糖尿病肾病患者维生素D结合蛋白水平及影响因素研究

Vitamin D Binding Protein Levels in Patients With Diabetic Nephropathy and Its Influencing Factors

目的探讨糖尿病肾病（ON）患者维生素D结合蛋白（VDBP）水平及其影响因素，以明确VDBP与DN的关系，为DN的诊断及治疗提供新的依据。方法选取2013年8月-2014年2月在大连医科大学附属二院住院的2型糖尿病（T2DM）患者66例。根据尿微量清蛋白与尿肌酐比值（UACR）将患者分为3个亚组：正常清蛋白尿组（UACR〈30mg／g）、微量清蛋白尿组（UACR30-300mg／g）和临床清蛋白尿组（UACR〉300mg／g），各22例。同时选取该院门诊的健康体检者20例为健康对照组。采用酶联免疫吸附试验（ELISA）法检测4组受试者血、尿VDBP水平，同时检测其相关生化指标：空腹血糖（FPG）、糖化血红蛋白（HbA1c）、血尿素（UREA）、血肌酐（SCr）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、血清蛋白（ALB）及尿微量清蛋白、尿肌酐。结果健康对照组及正常、微量、临床清蛋白尿组血VDBP水平分别为：（44．83±15．65）、（312．25±29．57）、（330．92±49．28）、（338．30±50．05）mg／L，4组间差异有统计学意义（F=409．42，P〈0．01）；其中正常、微量、临床清蛋白尿组均高于健康对照组，差异有统计学意义（P〈0．05）；而正常、微量及临床清蛋白尿3组比较，差异无统计学意义（P〉0．05）。健康对照组及正常、微量、临床清蛋白尿组尿VDBP水平分别为：（5．26±1．34）、（8．93±3．17）、（15．19±3．38）、（21．48±7．00）mg／L，4组间差异有统计学意义（F=58．66，P〈0．01）；其中两两组间比较，差异均有统计学意义（P〈0．05）。因尿VDBP检测采用晨尿点标本，无24h尿标本检测准确，故依据UACR法，用尿肌酐对尿VDBP值进行校正（尿VDBP／Cr）。健康对照组与正常、微量、临床清蛋白尿组尿VDBP／Cr水平分别为：（4．25±1．89）、（10．76±7．02）、（23．01±11．39）、（41．58±17．10）mg／g，4组间差异有统计学意义（F=47．38，P〈0．01）；其中两两组间比较，差异均有统计学意义（P〈0．05）。T2DM患者尿VDBP水平与估算肾小球滤过率（eGFR）呈负相关（r=一0．413，P：0．015）。另外，T2DM患者尿VDBP水平与UREA、SCr呈正相关（r值分别为0．505、0．454，P〈0．05）；而与ALB呈负相关（r=一0．454，P〈0．05）。结论T2DM患者血、尿VDBP水平均有明显升高，且伴随DN的进展，尿VDBP水平逐渐升高，尿VDBP水平与eGFR、UREA、SCr、ALB有关，故尿VDBP水平对评估DN的病情有一定价值。

Objective To investigate vitamin D binding protein （VDBP） levels in patients with diabetic nephropathy （DN） , and to determine the relation between VDBP and DN, in order to provide new references for the diagnosis and treatment of DN. Methods We enrolled 66 T2DM patients who were admitted into the Second Affiliated Hospital of Dalian Medical University from August 2013 to February 2014. According to the ratio of UALB to UCR （UACR） , the patients were divided into three groups： normal albuminuria group （UACR 〈 30 mg/g） , slight albuminurla group （UACR 30～ 300 mg/g） and clinical albuminuria group （ UACR 〉 300 mg/g） , with 22 patients in each group. We also enrolled 20 healthy people who received outpatient service as control group. ELISA method was employed to detect the serum and urine VDBP level of the subjects, and biochemical indexes were measured, including FPG, HbA1c, UREA, SCr, TC, TG, HDL-C, LDL-C, ALB, UALB, UCR. Results The serum VDBP levels of control group, normal albuminuria group, slight albuminuria group and clinical alhuminuria group were （44. 83 ± 15.65）, （312. 25 ±29.57）, （330. 92±49. 28） and （338.30±50. 05） mg/L respectively, with significant differences among the four groups （ F = 409.42, P 〈 0. 01 ） ; normal albuminuria group, slight albuminuria group and clinical albuminuria group were higher than control group （ P 〈 0. 05 ） , while normal albuminuria group, slight albuminuria group and clinical albuminuria group were not significantly different （ P 〉 0.05 ） . The urine VDBP levels of control group, normal albuminuria group, slight albuminuria group and clinical albuminuria group were （5.26 ± 1.34 ）, （8.93 ± 3.17）, （ 15. 19± 3.38 ） and （21.48 ±7.00） mg/L, with significant differences among the four groups （ F = 58. 66, P 〈 0. 01 ） ; the pairwise comparison among the four groups showed significant differences （ P 〈 0.05 ） . Since urine VDBP test was made on urine samples taken in the morning, which leaded to poorer accuracy compared with 24 h urine samples, so UCR was used to adjust urine VDBP level by UACR method （urine VDBP/Cr） . The urine VDBP/Cr levels of control group, normal albuminuria group, slight albuminuria group and clinical albuminuria group were （4.25 ± 1. 89）, （ 10.76±7.02）, （23.01 ±11.39） and （41.58 ± 17.10） mg/g, with significant differences among the four groups （F =47.38, P 〈0.01）; the pairwise comparison among the four groups showed significant differences （P 〈 0. 05 ） . The urine VDBP level of T2DM patients had negative correlation with eGFR in T2DM patients （r = -0. 413, P = 0. 015 ） . The urine VDBP level was positively correlated with UREA and SCr in T2DM patients （ r values were 0. 505 and 0. 454 ; P 〈 0.05 ） and were negatively correlated with ALB （ r = - 0. 454, P 〈 0. 05） . Conclusion T2DM patients have higher VDBP levels of serum and urine and see urine VDBP level increase as DN progresses, and urine VDBP level is related to eGFR, UREA, SCr and ALB, thus urine VDBP level has value in the assessment of DN to some extent.