血清血管生成素样蛋白4和血管内皮生长因子与2型糖尿病下肢动脉病变的相关性研究

Correlation research between angiopoietin-like protein 4 and vascular endothelial growth factor in serum and lower limb arterial lesions in Type 2 diabetes mellitus

目的探讨血清血管生成素样蛋白4(angiopoietin-like protein 4,ANGPTL4)和血管内皮生长因子(vascular endothelial growth factor,VEGF)与2型糖尿病下肢动脉病变的关系。方法采用回顾性队列研究方法,选取2017年10月至2018年12月上海市徐汇区大华医院内分泌科收治的164例2型糖尿病住院患者作为2型糖尿病组,收集同期健康体检者69名为正常对照组。按踝肱指数<0.9将糖尿病患者分为无下肢动脉病变组及合并下肢动脉病变组。检测所有研究对象的各项生化指标并计算胰岛素抵抗指数,用酶联免疫吸附法检测血清ANGPTL4及VEGF浓度。结果(1)与正常对照组比较:2型糖尿病合并下肢动脉病变组及2型糖尿病无下肢动脉病变组血清ANGPTL4浓度分别为(44.78±15.15)μg/L与(47.46±10.43)μg/L,均低于正常对照组(52.87±12.74)μg/L,差异有统计学意义(P均<0.05);血清VEGF浓度分别为(340.98±76.18)ng/L与(314.83±75.30)ng/L,均高于正常对照组(282.58±81.44)ng/L,差异有统计学意义(P均<0.05)。(2)与无下肢动脉病变组比较:2型糖尿病合并下肢动脉病变组血清ANGPTL4浓度低于2型糖尿病无下肢动脉病变组,但差异无统计学意义(P>0.05);2型糖尿病合并下肢动脉病变组血清VEGF浓度高于2型糖尿病无下肢动脉病变组,差异有统计学意义(P<0.05)。(3)相关性分析:合并糖尿病且糖尿病病程>10年(OR 4.594,95%CI 2.540~8.311,P<0.001)、空腹血糖>8 mmol/L(OR 2.353,95%CI 1.023~5.416,P=0.044)、糖化血红蛋白>8%(OR 6.442,95%CI 2.874~14.441,P<0.001)、VEGF升高(OR 3.745,95%CI 1.566~8.953,P=0.003)是2型糖尿病发生下肢动脉病变的危险因素,而ANGPTL4的升高(OR 0.154,95%CI 0.064~0.372,P<0.001)可减少2型糖尿病发生下肢动脉病变的发生。结论ANGPTL4为2型糖尿病下肢动脉病变保护因素而VEGF为危险因素,两者相互影响共同参与其发生、发展。

Objective To investigate the relationship between angiopoietin-like protein 4(ANGPTL4)and vascular endothelial growth factor(VEGF)in serum and lower limb arterial lesions in Type 2 diabetes mellitus.Methods Using the method of retrospective cohort study,164 inpatients with type 2 diabetes admitted to the Department of Endocrinology,Dahua hospital,Xuhui District,Shanghai from October 2017 to December 2018 were selected as the type 2 diabetes group,and 69 healthy people in the same period were collected as the normal control group.According to the ankle brachial index<0.9,diabetic patients were divided into two groups:the group without lower extremity artery disease and the group with lower extremity artery disease.The levels of ANGPTL4 and VEGF in serum were measured by enzyme-linked immunosorbent assay.Results(1)Compared with the normal control group:the concentration of ANGPTL4 in serum of lower extremity arterial disease group and no lower extremity arterial disease group((44.78±15.15),(47.46±10.43)μg/L)were lower than that of normal control group((52.87±12.74)μg/L),the difference was statistically significant(all P<0.05).The serum VEGF concentration in lower extremity arterial disease group and no lower extremity arterial disease group((340.98±76.18),(314.83±75.30)ng/L)were higher than that in normal control group((282.58±81.4)ng/L),the difference was statistically significant(all P<0.05).(2)Compared with no lower extremity arterial disease group:the concentration of ANGPTL4 in serum of lower extremity arterial disease group was lower than that of no lower extremity arterial disease group,but the difference was not statistically significant(P>0.05).The serum VEGF concentration in lower extremity arterial disease group was higher than that in no lower extremity arterial disease group,the difference was statistically significant(P<0.05).(3)Correlation analysis:Diabetes mellitus and diabetic course>10 years(OR 4.594,95%CI2.540-8.311,P<0.001),fasting blood glucose>8 mmol/L(OR 2.353,95%CI1.023-5.416,P=0.044),glycosylated hemoglobin>8%(OR 6.442,95%CI 2.874-14.441,P<0.001)and the increase of VEGF(OR 3.745,95%CI1.566-8.953,P=0.003)are risk factors for lower limb arterial disease in type 2 diabetes,while the increase of ANGPTL(OR 0.154,95%CI0.064-0.372,P<0.001)can reduce the occurrence of lower limb arterial disease in type 2 diabetes.Conclusion ANGPTL4 is a protective factor and VEGF is a risk factor of type 2 diabetes mellitus.Both of them influence each other and participate in its occurrence and development.