西格列汀与瑞格列奈对初诊2型糖尿病患者血管内皮功能的影响

Sitagliptin ameliorates vascular endothelial function in newly diagnosed type 2 diabetes patients

目的观察西格列汀和瑞格列奈对初诊2型糖尿病患者（T2DM）血管内皮功能的影响，并初步探讨其机制。方法92例糖化血红蛋白（HbA1c）在6．5％-8．5％的T2DM患者按随机数字表法分为西格列汀组（n=46）和瑞格列奈组（n=46），分别给予12周西格列汀和瑞格列奈治疗。比较两组患者治疗前后肱动脉血流介导的内皮依耐性舒张功能（FMD），一氧化氮（NO），纤溶酶原激活物抑制剂-1（PAI-1）及血生化等的变化。结果治疗后两组空腹血糖（FBG）、餐后血糖（PBG）和HbA1c均有显著下降，但瑞格列奈组下降更明显（P〈0．05）；两组患者FMD、NO和稳态模型评估-β细胞功能（HOMA-β）均上升（P〈0．05），PAI-1和稳态模型评估-胰岛素抵抗（HOMR-IR）均下降（P〈0．05），但西格列汀组FMD、NO、PAI-1改善更明显（P〈0．05）；以FMD为因变量，进行多元线性逐步回归分析提示，NO是保护内皮功能的主要因素，而PAI-1、平均动脉压（MAP）是损伤内皮功能的主要因素。进一步以△FMD为因变量，以体重指数（BMI）、MAP、HbA1c、HOMR-IR、甘油三酯（TG）、NO以及PAI-1为协变量行协方差分析，结果显示西格列汀治疗后FMD的改善与NO和PAI-1仍然相关。结论西格列汀较瑞格列奈能更好地改善初诊T2DM由FMD评价的内皮功能，部分机制与NO水平的增高和PAI-1水平的降低有关，其作用可能独立于降糖作用外。

Objective To investigate sitagliptin and repaglinide could ameliorate endothelial function in newly diagnosed type 2 diabetes patients and to explore its mechanism. Methods A total of 92 new- ly diagnosed type 2 diabetes patients with glycated hemoglobin Alc （HbAlc） from 6. 5% to 8.5% was randomly assigned to sitagliptin group （n =46）receiving sitagliptin, and repaglinide group （n =-46 ） receiving repaglinide for 12 weeks. The effect of sitagliptin on vascular endothelial function was measured with endothelium-dependent flow-mediated vasodilation （FMD）. FMD, level of serum nitric oxide （NO） , plasminogen activator inhibitor-1 （ PAI-1 ） and biochemical variables in the two groups were measured at baseline and 12 weeks after treatment. Results Fasting blood glucose （FBG） , postprandial blood glucose （ PBG）, and HbA1 e decreased significantly both in sitagliptin and repaglinide groups after treatment, but the descent more significantly in the repaglinide group than those in the sitagliptin group （ P 〈 0. 05 ）. FMD, NO, and homeostasis model assessment-β （HOMA-β） were increased, and PAI-1 and homeostasis model assessment-insulin resistance （HOMR-IR） decreased in both two groups of patients （P 〈 0. 05）. FMD, NO, and PAI- 1 improved more significantly in sitagliptin groups （ P 〈0. 05 ）. With FMD as dependent variables, multiple linear regression analysis showed that NO was a major protection factors of endothelial function, and PAI-1 and mean artery pressure （MAP） were major injury factors of endothelial function. Furthermore, with A FMD as the dependent variable, FMD as the dependent variable, and body mass index （ BMI）, MAP, HbAlc, HOMA-IR, triglycerides （TG）, NO, and PAI-1 as a covariate-linear analysis of covariance showed that improved FMD with NO and PAI-1 were still relevant after treatment with sitagliptin. Conclusions Sitagliptin could improve vascular endothelial function evaluated by FMD better than repaglinide in newly diagnosed type 2 diabetes, the partial mechanism was related to the increase of NO level and the decrease of PAI-1 level, and the effect may be independent of the hypoglycemic effect.