西格列汀对初治2型糖尿病患者胰岛素敏感性及胰岛α和β细胞功能的影响  

Effects of sitagliptin on insulin sensitivity and pancreaticα-andβ-cell function in drug-naïve type 2 diabetes mellitus

作　　者：王慧 邝建[2] 罗涌[3] 杨刚毅[4] 高政南[5] 董爱梅[6] 徐明彤[7] 张帆[8] 刘石平[9] 钱鑫 陈燕燕 李光伟 Wang Hui;Kuang Jian;Luo Yong;Yang Gangyi;Gao Zhengnan;Dong Aimei;Xu Mingtong;Zhang Fan;Liu Shiping;Qian Xin;Chen Yanyan;Li Guangwei(Department of Endocrinology,Fuwai Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China;Department of Endocrinology,Guangdong General Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;Department of Endocrinology,Chongqing Three Gorges Central Hospital,Chongqing 404000,China;Department of Endocrinology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China;Department of Endocrinology,Dalian Municipal Central Hospital,Dalian 116033,China;Department of Endocrinology,Peking University First Hospital,Beijing 100034,China;Department of Endocrinology,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China;Department of Endocrinology,Peking University Shenzhen Hospital,Shenzhen 518000,China;Department of Endocrinology,the Second Xiangya Hospital of Central South University,Changsha 410011,China)

机构地区：[1]中国医学科学院阜外医院内分泌与心血管代谢二病区,100037 [2]广东省人民医院内分泌科,广州510080 [3]重庆三峡中心医院内分泌科,404000 [4]重庆医科大学附属第二医院内分泌科,400010 [5]大连市中心医院内分泌科,116033 [6]北京大学第一医院内分泌科,100034 [7]中山大学孙逸仙纪念医院内分泌科,广州510120 [8]北京大学深圳医院内分泌科,518000 [9]中南大学湘雅二医院内分泌科,长沙410011

出　　处：《中华糖尿病杂志》2020年第6期382-386,共5页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的探讨西格列汀对初治2型糖尿病患者血糖控制、胰岛素敏感性、胰岛α和β细胞功能的影响。方法选取2012年10月至2014年11月来自全国9家医院就诊的2型糖尿病患者84例,患者病程<3年,未曾使用降糖药物治疗,空腹血糖(FPG)<10.0 mmol/L。纳入患者接受12周的西格列汀治疗。治疗前后采用高胰岛素-正葡萄糖钳夹技术评估胰岛素敏感性改善情况。以标准餐试验检测早相胰岛素分泌和胰高血糖素分泌变化以评估胰岛β细胞和α细胞功能改变。采用配对t检验或非参数检验比较治疗前后的差异,采用多因素回归分析评价相关性。结果患者经西格列汀治疗12周后,糖化血红蛋白(HbA1c)为(6.63±0.58)%,较基线值(7.70±1.22)%下降了(1.08±0.13)%,差异有统计学意义(t=-8.12,P<0.01);空腹血糖(FPG)、餐后2 h血糖(2 h PG)分别为(6.33±0.92)、(8.44±1.62)mmol/L,比基线的(7.71±1.70)、(13.27±2.74)mmol/L明显降低,差异均有统计学意义(t值分别为^-11.01、^-11.41,均P<0.01)。经过12周治疗,钳夹技术测定的葡萄糖输注率(GIR)明显升高,由治疗前的4.39(3.34,5.82)mg·kg^-1·min^-1升至5.71(4.34,6.48)mg·kg^-1·min^-1;早相胰岛素分泌指数(ΔI30/ΔG30)由2.42(1.09,4.42)mU/mmol升至5.17(3.44,8.56)mU/mmol;胰岛素分泌曲线下面积也较治疗前升高,上述3个参数的差异均有统计学意义(P均<0.05)。但治疗前后胰高血糖素曲线下面积差异无统计学意义(P>0.05)。多因素回归分析显示,治疗12周后血糖结局与基线HbA1c水平呈正相关(β=0.192,P=0.001),与基线胰岛素敏感性指数呈负相关(β=-0.070,P=0.03)。结论西格列汀治疗12周可使2型糖尿病患者HbA1c降低,不仅显著改善了胰岛β细胞功能,而且改善了其胰岛素敏感性。Objective To investigate the effects of Sitagliptin on blood glucose control,insulin sensitivity and pancreaticα-andβ-cell function in drug-naïve type 2 diabetes mellitus(T2DM).Methods Eighty four drug-naïve patients with duration of diabetes less than 3 years were treated with Sitagliptin for 12 weeks.Hyperinsulinemic-euglycemic clamp technique was used to evaluate insulin sensitivity,the glucose infusion rate(GIR),before and after Sitagliptin treatment.The early-phase insulin secretion and glucagon secretion after a standard meal were used to estimateβ-andα-cell function.Paired t test or rank sum test were used to compare the differences before and after treatment,and multivariate regression analysis was used to evaluate the correlation.Results After Sitagliptin treatment for 12 weeks,HbA1c decreased from(7.70±1.22)%to(6.63±0.58)%,decreased by(1.08±0.13)%in T2DM patients(t=-8.12,P<0.01).Accordingly,the fasting plasma glucose(FPG)and 2-h postprandial plasma glucose(2 h PG)levels were also significantly reduced[(6.33±0.92)and(7.71±1.70)mmol/L,(8.44±1.62)and(13.27±2.74)mmol/L,P<0.01].The GIR increased from 4.39 to 5.71 mg·kg^-1·min^-1 without significant weight reduction(P<0.01).The early-phase insulin secretion index(ΔI30/ΔG30)increased from 2.42(1.09,4.42)to 5.17(3.44,8.56)mU/mmol(P<0.05).The insulin-AUC was also significantly improved(P<0.01),but there was no significant change in glucagon-AUC(P>0.05).Multivariate regression analysis showed that baseline insulin sensitivity(β=-0.070,P=0.03)and HbA1c(β=0.192,P=0.001)were positively associated with the HbA1c after treatment.Conclusions A 12-week sitagliptin treatment reduced HbA1c by more than 1.0%in T2DM patients,and not only significantly improved pancreaticβ-cell function,but also significantly improved insulin sensitivity.

关 键 词：糖尿病 2型 胰岛素敏感性 葡萄糖钳夹技术 胰岛素分泌 西格列汀 

分 类 号：R587.1[医药卫生—内分泌]