Incidence Of Gout Research Articles

Relationship Between Changing Body Mass Index and Serum Uric Acid Alteration Among Clinically Apparently Healthy Korean Men.

Gout and hyperuricemia incidence is increasing worldwide, reflecting pandemic overweight and obesity. However, the magnitude of the association of body mass index (BMI) changes with serum uric acid (UA) level in the general population has remained unevaluated. This retrospective cohort study enrolled 27,422 Korean men who underwent a comprehensive health check-up between 2015 and 2017. BMI change was categorized into 7 groups. The relationship between BMI change and serum UA level alteration was determined using multivariable regression models. The mean age, BMI, and serum UA level were 38.8 years, 24.7 kg/m2 , and 6.2 mg/dl, respectively. All BMI change categories had a clear dose-response relationship with the serum UA level changes. The corresponding β coefficient of serum UA level changes was 0.13 (95% confidence interval [95% CI] 0.11, 0.16), 0.25 (95% CI 0.2, 0.3), and 0.44 (95% CI 0.36, 0.52) for a BMI decrease of 0.5-1.5, 1.5-2.5, and ≥2.5, respectively. Compared with no BMI change, the multivariate odds ratios of achieving normouricemia for a BMI increase of 0.5-1.5, 1.5-2.5, and ≥2.5 were 0.88 (95% CI 0.83, 0.95), 0.67 (95% CI 0.60, 0.75), and 0.60 (95% CI 0.49, 0.74), whereas those for a BMI decrease of 0.5-1.5, 1.5-2.5, and ≥2.5 were 1.17 (95% CI 1.07, 1.27), 1.28 (95% CI 1.08, 1.52), and 1.46 (95% CI 1.13, 1.88), respectively. BMI change could have a significant association with the alteration of serum UA levels of apparently healthy men. Despite its small effect size, the health risks and benefits of BMI change would be emphasized for serum UA level alteration.

Healthy lifestyle counteracts the risk effect of genetic factors on incident gout: a large population-based longitudinal study

BackgroundRisk genes linked to the development of gout have been identified, and lifestyle factors are related to gout risk. It remains unclear whether healthy lifestyle factors can mitigate the genetic risk of gout. Therefore, we aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors.MethodsWithin the UK Biobank, 416,481 gout-free participants (aged 37–74) were identified at baseline. Polygenic risk for gout was assessed and categorized as low (lowest tertile), middle (tertile 2), and high (highest tertile). Healthy lifestyle factors included no/moderate alcohol consumption, no smoking, physical activity, and a healthy diet. Participants were categorized into three groups according to their number of healthy lifestyle factors: unfavorable (0 or 1), intermediate (any 2), and favorable (3 or 4). Data were analyzed using Cox proportional hazard models.ResultsOver the follow-up (median: 12.1 years), 6206 participants developed gout. Compared to low genetic risk, the hazard ratios (HRs) and 95% confidence intervals (CIs) of gout was 1.44 (1.35–1.54) for middle and 1.77 (1.66–1.89) for high genetic risk. The HRs (95% CIs) of gout were 0.63 (0.59–0.67) for a favorable lifestyle and 0.79 (0.75–0.85) for an intermediate lifestyle, compared to an unfavorable lifestyle. In joint effect analysis, compared to participants with low genetic predisposition and a favorable lifestyle, the HRs (95% CIs) of gout were 2.39 (2.12–2.70)/3.12 (2.79–3.52) in those with middle and high genetic predisposition plus unfavorable lifestyle profiles, and 1.53 (1.35–1.74)/1.98 (1.75–2.24) for those with middle and high genetic predisposition plus favorable lifestyle profiles, respectively. Moreover, compared to an unfavorable lifestyle, the HRs of gout related to a favorable lifestyle was 0.64 (95% CI, 0.56–0.73) for low genetic risk, 0.65 (95% CI, 0.58–0.72) for middle genetic risk, and 0.62 (95% CI, 0.57–0.69) for high genetic risk. There was a significant additive interaction between unfavorable lifestyle and high genetic risk on gout.ConclusionsHealthy lifestyle was associated with a lower risk of gout and may attenuate the risk of gout related to genetic factors by almost a third.

Probiotic Characterization of Lactobacillus brevis MJM60390 and In Vivo Assessment of Its Antihyperuricemic Activity.

Uric acid is the final product of purine metabolism in human. The increase of serum uric acid is tightly related to the incidence of hyperuricemia and gout. Also, it has been reported that the intake of purine-rich foods like meat and seafood is associated with an increased risk of gout. Therefore, the reduction of purine absorption is one of therapeutic approaches to prevent hyperuricemia and gout. Currently, probiotics are being studied for the management of hyperuricemia and gout. In this study, we aimed to investigate the effect of Lactobacillus brevis MJM60390 on hyperuricemia induced by a high-purine diet and potassium oxonate in a mouse model. L. brevis MJM60390 among 24 lactic acid bacteria isolated from fermented foods showed the highest ability to assimilate inosine and guanosine in vitro and typical probiotic characteristics, like the absence of bioamine production, D-lactate production, hemolytic activity, as well as tolerance to simulated orogastrointestinal conditions and adherence to Caco-2 cells. In an in vivo animal study, the uric acid level in serum was significantly reduced to a normal level after oral administration of L. brevis MJM60390 for 2 weeks. The activity of xanthine oxidase catalyzing the formation of uric acid was also inhibited by 30%. Interestingly, damage to the glomerulus, Bowman's capsule, and tubules in the hyperuricemia model were reversed by supplementation with this strain. Fecal microbiome analysis revealed that L. brevis MJM60390 supplementation enhanced the relative abundance of the Rikenellaceae family, which produces the short-chain fatty acid butyrate and helps to maintain good gut condition. Therefore, these results demonstrated that L. brevis MJM60390 can be a probiotic candidate to prevent hyperuricemia.

The correlation of uric acid levels with biochemical parameters and dietary factors in individuals with asymptomatic hyperuricemia and gouty arthritis

Diet may play an important role in the development of asymptomatic hyperuricemia (ASH) and gouty arthritis (GOUT). However, the association between dietary factors and hyperuricemia remains unclear. Serum uric acid levels are affected by dietary factors. This study aimed to evaluate the correlation of uric acid levels with biochemical parameters and dietary factors in individuals with ASH and GOUT. This study was conducted in 145 individuals with ASH and GOUT. General characteristics of individuals were collected via face-to-face interviews. Food frequency questionnaire was used to obtain energy, macro- and micronutrients intakes. Biochemical parameters were obtained from patient files. The incidence of gout was higher in men comparing to women. Individuals in the GOUT group consumed more alcohol and higher serum levels of vitamin B12, C-reactive protein (CRP), triglyceride, and uric acid. Individuals in the GOUT group had higher intakes of energy, protein, carbohydrate, fat, fructose, vitamin C, and vitamin B12. Triglyceride, uric acid, CRP, vitamin B12, and homeostatic model assessment of insulin resistance were found to be affected by high uric acid levels. Dietary factors can pose a risk for health problems in addition to GOUT and ASH, such as cardiovascular disease, diabetes, and obesity.

Can SGLT2 inhibitors prevent incident gout? A systematic review and meta-analysis.

To collate the effect of SGLT2 inhibitors (SGLT2i) on adverse gout events in people with type 2 diabetes mellitus (T2DM). PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched using appropriate keywords/MeSH/Emtree terms till January 25, 2022, to identify observational studies, randomized controlled trials (RCTs) or post hoc analysis reporting incident gout events and/or commencement of anti-gout drug in people with T2DM receiving SGLT2i versus those not receiving SGLT2i. Subgroup analyses were performed using comparators as placebo/other antidiabetic drugs and presence/absence of baseline hyperuricemia (uric acid ≥ 7 or < 7mg/dl). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. We identified 5 studies (3 observational, 2 post hoc analysis of RCTs) pooling data retrieved from 568,010 people with T2DM. Pooled analysis showed that SGLT2i use was associated with 30% reduction in incident gout events/gout flares (HR 0.70, 95% CI: 0.59, 0.84, p < 0.001, I2 = 84%). Sensitivity analysis after excluding the retrospective observational study showed similar estimates (HR 0.65, 95% CI: 0.60, 0.70, p < 0.001, I2 = 0%). Subgroup analysis of data retrieved only from RCTs also showed significant benefits (HR 0.74, 95% CI: 0.55, 0.98, p = 0.03, I2 = 0%). Pooled analysis of data from 2 studies showed that SGLT2i use led to a significant reduction in the need for commencement of new anti-gout drug (pooled HR 0.58, 95% CI: 0.48, 0.71, p < 0.001, I2 = 0%). Consistent benefits were also observed for subgroup without baseline hyperuricemia (pooled HR 0.65, 95% CI: 0.47, 0.89, p < 0.01, I2 = 0%). SGLT2i may potentially prevent gout-related adverse events in people with T2DM.

Clinical features of gout in adult patients with type Ia glycogen storage disease: a single-centre retrospective study and a review of literature

BackgroundThis study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia).MethodsNinety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. All patients had hyperuricaemia; 31 patients complicated with gout were enrolled, and 64 adult GSD Ia patients with asymptomatic hyperuricaemia were selected as a control group during the same period. Clinical characteristics were analysed and compared between the two groups.ResultsThirty-one of the 95 patients had complications of gout (median age, 25 years; 11 (35.5%) females). All 31 patients had hepatomegaly, abnormal liver function, fasting hypoglycaemia, hyperuricaemia, hyperlipaemia, and hyperlacticaemia. A protuberant abdomen, growth retardation, recurrent epistaxis, and diarrhoea were the most common clinical manifestations. Among these 31 patients, 10 patients (32.3%) had gout as the presenting manifestation and were diagnosed with GSD Ia at a median time of 5 years (range, 1–14) after the first gout flare. The median age of gout onset was 18 years (range, 10–29). Fifteen of the 31 GSD Ia-related gout patients were complicated with gouty tophi, which has an average incidence time of 2 years after the first gouty flare. The mean value of the maximum serum uric acid (SUA) was 800.5 μmol/L (range, 468–1068). The incidence of gout in adult GSD Ia patients was significantly associated with the initial age of regular treatment with raw corn starch, the proportion of urate-lowering therapy initiated during the asymptomatic hyperuricaemic stage, maximum SUA level, and mean cholesterol level.ConclusionsDetermination of GSD Ia should be performed for young-onset gout patients with an early occurrence of gouty tophi, especially in patients with hepatomegaly, recurrent hypoglycaemia, or growth retardation. Early detection and long-term regulatory management of hyperuricaemia, in addition to early raw corn starch and lifestyle intervention, should be emphasized for GSD Ia patients in order to maintain good metabolic control.Trial registrationRetrospectively registered.

Incident Gout: Risk of Death and Cause-Specific Mortality in Western Sweden: A Prospective, Controlled Inception Cohort Study.

BackgroundExcess mortality in gout has been attributed to cardiovascular diseases (CVD). Considering the decline in CVD mortality in the general population, we wanted to evaluate overall mortality in gout and cause-specific contributions to mortality beyond CVD and temporal trends.MethodsAll incident cases of gout between 2006 and 2015 in western Sweden and 5 population controls per case matched for age, sex, and county were identified. Comorbidities were identified for 5 years preceding the index date. Follow-up ended at death, migration, or end of study on December 2017. Effect of gout on death risk was calculated using COX regression on the whole population and stratified by sex, adjusted for demographics, and comorbidities. Death incidence rates were compared between the two time periods, 2006–2010 and 2011–2015.ResultsWe identified 22,055 cases of incident gout and 98,946 controls, median age (Q1, Q3) 69–68 (57, 79/56, 78) years and 67.6–66.5% males. Except for dementia, all comorbidities were significantly more common at baseline among gout cases. Overall, the risk for death in incident gout was neither increased overall nor in men, but women had a 10% elevated risk. In adjusted models for cause-specific mortality, death from CVD, renal disease, and digestive system diseases were significantly increased in the total gout population while death from dementia, cancer, and lung diseases were significantly decreased. There were no significant differences in overall incident death rate ratios between cases and controls in the two time periods examined.ConclusionsAn increased risk for CVD, renal disease, and diseases of the digestive system in patients with gout highlights the importance of addressing CVD risk factors in gout management. Gout was associated with reduced mortality from dementia, which may have implications on urate lowering therapy and possible effects on dementia risk.

A Bioinformatic Studies of Moringaoleifera L. as A Gout Drug

Moringaoleifera Lam. (MO) is a plant that has been widely known for its usefulness by the people of Indonesia which is called Moringa. MO belongs to the Moringaceae family. Moringa plant is a local food material that has the potential to be developed to cure uric acid naturally, because the moringa leaves contain active compounds, namely phlovonoids and alkaloids which can prevent the formation of uric acid, besides that Moringa leaves can also be used as anti-inflammatory (inflammation) and analgesic (pain reliever). Gout is a disease of purine metabolic waste products that come from the food we eat. This disorder is associated with the accumulation of urosal crystals monosodium monohydrate and in the later stages of degeneration of joint cartilage, the incidence of gout is 1-2%, especially occurs at the age of 30-40 years and 20 times more often in men than in women. The method used is a computational study using various bioinformatics applications. From the research results, it was found that the active compound in Moringa leaves is effective as a uric acid drug.&#x0D; &#x0D; Keywords: Alkaloids; Curcuma; Moringaoleifera lam. (MO); Phlovonoids; Uric acid

A Philippine Tertiary Hospital Cross-sectional and Registry Feasibility Study: Gout Clinical Case Scenario

Background. Gout is one of the most common arthritides affecting Filipinos; yet, there is a lack of updated local data and Clinical Practice Guidelines.&#x0D; Objective. To describe Clinical Case Scenario (CCS) of Filipino patients with gout in a tertiary referral hospital seen over a year.&#x0D; Design. Cross-sectional study.&#x0D; Methods. Patients’ characteristics, risk factors, disease course, management, and CCS were obtained by a rheumatologist using a questionnaire. Descriptive statistics were used.&#x0D; Results. One hundred eight patients were included with a median age of 58 (range 26–80) years. 106 were male (98%); and, 2 were female (2%) who were menopause and had chronic kidney disease (CKD). Most prevalent CCS were stages 9 (29%), 1 (16%), and 2 (15%). The majority of cases had tophi and belonged to CCS 4-9 (62%). This signifies that most patients had advanced gout. Consistent with international and local data: almost half had hypertension (46%), a third had CKD (36%). Most were ethanol drinkers (65%) and smokers (57%). Unexpectedly, not many were obese (10%) or had metabolic syndrome (2%). The initial joint involved was the ankle (52%) rather than the first metatarsophalangeal joint (40%). Almost half of the patients presented with two or more joint involvement (46%) than monoarthritis (54%). Patients with acute flare were most commonly prescribed NSAIDs (77%), followed by colchicine (62%). Most were prescribed allopurinol (44%) compared with febuxostat (37%) for urate-lowering therapy. Only 16% received patient education. Medication compliance was 65%, but follow-up compliance was less than 18%. Comparing the Filipino clinical profile to historical data suggests an increased incidence of gout in the young and an increase in comorbidity prevalence.&#x0D; Conclusion. This study reports a cohort of Filipino gout patients. Comorbidities are similar to world figures but differ in the low incidence of obesity and metabolic syndrome. It also differs from literature in having the ankle as the most common initial joint presentation. Management and compliance were also described. As a pilot study for a registry, this study can be implemented at different institutions to broaden and monitor the ever-changing Filipino gout profile.&#x0D; Recommendation. A larger sample size and a more extended observation period are recommended to estimate gout CCS prevalence, flare risk factors, and treatment response more accurately. Other outcomes that can be measured are mortality rates and etiologies for each CCS.

Is repeat serum urate testing superior to a single test to predict incident gout over time?

Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These observations may be due to subsequent variations in serum urate over time. Our analysis examined whether single or repeat testing of serum urate more accurately predicts incident gout over time. Individual participant data from three publicly-available cohorts were included. Data from paired serum urate measures 3–5 years apart, followed by an assessment of gout incidence 5–6 years from the second urate measure were used to calculate the predictive ability of four measures of serum urate on incident gout: the first measure, the second measure, the average of the two measures, and the highest of the two measures. Participants with prevalent gout prior to the second measure were excluded. Receiver operator characteristic (ROC) curves and area under the curve (AUC) statistics were computed to compare the four measures. A total of 16,017 participants were included across the three cohorts, with a mean follow-up from the first serum urate test of 9.3 years (range 8.9–10.1 years). Overall, there was a small increase in the mean serum urate between the first and second measures (322 μmol/L (5.42 mg/dL) vs. 340 μmol/L (5.71 mg/dL), P<0.001) which were a mean of 3.5 years apart, but the first and second measures were highly correlated (r = 0.81, P<0.001). No differences were observed in the predictive ability of incident gout between the four measures of serum urate measurement with ROC curve AUC statistics ranging between 0.81 (95% confidence intervals: 0.78–0.84) and 0.84 (95% confidence intervals: 0.81–0.87). These data show that repeat serum urate testing is not superior to a single measure of serum urate for prediction of incident gout over approximately one decade.

Modifiable Factors and Incident Gout Across Ethnicity Within a Large Multiethnic Cohort of Older Adults.

Gout disproportionately affects older Pacific Islander and Black populations relative to White populations. However, the ethnic-specific determinants remain understudied within these groups, as well as within other ethnicities. We examined gout incidence and associations with behavioral factors, including diet, alcohol, and smoking, within a large multiethnic population of older adults from the Multiethnic Cohort Study, which linked prospective cohort data to Medicare gout claims between 1999-2016. Using samples of Black (n = 12,370), Native Hawaiian (n = 6459), Japanese (n = 29,830), Latino (n = 17,538), and White (n = 26,067) participants, we conducted multiple Cox regressions, producing hazard ratios (HRs) and 95% CIs. Relative to White individuals, Native Hawaiians had the highest risk of gout (HR 2.21, 95% CI 2.06-2.38), followed successively by Black and Japanese participants, whereas Latino individuals had a lower risk of gout (HR 0.78, 95% CI 0.73-0.83). Alcohol use was associated with an increased risk, with significantly greater effects observed among Japanese participants drinking ≥ 3 drinks per day (HR 1.46, 95% CI 1.27-1.66), or > 5 beers per week (HR 1.29, 95% CI 1.17-1.43), compared to White individuals (Pinteraction < 0.001). Former smokers with ≥ 20 pack-years had an increased risk (HR 1.14, 95% CI 1.06-1.22). Higher dietary quality was associated with a decreased gout risk, with the largest effect observed among White participants (HRQ5vsQ1 0.84, 95% CI 0.79-0.90), whereas vitamin C was weakly associated with a decreased risk of gout only among Japanese individuals (HR 0.91, 95% CI 0.85-0.98). Overall, notable ethnic differences were observed in both gout risk and associations with modifiable behavioral factors. Our findings offer crucial insights that may improve precision in preventing and managing gout.

Adherence to 2020 to 2025 Dietary Guidelines for Americans and the Risk of New-Onset Female Gout

Female-specific gout data are scarce despite perceived differences from males in its risk factors and disproportionate worsening in disease and comorbidity burden globally. The 2020 to 2025 Dietary Guidelines for Americans recommend multiple healthy eating patterns for prevention of cardiovascular-metabolic outcomes, which may also be relevant to the prevention of female gout. To examine the associations of dietary scores for the latest guideline-based healthy eating patterns with risk of incident female gout. This prospective cohort study included 80 039 US women in the Nurses' Health Study followed up through questionnaires every 2 years starting from 1984. Participants had no history of gout at baseline, and the study used questionnaire responses through 2018. Statistical analyses were performed over September 2020 to August 2021. Four healthy eating patterns: Dietary Approaches to Stop Hypertension (DASH), Alternate Mediterranean Diet Score, Alternative Healthy Eating Index (AHEI), and Prudent, plus Western (unhealthy) for comparison, with scores derived from validated food frequency questionnaires. Incident, physician-diagnosed female-specific gout. During 34 years of follow-up, we documented 3890 cases of incident female gout. Compared with the least-adherent quintile, women most adherent to healthy diets had significantly lower risk of incident gout, with multivariable-adjusted hazard ratios (HRs) 0.68 (95% CI, 0.61-0.76) (DASH), 0.88 (95% CI, 0.80-0.98) (Mediterranean), 0.79 (95% CI, 0.71-0.89) (AHEI), and 0.75 (95% CI, 0.73-0.90) (Prudent); all P for trend ≤.009. Conversely, women with highest-quintile Western diet score had 49% higher risk of gout (HR, 1.49; 95% CI, 1.33-1.68], P <.001). When combined, the most DASH-diet adherent women with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) had a 68% lower risk of gout compared with the least adherent women with overweight or obese BMI; the corresponding risk reduction was 65% combining high DASH diet adherence with no diuretic use. These large-scale, long-term prospective cohort findings extend the pleotropic benefits of the 2020 to 2025 Dietary Guidelines for Americans to female gout prevention, with multiple healthy diets that can be adapted to individual food traditions, preferences, and comorbidities.

Association between female reproductive factors and gout: a nationwide population-based cohort study of 1 million postmenopausal women

BackgroundPrevious studies have shown that the incidence and risk factors of gout differs according to sex. However, little research has been done on the association between reproductive factors and gout. We conducted an analysis of a large nationwide population-based cohort of postmenopausal women to determine whether there is an association between reproductive factors and the incidence of gout.MethodsA total of 1,076,378 postmenopausal women aged 40–69 years who participated in national health screenings in 2009 were included in the study. The outcome was the occurrence of incident gout, which was defined using the ICD-10 code of gout (M10) in the claim database. Cox proportional hazard models were used for the analyses and stratified analyses according to body mass index (BMI) and the presence/absence of chronic kidney disease (CKD) were performed.ResultsThe mean follow-up duration was 8.1 years, and incident cases of gout were 64,052 (incidence rate 7.31 per 1000 person-years). Later menarche, earlier menopause, and a shorter reproductive span were associated with a high risk of gout. No association between parity and gout incidence was observed. Use of oral contraceptives (OC) and hormone replacement therapy (HRT) were associated with an increased risk of gout. The association between reproductive factors and gout was not statistical significant in the high BMI group. The effects of OC and HRT usage on gout were not significant in the CKD group.ConclusionShorter exposure to endogenous estrogen was associated with a high risk of gout. Conversely, exposure to exogenous estrogen such as OC and HRT was associated with an increased risk of gout.

Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

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.

Medical Students' Perspective and Knowledge of Asymptomatic Hyperuricemia and Gout Management: A Cross-Sectional Study.

The prevalence and incidence of gout doubled from 1990 to 2017. Therefore, we can expect that a number of doctors have come across a patient with gout in their daily practice. Hence, we wanted to investigate how familiar our medical students, as future medical professionals, are with gout. This cross-sectional survey included Medical Studies students from the two largest universities in Croatia: the University of Split School of Medicine, and the University of Zagreb School of Medicine, and included a total of 221 fifth or sixth year medical students. Most students gave correct answers to questions about treatment approach and non-pharmacological interventions in asymptomatic hyperuricemia (>80%). Less than 3% of all students agreed they knew enough about care for patients with asymptomatic hyperuricemia, whereas almost 15% thought they were well familiar with care for gout patients. Less than 8% of students considered their school education adequate on both topics, and less than 2% were aware of the existence of EULAR guidelines. Physicians lacking in the latest knowledge on the pathophysiology of gout, the influence of lifestyle, and genetic factors limits their ability to properly manage gout. With increasing prevalence, gout should be more represented in medical students’ education.

Association of Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and Incidence of Gout in Taiwan

The use of sodium-glucose transport protein 2 (SGLT2) inhibitors is currently a standard intervention in patients with type 2 diabetes (T2DM) and exerts favorable pleiotropic effects to consistently lower blood urate levels. However, to date, no association between SGLT2 inhibitor use and the incidence of gout have been established. To investigate whether prescribed SGLT2 inhibitors are associated with lower gout incidence in patients with T2DM. In a cohort study, all patients with incident T2DM in Taiwan National Health Institution databases between May 1, 2016, and December 31, 2018, were retrospectively analyzed. As a comparator, patients using dipeptidyl peptidase 4 (DPP4) inhibitors were included. A total of 47 905 individuals receiving an SGLT2 inhibitor and 183 303 receiving a DPP4 inhibitor were evaluated, along with 47 405 pairs of patients using an SGLT2 inhibitor or DPP4 inhibitor in 1:1 propensity score-matched analyses. Data analysis was conducted from April 1 to June 30, 2021. A gout diagnosis was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Multiple Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs. In total, 231 208 patients with T2DM were included in the population; 113 812 individuals (49.22%) were women, and the mean (SD) age was 61.53 (12.86) years. The overall gout incidence was 20.26 per 1000 patient-years for SGLT2 inhibitor users and 24.30 per 1000 patient-years for DPP4 inhibitor users. When potential risk factors were adjusted in the propensity score-matched population, use of SGLT2 inhibitors was associated with a lower risk of gout (HR, 0.89; 95% CI, 0.82-0.96) compared with DPP4 inhibitors, particularly for patients receiving dapagliflozin (HR, 0.86; 95% CI, 0.78-0.95). A sensitivity analysis, performed when a gout diagnosis was ascertained using the ICD-9-CM or ICD-10-CM code with gout-related medication, also showed a significantly lower risk for gout incidence of 15% with SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74-0.97). Subgroup analysis indicated that SGLT2 inhibitor benefits in patients with T2DM to achieve a lower gout risk were not different across subgroups. The findings of this study suggest that patients with T2DM who are receiving SGLT2 inhibitors may have a lower risk for gout compared with those receiving DPP4 inhibitors.

The Association between Clonal Hematopoiesis and Gout

▪Background: Gout is a highly prevalent arthritis associated with debilitating joint pain and functional impairment. It is caused by elevated serum uric acid levels (hyperuricemia) and triggered by precipitation of urate crystals in and around joints. Urate crystals are ingested by macrophages and provoke an innate immune response with subsequent secretion of inflammatory cytokines including interleukin 1 beta (IL-1B). Clonal hematopoiesis of indeterminate potential (CHIP) is a precursor to hematologic malignancies defined by somatic mutations in hematopoietic cells that drive clonal expansion and inflammation. Specifically, CHIP is associated with an increased risk of cardiovascular events and can accelerate atherosclerosis. Mutations in TET2, one of the most commonly mutated genes in CHIP, lead to increased expression of IL-1B through inflammasome activation. Here we investigate the role of CHIP in the development of gout using a combination of human genetic studies and mouse models of CHIP.Methods: To determine the clinical association between CHIP and gout, we analyzed exome sequencing and clinical data from >50,000 individuals included in the UK Biobank (UKB) and Mass General Brigham Biobank (MGBB). To test whether mutant blood cells can promote gout, Tet2- and Dnmt3a-deficient mouse models were used.Results: CHIP was more prevalent in individuals with gout than without gout (MGBB: 12.3% vs. 7.9%, P=0.017; UKB: 8.2% vs. 5.8%, P=0.011) and individuals with CHIP were at increased risk of developing gout (UKB: hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.27-2.00; P<0.001). In multivariable analyses, CHIP with variant allele fraction (VAF) ≥10% was associated with higher risk of incident gout compared to no CHIP after adjusting for common gout risk factors (UKB: HR, 1.46; 95% CI, 1.07-2.01; P=0.019). To determine if somatically mutated blood cells directly contribute to the aberrant immune response in gout, we utilized a mouse model of MSU-mediated peritonitis. Compared to control animals, mice with hematopoietic-specific Tet2 deficiency demonstrated markedly increased IL-1B serum levels after injection with MSU (P<0.05). To study gene-specific contributions to joint tissue injury, we established an in vivo model that closely represents the clinical phenotype of gout. Following MSU treatment in situ, Tet2-deficient animals developed exacerbated paw edema compared to wild-type controls (P<0.05). We next generated bone-marrow derived macrophages (BMDM) from Tet2- and Dnmt3a-deficient mice to specifically investigate the MSU-induced cytokine profile in mutant macrophages. Consistent with our in vivo data, IL-1B was the most differentially secreted cytokine after MSU treatment in both Tet2-deficient and Dnmt3a-deficient BMDM compared to wild-type cells (P<0.05). RNA-sequencing confirmed a strong pro-inflammatory gene expression signature of MSU-treated Tet2- and Dnmt3a-deficient macrophages. Finally, we found that pharmacologic inhibition or genetic loss of inflammasome abrogated IL-1B secretion in Tet2- and Dnmt3a-deficient macrophages treated with MSU.Conclusion: CHIP is associated with an increased risk of having and developing gout in human cohorts and distinct mouse models confirm a direct influence of mutant hematopoietic cells on gout-induced inflammation and arthropathy. CHIP may provide a mechanistic explanation for the heterogeneity in clinical symptoms and inflammation due to gout. Our findings substantiate the biologic rationale for interventional strategies directed at CHIP-associated inflammatory conditions beyond cardiovascular disease and thereby define a path for clinical evaluation of targeted therapies for patients with CHIP-positive gout. DisclosuresMiller: Foundation Medicine: Consultancy. Neuberg: Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Other: Stock ownership. Natarajan: Amgen: Research Funding; Apple: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Boston Scientific: Research Funding; Blackstone Life Sciences: Consultancy; Genentech: Consultancy; Foresite Labs: Consultancy. Rao: Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; GlaxoSmithKline: Honoraria; Merck: Honoraria; Scipher Medicine: Honoraria.

Association of Serum Bicarbonate with Incident Gout in Patients with Advanced CKD

Association of Serum Bicarbonate with Incident Gout in Patients with Advanced CKD

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives.

Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered “self-inflicted”, as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions remain unanswered, such as the relationships between diet, hyperuricemia and gout flares or the mechanisms by which urate induces inflammation. Recent advances have identified gene variants associated with gout incidence. Nevertheless, genetic origins of gout combined to diet-related possible uric acid overproduction account for the symptoms in only a minor portion of patients. Hence, additional factors must be at play. Here, we review the impact of epigenetic mechanisms in which nutrients (such as ω-3 polyunsaturated fatty acids) and/or dietary-derived metabolites (like urate) trigger anti/pro-inflammatory responses that may participate in gout pathogenesis and severity. We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients.

Hubungan Status Gizi Lansia Dengan Angka Kejadian Asam Urat di Wilayah Kerja UPTD Puskesmas Sukaraya Tahun 2020

Hyperuricemia is a condition where there is an increase in blood uric acid levels above normal. In recent years, an increase in the prevalence of hyperuricemia and gout has been observed in epidemiological studies, and both diseases have become public health problems that need to be addressed as soon as possible.in general, the purpose of the research is to know it relationship of lansian nutrition status with uric acid event numbers in the working area puskesmas Sukaraya year 2020. This research includes research using quantitative correlation methods with a cross sectional approach and a sample size of 30 people. The variables studied are presented in the form of a frequency distribution table and tested with univariate and bivariate analysis, namely by using the demographic data questionnaire instrument, measuring the nutritional status of the elderly. The results of the study concluded that of the 30 respondents based on the frequency distribution, it was found that there were 0 (0%) respondents with normal nutrition who were exposed to ura acid and 15 (100%) respondents who were not exposed to gout. 10 (90.0%) respondents who were not affected by uric acid were 1 (9.1%) respondents, and out of 4 (100%) low nutrition respondents who were affected by gout were 4 (100%) respondents and those who not exposed to aric acid as much as 0 (100%) respondents. Based on the bivariate analysis, the p value was 0.000, meaning that there was a significant relationship with the nutritional status of lanisa and the incidence of gout. It is recommended that health workers check uric acid levels more frequently, especially for the elderly with a history of uric acid, so that the elderly can be more careful in choosing healthy food intake and normal nutrition.