| OBJECTIVE With the continuous improvement of living standards of our country, the prevalence of hyperuricemia increased year by year. Hyperuricemia and diabetes are serious metabolic diseases which harmful to human health, are there any links between the two diseases? Currently, there are no system epidemiological investigation of diabetes mellitus with hyperuricemia. Uric acid excretion is an important factor affecting the level of serum uric acid. Most of previous studies used 24-hour urinary uric acid to distinguish uric acid underexcretion and overproduction. However, this method is the affacted by diet, drinking water, urine and serum uric acid. Currently, fraction excertion of uric acid(FEUA) was used to evaluate the excretion of uric acid, which could eliminat the effects of serum uric acid, urine volume and other confounding factors, and was more reliable than 24-hour urinary uric acid. The relationship among uric acid, hyperuricemia and renal function in diabetic patients had not been reported. Moreover, in clinical work fasting blood samples were typically selected to test the uric acid level, the influence of eating to the level of serum uric acid is unclear. Calculating FEUA needs to collect 24-hour urine, which is inconvenient to patient. There are no studies reported the relationship among FEUA, serum uric acid, serum creatinine, urinary uric acid and creatinine at any point. There are no conclusions about whether could use urinary uric acid at any point instead of FEUA. Therefore, The purpose of this study are as follows: 1, the analysis of prevalence, risk factors of diabetic patients with hyperuricemia and relationship between hyperuricemia and renal function in diabetic patients; 2, the analysis of uric acid excretion in diabetic patients with hyperuricemia, its affected factors and relationship between uric acid excretion and renal function; 3, the analysis of changes of serum uric acid levels before and after meal, and assessment of uric acid excretion and kidney function in diabetes.METHODS In this cross-sectional study, we used data from diabetic patients between July 2011, and September2012, at the Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital. We also recruited 80 healthy volunteers with normal glucose tolerance without hyperuricemia as control group. The collected data included gender, age, body height, body weight, and m GFR. Fasting blood was taken from selected patients to analyze creatinine, urea nitrogen, fasting plasma glucose, Hb A1 c, et al. One-way analysis of variance(ANOVA) followed by multiple comparison test with the least significant difference was used to compare the differences of characteristics among groups. Pearson correlation coefficients between uric acid and covariates were calculated for different genders. Linear regression was used to analysis the independent relevant factor associated with uric acid as the independent variable by stepwise method. We performed a cross-sectional analysis of uric acid and kidney function using multinomial logistic regression. Uric acid level was modeled as a categorical variable and as a continuous variable. The Bland–Altman method was used to evaluate the agreement among the equations with respect to the m GFR, and the receiver-operating characteristic curve method was used to evaluate the diagnostic value of the three equations with respect to the detection of moderate renal failure and hyperfiltration.RESULTS 1. The analysis of prevalence, risk factors of diabetic patients with hyperuricemia and relationship between hyperuricemia and renal function in diabetic patients. This study shows that in Chinese diabetic patients, the prevalence of hyperuricemia is 15.87% in all diabetes, 14.52% in men and 17.80% in women. Serum uric acid independently associated with GFR, Cp, urinary albumin, age, Hb A1 c and BMI. Our research shows that the prevalence of hyperuricemia in diabetic women more than 49 years old was significantly higher than men, and the prevalence of hyperuricemia in diabetic women increased gradually with increasing of age; with the increasing of BMI, fasting C-peptide, HOMA-IR calculated by C-peptide and urine albumin, and the decreasing of GFR, the prevalence of hyperuricemia in diabetes increased; with the increasing of GA, the prevalence of hyperuricemia decreased. Hyperuricemia is strongly associated with an increased incidence of abnormal albuminuria and GFR<60m L/min/1.73 m2, and decreased incidence of hyperfiltration in Chinese diabetic individuals. In continuous analyses, a 1-SD increment(i.e., 94μmol/L) in the serum uric acid level was associated with a 0.8% increased risk of incident GFR<60 m L/min/1.73 m2, a 0.3% increased risk of incident abnormal albuminuria, and a 0.5% decreased risk of incident hyperfiltration after adjusting for potential confounders(model 2). 2. The analysis of uric acid excretion in diabetic patients with hyperuricemia, its affected factorsand relationship between uric acid excretion and renal function. Uric acid underexcretion and overproduction were existed in diabetic patients without hyperuricemia, the main type of hyperuricemia was uric acid overproduction; in diabetic patients with hyperuricemia, the main type of hyperuricemia was uric acid underexcretion. In diabetic patients with normal renal function, the main type of hyperuricemia was uric acid overproduction in type 1 diabetic patients, and uric acid underexcretion in type 2 diabetic patients. In diabetic patients with GFR> 60 ml/min/1.73m2, uric acid excretion(FEUA) were independently associated with HDL, BMI, age, GA, sex, LDL, Ln ACR and TG. With the increasing of age, the FEUA level of women did not change significantly, the FEUA level of men more than 57 years old significantly higher than that less than 57 years old; in each age group, the FEUA level of women significantly higher than men. With increasing of BMI, GA and proteinuria, FEUA levels were significantly increased. In non-proteinuria diabetic population, the levels of GFR are higher with increasing of FEUA; in diabetes with proteinuria, the levels of GFR are lower with increasing of FEUA and ACR. Uric acid overproduction is strongly associated with an increased incidence of abnormal albuminuria and GFR<60m L/min/1.73 m2 in Chinese diabetic individuals, the value of OR is 5.187(3.594-7.488, P<0.001) and 1.875(1.465-2.401, P<0.001), respectively. In continuous analyses, a 1-SD increment(i.e., 2.64%) in the FEUA level was associated with a 24.7% increased risk of incident GFR<60 m L/min/1.73 m2, a 13.9% increased risk of incident abnormal albuminuria(model 2). 3. The changes of serum uric acid levels before and after meal, and assessment of uric acid excretion and kidney function in diabetes. There are no significent differences of serum uric acid levels before and after meal among control, impaired glucose tolerance and diabetes group. The FEUA independently associated with serum uric acid and urine uric acid, the regression formula is: FEUA=14.02-0.02×SUA-0.002×UUA(mg/L),R=0.617. Among creatinine-based equations, the CDK-EPI equation exhibits the best performance in detecting hyperfiltration in diabetic patients, and the highest accuracy within ± 15%, and ± 30%. Among MDRD, cystatin C and creatinine-cystatin C equation, the creatinine-cystatin C equation exhibits the best performance in detecting hyperfiltration in diabetic patients and the highest accuracy within ± 15%, and ± 30%.CONCLUSION 1、In Chinese diabetic patients, the prevalence of hyperuricemia is 15.87% in all diabetes, 14.52% in men and 17.80% in women. The prevalence of hyperuricemia in diabetic women more than 49 years old was significantly higher than men, and the prevalence of hyperuricemia in diabetic women increased gradually with increasing age; with the increasing of BMI, fasting C-peptide, HOMA-IR calculated by C-peptide and urine albumin, and the decreasing of GFR, the prevalence of hyperuricemia in diabetes increased; with the increasing of GA, the prevalence of hyperuricemia decreased. 2、Hyperuricemia is strongly associated with an increased incidence of abnormal albuminuria and GFR<60m L/min/1.73 m2, and decreased incidence of hyperfiltration in Chinese diabetic individuals. 3 、 Uric acid underexcretion and overproduction were existed in diabetic patients without hyperuricemia, the main type of hyperuricemia was uric acid overproduction; in diabetic patients with hyperuricemia, the main type of hyperuricemia was uric acid underexcretion. In diabetic patients with normal renal function(GFR>60 m L/min/1.73 m2), the main type of hyperuricemia was uric acid overproduction in type 1 diabetic patients, and uric acid underexcretion in type 2 diabetic patients. 4、In non-proteinuria diabetic population, the levels of GFR are higher with increasing of FEUA; in diabetes with proteinuria, the levels of GFR are lower with increasing of FEUA and ACR. 5 、Uric acid overproduction is strongly associated with an increased incidence of abnormal albuminuria and GFR<60m L/min/1.73 m2 in Chinese diabetic individuals. 6、There are no significent differences of serum uric acid levels before and after meal among control, impaired glucose tolerance and diabetes group. 7、The FEUA independently associated with serum uric acid and urine uric acid, the regression formula is: FEUA=14.02-0.02×SUA-0.002×UUA(mg/L),R=0.617. 8、Among creatinine-based equations, the CDK-EPI equation exhibits the best performance in Chinese diabetic patients; Among MDRD, cystatin C and creatinine-cystatin C equation, the creatinine-cystatin C equation exhibits the best performance in Chinese diabetic patients. |
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