2型糖尿病不同血管并发症中循环内皮祖细胞数目和功能的变化

目的 研究2型糖尿病(T2DM)合并有各类血管并发症的患者循环内皮祖细胞(EPC)的数目和功能变化以及与血管内皮功能的关系.方法 选择415例2007年至2008年武汉协和医院内分泌科就诊的T2DM患者.心脑血管并发症诊断根据明确的心脑血管事件和客观的实验室检查资料.所有患者均做血管超声检查外周血管并发症;免散瞳眼底拍照检查糖尿病视网膜病变;6个月内连续两次24 h尿白蛋白检查糖尿病肾病.采用流式细胞仪检测循环EPC的数目;体外培养计数集落形成和迁移能力评估EPC的功能.采用血流介导的肱动脉血管舒张功能(FMD)评估血管内皮功能.结果 其中T2DM无血管并发症组(TC组)97例,T2DM合并大血管并发症组(TA组)106例,T2DM合并微血管并发症组(TI组)100例,T2DM合并大血管及微血管并发症组(TAI组)112例.4组循环EPC数目和集落形成能力按顺序排列为TA组＜TAI组＜TI组＜TC组;(532±90)个/ml、(616±93)个/ml、(768±97)+/ml和(1045 ±106)个/ml];(个/孔:21±4、28±5、43±7和70±9),组间两两比较差异均有统计学意义(P＜0.05).TA组与TAI组的迁移能力差异无统计学意义(个/高倍视野:24±6;28±7),其余组的迁移能力与循环EPC数目变化一致(个/高倍视野:125±12,90±9).影响大血管并发症患者EPC数目的 因素为年龄、糖化血红蛋白(HbA1c)、收缩压、体重指数和糖尿病患病时间(P＜0.05);而影响微血管并发症患者EPC数目的 因素为年龄、HbA1c和糖尿病患病时间(P＜0.05).在排除了常见危险因素的影响后,循环EPC数目与FMD呈正相关(标准回归系数=0.61,P=0.01).结论 循环EPC数目与血管内皮功能密切相关,可作为衡量T2DM患者血管内皮功能的标志物之一.

Number and function of circulating endothelial progenitor cell in diabetics with different vascular complications

Objective To investigate the number and function of circulating endothelial progenitor cell (EPC) in different vascular complications of type 2 diabetes (T2DM) and its associations with vascular endothelial function.Methods A total of 415 T2DM patients were recruited from the outpatients and inpatients of the Endocrinology Department at Union Hospital Assessments of cardiovascular disease and cerebrovascular disease were based on each patient's medical records.Peripheral vascular disease was diagnosed by bilateral ultrasonography bilaterally.Non-mydriatic fundus camera screening was used as a tool to identify diabetic retinopathy.Urinary albumin exceeding 30 mg/24 h occurring twice over a period of six months was diagnosed as diabetic nephropathy.Circulating EPC was quantified by flow cytometry.Colony forming count (CFU) and migration assay were used for evaluating the function of circulating EPC.Vascular endothelial function was assessed by flow-mediated brachial artery dilatation (FMD).Results There were four groups in the study:T2DM without vascular disease(TC,n =97) ,T2DM with macrovascular disease (TA,n = 106),T2DM with microvascular disease(TI,n = 100),T2DM with macro- and micro-vascular diseases(TAI,n = 112).The sequence of circulating EPC number and CFU in four groups was TA ＜ TAI ＜TI ＜ TC (532 ± 90,616 ± 93,768 ± 97 and 1045 ± 106 cell/ml ;21 ± 4,28 ± 5,43 ± 7 and 70 ± 9 unit/chamber) and there was a significant difference between any two groups (P ＜ 0.05 ).The results of migration were consistent with circulating EPC number( 125 ± 12;90 ± 9 cell/HP field)except there were no significant differences in TA and TAI groups(24 ± 6;28 ± 7 cell/HP field).Age,HbA1c,SBP,BMI and duration of T2DM were the independent risk factors of circulating EPC number in T2DM patients with macrovascular disease(P ＜ 0.05).Age,HbA1c and duration of T2DM were the independent risk factors of circulating EPC number in T2DM patients with microvascular disease (P ＜ 0.05 ).After the adjustment of traditional risk factors,the number of circulating EPC had a close correlation with FMD(standardized coefficien,t =0.61,P =0.01).Conclusion The number and function of circulating EPC decreased with different degrees in T2DM patients of different vascular diseases.Circulating EPC number was associated with endothelial function and can be considered as a surrogate biological marker of vascular endothelial function for T2DM.