Uric Acid: Friend or Foe?

Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A.

There are existing reports of an association of uric acid with glucose metabolism and their impact on adverse pregnancy outcomes. Hyperuricemia is linked to glucose homeostasis and basically to all components of the metabolic syndrome in the general population. Based on this premise, our study aimed at determining the level of serum uric acid and plasma glucose in second and third-trimester normal pregnancies with a view of establishing cut off values in Makurdi, Nigeria. The hospital-based case-control study involved a total of 103 participants aged 18-35 years attending the antenatal and the general health check up clinics. The participants comprised of 81 normal pregnant females in their second and third trimesters compared with 22 non pregnant controls. Their fasting plasma glucose and serum uric acid levels were compared among age-matched non-pregnant women (n=22), second (n=38), and third (n=43) trimester pregnancies. Serum uric acid level in second (5.89±0.85mg/dl) and third (6.23±1.30mg/dl) trimester pregnancies were significantly (p=0.000) higher than the non-pregnant controls (3.80±1.11mg/dl). A significant (p<0.01) increase in plasma glucose was observed in third-trimester pregnancies (5.19±0.64mmol/l) compared to second-trimester pregnancies (4.87±0.79mmol/l) and controls (4.65±0.51mmol/l). The study provided cut-off values for uric acid, glucose, and further points the need for prenatal care in terms of screening and diagnosis of pregnancy complications in all pregnant women including those considered at low risk.

BackgroundTo examine association between gestational weight gain (GWG) in women with gestational diabetes mellitus (GDM) and adverse pregnancy outcomes (APOs).MethodsThis retrospective cohort study enrolled women with GDM who delivered at 2010–2020 in Changzhou, Jiangsu. Total GWG, rates of GWG in second trimester and third trimesters were stratified into three categories according to IOM guidelines: within, below, and above IOM guidelines. Univariable and multivariable logistic regression analyses were used.ResultsOverall, 1606 women with GDM fulfilled inclusion criteria. Compared with within IOM guidelines and after adjusting for confounders, total GWG above IOM guidelines in pregnancy was associated with an increased odds of caesarean delivery [adjusted odds ratio (aOR) = 1.34, 95% confidence interval (CI): 1.04–1.72], hypertensive disorders of pregnancy (HDP) (aOR = 2.00, 1.28–3.12), preeclampsia (aOR = 2.06, 1.01–3.12), macrosomia (aOR = 1.55, 1.13–2.13) and large for gestational age (LGA) (aOR = 2.82, 1.94–3.23), and a decreased odds of premature rupture of membrane (PROM) (aOR = 0.46, 0.36–0.60) and preterm birth (aOR = 0.35, 0.26–0.44); total GWG below IOM guidelines in pregnancy was associated with an increased risk of preterm birth (aOR = 1.96, 1.44–2.66), small for gestational age (SGA) (aOR = 1.32, 1.11–1.50) and a decreased odds of macrosomia (aOR = 0.35, 0.23–0.53) and LGA (aOR = 0.54, 0.42–0.72). Further, in both second and third trimesters of pregnancy, rates of GWG above IOM guidelines was found to be associated with a high odds of HDP (aOR = 2.55, 1.86–3.38; aOR = 1.93, 1.08–2.98), preeclampsia (aOR = 2.28, 1.21–3.81; aOR = 2.17, 1.35–4.37), macrosomia (aOR = 1.20, 1.02–1.82; aOR = 2.02, 1.51–2.64) and LGA (aOR = 1.42, 1.24–1.97; aOR = 1.79, 1.51–2.54). Rates of GWG above IOM guidelines in third trimester of pregnancy also increased odds of caesarean delivery (aOR = 1.48, 1.16–2.34) when compared with within IOM guidelines. While rates of GWG below IOM guidelines in both second and third trimesters of pregnancy was associated with a decreased odds of macrosomia (aOR = 0.66, 95% CI: 0.52–0.78; aOR = 0.52, 0.39–0.63) and LGA(aOR = 0.71, 0.51–0.82; aOR = 0.67, 0.55–0.79). In addition, rate of GWG below IOM guidelines in third trimester of pregnancy was associated with an increased odds of preterm birth (aOR = 1.52, 1.12–2.05) and SGA (aOR = 1.21, 1.10–1.69).ConclusionGWG, outside IOM guidelines has increased risks of APOs among women with GDM, implying that careful surveillance for GWG during different stages of pregnancy is warranted.

Problem Prior results on the association between serum uric acid (UA) levels in the early trimester and the risk of small for gestational age (SGA) remain unclear. This study evaluated the association of maternal first-, second-, and third-trimester UA levels with the risk of SGA infants. Method of study A total of 23, 194 singleton mothers from the International Peace Maternity and Child Health Hospital between January 2014 and January 2017 were included. Maternal UA levels were measured at 12.1 ± 1.08th (UA1) and 32.2 ± 1.03th (UA2) gestational weeks. △UA was calculated as the difference between UA2 and UA1. Logistic regression and restricted cubic spline (RCS) were performed to evaluate the association between maternal UA and △UA during pregnancy and SGA. Receiver operating characteristic (ROC) analysis was employed to assess the serum uric acid prediction value. Results Women in the higher quartiles of UA1 had a significantly higher risk of SGA. A clear increased risk for SGA was observed with higher quartiles for UA2 (p for trend <0.05). An approximately “J-shaped” relationship was observed between UA2 and △UA, and the risk of SGA was observed. When compared with those with a lower level of UA in the first trimester, those with a higher level of UA1, the more increase in the later UA levels were associated with a higher risk of SGA [adjusted odds ratio (aOR) = 1.67, 95% CI:1.37–2.05]. The ROC curve areas were 0.525 for UA1, 0.582 for UA2 and 0.576 for △UA. Conclusions The findings suggested that non-preeclamptic and non-hypertensive women who experienced early pregnancy with high UA levels had an elevated risk of SGA. Moreover, a high maternal UA level in the earlier trimester may be an early predictor of SGA.

Introduction: There is an intricate association between serum Uric Acid (UA) levels and Primary Open Angle Glaucoma (POAG). UA levels in the blood are known to be a good indicator of antioxidant function, and a decrease in UA plays a key role in the pathogenesis of POAG. However, the association of serum UA and Uric Acid Creatinine Ratio (UACR) in POAG cases in the Indian population remains unexplored. Aim: To investigate the association of serum UA levels and serum UACR with POAG. Materials and Methods: This cross-sectional study was conducted among patients who attended the Outpatient Department (OPD) of Opthalmology at Maharajah’s Institute of Medical Sciences, Vizianagaram, Andhra Pradesh, India. The duration of the study was one year and six months, from January 15, 2021 to July 15, 2022. The study included 200 recently diagnosed patients with POAG, who were divided into three groups based on Intraocular Pressure (IOP): Group 1 (mild) with an IOP of 21-30 mmHg, group 2 (moderate) with an IOP of 31-50 mmHg, and group 3 (severe) with an IOP greater than 51 mmHg. Age and gender-matched 199 healthy subjects were included as the control group. Blood samples were collected from the study subjects after obtaining informed consent and were tested for serum UA (using the modified Trinder method) and serum creatinine (using Jaffe’s method) in a semiautomatic analyser (Erba chem 7). The data were analysed using Statistical Package for Social Sciences (SPSS) version 21.0 software and MS Excel 2007. Results: The mean age of the study participants of all three groups was found to be 51.19±5.06 years with 46.7% male and 53.3% female subjects. The serum UA levels were 5.55±0.74 mg/dL in the mild POAG group, 4.1±0.5 mg/dL in the moderate POAG group, and 2.67±0.6 mg/dL in the severe POAG group (p-value &lt;0.001). The present study also found that among the three study groups of POAG, UA levels were the lowest in the severe POAG group, followed by the moderate POAG group, and then the mild POAG group. This pattern was observed in both the males and females population. Conclusion: The present study found that serum UA levels were decreased in POAG patients compared to the normal healthy control group. Furthermore, the study revealed a significant negative association between serum UA levels and serum UACR levels with the severity of POAG.

Hypertension (HT) in obesity has been reported frequently in children in recent years. The role of copeptin and uric acid here are not well known. We aimed to investigate the relationship between HT and serum copeptin and uric acid levels in children with obesity. We included 80 children with obesity who were admitted to our hospital between April 2018 and September 2018. The patients were separated into two groups: hypertensive and non-hypertensive. Serum copeptin levels were measured using the enzyme-linked immunosorbent assay. Copeptin levels were significantly higher in patients with HT than in those without (p= 0.0001). In addition, serum uric acid levels in patients with HT were significantly higher, while the serum potassium levels were significantly lower (p= 0.01) than in those without HT (p= 0.001). In correlation analyses, a positive correlation was detected between blood sodium and copeptin levels (p= 0.037). Hypertensive children with obesity had higher serum copeptin and uric acid and lower blood potassium levels. Moreover, copeptin levels were positively correlated with blood sodium levels. Thus, in addition to copeptin, serum uric acid, potassium, and sodium levels may be important in the diagnosis and follow-up of children with HT.

Prognostic Value of Serum Uric Acid in Hospitalized Heart Failure Patients With Preserved Ejection Fraction (from the Japanese Nationwide Multicenter Registry)

High levels of serum uric acid (UA) are associated with cerebro-cardiovascular disease risk factors. This study aimed at evaluating the main determinants of serum UA levels in relation to biochemical, lifestyle, and clinical variables. The study population included 15,594 participants (48% men, age ≥ 35years) to the Moli-sani Study, for whom data on serum UA levels were available. Association of UA with dependent variables was investigated by multivariable linear regression analysis separately for men and women. Average serum UA levels were higher in men than in women (6.1 ± 1.3 vs 4.6 ± 1.2mg/dL, respectively). Cystatin C, creatinine, albumin, triglycerides, body mass index (BMI), and diuretic therapy were the major determinants of the heterogeneity of UA levels. In women, the final model, resulting from the stepwise analysis, explained 41.6% of the UA variability. In particular, cystatin C explained 22.5% of UA variance, followed by BMI (7.2%), albumin (4.0%), and creatinine (1.9%). The final model in men fitted the data less than in women (total R2 = 29.1%), and creatinine was found to be the main determinant of UA levels (10.1%), followed by triglycerides (7.6%), BMI (3.7%), and albumin (2.0%). In a general adult population, the major determinants of serum UA levels are cystatin C, creatinine, BMI, triglycerides, albumin, and the use of diuretics. Knowledge of its main determinants will be useful to better evaluate the relationship between UA levels and detrimental health outcomes and to clarify if an increase in uricemia is a marker or an independent risk factor. Key Points • Increased serum uric acid (UA) levels are reportedly associated with cardiovascular disease risk factors. • The major determinants of heterogeneity of UA levels are cystatin C, creatinine, BMI, triglycerides, albumin, and the use of diuretics, in a general adult population. • Studying the main determinants associated with high levels of serum uric acid would help better understanding if uric acid is a marker or an independent cardiovascular risk factor.

BACKGROUND Relationship between serum uric acid and cardiovascular system has been recognised since years. High-sensitivity C-reactive protein (hs-CRP) is a known risk factor for cardiovascular and cerebrovascular events. The role of uric acid as a risk factor for vascular disease and acute stroke is controversial and there is little information about it.1 It is unclear as to whether high uric acid concentrations promote or protect against the development of cerebrovascular disease, or simply acts as a passive marker of increased risk. As serum hs-CRP is an established risk factor for stroke, its positive correlation with serum uric acid levels would suggest that high serum uric acid could predict stroke risk. Also, it would prove to be a more cost-effective investigative tool in our present set up. METHODS In this cross-sectional study, we assessed 100 patients admitted with acute stroke in Victoria and Bowring and Lady Curzon Hospital from October 2016 to November 2018. Clinical records, routine investigations, radiological imaging, serum uric acid and hs-CRP of the patients were investigated. RESULTS Majority of the patients (33 %) belonged to the age group of &gt; 70 yrs., followed by 61 - 70 yrs. (26 %). 69 % of the patients were males and 31 % were females. 67 % of them were hypertensive and 32 % were diabetic. 91 % had an hs-CRP level of &gt; 3.0 mg / L and 8 % had hs-CRP levels between 1.0 and 3.0 mg / L. None of the female patients had a serum uric acid value &gt; 6.5 mg / dL and none of the male patients had a uric acid level of &gt; 7.0 mg / dL. There was a correlation between serum uric acid levels and serum hs-CRP levels in patients ≤ 50 yrs. of age. There was no correlation between serum hs-CRP levels and serum uric acid levels in patients more than 50 yrs. of age. CONCLUSIONS Our study showed that stroke is most common in persons &gt; 70 yrs. of age and is more common in males compared to females. Hypertension is an independent risk factor for stroke. hs-CRP is a well-established risk marker for stroke, being raised in majority of stroke patients. Serum uric acid is not raised in all patients of acute stroke. So, it cannot be used as a risk marker for stroke. KEY WORDS hs-CRP, Serum Uric Acid, Acute Stroke

Uric acid and estimate of renal function. Let's stick together

Background: Hypothyroidism is a progressive disorder that presents with diverse degrees of thyroid failure and metabolic consequences. Purine metabolism can be affected by disturbance in thyroid hormones, which leads to alteration in the uric acid levels, leading to hyperuricemia and subsequently causing gout. Also, hemodynamic changes occur in hypothyroidism that leads to reduction in renal plasma flow and glomerular filtration rate, which also causes increase in the levels of serum uric acid and serum creatinine. Aims and Objective: To determine whether thyroid dysfunction, subclinical and overt, has deleterious effects on renal function. Materials and Methods: This was a cross-sectional study that comprised 108 individuals (56 cases and 52 controls; 52 men and 56 women) aged between 20 and 60 years. Case group comprised suspected cases of hypothyroidism. Serum TSH, T4, T3, uric acid, and creatinine were estimated after applying inclusion and exclusion criteria. Result: Uric acid and creatinine levels were significantly elevated in case group as compared to control group (7.09 ± 0.45 and 1.52± 0.16 mg/dL versus 4.08 ± 0.25 and 0.62 ± 0.05 mg/dL, respectively; p < 0.001). There was insignificant correlation between serum uric acid and creatinine levels with hypothyroidism (r = 0.185, p = 0.172 and r = 0.082, p = 0.550). Also, there was no significant correlation between serum uric acid and creatinine levels with the age in hypothyroidism (r = 0.143; p = 0.292 and r = -20.154; p = 0.257, respectively). Conclusion: Hypothyroidism causes significant increase in serum uric acid and creatinine levels. Therefore, we would emphasize the importance of the routine evaluation of serum uric acid and creatinine levels in patients with hypothyroidism.

Introduction: The relationship between Vitamin D levels and asymptomatic hyperuricaemia is gaining attention due to its potential implications for public health. This study investigates this association, focussing on the interplay between Vitamin D, serum uric acid and parathyroid hormone (PTH) levels in adults. Materials and Methods: This cross-sectional observational study, conducted from April to June 2023, involved 100 adult participants (65 males, 35 females) from the general population. Participants were selected based on specific inclusion and exclusion criteria. Data collection included a comprehensive questionnaire, physical examinations and blood sample analysis. Vitamin D levels were measured using liquid chromatography-tandem mass spectrometry, uric acid levels through an enzymatic colorimetric test, and PTH levels via a chemiluminescent immunoassay. Statistical analysis was performed using SPSS version 25.0, IBM Corp, Chicago, IL, USA. Results: The study found an inverse correlation between Vitamin D and serum uric acid levels. Participants with lower Vitamin D levels had higher serum uric acid and PTH levels. The mean serum Vitamin D level was 32.17 ng/mL, and the mean serum uric acid level was 9.99 mg/dL. The study categorised Vitamin D levels as deficient, insufficient and sufficient, observing significant variations in PTH and uric acid levels across these categories. Conclusion: The study suggests a significant relationship between Vitamin D levels and serum uric acid concentrations in adults, with implications for the management of asymptomatic hyperuricaemia and related metabolic conditions. Despite limitations, such as the cross-sectional design and small sample size, this study highlights the potential significance of Vitamin D levels in the management of asymptomatic hyperuricaemia and related metabolic disorders.

Objective To evaluate the value of serum uric acid(UA) levels with reference to the age, waist circumference, and body mass index(BMI) in predicting the metabolic syndrome(MS) in obese children. Methods A total of 300 obese children, including 180 boys and 120 girls, were enrolled in this study.The height, BMI, waist and hip circumference, blood pressure, serum glucose, insulin and lipid profile in all participants were measured.Oral glucose tolerance test and insulin releasing test were performed.The boys or girls were divided into 4 groups according to the 4 quantile of UA level, respectively.The clinical characteristics and correlation of UA with the clinical indexes and MS components were compared.The binary Logistic regression analysis was applied in the risk of MS and its components for the 4 groups of obese children.The area under the receiver operating characteristic curve(ROC curve) of UA level, age, waist circumference and BMI were used to predict the MS. Results UA level was increased with the increase of age, waist circumference and BMI, and the UA level was significantly correlated with triacylglycerol, postprandial 2 h glucose(2 h PG)(r=0.196, 0.174 in boys; r=0.291, 0.179 in girls). In boys, the adjusted odds ratio and 95%CI of the highest quartile of UA for triglyceridemia was 2.71(95%CI: 0.77-9.58); which in girls, the adjusted odds ratio and 95%CI of the highest quartile of UA for hyperglycemia, hypertension were 8.45(95%CI: 1.76-40.52) and 3.93(95%CI: 0.66-23.33), respectively, with significant differences.In boys, the area under the ROC curve of UA level, age, waist circumference and BMI which predict the MS were 0.652 0.626, 0.621, 0.62, respectively, and the differences were significant(all P<0.05). Conclusions The UA level is significantly correlated with the composition of MS, UA detection combining with reference to the age, waist circumference, and BMI is helpful for the identification of high risk groups of metabolic syndrome. Key words: Uric acid; Metabolic syndrome; Obesity; Child

Background: The hyperuricaemia in gestational diabetes mellitus (GDM) has been explained to be a component of the metabolic syndrome which reflects insulin resistance. Gestational huperuricaemia was found to be significantly associated with a high rate of maternal and foetal complications along with proteinuria and hypertension. Aims of this study were to evaluate the serum uric acid levels in Bangladeshi women with GDM in their second and third trimesters of pregnancy.&#x0D; Methods: This descriptive cross-sectional study was conducted at Mymensingh Medical College Hospital from July 2013 to June 2014. Pregnant women, in their second and third trimester, attending the outpatient department of Obstetrics and Gynecology and the Department of Endocrinology were enrolled by purposive sampling technique. GDM was diagnosed on the basis of oral glucose tolerance test (OGTT) as defined in WHO criteria 2013.&#x0D; Results: Out of 172 participants, 86 had GDM (case) and 86 were normoglycemic (control). The mean age of GDM and control groups was 28.6±3.2 years and 27.3±3.1 years respectively. The BMI was 26.4±1.5 kg / m 2 and 26.3±1.3 kg / m 2. In this study we found serum uric acid levels in GDM and without GDM were 4.47±0.42 mg/dl and 4.48±0.41 mg/dl respectively (p&gt;0.05). Serum uric acid level in GDM group was significantly (p&lt;0.001) higher in third trimesters (4.48 ±0.41 mg/dl) compared to those without GDM (3.52 ±0.74 mg/dl).&#x0D; Conclusion: There was distinct alteration of serum uric acid level in GDM compared to normal pregnancy. Estimation of serum uric acid levels might be incorporated in every GDM cases for prevention of complications. Birdem Med J 2019; 9(1): 55-58

This narrative review aims to highlight recent findings on the relation between uric acid level and cognitive decline or dementia. The antioxidant properties of uric acid, which have supported the hypothesis that uric acid may be neuroprotective, have been questioned by preclinical data. Studies investigating the relation between serum uric acid (SUA) level and Alzheimer disease are mostly cross-sectional, and results are often inconclusive. Similarly, data for an association between uric acid level and cognitive performance are inconsistent. There is some evidence that low SUA level might be associated with Parkinson disease, but studies are limited by methodological heterogeneity and risk of bias. Patients with gout may have decreased risk for Alzheimer disease, but the impact of treatment is unclear. Recent data suggest an increased risk of vascular dementia with high SUA level via increased cerebrovascular burden in older patients. The relation between SUA level and neurologic disorders may be U-shaped. We lack strong evidence for an association between low SUA level and cognitive decline over time. Conversely, high SUA level might increase the cerebrovascular burden and the risk of vascular dementia; physicians should continue to treat hyperuricemia when appropriate.