2型糖尿病患者正常水平血清肌酐与糖尿病肾病的前瞻性队列研究

Normal serum creatinine levels and diabetic kidney disease in patients with type 2 diabetes mellitus: A prospective cohort study

目的探讨正常水平血清肌酐(serum creatinine, Scr)与2型糖尿病(type 2 diabetes mellitus, T2DM)患者糖尿病肾病(diabetic kidney disease, DKD)的关系。方法本研究为前瞻性队列研究, 选取2002年1月1日至2018年12月31日在中国台湾李氏联合诊所6个中心定期随访的T2DM患者作为研究对象。基线时患者无DKD, 收集患者的一般资料、实验室检查指标。根据患者随访时间内是否发生DKD将患者分为DKD组和无DKD组(nondiabetic kidney disease, NDKD)。暴露因素是Scr(μmol/L)值, 并作为分类变量, 根据Scr四分位数分为4组:Q1组(Scr<57.68 μmol/L)、Q2组(57.68 μmol/L≤Scr<68.51 μmol/L)、Q3组(68.51 μmol/L≤Scr<80.44 μmol/L)和Q4组(Scr≥80.44 μmol/L)。使用Cox回归模型来探讨Scr水平与DKD发病之间的关系, 采用受试者工作特征(receiver operating characteristic, ROC)曲线分析正常水平Scr对DKD的预测作用。结果共纳入在基线时无DKD的2 202例T2DM患者, 经过(5.2±2.17)年随访时间后, 共有966例患者发生了DKD, 1 236例患者未发生DKD。与NDKD组相比, DKD组年龄更大, 糖尿病病程更长, 体重指数、收缩压、舒张压、低密度脂蛋白胆固醇、Scr、尿蛋白/肌酐比值更高(均P<0.05)。Cox回归分析结果显示:以Q1组为对照, 在校正混杂因素后, Q2、Q3、Q4组发生DKD结局的风险分别为1.394、1.688、2.821倍(均P<0.05), ROC曲线分析结果显示:正常水平Scr预测DKD发生的曲线下面积(AUC)为0.70(95%CI 0.678~0.722), 最佳截断值为74.27 μmol/L, 敏感度为0.54, 特异度为0.76。累积风险图显示:在校正混杂因素后Q4组患者DKD发病累积风险高于Q1、Q2、Q3组, 差异有统计学意义(均P<0.05)。结论 Scr是T2DM患者发生DKD的独立危险因素, T2DM患者较高的Scr水平发生DKD风险越大, 特别是当Scr>74.27 μmol/L时, 更应高度关注DKD发生的可能性。

Objective To explore the relationship between normal serum creatinine(Scr)level and diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods This was a prospective cohort study.Patients with yet not DKD who were regularly followed up at six centers of Li′s United Clinic in Taiwan,China from January 1,2002 to December 31,2018 were selected.At baseline,clinic information and lab tests were collected.According to whether the patients developed DKD during the follow-up period,they were divided into DKD group and non-DKD(NDKD)group.The exposure factor was the Scr(μmol/L)value,and it was used as a categorical variable.According to the quartiles of Scr,they were divided into 4 groups:Q1 group(Scr<57.68μmol/L),Q2 group(57.68μmol/L≤Scr<68.51μmol/L),Q3 group(68.51μmol/L≤Scr<80.44μmol/L)and Q4 group(Scr≥80.44μmol/L).The Cox regression model was used to explore the relationship between Scr level and the incidence of DKD.Receiver operating characteristic(ROC)curve was used to analyze the predictive effect of normal level Scr on DKD.Results A total of 2202 T2DM patients without DKD at baseline were included.After a follow-up period of(5.2±2.17)years,there were 966 patients in the DKD group and 1236 patients in the NDKD group.Compared with the NDKD group,the DKD group had older age,longer duration of diabetes,higher BMI,SBP,DBP,LDL-C,Scr,and UACR(all P<0.05).Cox regression analysis results showed that compared with the Q1 group as the reference,the risk of developing DKD in the Q2,Q3,and Q4 groups after adjusting for confounding factors was 1.394,1.688,and 2.821 times higher,respectively(all P<0.05).ROC curve analysis results showed that the area under the curve(AUC)for predicting DKD occurrence using normal serum creatinine level was 0.70(95%CI 0.678-0.722),with an optimal cutoff value of 74.27μmol/L,sensitivity of 0.54,and specificity of 0.76.The cumulative risk plot showed that after adjusting for confounding factors,patients in the Q4 group had a higher cumulative risk of developing DKD compared to the Q1,Q2,and Q3 groups(all P<0.05).Conclusion Scr is an independent risk factor for developing DKD in patients with T2DM.The higher the Scr level,the greater the risk,especially when Scr is greater than 74.27μmol/L.