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Background: As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis., Methods: In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately., Results: In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR=1.068, p=0.0349; OR=1.122, p=0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β=0.203, p<0.0001; β=0.255, p<0.0001; β=0.142, p<0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR=1.184, p=0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted., Conclusions: Using the uric acid-related weighted GRS as an instrumental variable for Mendelian randomization analysis, our study provided an evidence for causal relationship between uric acid and diabetic macrovascular disease in Chinese females with type 2 diabetes mellitus., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Association between hyperuricaemia and chronic kidney disease has been studied widely, but the influence of uric acid on the kidneys remains controversial. We aimed to summarize the association between uric acid and diabetic kidney disease (DKD), and to evaluate the role of uric acid in DKD., Methods: We enrolled 3,212 type 2 diabetic patients in a cross-sectional study. The patients' basic characteristics (sex, age, BMI, duration of disease, and blood pressure) and chemical parameters (triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), microalbuminuria, creatinine, and uric acid) were recorded, and the association between uric acid and DKD was evaluated., Results: In the 3,212 diabetic patients, the prevalence of diabetic kidney disease was higher in hyperuricaemic patients than in patients with normouricaemia (68.3% vs 41.5%). The prevalence of DKD increased with increasing uric acid (p < 0.0001). Logistic analysis identified uric acid as an independent predictor of DKD (p < 0.0001; adjusted OR (95%CI) = 1.005 (1.004-1.007), p < 0.0001). Uric acid was positively correlated with albuminuria and creatinine levels (p < 0.0001) but negatively correlated with eGFR (p < 0.0001) after adjusting for confounding factors., Conclusions: Hyperuricaemia is a risk factor for DKD. Serum uric acid levels within the high-normal range are independently associated with DKD.

Background: Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion., Method: We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined., Results: SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively)., Conclusions: Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population.

Irisin is a novel hormone secreted by skeletal muscle after exercise, which may ameliorate insulin resistance. In this study, we aimed to explore the relationship between circulating irisin levels and type 2 diabetes mellitus (T2DM) as well as related metabolic traits in a Chinese population. A total of 203 subjects were recruited. Of these, 68 subjects with normal glucose tolerance (NGT), 63 subjects with impaired glucose regulation (IGR) and 72 subjects with new-onset T2DM. Circulating irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Detailed clinical investigations and biochemistry measurements were carried out in all of the subjects. Multivariate linear regression analysis was performed to assess the association between irisin levels and related metabolic characteristics. All subjects were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). No significant differences in circulating irisin levels were identified among the three groups ( P = 0.9741). After adjusting for covariates, multiple linear regression analysis revealed that serum irisin level was independently and significantly associated with total cholesterol ( P = 0.0005), low-density lipoprotein cholesterol ( P = 0.0014), fasting fatty acids ( P = 0.0402) and uric acid ( P = 0.0062). By dividing the serum irisin levels into three tertile groups, the values of total cholesterol, low-density lipoprotein cholesterol, fasting fatty acids and uric acid were all increased significantly with the increase of irisin ( P < 0.05). Moreover, serum irisin levels remain closely related to total cholesterol in both normal weight and overweight/obese subgroups. Our study suggests that circulating irisin concentrations are significantly associated with lipid and uric acid metabolism in a Chinese population. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients.Methods: Seventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated.Results: In this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively).Conclusions: Our study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes. [ABSTRACT FROM AUTHOR]