Changes In Serum Uric Acid Research Articles

Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

Objective This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). Methods A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Results Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Conclusions Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

Association between change in serum uric acid and rapid decline in kidney function in China

While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P < 0.001), being female, being single, having hypertension, a higher baseline eGFR, a higher baseline SUA (OR per-1 mg/dL increase: 1.68, 95% CI 1.48–1.90, P < 0.001), and increase in change in SUA (OR per-1 mg/ dL increase: 1.92,95% CI 1.71–2.16, P < 0.001). Pearson’s analysis showed a significant inverse correlation between SUA changes and eGFR decline, particularly pronounced in females, with correlation coefficients of − 0.349 for females and − 0.306 for males (95% CI − 0.347 to − 0.299, P < 0.001). A significant correlation was found between the change in SUA and the rapid decline in eGFR, with this association being particularly pronounced in females.

Pegloticase-Induced Rapid Uric Acid Lowering and Kidney and Cardiac Health Markers in Youth-Onset Type 2 Diabetes: A Pilot Clinical Trial

Rationale & ObjectiveElevated serum uric acid (SUA) is a risk factor for incident hypertension and diabetic kidney disease in young persons with type 2 diabetes (T2D), particularly men. The acute benefit of aggressively lowering SUA on kidney and cardiovascular function in this population remains underexplored. This study was conducted to investigate the impact of a single pegloticase infusion on kidney and cardiovascular function. Study DesignAn open-label pilot trial. Setting & ParticipantsThe study involved 10 young adult males with youth-onset T2D and SUA levels ≥5 mg/dL. Intervention(s)Participants received a single infusion of pegloticase (8 mg). Evaluations were conducted using iohexol-based measured glomerular filtration rate (mGFR) and cardiac/kidney MRI before and one week after infusion. OutcomesThe primary outcomes were changes in SUA and mGFR one week after pegloticase infusion. ResultsNine participants (mean [±SD] age 22±5 years, HbA1c 8.6±3.3%, BMI 40.1±11.0 kg/m2, SUA 6.7±1.1 mg/dL) completed the pegloticase infusion and were included in the analysis. One week after the infusion, median [p25,p75] SUA concentrations dropped from 6.4 [5.6,7.6] to 0.5 [0.5,4.6] mg/dL (p=0.01). Mean mGFR increased from 113±20 to 122±19 ml/min per 1.73 m2 (p=0.004). Among responders (SUA reduction ≥3 mg/dL), an increase in mGFR correlated with an increase in renal artery blood flow (r:0.60, p=0.24) and decrease in SUA (r:-0.79, p=0.05). Mean MRI peak longitudinal cardiac strain additionally decreased from 15.4±2.2 to 13.1±2.2 % (p=0.03) in these responders. LimitationsThe pilot nature of the study and the small sample size limit the generalizability of the findings. ConclusionsIn young adult males with T2D, a single pegloticase infusion decreased SUA levels, which increased mGFR and was strongly associated with increased renal blood flow and impaired cardiac global longitudinal strain. Further research is required to assess the long-term efficacy and safety of pegloticase in patients with T2D.

Uric Acid and SGLT2 Inhibition With Empagliflozin in HeartFailure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcome in patients with heart failure (HF) and reduce serum uric acid (SUA). The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF. This post hoc analysis of the EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951) trial assessed the clinical effect of SUA reduction in relation to the outcome endpoints of the trial (composite primary outcome of cardiovascular mortality or hospitalization for HF, its individual components, and all-cause mortality in patients with HFpEF). Hyperuricemia (SUA >5.7mg/dL for women, >7.0mg/dL for men) was prevalent in 49% of patients. Elevated SUA (highest tertile SUA 8.8 ± 1.4 g/dL) was associated with advanced HF severity and with higher risk of adverse outcome (primary endpoint HR: 1.23 [95%CI: 0.98-1.53]; P = 0.07; HF hospitalization HR: 1.42 [95%CI: 1.08-1.86]; P= 0.01). SUA was reduced early (after 4weeks vs placebo-0.99 ± 0.03mg/dL; P< 0.0001) and throughout follow-up, with reduction in all prespecified subgroups. Empagliflozin reduced clinical events of hyperuricemia (acute gout, gouty arthritis, or initiation of antigout therapy) by 38% (HR: 0.62 [95%CI: 0.51-0.76]; P< 0.0001). The treatment benefit on the primary endpoint was not influenced by baseline SUA (HR: 0.79 [95%CI: 0.69-0.90]; P = 0.0004). The change in SUA was an independent correlate of the treatment benefit on the primary endpoint (P = 0.07). Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricemia.

Serum uric acid-lowering effect of sacubitril/valsartan in hypertensive patients: evaluation by switching from angiotensin II receptor blockers.

Since hyperuricemia is a risk factor for cardiovascular disease and chronic kidney disease, it is necessary to pay attention to trends in uric acid levels when treating hypertensive patients with drugs. The present study investigated the effect of switching from angiotensin II receptor blocker (ARB) to sacubitril/valsartan on serum uric acid levels in treated hypertensive patients and further examined what factors could be associated with its effect. In 75 hypertensive patients under treatment with at least one antihypertensive agent including ARB, clinic blood pressure and biochemical parameters were assessed before and after drug switching to sacubitril/valsartan (200 mg/day). Clinic SBP and DBP significantly decreased after drug switching to sacubitril/valsartan (P < 0.0001, respectively). Serum creatinine, estimated glomerular filtration rate (eGFR), and urinary protein did not change after switching to sacubitril/valsartan, but serum uric acid significantly decreased (5.70 ± 1.44 to 5.40 ± 1.43 mg/dl, P = 0.0017). The degree of uric acid lowering was greater in patients switching from ARB plus diuretic than in those switching from ARB, but switching to sacubitril/valsartan from ARB only (except losartan) also significantly decreased uric acid levels. In all subjects, the change in serum uric acid after drug switching to sacubitril/valsartan was closely correlated with the change in eGFR (r = -0.5264, P < 0.0001). Our findings indicate that switching from ARB to sacubitril/valsartan reduces serum uric acid levels in hypertensive patients and suggest that this uric acid-lowering effect may be associated with an increase in eGFR.

Effects of Xanthine Oxidase Inhibition by Febuxostat on Lipid Profiles of Patients with Hyperuricemia: Insights from Randomized PRIZE Study.

Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

Poor serum uric acid control increases risk for developing hypertension: a retrospective cohort study in China.

Serum uric acid (SUA) has been suggested as a contributor of hypertension. However, reports on the relationship between changes in SUA and hypertension are limited. Hence, we aimed to investigate the potential impact of SUA, especially its change over time, on hypertension incidence. This dynamic cohort included 6052 participants without hypertension at baseline. Participants were categorized into six grades based on whether baseline SUA was high and whether changes in SUA progressed to hyperuricemia or decreased to normal levels. Grades 1 to 6 represented the participants' SUA control from best to worst. Logistic regression and restricted cubic spline (RCS) models were used to explore the association of the grades of SUA control and hypertension incidence. During a median follow-up of 6 years, 2550 (42.1%) participants developed hypertension. After adjusting confounding factors, compared to grade 1 with the best control of SUA, the odds ratios for grades 2 to 6 with worse control were 1.347 (1.109-1.636), 1.138 (0.764-1.693), 1.552 (1.245-1.934), 1.765 (1.170-2.663), and 2.165 (1.566-2.993), respectively. RCS indicated a linear correlation between the risk of hypertension and changes in SUA, and an elevated risk in participants with baseline hyperuricemia. Subgroup analyses showed that grades of SUA control had an interaction with systolic (P = 0.003) and diastolic blood pressure (P < 0.001). Sensitivity analyses further determined the robustness of the result that participants with poor SUA control have a higher risk of developing hypertension. Poor SUA control, an increase in SUA over time, rises the risk of developing hypertension regardless of whether the initial SUA is normal or not. Initial hyperuricemia will exacerbate this risk. Effective SUA control should be an important measure for primary prevention of hypertension.

Progression of cognitive impairment in Parkinson's disease correlates with uric acid concentration.

This study assessed the relationship between the progression of Parkinson's disease (PD) with cognitive impairment and changes in serum uric acid (UA) and homocysteine (Hcy) concentrations and explored the factors influencing PD with cognitive impairment. The study randomly selected 74 patients with PD and evaluated their cognitive function using the Montreal Cognitive Assessment Scale (MoCA). Patients with PD were divided into two subgroups: those with and without cognitive impairment. PD severity was evaluated and graded using the Hoehn and Yahr (H-Y) scale. Another 60 middle-aged and older individuals without PD during the same period were selected as a control group. Blood UA and Hcy concentrations in each group were measured to assess the relationship between PD, cognitive impairment, and changes in UA and Hcy concentrations. The PD group with cognitive impairment had a lower UA concentration and higher Hcy concentration. The UA concentration was significantly higher in the early PD stages than in the middle and late stages (P<0.05). A significant negative relationship between MoCA scores and serum UA levels was found in patients with PD, whereas a positive relationship existed between MoCA scores and serum Hcy concentrations. Regression analysis showed that a higher UA concentration was an independent protective factor for PD with cognitive impairment, while a higher Hcy concentration was a risk factor (P<0.05). A serum UA concentration of 212.9 mmol/L and Hcy concentration of 13.35 mmol/L could distinguish between patients with PD with or without cognitive impairment with a sensitivity of 93.2% and specificity of 43.3%. PD and cognitive impairment were associated with a decrease in UA concentration; the later the H-Y stage was, the lower the UA concentration was. The increase in Hcy concentration was related to PD and its cognitive impairment, whereas it is not significantly correlated with PD progression.

Allopurinol versus Febuxostat: A New Approach for the Management of Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).

Baseline Sodium-Glucose Cotransporter-2 Inhibitor Use Strongly Attenuates the Uric Acid-Elevating Effect of Thiazide Exposure

Objective: Thiazide diuretics are among the major anti-hypertensive medications. However, their hyperuricemic effect restricts their use in patients with gout. Sodium glucose co-transporter 2 inhibitor (SGLT-2i) initiation lowers serum uric acid (SUA) levels. It is not known whether existing SGLT-2i use affects the SUA increasing effect of thiazides. Methods: Post-hoc data analysis of our published study was conducted. Hypertensive patients who were initiated on thiazide diuretics or whose dose escalated were included (thiazide exposure). Demographic, clinical, and laboratory data were acquired via an electronic database. Patients were grouped according to SGLT-2i presence at the time of thiazide exposure. Since the number of SGLT-2i users was low, bootstrapping via simple random sampling was performed. Results: 144 patients were included in the study, of whom 13 were on SGLT-2i. Initial sample analysis revealed that while baseline SUA levels were similar between groups, SUA change was significantly lower after thiazide exposure among patients receiving SGLT-2i (0.6 vs. 0.2, p = 0.039). Similarly, baseline SUA levels were similar, but SUA change after thiazide exposure was significantly lower among patients receiving SGLT-2 on bootstrapped data (0.13 [-0.25 - 0.57, 95%CI], vs. 0.61 [0.45 - 0.78, 95%CI], mean difference = 0.48, [0.04 - 0.91, 95%CI], p = 0.029). Conclusion: This study revealed that thiazide diuretics may be a safe anti-hypertensive medication in terms of hyperuricemia among patients using SGLT-2i. Further studies with similar outcomes may result in the elimination of restrictive recommendations for the use of thiazides in patients with hyperuricemia or gout, provided patients are on SGLT-2i.

The role of high fat diet on serum uric acid level among healthy male first degree relatives of type 2 diabetes mellitus

First-degree relatives (FDR) of type 2 diabetes mellitus have increased risk of developing insulin resistance-related disorders including hyperuricemia. We investigated metabolic profile and serum uric acid (SUA) metabolism in response to high-fat diet among healthy male FDR in comparison to those without family history of diabetes. A total of 30 FDR and 30 non-FDR subjects completed a 5-days-hypercaloric diet with fat added to regular daily intake. Despite similar insulin response, FDR displayed different changes in SUA compared to non-FDR subjects (0.26 ± 0.83 mg/dL vs − 0.21 ± 0.78 mg/dL, p = 0.028). In subgroup analyses stratified by body mass index and waist circumference, significant different SUA changes between FDR and non-FDR subjects were only found in obese (0.48 ± 0.87 mg/dL vs − 0.70 ± 0.71 mg/dL, p = 0.001) and centrally obese (0.59 ± 0.83 mg/dL vs − 0.55 ± 0.82 mg/dL, p = 0.011) subgroups. In multivariate analysis, visceral adiposity seemed mediating the different response in SUA metabolism between FDR and non-FDR subjects induced by short-term obesogenic diet.

Long-term increase in serum uric acid and its predictors over a 25 year follow-up: Results of the PAMELA study

Background and aimsHyperuricemia (HU) has been shown to be associated with an adverse impact on cardiovascular and metabolic risk. Scanty data are available in the general population on the longitudinal changes in serum uric acid (SUA), the occurrence of HU and their potential predictors. We examined during a 25-year follow-up the SUA changes and the factors associated with HU development in the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study. Methods and resultsWe analyzed data collected in 561 subjects of the PAMELA study evaluated during an average follow-up time amounting to 25.4 ± 1.0 years (mean ± SD). HU was defined by the Uric Acid Right for Heart Health (URRAh) cutoff (5.1 for females and 5.6 mg/dl for males). Mean SUA values during follow-up increased from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dl (P<0.001), the average SUA elevation amounting to of 0.3 ± 1.1 mg/dl 26.7 % of the subjects displayed HU at the follow-up. This was associated at the multivariable analysis with female gender, office, home and 24-h blood pressure, diuretic treatment, serum triglycerides and baseline SUA, as well as the increase in waist circumference and the reduction in renal function. ConclusionThe present study provides longitudinal evidence that in the general population during a 25 year follow-up there is a progressive increase in SUA and HU development. Baseline SUA represents the most important factor associated with these modifications. Gender, renal dysfunction, triglycerides, obesity, diuretic treatment and blood pressure represent other variables capable to predict future occurrence of HU.

Relationship between serum uric acid in early pregnancy and gestational diabetes mellitus: a prospective cohort study.

The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) μmol/l vs. 201.9(176.0, 232.0) μmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 μmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. NCT03246295.

The Association Between Serum Uric Acid and Cognitive Function Among Middle-Aged and Older Adults Without Hyperuricemia: The Mediating Role of Depressive Symptoms.

The association between serum uric acid (SUA) and cognitive function remains unclear, especially among individuals without hyperuricemia. We examined the cross-sectional and longitudinal bidirectional associations between SUA and cognition, as well as the mediating effect of depressive symptoms among Chinese adults. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). SUA (continuous) and cognitive function (based on mental intactness and episodic memory) were measured at Wave 1 and Wave 3. Depressive symptoms (Center for Epidemiologic Studies Depression scale) were assessed at Wave 1. Bivariate latent change score models and mediation analysis were used to investigate these possible associations. A total of 6 236 participants free of hyperuricemia (aged 58.3 ± 8.5 years) were included. After controlling for potential confounders, the SUA level was associated with cognition at baseline (standardized r = 0.042; p = .001). Higher baseline SUA level was associated with slower subsequent cognitive decline (standardized β = 0.026; p = .027), whereas baseline cognition was not significantly associated with subsequent change in SUA (standardized β = 0.003; p = .817). In mediation analysis, baseline SUA was indirectly associated with subsequent cognition via baseline depressive symptoms (mediation effect 13.3%; p < .001). Higher baseline SUA level is associated with better baseline cognition and less subsequent cognitive decline among Chinese adults without hyperuricemia. Baseline depressive symptoms may partially mediate the association between baseline SUA and later cognition. Continued research is warranted to verify these findings and elucidate the causality and underlying mechanisms.

The association between the thyroid feedback quantile-based index and serum uric acid in U.S. adults

ObjectivesPrevious studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form.Research design and methodsThis is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings.ResultsHigher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI < 18.85, the relationship between serum uric acid and TT3RI was not significant [β(95% CI) 0.47 (− 0.05, 1.00), P = 0.077], but when TT3RI > 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [β(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels.ConclusionsDecreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.

Relationship between baseline and changed serum uric acid and the incidence of type 2 diabetes mellitus: a national cohort study.

To explore the correlation between baseline serum uric acid (SUA) and SUA changes with the incidence of type 2 diabetes mellitus (T2DM) among middle-aged and older individuals. Binary logistic regression was used to calculate the odds ratio (ORs) and 95% confidence intervals (CIs) of the effects of baseline and changes in SUA on the incidence of T2DM. Stratified analysis was conducted based on sex, and the SUA levels were classified into four quartiles to assess the effect of baseline and relative changes in SUA on the incidence of T2DM. Furthermore, interaction analysis was performed between body mass index (BMI) and SUA, age and SUA, and sex and SUA. In the cohort study, the highest quartiles of SUA were significantly correlated with an increased incidence of T2DM among females in model 1 [OR = 2.231 (1.631, 3.050)], model 2 [OR = 2.090 (1.523, 2.867)], model 3 [OR = 2.075 (1.511, 2.849)], and model 4 [OR = 1.707 (1.234, 2.362)]. The highest quartiles of SUA had a statistically significant effect on the incidence of T2DM among all participants in model 1 [OR = 1.601 (1.277, 2.008)], model 2 [OR = 1.519 (1.204, 1.915)], model 3 [OR = 1.597 (1.257, 2.027)], and model 4 [OR = 1.380 (1.083, 1.760)]. Regarding the relative change of SUA, the highest quantiles of SUA were significantly correlated with an increased incidence of T2DM among females in model 1 [OR = 1.409 (1.050, 1.890)], model 2 [OR = 1.433 (1.067, 1.926)], and model 3 [OR = 1.420 (1.056, 1.910)], and there was a statistically significant correlation with incident T2DM among all participants in model 4 [OR = 1.346 (1.079, 1.680)] after adjusting for all covariates. However, there was no significant correlation between baseline, relative, and absolute changes in SUA and the incidence of T2DM among males. The interaction analysis demonstrated that sex, BMI, and the relative changes in SUA had a combined effect on the incidence of T2DM, while age and the changes in SUA had a joint effect on the incidence of T2DM only in females. There was a positive association between SUA and the incidence of T2DM for all participants. However, significant sex differences in incidence were observed only in women, not men.

A 5-Year Follow-Up Study to Explore Factors Associated with Rapid Kidney Function Decline Among Bus Drivers.

Owing to the stressful occupational characteristics, bus drivers have been reported to have a higher risk of renal dysfunction. However, the related factors associated with rapid kidney function decline among bus drivers have not been explored in the existing literature. Therefore, our research aimed to investigate factors related with rapid kidney function decline, and to explore the correlation of baseline SUA (serum uric acid), longitudinal changes in SUA, and rapid eGFR (estimated glomerular filtration rate) decline for bus drivers. This was a five-year cohort study in Shenzhen, China, between 2017 and 2021. We included 832 bus drivers with normal kidney function at baseline. Study subjects were stratified into four quartiles of change in eGFR, and rapid eGFR decline was regarded as the highest (4th) quartile of ΔeGFR (eGFR in 2017-eGFR in 2021). Univariable and multivariable logistic regressions were conducted to explore factors affecting rapid eGFR decline. The incidence of hyperuricemia among bus drivers was 37.7% in 2017 and 40.5% in 2021. The overall subjects had a median 5-year decrease in eGFR of 6.72 mL/min/1.73 m2, and individuals with increased SUA from normal to hyperuricemia group had the greatest decline of eGFR. Multivariate analysis showed bus drivers' age (Odds radio: OR, 1.04), elevated baseline eGFR (OR, 1.08), and SUA increase (OR, 1.38) were significantly associated with rapid eGFR changes. The high prevalence of hyperuricemia among bus drivers should warrant more attention from health professionals. Subjects' age, elevated baseline eGFR, and SUA increase were risk factors for rapid eGFR decline over 5-year. The findings can provide significant evidence for timely prevention and intervention to decrease the incidence of rapid renal function decline among bus drivers.

The effect of dietary approaches to stop hypertension and ketogenic diets intervention on serum uric acid concentration: a systematic review and meta-analysis of randomized controlled trials

Hyperuricemia as a risk factor for metabolic diseases is proved to be profoundly modified by dietary approaches. This systematic review and meta-analysis of randomized control trials (RCT) was conducted to investigate the effect of two nutritional interventions; dietary approaches to stop hypertension (DASH) diet and ketogenic diet (KD) on serum uric acid (UA) concentrations. Our systematic search was for RCTs in which KD or DASH diet were assigned to adults for at least 2 weeks or more. Until March 2023 in Embase, Web of Science, PubMed, and Scopus databases, 10 eligible RCTs that intervened with DASH diet (n = 4) or KD (n = 6) and had provided laboratory data on serum UA were found. Summary effect was calculated by random-effects model. Results from the meta-analysis of the 4 DASH diet RCTs with a total of 590 participants revealed significant decrease in serum UA after at least 4 weeks of interventions (mean difference (MD) = ‒0.25; 95% CI ‒0.4 to ‒0.1 mg/dL; p < 0.01; I2 = 0%). The pooled meta-analysis of the 6 included RCTs of KD reporting data of 267 participants showed no significant changes in serum UA (MD = 0.26; 95% CI ‒0.47 to 0.98 mg/dL, I2 = 95.32%). However, a non-significant reduction of UA in the subgroup analysis of very low-calorie KD (VLCKD) studies (MD = ‒0.04; 95% CI ‒0.29 to 0.22, I2 = 0%) was obtained. DASH diet has an ameliorating effect on serum UA and may be recommended for hyperuricemia states such as gout. In addition, we have shown that serum UA level following KD remained unchanged. Although, in view of the heterogeneity across the studies, further investigations are needed to determine the effect of KD and VLKD on serum UA concentrations.

Changes in serum uric acid, serum uric acid/serum creatinine ratio, and gamma-glutamyltransferase might predict the efficacy of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

The purpose of this study was to investigate the predictive value of changes in serum uric acid (SUA), the ratio of serum uric acid to serum creatinine (SUA/SCr), and serum gamma-glutamyltransferase (GGT) from before to after therapy in patients with locally advanced rectal cancer (LARC). Data from 114 LARC patients from January 2016 to December 2021 were included in this retrospective study. All patients received neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME). The change in SUA was calculated as aratio: (SUA level after nCRT-SUA level before nCRT)/SUA level before nCRT. The change ratios of SUA/SCr and GGT were calculated in the same way. The efficacy of nCRT was evaluated by magnetic resonance (MR) and postoperative pathological response. Anonlinear model was used to evaluate whether the change ratios of SUA, SUA/SCr, and GGT were associated with the efficacy of nCRT. The predictive power of the change ratios of SUA, SUA/SCr, and GGT was assessed by receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression analyses were employed to measure the associations between disease-free survival (DFS) and other predictive indicators. The Kaplan-Meier method was used to further compare DFS between groups. The nonlinear model indicated that the change ratios of SUA, SUA/SCr, and GGT were associated with the efficacy of nCRT. The change ratios of SUA, SUA/SCr, and GGT were used to predict the area under the ROC curve of efficacy for nCRT (0.95, 0.91-0.99), which was better than the prediction by the change ratio of SUA (0.94, 0.89-0.99), SUA/SCr (0.90, 0.84-0.96), or GGT alone (0.86, 0.79-0.93; p < 0.05). The optimal cut-off values of SUA, SUA/SCr, and GGT change were 0.02, 0.01, and 0.04, respectively. The Kaplan-Meier method indicated that patients with SUA, SUA/SCr, or GGT changes greater than the cut-off values had shorter DFS (p < 0.05). Change ratios of SUA, SUA/SCr, or GGT greater than the cut-off values implied arisk of poor pathological response after nCRT and shorter DFS in LARC patients.