血清25羟维生素D和视黄醇结合蛋白4在2型糖尿病肾病中的临床研究

Clinical study on serum 25-hydroxy vitamin D and retinol binding protein 4 in type 2 diabetic nephropathy

目的回顾性分析2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清25羟维生素D[25(OH)D]和视黄醇结合蛋白4(retinol binding protein 4,RBP-4)及其他临床资料,对比上述临床指标在T2DM伴或不伴糖尿病肾病(diabetic nephropathy,DN)患者中的差异,探讨其对DN的临床意义。方法选择1946例T2DM患者,根据T2DM是否合并DN分为DN组及糖尿病无肾病(nondiabetic nephropathy,NDN)组,进一步根据尿白蛋白/肌酐比值(urine albumin-to-creatinine ratio,UACR)将DN组分为微量蛋白尿组(UACR 30~300 mg/g)和大量蛋白尿组(UACR>300 mg/g)。收集所有患者的一般资料、血清25(OH)D、和RBP-4及其他临床指标。结果DN组病程、年龄、糖化血红蛋白、RBP-4、超敏C反应蛋白、总胆固醇和甘油三酯高于NDN组,25(OH)D和高密度脂蛋白胆固醇低于NDN组(P<0.05)。DN患者中大量蛋白尿组的RBP-4高于微量蛋白尿组,年龄、25(OH)D、高密度脂蛋白胆固醇低于微量蛋白尿组(P<0.05)。在DN组中控制年龄、性别和病程后进行偏相关分析示,25(OH)D与肾小球滤过率估测值(estimated glomerular filtration rate,eGFR)呈正相关,与RBP-4、UACR呈负相关(P均<0.05)。UACR与RBP-4、总胆固醇呈正相关,与eGFR呈负相关(P均<0.05)。eGFR与RBP-4、总胆固醇、UACR呈负相关(P均<0.05)。对T2DM合并DN的影响因素进行多因素二元Logistic回归分析示,病程、糖化血红蛋白、RBP-4、超敏C反应蛋白为T2DM合并DN的危险因素,25(OH)D为T2DM合并DN的保护因素。结论血清25(OH)D降低和RBP-4升高使T2DM合并DN的风险增加,而且在DN患者中血清25(OH)D降低和RBP-4升高与蛋白尿增加及肾功能恶化相关,并且25(OH)D与RBP-4之间存在负相关。因此临床上要加强对T2DM患者血清25(OH)D和RBP-4的监测以及维生素D的补充,以预防和延缓DN的发生和进展。

Objective This was a retrospective study to compare the serum 25-hydroxy vitamin D[25(OH)D],retinol binding protein 4(RBP-4)and other clinical data in type 2 diabetes mellitus(T2DM)patients with or without diabetic nephropathy(DN)and to explore the clinical significance of these indicators in DN.Methods 1946 T2DM patients were enrolled in this study.The T2DM patients were divided to group with diabetic nephropathy(DN group)and without diabetic nephropathy(NDN group).According to the urine albumin to creatinine ratio(UACR),DN patients were further divided into microalbuminuria subgroup(UACR 30~300 mg/g)and massive proteinuria subgroup(UACR>/g).Clinical characteristics including serum 25(OH)D,RBP-4 and other biochemical indicators were collected.Results Compared with NDN group,DN group showed longer disease duration,older age and higher levels of HbA1c,RBP-4,hs-CRP,TC and TG;25(OH)D and HDL-C in DN group were lower than those in NDN group(P<0.05).Within DN group,massive proteinuria subgroup showed higher RBP-4,younger age and lower 25(OH)D and HDL-C than microalbuminuria subgroup(P<0.05).After adjusted for age,gender and disease duration in DN,partial correlation analysis showed that 25(OH)D is positively correlated with eGFR,and negatively correlated with RBP-4 and UACR(P<0.05).UACR is positively correlated with RBP-4 and TC,and negatively correlated with eGFR(all P<0.05).eGFR is negatively correlated with RBP-4,TC and UACR(all P<0.05).Multivariate logistic regression showed that disease duration,HbA1c,RBP-4 and hs-CRP are risk factors for DN,and 25(OH)D is the protective factor for DN.Conclusions Decreased 25(OH)D and increased RBP-4 are associated with increased DN risk in T2DM patients,and also associated with exacerbated albuminuria and deteriorated renal function in DN patients.There is a negative correlation between 25(OH)D and RBP-4 in DN.Therefore,it is necessary to strengthen the monitoring of serum 25(OH)D and RBP-4 and enhance vitamin D supplementation in T2DM patients to prevent the occurrence and delay the progression of diabetic nephropathy.