血管内皮生长因子、血小板源性生长因子-BB与2型糖尿病患者血糖波动及微血管病变的关系

目的观察糖化血红蛋白（HbAlC）〈7．0％的2型糖尿病患者血糖波动与糖尿病微血管病变（视网膜病变、糖尿病肾病）及血清血管内皮生长因子（VEGF）、血小板源性生长因子-BB（PDGF—BB）水平之间的关系，探讨其在HbAlC达标患者中的相互影响机制。方法选取2010年10月至2012年8月在黑龙江省医院内分泌科就诊的2型糖尿病患者100例，其中男52例、女48例，年龄40～66岁。根据是否合并糖尿病微血管病变分为单纯2型糖尿病组A组，n=30，男14例，女16例，年龄（50±11）岁]，糖尿病肾病组B组，n=38，男20例，女18例，年龄（52±10）岁]和糖尿病视网膜病变组C组，n=32，男18例，女14例，年龄（53±13）岁]。另以同期于黑龙江省医院进行体检的25名健康者为正常对照组Con组，n=25，男12例，女13例，年龄（48±9）岁]。人院前糖尿病患者均使用药物治疗。所有参试者均测定空腹血糖浓度（FPG）、总胆固醇（TC）、甘油i酯（TG）、低密度脂蛋白胆同醇（LDL—C）、高密度脂蛋白胆固醇（HDL—C）、餐后2h血糖浓度（2hPG）、24h尿微量白蛋白（24h尿ALB）和HbAlc。应用动态血糖监测系统连续监测血糖3d，计算平均血糖（MBG）、平均血糖标准差（SDBG）、平均血糖波动幅度（MAGE）、日内最大血糖波动幅度（LAGE）、日间血糖平均绝对差（MODD）和曲线下面积（AUC）。采用酶联免疫吸附法分别检测血清中VEGF和PDGF—BB水平。计量资料组间比较采用t检验，多组间比较采用单因素方差分析，糖尿病微血管并发症的影响因素采用logistic回归分析，PDGF．BB、VEGF相关因素采用多元线性回归分析。结果（1）B组PDGF—BB水平高于A组和Con组分别为（53±12）、（31±6）、（26±4）μg／ml，F=9．56，P〈0．05]；C组VEGF水平高于A组和Con组分别为（217±57）、（105±12）、（74±10）μg／ml，F=8．13，P〈0．05]。（2）动态血糖监测指标B组与A组比较，SDBG、LAGF、MAGE、MODD、AUC明显升高（t=2．57、3．46、5．75、3．59、4．28，均P〈0．05），C组与A组比较，SDBG、LAGF、MAGE、MODD、AUC明显升高（t=3．29、3．77、5．38、4．54、3．16，均P〈0．05），而MBG在3组间的差异无统计学意义，均P〉0．05。（3）logistic回归分析显示PDGF-BB、VEGF及血糖波动是糖尿病微血管并发症独立危险因素。分别以PDGF-BB、VEGF为因变量，以血糖波动指标SDBG、LAGF、MAGE、MODD、AUC及2hPG为自变量，采用多元线性回归分析可能影响PDGF-BB、VEGF的相关因素，结果显示，MAGE、SDBG和2hPG对PDGF-BB、VEGF影响最大。结论2型糖尿病患者微血管病变的发生发展与血糖波动具有明显相关性，血糖波动可导致血清血管内皮生长因子和血小板源性生长因子-BB水平增高，从而参与糖尿病视网膜病变、糖尿病肾病等微血管病变的进展。

The level of serum vascular endothelial growth factor and platelet-derived growth factor correlates with glucose fluctuation and microangiopathy in type 2 diabetic patients

Objective To evaluate whether the level of serum vascular endothelial growth factor （VEGF） and platelet-derived growth factor （PDGF-BB）correlates with the glucose fluctuation and microangiopathy, and to explore the mechanism of interaction in type 2 diabetic patients with normal glycosylated hemoglobin values. Methods A total of 100 type 2 diabetic patients with HbAlc less than 7% treated in the Heilongjiang Province Hospital were enrolled in the study with 52 males and 48 famales, aged 40-66 years old. According to the existing diabetic microangiopathy, the subjects were divided into the following three groups： the T2DM group without documented microangiopathy （n = 30, 14 males and 16 females, aged （50 ＋ 11 ） years old） ;the diabetic nephropathy （DN） group （n = 38, 20 males and 18 females, aged （52 _＋ 10） years old）;the diabetic retinopathy （DR） group （n = 32, 18 males and 14 females, aged （53 -＋ 13） years old）. The healthy control group consisted of 25 subjects with 12 males and 13 famales aged （48 -＋9） years old, who carried out routine health examination in the same hospital during the same enrollment period. All the patients went through the laboratory examination and the following parameters were taken： fasting plasma glucose （FPG）, total cholesterol （TC）, tliglyceride （TG）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein （HDL-C）, 2 h postprandial plasma glucose （2 h PG）, 24 h urine albumin （24 h urine ALB） and glycosylated hemoglobin （HbAlc）. The continuous glucose monitoring system was used to detect mean blood glucose （MBG） , standard deviation of mean blood glueosc（SDBG） , mean amplitude of glucose excursions（MAGE） , largest amplitude of glucose excursions （LAGE） , absolute means of daily differences （MODD） and area under curve （AUC）. The level of serum VEGF and PDGF-BB were measured by the enzyme-linked immunosorbent assay （ELISA）. SPSS 19.0 was used for the statistical analysis with the data shown as （Yc -＋ s ）. The t test, was used to compare difference between the groups and the single factor analysis of variance was used to investigate the correlation among the groups. The logistic regression analysis was used to explore the correlation factors for the diabetic microvascular complications, while the multiple linear regression analysis was adopted to investigate the correlation factors for the level of VEGF and PDGF-BB, Statistical difference was accepted at P 〈 0. 05. Results The level of PDGF-BB was significantly increased in the DN group than that of the T2DM group without documented microangiopathy and the normal control group （（53 ＋ 12）, （31 -＋ 6）, （26 ~ 4） ~g/ml, respectively with F = 9.56 and P 〈 0. 05 ）. The level of VEGF was significantly increased in the DR group than that of the T2DM group without documented mieroangiopathy and the normal control group （（ 217 -＋ 57 ）, （ 105 -＋ 12）, （74 --- 10） ~g/ml, respectively with F = 8. 13 and P 〈 0. 05 ）. Compared with the T2DM group without documented mieroangiopathy, the DN group showed significantly higher SDBG, MAGE, LAGE, MODD and AUG （（2.41 -＋0. ~）, （7.9-＋0.4）, （8. 1 ＋0.4）, （2.51 ~0.3）, （8.0-＋0. 7）mmol/L, respectively with t = 2. 57, 3.46, 5.75, 3.59, 4. 28 and P 〈 0. 05）, while the DR group showed significantly higher SDBG, MAGE, LAGE, MODDand AUC（（2.4-＋1.7）, （7.9 ＋0.4）, （8.1 -＋0.4）, （3.1 ＋1.6）, （8.2 ＋0.6）mmol /L, respectively with t =3.29, 3.77, 5.38, 4. 54, 3. 16 and P 〈0. 05）. The level of PDGF-BB, VEGF and the blood glucose fluctuation were the independent risk factors for the diabetic microangiopathy revealed by the logistic regression analysis. Taken the level of PDGF-BB and VEGF as the dependent variables, and the blood glucose fluctuation index of SDBG, LAGF, MAGE, MODD, AUC and 2 h PG as the independent variables, the multiple linear regression analysis showed the greatest impact of MAGE, SDBG and 2 h PG on the level of PDGF-BB and VEGF. Conclusion Blood glucose fluctuation significantly correlates with the development and progression of the microangiopathy in type 2 diabetics. The level of VEGF and PDGF-BB could be increased by the blood glucose fluctuation, which may involve in the in the progression of the diabetic retinopathy and nephropathy.