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Serum Uric Acid Level Is Positively Associated With Higher Bone Mineral Density at Multiple Skeletal Sites Among Healthy Qataris.
Ibrahim, WN, Younes, N, Shi, Z, Abu-Madi, MA
Frontiers in endocrinology. 2021;:653685
Abstract
BACKGROUND Oxidative stress has been implicated as a fundamental mechanism in the decline of bone mass. Although serum uric acid (SUA) has potent antioxidant properties, the findings of many epidemiological and experimental studies couldn't draw a clear conclusion on the relation between SUA and bone health. We aim to investigate the association between SUA and bone mineral density (BMD) at different skeletal sites among healthy Qataris. METHODOLOGY A cross-sectional analysis including total-body and site-specific bone mineral density scores and other serological markers of 2981 healthy Qatari adults (36.4 ± 11.1 years) from the Qatar biobank database was conducted. The study participants were divided into quartiles based on the level of SUA, and the BMD was measured using dual-energy X-ray absorptiometry (DXA). Multiple regression analyses were applied to investigate the association between SUA and BMD adjusting for multiple confounding factors. RESULTS High levels of SUA were significantly associated with the increased bone mineral density of the total body and at site-specific skeletal locations after adjusting for age and gender (p-value < 0.001). Further adjustment for body mass index (BMI), smoking, vitamin D, alkaline phosphatase, and estimated glomerular filtration rate (eGFR) levels attenuated the association but the association remained significant for individuals with high SUA levels (p-value ≤ 0.01).The association between SUA and BMD was not significant in non-obese, females, young adults, and smokers. However, no interaction was found between SUA and age, gender, BMI and smoking. CONCLUSION Higher SUA levels are associated with a high bone density among healthy Qatari adults. However, such observation demands further investigations to outline the underlying mechanisms.
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A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout.
Juraschek, SP, Miller, ER, Wu, B, White, K, Charleston, J, Gelber, AC, Rai, SK, Carson, KA, Appel, LJ, Choi, HK
Nutrients. 2021;(2)
Abstract
The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: -0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by -0.48 mg/dL (95% CI: -0.98, 0.01) compared to DDG by -0.05 mg/dL (95% CI: -0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: -34.0, -8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.
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Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients.
Hu, Y, Chan, Z, Li, C, Shi, Y, She, X, Gu, C, Wang, Y, Zhou, C, Zhao, S, Zheng, Z, et al
Investigative ophthalmology & visual science. 2021;(4):23
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Abstract
PURPOSE To investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes. METHODS This cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed. RESULTS A total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04-1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07-2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07-2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37-3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed. CONCLUSIONS Higher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.
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Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance.
Debray, FG, Seyssel, K, Fadeur, M, Tappy, L, Paquot, N, Tran, C
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4246-4254
Abstract
BACKGROUND & AIMS Hyperuricemia is an independent risk factor for the metabolic syndrome and cardiovascular disease. We hypothesized that asymptomatic carriers for hereditary fructose intolerance (OMIM 22960) would have increased uric acid and altered component of the metabolic syndrome when exposed to fructose overfeeding. METHODS Six heterozygotes for HFI (hHFI) and 6 controls (Ctrl) were studied in a randomized, controlled, crossover trial. Participants ingested two identical test meals containing 0.7 g kg-1 glucose and 0.7 g kg-1 fructose according to a cross-over design, once after a 7-day on a low fructose diet (LoFruD, <10 g/d) and on another occasion after 7 days on a high fructose diet (HiFruD, 1.4 g kg-1 day-1 fructose + 0.1 g kg-1 day-1 glucose). Uric acid, glucose, and insulin concentrations were monitored in fasting conditions and over 2 h postprandial, and insulin resistance indexes were calculated. RESULTS HiFruD increased fasting uric acid (p < 0.05) and reduced fasting insulin sensitivity estimated by the homeostasis model assessment (HOMA) for insulin resistance (p < 0.05), in both groups. Postprandial glucose concentrations were not different between hHFI and Ctrl. However HiFruD increased postprandial plasma uric acid, insulin and hepatic insulin resistance index (HIRI) in hHFI only (all p < 0.05). CONCLUSIONS Seven days of HiFruD increased fasting uric acid and slightly reduced fasting HOMA index in both groups. In contrast, HiFruD increased postprandial uric acid, insulin concentration and HIRI in hHFI only, suggesting that heterozygosity for pathogenic Aldolase B variants may confer an increased susceptibility to the effects of dietary fructose on uric acid and hepatic insulin sensitivity. This trial was registered at the U.S. Clinical Trials Registry as NCT03545581.
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Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial.
, , Schwarzschild, MA, Ascherio, A, Casaceli, C, Curhan, GC, Fitzgerald, R, Kamp, C, Lungu, C, Macklin, EA, Marek, K, et al
JAMA. 2021;(10):926-939
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Abstract
IMPORTANCE Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. OBJECTIVE To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression. DESIGN, PARTICIPANTS, AND SETTING Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (<5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites, and were followed up through June 2019. INTERVENTIONS Inosine, dosed by blinded titration to increase serum urate concentrations to 7.1-8.0 mg/dL (n = 149) or matching placebo (n = 149) for up to 2 years. MAIN OUTCOMES AND MEASURES The primary outcome was rate of change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS; parts I-III) total score (range, 0-236; higher scores indicate greater disability; minimum clinically important difference of 6.3 points) prior to dopaminergic drug therapy initiation. Secondary outcomes included serum urate to measure target engagement, adverse events to measure safety, and 29 efficacy measures of disability, quality of life, cognition, mood, autonomic function, and striatal dopamine transporter binding as a biomarker of neuronal integrity. RESULTS Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P = .18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P<.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years). CONCLUSIONS AND RELEVANCE Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02642393.
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Association between baseline serum uric acid and development of LDL-C level in patients with first acute myocardial infarction.
Chen, Y, Ding, C, Hu, L, Ruan, Y, Zou, K, Dai, C, Liao, Y, Liao, H, Xia, Y, Zhao, Y, et al
BMC cardiovascular disorders. 2021;(1):572
Abstract
BACKGROUND Data on the relationship of baseline serum uric acid (SUA) with development of low-density lipoprotein cholesterol (LDL-C) level in patients with first acute myocardial infarction (AMI) are limited. The present study is to evaluate whether elevated SUA predicts the development of LDL-C in the first AMI. METHODS This is a retrospective 6-month cohort study of 475 hospitalized Chinese patients who underwent first AMI between January 2015 and December 2019 and were reevaluated half a year later at the Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The associations of baseline SUA with the percentage decrease of LDL-C (%) and LDL-C control were analyzed by using logistic regression analyses, multivariate linear regression analyses and the restricted cubic spline. RESULTS Over the 6-month follow-up, baseline SUA was independently and positively associated with the percentage decrease of LDL-C (%) and LDL-C control in a dose response fashion. After multivariable adjustment, per SD increment of baseline SUA (120.58 μmol/L) was associated with 3.96% higher percentage decrease of LDL-C(%). The adjusted OR (95% CI) for LDL-C control was 5.62 (2.05, 15.36) when comparing the highest tertile (SUA ≥ 437.0 μmol/L) to the lowest tertile (< 341.7 μmol/L) of baseline SUA. CONCLUSIONS Among Chinese patients with first AMI, higher baseline SUA was associated with higher LDL-C deduction percentage (%), and higher rate of LDL-C control in the short-term follow-up, respectively. SUA acquired when AMI occurred was prone to be profitable in predicting the risk stratification of uncontrolled LDL-C and dyslipidemia management.
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Effect of Curcumin on Serum Urate in Asymptomatic Hyperuricemia: A Randomized Placebo-Controlled Trial.
Bupparenoo, P, Pakchotanon, R, Narongroeknawin, P, Asavatanabodee, P, Chaiamnuay, S
Journal of dietary supplements. 2021;(3):248-260
Abstract
BACKGROUND/OBJECTIVE Hyperuricemia leads to gout and renal complications and may increase cardiovascular risk. Curcumin inhibits xanthine oxidase and increases uricosuric activity and, as a result, decreases serum urate (SU). This randomized controlled trial aimed to determine the effects of curcumin versus placebo on SU in subjects with asymptomatic hyperuricemia (SU level ≥ 6 mg/dL in women or ≥ 7 mg/dL in men). METHODS Thirty-nine subjects with persistent hyperuricemia were randomized to receive curcumin (500-mg capsules twice daily, 20 subjects) or placebo (19 subjects). Primary outcome was the difference between SU before and 8 weeks after randomization. Secondary outcomes were differences between urine uric acid (UUA) clearance, fasting plasma glucose (FPG), and lipid profiles before and 8 weeks after randomization and adverse events. RESULTS Out of 39 subjects, there were no differences at baseline SU, UUA clearance, FPG, lipid profiles, and demographics between curcumin and placebo groups. After 8 weeks, SU was significantly decreased in both groups (6.9% in curcumin group, p = 0.002, and 5.0% in placebo group, p = 0.009). However, there was no difference in SU reduction between the two groups (p = 0.532). There were no differences in UUA, FPG, lipid profiles, or adverse events in either group at 8 weeks after randomization. The most common adverse event was diarrhea with no treatment required. CONCLUSION Curcumin was not superior to placebo in reducing serum urate and in increasing UUA clearance.
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Serum uric acid and blood pressure among adolescents: data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2010-2011.
Lin, KH, Yen, FS, Chen, HS, Hwu, CM, Yang, CC
Blood pressure. 2021;(2):118-125
Abstract
PURPOSE Elevated serum uric acid (UA) is frequently observed in adults with high blood pressure (BP); however, data from adolescents are limited. We examined the association between serum UA and BP in a nationally representative sample of Taiwan adolescents. MATERIAL AND METHODS Some 1384 participants, aged 14-19 years, from the Nutrition and Health Survey in Taiwan 2010-2011 were included for the study. Elevated BP was defined as systolic or diastolic BP ≥120/80 mmHg. The analyses examined the relationship between serum UA and BP using linear regression and odds ratios of having an elevated BP using logistic regression. RESULTS In this study population, the mean age was 16.0 years, mean serum UA was 5.8 mg/dL, 22.5% were obese (body mass index ≥24 kg/m2) and 9.8% had an elevated BP. Compared to girls, boys are more likely to be obese and to have higher serum UA and BP. After full adjustments, systolic BP, diastolic BP and mean arterial pressure increased 0.45, 0.48 and 0.47 mmHg, respectively, for each 1-mg/dL increase in UA (p = 0.07, 0.03 and 0.02, respectively). The odds of having an elevated BP were 3.4 times higher in subjects of the upper tertile of serum UA than those of the lower tertile (p = 0.02). CONCLUSION Adolescents with factors as male, obesity, and UA ≥5.5 mg/dL were prone to have an elevated BP, regardless of age and family history of hypertension. The present study found that serum UA levels are significantly correlated to BP in Taiwanese adolescents.
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Clinical implications of synovial fluid specimen handling for crystal associated arthritides: A systematic review.
Meyer, MM, Marks, LA, Aslam, F
International journal of rheumatic diseases. 2021;(1):10-20
Abstract
AIM: To identify the appropriate methods of synovial fluid (SF) specimen storage, manipulation and handling for crystal associated arthritides (CAA) diagnosis. METHOD A systematic literature review was conducted using 5 medical databases to identify diagnostic studies assessing SF specimen handling for calcium pyrophosphate (CPP) and monosodium urate (MSU) crystals identification. All included studies were rated for quality using the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS Fifteen studies, including 2 non-English language manuscripts, were included. Eight studies examined both types of crystals, while 3 studies examined CPP and 4 studies examined MSU crystals only. Overall, MSU crystals were more stable over time compared to CPP crystals. MSU stability was generally independent of time, preservative and temperature. CPP crystals deteriorated with time and were more stable if refrigerated. Ethylenediaminetetraacetic acid (EDTA) was a suitable preservative. Re-examining an initially negative SF sample at 24 hours facilitated detection of additional cases. Very few studies had an overall low risk of bias and applicability. CONCLUSION Monosodium urate crystals remain stable over time independent of storage time, temperature and preservative. CPP crystals are mostly stable for 24-48 hours but can deteriorate with time. Overall, SF crystal examination should ideally be done within 24-48 hours. They may be stored at room temperature without any preservative. Otherwise, refrigeration (4°C/39°F) and EDTA preservation is reasonable. Stored SF re-examination, at 24 hours, helps identify a small number of additional MSU and CPP cases. Centrifugation techniques allow better and easier crystal identification, particularly CPP. Most studies were of unclear or low quality.
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus.
Tin, A, Schlosser, P, Matias-Garcia, PR, Thio, CHL, Joehanes, R, Liu, H, Yu, Z, Weihs, A, Hoppmann, A, Grundner-Culemann, F, et al
Nature communications. 2021;(1):7173
Abstract
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.