[收稿日期]2021-06-22 [修回日期]2022-02-27[基金项目]蚌埠医学院自然科学研究重点项目(BYKY2019246ZD)[作者单位]蚌埠医学院第三附属医院内分泌科,安徽宿州234000[作者简介]常 丽(1996-),女,硕士研究生.[通信作者]黄莹芝,硕士研究生导师,主任医师.E⁃mail:hyz598@[文章编号]1000⁃2200(2023)10⁃1395⁃04㊃临床医学㊃2型糖尿病血清同型半胱氨酸㊁视黄醇结合蛋白与尿微量白蛋白/肌酐比值的相关性分析常 丽,黄莹芝[摘要]目的:探讨2型糖尿病病人血清中同型半胱氨酸(homocysteine,Hcy)㊁视黄醇结合蛋白(retinol binding protein,RBP)与尿微量白蛋白/肌酐比值(urine microalbumin⁃creatinine ratio,ACR)的关系㊂方法:根据尿ACR 将490例糖尿病病人分为3组,其中378例为正常白蛋白尿组(NA 组,ACR <30mg /g),71例为微量白蛋白尿组(MA 组,ACR 为30~300mg /g ),41例为大量白蛋白尿组(LA 组,ACR >300mg /g)㊂所有研究对象均测量身高㊁体质量,计算体质量指数(BMI),并检测尿素(BUN)㊁肌酐(Cr)㊁Hcy㊁RBP㊁尿ACR㊁胆固醇(TC)㊁三酰甘油(TG)㊁低密度脂蛋白(LDL)㊁高密度脂蛋白(HDL)㊁空腹血糖(FPG)和糖化血红蛋白(HbA1c),并分析3组血清Hcy㊁RBP㊁Cr㊁BUN 与尿ACR 的相关性㊂结果:3组间年龄㊁BMI㊁HbA1C㊁FPG㊁TG 差异均无统计学意义(P >0.05)㊂病程和LDL 水平,NA 组低于MA 组和LA 组,MA 组低于LA 组;HDL 水平,NA 组高于MA 组和LA 组,MA 组高于LA 组;TC 水平,LA 组高于MA㊁NA 组,差异均有统计学意义(P <0.05~P <0.01);LA 组血清Hcy㊁RBP㊁Cr㊁BUN 水平较MA㊁NA 组均升高,MA 组RBP㊁Hcy㊁Cr㊁BUN 水平较NA 组升高,差异均有统计学意义(P <0.01);病人血清Cr㊁BUN㊁Hcy 和RBP 水平与尿ACR 水平均呈正相关关系(P <0.01)㊂结论:血清Hcy㊁RBP 能反映糖尿病早期肾损伤,与尿ACR 呈正相关关系,血清RBP 敏感性更高,两者对2型糖尿病肾病的早期诊断有重要的价值㊂[关键词]糖尿病肾病;视黄醇结合蛋白;同型半胱氨酸;尿微量白蛋白/肌酐比值[中图法分类号]R 692.39 [文献标志码]A DOI :10.13898/ki.issn.1000⁃2200.2023.10.015Correlation analysis of the serum levels of homocysteine ,retinol binding protein and urine microalbumin⁃creatinine ratio in patients with type 2diabetes mellitusCHANG Li,HUANG Ying⁃zhi(Department of Endocrinology ,The Third Affiliated Hospital of Bengbu Medical College ,Suzhou Anhui 234000,China )[Abstract ]Objective :To explore the relationship between the serum levels of homocysteine(Hcy),retinol binding protein(RBP)and urine microalbumin⁃creatinine ratio (ACR)in patients with type 2diabetes mellitus.Methods :According to the urine ACR,490diabetic patients were divided into the normal albuminuria group(NA group,378cases with ACR <30mg /g),microalbuminuria group (MA group,71cases with ACR 30-300mg /g)and large amount of albumin group(LA group,41cases with ACR >300mg /g).The height,weight and body mass index(BMI)in all cases were measured,the serum levels of blood urea nitrogen(BUN),creatinine(Cr),Hcy,RBP,ACR,total cholesterol (TC),triglycerides (TG),low⁃density lipoprotein (LDL),high⁃density lipoprotein (HDL),fasting plasma glucose(FPG)and glycosylated hemoglobin(HbA1c)in three groups were examined,and the correlation between the serum levels of Hcy,RBP,Cr,BUN and ACR among three groups were analyzed.Results :There was no statistical significance in the age,BMI,HbA1C,FPG and TG among three groups(P >0.05).The course of disease and LDL level in NA group was lower than those in MA group and LA group,and which in MA group was lower than that in LA group;the level of HDL in NA group was higher than that in MA group and LA group,and which in MA group was higher than that in LA group;the TC level in LA group was higher than that in MA group and NA group(P <0.05to P <0.01).The serum levels of Hcy,RBP,Cr and BUN in LA group increased compared with MAgroup and NA group,the serum levels of RBP,Hcy,Cr and BUN in MA group increased compared with the NA group,and the differences of which were statistically significant(P <0.01).The serum levels of Cr,BUN,Hcy and RBP in patients were positively correlated with the urinary ACR level(P <0.01).Conclusions :The serum levels of Hcy and RBP can reflect the early diabetic kidney injury,and are positively correlated with urinary ACR,the serum RBP sensitivity is higher,and both of which have important value for early diagnosis of type 2diabetic nephropathy.[Key words ]diabetic nephropathy;retinol binding protein;homocysteine;urine microalbumin⁃creatinine ratio 糖尿病是代谢性疾病,据估计,2019年全球有4.63亿20~79岁的成年人(占成年人口的8.8%)患有糖尿病,到2030年将上升至10.2%(5.78亿人),到2045年上升至10.9%(7亿人)[1]㊂中国是世界糖尿病高发地区,多中心流行病学调查显示,我国成人中糖尿病的患病率已高达12.8%[2]㊂其中90%~95%为2型糖尿病,长期处于高血糖环境将会发生一系列并发症,其中糖尿病肾病(DKD)是一种严重且进行性的糖尿病慢性并发症,影响到30%以上的2型糖尿病㊂糖尿病史20年以上,DKD发生率几乎100%,它导致了2型糖尿病病人寿命的缩短㊂本文通过分析2型糖尿病病人血清中同型半胱氨酸(Hcy)㊁视黄醇结合蛋白(RBP)与尿微量白蛋白/肌肝比值(ACR)的相关性,从而探讨检测Hcy㊁RBP在诊断早期2型DKD中的价值㊂现作报道㊂1 资料与方法1.1 一般资料 选取2019年8月至2020年8月在蚌埠医学院第三附属医院内分泌科收治住院的490例2型糖尿病病人㊂其中男306例,女184例,年龄25~96岁,平均年龄(58.60±12.57)岁㊂病程1个月至39年,平均病程(8.71±7.41)年㊂入组标准:符合1999年WHO糖尿病的诊断标准,临床资料完整㊂排除标准:(1)糖尿病急性并发症;(2)合并严重感染;(3)原发性肾脏疾病;(4)近3个月内使用过影响肾功能的药物;(5)由其他原因引起的肝肾功能障碍;(6)哺乳期㊁妊娠期女性㊂1.2 分组 根据尿ACR将所有入选病例分为3组,其中ACR<30mg/g者378例为正常白蛋白尿(NA)组,男231例,女147例;ACR为30~ 300mg/g者71例为微量白蛋白尿(MA)组,男48例,女23例;ACR>300mg/g者41例为大量白蛋白尿(LA)组,男27例,女14例㊂1.3 检测指标 所有病人均测量身高㊁体质量,计算体质量指数(BMI),并检测血尿素(BUN)㊁肌酐(Cr)㊁RBP㊁Hcy㊁尿ACR㊁胆固醇(TC)㊁三酰甘油(TG)㊁低密度脂蛋白(LDL)㊁高密度脂蛋白(HDL)㊁空腹血糖(FPG)和糖化血红蛋白(HbA1c)㊂1.4 仪器及方法 所有病人空腹8h以上,于入院当天或第2天采集肘静脉血3~5mL,以3000r/ min离心10min,检测血清BUN㊁Cr㊁Hcy㊁RBP㊁TG㊁TC㊁LDL㊁HDL㊁FPG㊁HbA1c含量及尿ACR㊂FPG采用葡萄糖氧化酶法,HbA1c采用高压液相色谱法, BUN㊁Cr㊁Hcy㊁RBP使用北京九强生物技术有限公司生产的试剂及配套的校准品和质控品,检测方法选用颗粒增强免疫比浊法,在日立7600⁃020型全自动生化分析仪上进行检测㊂所有测定均严格按照实验室标准操作规程操作㊂1.5 统计学方法 采用单因素方差分析㊁q检验和Pearson相关性分析㊂2 结果2.1 3组一般资料和生化指标及Hcy㊁RBP㊁Cr㊁BUN比较 3组间病程㊁TC㊁HDL㊁LDL差异均有统计学意义(P<0.01);3组病人的年龄㊁BMI㊁HbA1c㊁FPG㊁TG差异均无统计学意义(P>0.05)㊂两两比较结果显示,病程和LDL水平,NA组低于MA组和LA组,MA组低于LA组;HDL水平,NA组高于MA组和LA组,MA组高于LA组;TC水平, LA组高于MA㊁NA组,差异均有统计学意义(P< 0.05~P<0.01)(见表1~2)㊂LA组血清Hcy㊁RBP㊁Cr㊁BUN水平较MA㊁NA组均升高,MA组RBP㊁Hcy㊁Cr㊁BUN水平较NA组升高,差异均有统计学意义(P<0.01)(见表2)㊂表1 3组研究对象的一般资料比较(x±s)分组n年龄/岁病程/年 BMI/(kg/m2) HbA1c/%FPG/(mmol/L) NA组378 58.01±11.92 7.79±6.90 25.81±3.14 9.11±2.049.56±3.38 MA组7160.34±14.8110.74±8.88**26.25±3.549.26±1.939.94±3.57 LA组4161.12±13.9913.81±6.64**#26.65±3.869.37±2.299.40±4.17 F 1.9016.15 1.53 0.430.43P >0.05<0.01>0.05 >0.05>0.05 MS组内 157.29951.75310.630 4.19012.118 q检验:与NA组比较**P<0.01;与MA组比较#P<0.052.2 Hcy㊁RBP㊁BUN㊁Cr与尿ACR的相关性分析 结果显示,2型糖尿病病人血清Cr㊁BUN㊁Hcy和RBP水平与尿ACR水平均呈正相关关系(P< 0.01)(见表3)㊂3 讨论 DKD已成为慢性肾脏衰竭的主要原因,其发生发展经历几个阶段,从正常白蛋白尿㊁微量白蛋白尿㊁大量白蛋白尿最终导致终末期肾脏疾病(ESRD)㊂美国肾脏病基金会推荐尿ACR作为DKD的早期诊断指标,本研究即以此来进行分组㊂RBP作为一种与胰岛素抵抗相关的因子,在体内主要以前蛋白㊁视黄醇结合的复合物形式存在,仅有着21000的低相对分子质量,可以通过肾小球自由过滤,大部分由近端肾小管上皮细胞重新吸收㊁降解,成为反映肾小管损伤的有用指标㊂肾脏疾病时,肾小球滤过下降等因素血RBP会升高㊂本研究中,各组病人血清RBP呈逐渐升高趋势,同时相关分析结果显示RBP与尿ACR呈正相关关系(r=0.606),表明RBP与DKD诊断指标尿ACR有较好的相关性㊂有研究[3]显示相比较单纯2型糖尿病组而言,2型糖尿病合并DKD组的RBP水平均较高,本研究结果与之一致㊂萨如拉等[4]研究显示RBP 升高使2型糖尿病合并DKD的风险增加,而且在DKD病人中血清RBP升高与蛋白尿增加及肾功能恶化相关㊂同传统的肾脏损伤标志物Cr相比,Cr 受肾小管分泌和肌肉质量或蛋白质摄入对其浓度的影响,有其一定的局限性㊂同时有国内研究[5]发现,出现肾功能损害时,与传统的Cr㊁BUN等肾功能指标相比,RBP变化较早㊂通过检测该物质,可在早期肾功能轻微受损时进行精确㊁快速的诊断㊂表2 3组研究对象的临床相关指标比较(x±s)分组n TC/(mmol/L)TG/(mmol/L)HDL/(mmol/L)LDL/(mmol/L)Cr/(μmol/L)BUN/(mmol/L)RBP/(mg/L)Hcy/(μmol/L) NA组378 4.59±1.15 2.21±2.18 1.19±0.32 2.65±0.7758.06±16.57 5.81±1.5740.31±11.2811.56±3.16MA组71 4.46±1.28 2.28±1.75 1.11±0.28* 2.90±0.87**69.31±26.29* 6.90±2.28*45.54±14.20**13.94±4.58* LA组41 5.51±1.56*# 2.96±3.770.99±0.23* 3.37±1.14**#87.05±24.87**##7.76±3.20**#59.41±17.45**##17.83±4.76**#F 11.87 2.009.4515.5865.8027.13241.8364.98P <0.01>0.05<0.01<0.01<0.01<0.01<0.01<0.01MS组内 1.459 5.280.0940.677301.705 3.482152.44612.634 q检验:与NA组比较*P<0.05,**P<0.01;与MA组比较#P<0.05,##P<0.01表3 糖尿病病人肾功能指标与ACR的相关性分析ACR与肾功能指标的相关性Cr BUN Hcy RBP r0.3490.1860.4630.606P<0.01<0.01<0.01<0.01 目前认为Hcy是心血管疾病的一个独立危险因子㊂李栋等[6]认为Hcy可能通过促进体内炎症反应进一步导致血管内皮功能紊乱而参与了冠心病的发病过程㊂血浆Hcy也是2型糖尿病病人DKD 进展的独立危险因素和早期预测因子㊂有研究[7]表明在中国糖尿病病人中,循环Hcy水平升高与DKD风险增加有因果关系㊂血清Hcy随着尿白蛋白排泄率增加不断升高,与DKD的进展密切相关[8]㊂Hcy与eGFR有显著的相关性,Hcy对于肾脏功能的损伤以及肾脏功能受损以后Hcy排泄受阻,在Hcy与eGFR的相关性中都发挥了重要的作用[9]㊂本研究中,各组病人血清Hcy水平逐渐升高,且LA组明显高于NA和MA组,MA组明显高于NA组,表明随着DKD的进展,Hcy水平进一步升高㊂Hcy可以通过增加活性氧的产生或破坏抗氧化系统来促进氧化应激[10]㊂血清Hcy水平的升高可能推进导致肾动脉硬化性血管病,从而导致DKD的发生㊂Hcy造成的内皮功能的损害也是动脉粥样硬化和心血管疾病发生的关键因素,增加了糖尿病病人的死亡风险㊂本研究还发现,血脂(TC㊁HDL㊁LDL)参与DKD的进展,因此,监测血脂水平有助于对DKD的早期诊治㊂综上所述,血清Hcy㊁RBP均能反映早期肾损伤,血清RBP敏感性更高,两者对2型DKD的早期诊断有重要的临床价值,可以很好地指导DKD的早期诊断㊂采取积极有效的措施对延缓和防止DKD 的发生㊁发展具有非常重要的意义㊂降低血清Hcy㊁RBP水平能减少对血管内皮细胞的损伤,延缓肾动脉硬化,延缓DKD的进展㊂因此,在2型糖尿病的诊治中,应该密切监测Hcy㊁RBP的水平,及早发现DKD㊂[参考文献][1] SAEEDI P,PETERSOHN I,SALPEA P,et al.Global and regionaldiabetes prevalence estimates for2019and projections for2030 and2045:Results from the International Diabetes Federation Diabetes Atlas,9th edition[J].Diabetes Res Clin Pract,2019, 157:107843.[2] LI Y,TENG D,SHI X,et al.Prevalence of diabetes recorded inmainland China using2018diagnostic criteria from the American Diabetes Association:national cross sectional study[J].BMJ, 2020,369:m997.[3] 常杰.血清视黄醇结合蛋白与尿微量白蛋白在2型糖尿病早期肾病中的诊断价值探讨[J].中国全科医学,2020,23(S2): 132.[4] 萨如拉,闫朝丽,何欣.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[J].中华临床营养杂志, 2021,29(2):8.[5] 操金金,朱文娟,周敬敬,等.血清视黄醇结合蛋白,胱抑素C和尿微量清蛋白/尿肌酐比值在2型糖尿病肾病早期诊断中的价值[J].检验医学与临床,2019,16(21):3.[收稿日期]2021-03-24 [修回日期]2023-03-08[作者单位]河北省邢台市第三医院神经内一科,054000[作者简介]李利峰(1980-),男,硕士,副主任医师.[文章编号]1000⁃2200(2023)10⁃1398⁃05㊃临床医学㊃清晨血压与非致残性急性缺血性脑卒中病人神经功能及动脉弹性的相关性研究李利峰,霍旭宁,路 峰,黄 津,刘秀君[摘要]目的:探讨分析清晨血压与非致残性急性缺血性脑卒中病人神经功能及动脉弹性之间的相关性㊂方法:选取126例急性非致残性缺血性脑卒中病人作为研究对象,另选取同期健康体检的100名健康体检者作为对照组㊂检测并比较2组病人清晨血压㊁动脉弹性指标及神经功能评分,分析清晨血压与动脉弹性㊁神经功能的相关性㊂结果:病例组病人清晨收缩压和舒张压均高于对照组(P <0.01),动脉弹性指标颈-桡动脉脉搏波传导速度(CrPWV)㊁颈动脉内膜中层厚度(IMT)和僵硬度指数β均明显高于对照组(P <0.01),美国国立卫生研究所脑卒中量表(NIHSS)评分也明显高于对照组(P <0.01)㊂病例组病人根据清晨收缩压和舒张压水平将其分为低水平组㊁中水平组和高水平组,血压水平越高,CrPWV㊁IMT㊁僵硬度指数β和NIHSS评分越高(P <0.01)㊂相关性分析显示,清晨血压水平与CrPWV㊁IMT㊁僵硬度指数β和NIHSS 评分均呈正相关关系(P <0.01)㊂多元线性回归分析显示年龄㊁清晨收缩压是CrPWV 的独立影响因素(P <0.01和P <0.05),LDL⁃C 和清晨收缩压是IMT 的独立影响因素(P <0.01),年龄㊁BMI㊁清晨收缩压㊁清晨舒张压均是僵硬度指数β和NIHSS 评分的独立影响因素(P <0.05~P <0.01)㊂结论:清晨血压与非致残性急性缺血性脑卒中病人神经功能缺损程度和动脉弹性相关㊂[关键词]非致残性急性缺血性脑卒中;清晨血压;神经功能;动脉弹性[中图法分类号]R 743.3 [文献标志码]A DOI :10.13898/ki.issn.1000⁃2200.2023.10.016Relationship between early morning blood pressure and neurological function and arterial elasticity in patients with non⁃disabling acute ischemic strokeLI Li⁃feng,HUO Xu⁃ning,LU Feng,HUANG Jin,LIU Xiu⁃jun(Department of Neurology ,Xingtai Third Hospital ,Xingtai Hebei 054000,China )[Abstract ]Objective :To investigate the relationship between early morning blood pressure and neurological function and arterialelasticity in patients with non⁃disabling acute ischemic stroke.Methods :A total of 126patients with acute non⁃disabling ischemic stroke were selected as the research object,and 100healthy people who had physical examination during the same period were selected as the control group.Blood pressure,arterial elasticity index and neurological function score were detected and compared between the two groups,and the correlation between early morning blood pressure and arterial elasticity and neurological function was analyzed.Results :The mean systolic blood pressure and mean diastolic blood pressure in the morning in the case group were significantly higher than those in the control group (P <0.01).The indexes of arterial elasticity,such as carotid radial pulse wave velocity (CrPWV),carotid intima⁃media thickness (IMT)and stiffness index βwere significantly higher than those in the control group (P <0.01).NIHSS score was also significantly higher than that of the control group (P <0.01).According to the early morning systolic and diastolic blood pressurelevels,the patients in the case group were divided into low⁃level group,medium⁃level group and high⁃level group.The differences of CrPWV,IMT,stiffness index βand NIHSS score of each group were statistically significant (P <0.01).Correlation analysis showedthat early morning blood pressure level was significantly 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