Effects of Uric Acid on Diabetes Mellitus and Its Chronic Complications.
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ABSTRACT:
SUBMITTER: Xiong Q
PROVIDER: S-EPMC6815590 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Effects of Uric Acid on Diabetes Mellitus and Its Chronic Complications.
Xiong Qing Q Liu Jie J Xu Yancheng Y
International journal of endocrinology 20191013
With the deepening of the researches on uric acid, especially in the study of metabolic diseases, uric acid has been found to be closely related to obesity, metabolic syndrome, nonalcoholic fatty liver disease, diabetes, and other metabolic diseases. Uric acid causes a series of pathophysiological changes through inflammation, oxidative stress, vascular endothelial injury, and so on and thus subsequently promotes the occurrence and development of diseases. This review confirmed the positive corr ...[more]
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Project description:BackgroundThe relationship between serum uric acid (SUA) and several diabetic complications or co-morbidities remains a matter of debate. The study aims to explore the association between SUA levels and the prevalence of non-alcoholic fatty liver disease (NAFLD), diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 2,809 participants (1,784 males and 1,025 females) were included in this cross-sectional study. Clinical characteristics and the prevalence of each of the four diseases were analyzed based on gender-specific quartiles of SUA levels. The Pearson correlation analysis and linear-regression analysis were used to access the correlation between SUA levels and clinical characteristics. Furthermore, a binary logistic regression analysis was carried out to determine whether SUA was an independent risk factor for each of the four complications.ResultsSUA levels were positively correlated to BMI, BUN, Scr and TG, but negatively associated with eGFR, HDL, FBG, 2h-PG and HbA1c% for the patients with T2DM. The prevalence of NAFLD and DN, but not DR or DPN, were increased with SUA levels from the first to the fourth quartile. Binary logistic regression further disclosed that SUA was an independent risk factor for NAFLD (ORs Male = 1.002, ∗ P = 0.0013; ORs Female = 1.002, ∗ P = 0.015) and DN (ORs Male = 1.006, ∗ P < 0.001; ORs Female = 1.005, ∗ P < 0.001), but not for DR and DPN. After adjustment for the confounders, SUA levels were significantly associated with NAFLD within the 3rd (ORs = 1.829, P = 0.004) and 4th quartile (ORs = 2.064, P = 0.001) for women, but not independently associated with SUA for man. On the other hand, our results revealed increased prevalence of DN for SUA quartile 2 (ORs = 3.643, P = 0.039), quartile 3 (ORs = 3.967, P = 0.024) and quartile 4 (ORs = 9.133, P < 0.001) in men; however, SUA quartiles were significantly associated with DN only for quartile 4 (ORs = 4.083, P = 0.042) in women.ConclusionFor patients with T2DM, elevated SUA concentration is an independent risk factor for the prevalence of NAFLD and DN after adjustment for other indicators, but not DR or DPN.
| S-EPMC7811288 | biostudies-literature
Project description:BackgroundThe impact of long-term serum uric acid (SUA) exposure and time course of SUA accumulation on diabetes mellitus (DM) is unknown. This study aimed to evaluate the association of cumulative SUA (cumSUA) exposure and its accumulation time course with risk of DM.MethodsThis prospective study included 46,434 participants without DM and underwent three examinations at 2006, 2008, and 2010. CumSUA from 2006 to 2010 was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Time course of SUA accumulation was categorized as the slope of SUA versus time from 2006 to 2010, or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10).ResultsDuring 6.99 years of follow-up, we identified 2971 incident DM cases. In the fully adjusted model, a higher risk of DM was observed in participants with the highest quartile of cumSUA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.17-1.46), cumulative burden >0 (HR, 1.23; 95% CI, 1.08-1.40), and with 6 year of hyperuricemia exposure duration (HR, 1.25; 95% CI, 1.01-1.55). When considering the time course of SUA accumulation, participants with a negative slope (HR, 1.05; 95% CI, 1.01-1.12), or combined with cumSUA ≥ median and a negative slope had elevated risk of DM (HR, 1.58; 95% CI, 1.18-2.11).ConclusionsIncident DM risk depends on cumulative exposure of SUA and time course of SUA accumulation. Early SUA accumulation resulted in a greater risk increase compared with later accumulation, emphasizing the importance of optimal SUA control early in life.
| S-EPMC8748907 | biostudies-literature
Project description:Diabetes is one of the fastest growing diseases worldwide, projected to affect 693 million adults by 2045. Devastating macrovascular complications (cardiovascular disease) and microvascular complications (such as diabetic kidney disease, diabetic retinopathy and neuropathy) lead to increased mortality, blindness, kidney failure and an overall decreased quality of life in individuals with diabetes. Clinical risk factors and glycaemic control alone cannot predict the development of vascular complications; numerous genetic studies have demonstrated a clear genetic component to both diabetes and its complications. Early research aimed at identifying genetic determinants of diabetes complications relied on familial linkage analysis suited to strong-effect loci, candidate gene studies prone to false positives, and underpowered genome-wide association studies limited by sample size. The explosion of new genomic datasets, both in terms of biobanks and aggregation of worldwide cohorts, has more than doubled the number of genetic discoveries for both diabetes and diabetes complications. We focus herein on genetic discoveries for diabetes and diabetes complications, empowered primarily through genome-wide association studies, and emphasize the gaps in research for taking genomic discovery to the next level.
| S-EPMC9639302 | biostudies-literature
Project description:BackgroundSerum uric acid levels are higher in patients with type 2 diabetes and prediabetes compared to healthy individuals, and hyperuricemia causes a significant rate of complications and mortality through heart and kidney diseases. Accordingly, the present systematic review and meta-analysis aimed to investigate the effect of empagliflozin on serum uric acid levels.Materials and methodsElectronic databases, including PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were used to search papers until May 22, 2023. Data analysis was conducted by STATA Version 14, and P-value < 0.05 were considered statistically significant.ResultsThe results obtained from the combination of 12 studies with 7801 samples of diabetic patients indicated that in the empagliflozin group, the serum uric acid levels of the patients decreased ([standardized mean difference (SMD): - 1.97 (95%CI - 3.39, - 0.55)], Systolic blood pressure (SBP) [SMD: - 2.62 (95%CI - 3.87, - 1.37)] and diastolic blood pressure (DBP) [SMD: - 0.49 (95%CI - 0.68, - 0.29)]). On the other side, empagliflozin treatment did not affect the patients' HbA1c levels ([SMD: - 2.85 (95%CI - 6.14, 0.45)], eGFR [SMD: 0.78 (95%CI - 0.63, 2.18)], creatinine [SMD:0.11 (95%CI - 0.10, 0.31)], LDL [SMD: 0.14 (95%CI - 0.43, 0.71)], and HDL [SMD:1.38 (95%CI - 0.22, 2.99)]). Compared with the placebo, empagliflozin was more effective in reducing the uric acid levels ([SMD: - 1.34 (95%CI - 2.05, - 0.63)], SBP [SMD: - 2.11 (95%CI - 3.89, - 0.33)], and HbA1c [SMD: - 1.04 (95%CI - 1.95, - 0.13)]). Moreover, compared with sitagliptin also, empagliflozin was more effective in reducing uric acid levels ([SMD: - 1 (95%CI - 1.78, - 0.22)], and creatinine [SMD: - 1.60 (95%CI - 2.28, - 0.92)]) and increasing eGFR levels [SMD: 0.99 (95%CI: 0.37, 1.62)] of the patients. Compared with dapagliflozin also, empagliflozin caused a reduction in eGFR level [SMD: - 0.45 (95%CI - 0.82, - 0.08)].ConclusionEmpagliflozin treatment was effective in controlling diabetic patients' hyperuricemia and hypertension.
| S-EPMC10577917 | biostudies-literature
Project description:Diabetes mellitus is a metabolic disease closely related to a disordered gut microbiome. Diabetic patients usually suffer from various metabolic disorders, such as increased serum uric acid levels. Although serum uric acid levels depend partially on intestine excretion, the relationship between uric acid and gut microbiome in diabetic patients remains unknown. We collected a total of 126 fecal samples from diabetic patients for 16S ribosomal RNA gene amplicon sequencing and recorded clinical data. We analyzed the correlation between clinical indicators and gut microbiota of diabetic patients using Spearman analysis. Since uric acid was the most prominent one, we classified diabetic patients based on their uric acid levels to find the microbiome associated with uric acid disturbance. We constructed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway profiles using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to identify variations between the different groups. Among all the clinical indicators, uric acid had the strongest correlation with gut microbiota. First, we divided the patients into three groups according to their uric acid levels. The two low uric acid groups were similar, while the elevated uric acid group had significant differences in gut microbiota and metabolic pathways. The elevated uric acid group had a significantly lower gut microbiota diversity. At the genus level, this group had remarkably higher Escherichia–Shigella amounts and notably lower Faecalibacterium, Oscillospiraceae_UCG−002, and Oscillospiraceae_UCG−005 amounts. The gut microbiota of the high uric acid group was predicted to be enriched in metabolism, human diseases, and lipopolysaccharide biosynthesis. Since the two low uric acid groups were similar, we regrouped and matched the abnormal uric acid patients with normal uric acid patients. The differences in gut microbiota and metabolic pathways related to nucleotide metabolism became more significant. The serum uric acid levels were associated with gut microbiome changes. This might be related to uric acid metabolism by gut microbes. Our study indicates that targeting the gut microbiome could help manage elevated uric acid levels.
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Project description:ObjectiveOur aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship.Methods684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis.ResultsIn the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95% confidence interval [CI]: 1.475-2.625; P < 0.001). Restricted cubic spline analyses showed a linear relationship between UA and GDM when UA exceeded 222 µmol/L. GDM and UA levels maintained a statistically significant positive correlation in different stratified regression analyses (P < 0.001). However, no evidence of a causal relationship between uric acid and GDM was found by MR analyses with an OR of 1.06 (95% CI: 0.91-1.25) per unit increase in UA.ConclusionThere is a positive correlation between UA levels in early pregnancy and the subsequent risk of developing GDM. However, no genetic evidence was found to support a cause-effect relationship between UA and GDM.
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Project description:With an escalating global burden, T2DM is associated to long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications for a more enhanced disease management and improve therapeutic targets.
2023-04-12 | GSE226084 | GEO
Project description:Glycation is the process of linking a sugar and free amino groups of proteins. Cross-linking of glycation products to proteins results in the formation of cross-linked proteins that inhibit the normal functioning of the cell. Advanced glycation end products (AGEs) are risk molecules for the cell aging process. These ends products are increasingly synthesized in diabetes and are essentially responsible for diabetic complications. They accumulate in the extracellular matrix and bind to receptors (receptor of AGE [RAGE]) to generate oxidative stress and inflammation. particularly in the cardiovascular system. Treatment methods targeting the AGE system may be of clinical importance in reducing and preventing the complications induced by AGEs in diabetes and old age. The AGE cross-link breaker alagebrium (a thiazolium derivative) is the most studied anti-AGE compound in the clinical field. Phase III clinical studies with alagebrium have been successfully conducted, and this molecule has positive effects on cardiovascular hypertrophy, diabetes, hypertension, vascular sclerotic pathologies, and similar processes. However, the mechanism is still not fully understood. The primary mechanism is that alagebrium removes newly formed AGEs by chemically separating ?-dicarbonyl carbon-carbon bonds formed in cross-linked structures. However, it is also reported that alagebrium is a methylglyoxal effective inhibitor. It is not yet clear whether alagebrium inhibits copper-catalyzed ascorbic acid oxidation through metal chelation or destruction of the AGEs. It is not known whether alagebrium has a direct association with RAGEs. The safety profile is favorably in humans, and studies have been terminated due to financial insufficiency and inability to license as a drug.
| S-EPMC6812920 | biostudies-literature
Project description:IntroductionDiabetes mellitus is a complex disease that affects many organ systems, leading to concerns about deteriorating population health status and ever-increasing healthcare expenditure. Many people with diabetes do not achieve optimal glycaemic control and other metabolic indices, leading to a heightened risk of developing complications. Adequate knowledge of diabetes complications is a prerequisite for risk-factor reduction and prevention of the consequences of the disease. Therefore, this study aimed to evaluate the knowledge of chronic complications of diabetes among persons living with type 2 diabetes mellitus in northern Ghana.MethodA descriptive cross-sectional study was conducted among 320 patients with type 2 diabetes mellitus in northern Ghana. The consecutive sampling technique was employed to recruit participants from September to November 2018. Data analysis was performed using IBM statistical package for social science version 23. Descriptive statistics such as frequencies and percentages were used. Both bivariate and multivariate logistic regression analysis were employed to determine associations between knowledge of diabetes complications and demographic/clinical characteristics of participants, at 95% confidence interval with statistical significance at P<0.05.ResultsThe majority of participants (54.1%) had inadequate knowledge and 45.9% had adequate knowledge of diabetes complications. The factors associated with inadequate level of knowledge were female gender [AOR = 0.29 (95%CI: 0.14-0.56), p<0.001], older age [AOR = 0.45 (95%CI:0.20-0.99), p = 0.049], primary education [AOR = 0.13 (95%CI: 0.03-0.51), p = 0.004], no formal education [AOR = 0.16 (95%CI: 0.05-0.50), p = 0.002], rural dwellers [AOR = 0.50 (95%CI: 0.27-0.95), p = 0.033] and unknown family history diabetes [AOR = 0.38 (95%CI: 0.17-0.82), p = 0.014].ConclusionMore than half of the studied population had inadequate knowledge of diabetes complications. Female gender, rural dwellers, and low education level were factors positively associated with inadequate knowledge of diabetes complications. A multisectoral approach is needed, where the government of Ghana together with other sectors of the economy such as the health, education and local government sectors work collaboratively in the development of locally tailored diabetes education programmes to promote healthy self-care behaviours relevant for the prevention of diabetes and its complications.
| S-EPMC7592765 | biostudies-literature
Project description:AimRecent studies found that levels of serum uric acid (SUA) were positively associated with serum 1,5-anhydroglucitol (1,5-AG) in subjects with type 2 diabetes mellitus (T2DM). In the current study, we investigated the association between 1,5-AG and UA in T2DM patients with different renal functions.MethodsA total of 405 T2DM patients, 213 men and 192 women, participated in the study. Patients' clinical information was collected, and serum 1,5-AG, SUA, and other clinical characteristics were measured. Correlation analyses were carried out to analyze their correlation with serum 1,5-AG and SUA.ResultsThe male group showed higher levels of SUA than the female group (282.1 ± 91.2 and 244.7 ± 71.89 μmol/L, respectively, P < 0.01). Pearson's correlation coefficients determine that SUA was positively associated with 1,5-AG in both men (r = 0.213, P < 0.05) and women (r = 0.223, P < 0.05), and such relationship can be influenced by the renal function. The positive association still existed with moderate impaired renal function. Moreover, 1,5-AG had a negative association with haemoglobin A1c (HbA1c) in T2DM subjects with eGFR ≥ 30 mL/min/1.73 m2 (P < 0.01).ConclusionThe positive association between SUA and 1,5-AG still exists in T2DM with moderate renal failure. 1,5-AG can still reflect the glucose levels in patients with CKD stages 1-3.
| S-EPMC6431393 | biostudies-literature