Dandan Yan

Uric Acid Is Independently Associated with Diabetic Kidney Disease: A Cross-Sectional Study in a Chinese Population

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.

Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population

Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 × 10−5 and 6.54 × 10−4). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 × 10−4 and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 × 10−8 and 4.43 × 10−8). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 × 10−4 and 4.65 × 10−3). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.

A causal relationship between uric acid and diabetic macrovascular disease in Chinese type 2 diabetes patients: A Mendelian randomization analysis

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.

CDKAL1 rs7756992 is associated with diabetic retinopathy in a Chinese population with type 2 diabetes

Diabetic retinopathy (DR) is a major microvascular complication of diabetes. Susceptibility genes for type 2 diabetes may also impact the susceptibility of DR. This case-control study investigated the effects of 88 type 2 diabetes susceptibility loci on DR in a Chinese population with type 2 diabetes performed in two stages. In stage 1, 88 SNPs were genotyped in 1,251 patients with type 2 diabetes, and we found that ADAMTS9-AS2 rs4607103, WFS1 rs10010131, CDKAL1 rs7756992, VPS26A rs1802295 and IDE-KIF11-HHEX rs1111875 were significantly associated with DR. The association between CDKAL1 rs7756992 and DR remained significant after Bonferroni correction for multiple comparisons (corrected P = 0.0492). Then, the effect of rs7756992 on DR were analysed in two independent cohorts for replication in stage 2. Cohort (1) consisted of 380 patients with DR and 613 patients with diabetes for ≥5 years but without DR. Cohort (2) consisted of 545 patients with DR and 929 patients with diabetes for ≥5 years but without DR. A meta-analysis combining the results of stage 1 and 2 revealed a significant association between rs7756992 and DR, with the minor allele A conferring a lower risk of DR (OR 0.824, 95% CI 0.743–0.914, P = 2.46 × 10−4).

Association of bone turnover markers with glucose metabolism in Chinese population

The association between type 2 diabetes (T2DM) and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Participants were classified according to their glucose tolerance as normal glucose tolerance (NGT), impaired glucose regulation (IGR) or T2DM. Males and females were analyzed separately, and then associations between bone turnover markers (BTMs) and glucose metabolism were evaluated. The results showed that in females, the serum levels of N-terminal osteocalcin (N-MID), N-terminal procollagen of type I collagen (PINP) and β-cross-linked C-telopeptide of type I collagen (β-CTX) were significantly decreased in the T2DM group compared to the NGT group (P<0.01). When age, body mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat area, anti-diabetic medicines, PINP, N-MID and β-CTX were included in one logistic model, N-MID (OR [95% CI]: 0.954 [0.932; 0.976]; P=0.0001) was significantly associated with T2DM in females. In females, N-MID was associated with insulin sensitivity and HOMA-β. PINP was significantly associated with HOMA-β, GUTT-ISI, Stumvoll first-phase insulin secretion index (STU-1) and Stumvoll second-phase insulin secretion index (STU-2), but β-CTX was associated only with HOMA-β (β±SE: 0.1331±0.0311; P=1.95×10-5) and GUTT-ISI (β±SE: 0.0727±0.0229; P=0.0015). In males, N-MID was significantly correlated with HOMA-β (β±SE: 0.3439±0.0633; P=7.75×10-8), GUTT-ISI (β±SE: 0.1601±0.0531; P=0.0027) and STU-1 (β±SE: 0.2529±0.1033; P=0.0146). Significant associations were also detected between β-CTX and HOMA-β (β±SE: 0.2736±0.0812; P=0.0009). This study reveals that BTMs are highly associated with T2DM, insulin sensitivity and beta cell function in both Chinese males and postmenopausal females.

Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population

Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. The levels of serum uric acid and bone turnover markers (BTMs) were detected along with other biochemical traits. In addition, the fat distribution was calculated through MRI and image analysis software, and bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. For postmenopausal females, the prevalence of osteoporosis was significantly lower in the hyperuricemia group compared with the normouricemic group (P=4.65E-06). In females, serum uric acid level was significantly associated with osteoporosis, with odds ratio (OR) and 95% confidence interval (95% CI) of 0.844 [0.763; 0.933] (P=0.0009) after adjusting for age, body mass index, HbA1c, lean mass, visceral and subcutaneous fat areas, albumin, 25-hydroxyvitamin D3 [25(OH)D3], and parathyroid hormone (PTH). In females, serum uric acid level was positively correlated with the BMD of the femoral neck (β±SE: 0.0463±0.0161; P=0.0042), total hip (β±SE: 0.0433±0.0149; P=0.0038) and L1-4 (β±SE: 0.0628±0.0165; P=0.0001) after further adjusting for age, BMI, HbA1c, lean mass, VFA, SFA, albumin, 25(OH)D3 and PTH. Regarding BTMs, serum uric acid level was negatively correlated with N-terminal procollagen of type I collagen (PINP) in females (β±SE: -0.1311±0.0508; P=0.0100). In summary, our results suggest that uric acid has a protective effect on bone metabolism independent of body composition in Chinese postmenopausal females.

Association between serum uric acid related genetic loci and diabetic kidney disease in the Chinese type 2 diabetes patients

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.