.

Effects of intravenous infusion of urographic contrast agents on glomerular filtration rate, serum concentration and urinary excretion of uric acid in subjects with normal renal function.

The utilization of modern triiodinated radiocontrast agents for intravenous urography (IVU) is widely considered as a very safe procedure in patients free of currently well defined risk factors, amongst which the prominent ones are preexisting renal disease and diabetes mellitus complicated by deteriorated renal function (1,2,3). Whereas the incidence of nephrotoxicity accidents is extremely low in patients with no preexisting renal insufficiency, the risk of an acute, and sometimes definitive, deterioration of renal function following administration of radiocontrast agents has been evaluated as high as 90 % in insulin dependent diabetic patients with severe preexisting renal impairment (1).