【摘要】 目的:探讨联合临床一线降糖药与DDP4抑制剂治疗对应用大剂量胰岛素但血糖控制仍欠佳的2型糖尿病(T2DM)的临床疗效及安全性。方法:将180例应用大剂量胰岛素效果欠佳的T2DM患者按照联合用药不同方案分为A组(西格列汀治疗24周)、B组(二甲双胍治疗24周)和C组(吡格列酮治疗24周),每组各60例。所有患者均给予胰岛素基础治疗,每日剂量>50 U。评价各组治疗后的临床疗效,检测各组治疗前后空腹胰岛素(FINS)、餐后2 h胰岛素(2 h INS)、空腹C肽(FCP)、餐后2 h C肽(2 h CP)、胰岛B细胞功能水平(HOMA-B)及胰岛素抵抗指数(HOMA-IR)。比较各组治疗前后空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白-胆固醇(LDL-C)和高密度脂蛋白-胆固醇(HDL-C)。检测各组治疗前后尿素氮(BUN)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血肌酐(Scr)及炎性因子血清白细胞介素6(IL-6)、C反应蛋白(CRP)及肿瘤坏死因子α(TNF-α)水平。记录治疗过程中出现的不良反应事件。结果:与治疗前比较,治疗后A组总有效率为95.0%, B组为91.7%、C组为88.3%,差异无统计学意义(P>0.05);治疗后各组FINS、2 h INS、FCP、2 h CP、HOMA-B水平明显升高,HOMA-IR显著降低(P<0.05),A组HOMA-B水平高于B和C组(P<0.05);治疗后各组HbAlc、FPG、TG、LDL-C水平均明显下降(P<0.05),组间比较差异无统计学意义(P>0.05);治疗后各组CRP、IL-6和TNF-α水平显著降低(P<0.05),组间比较差异无统计学意义(P>0.05);治疗前后,各组ALT、AST、BUN和Scr水平比较,差异无统计学意义(P>0.05);A组低血糖等不良反应发生率为6.7%,低于B组的23.3%和C组的25.0%(P<0.05)。结论:西格列汀相比传统口服降糖药,在显著改善患者血糖状况的同时,不增加低血糖等不良反应的发生率,并对胰岛B细胞有潜在的保护作用,可作为与胰岛素联合用药治疗的理想选择。更多还原

【Abstract】 Objective:To investigate the clinical efficacy and safety of high dose insulin combined with DDP4 inhibitors in patients with type 2 diabetes mellitus(T2 DM).Methods:A total of 180 patients with T2 DM with poor efficacy of high-dose insulin were randomly divided into group A(n=60,24 weeks of treatment with sitagliptin),group B(n=60,24 weeks of treatment with metformin) and group C(n=60,24 weeks of treatment with pioglitazone).All patients were given basic insulin therapy, daily dose >50 U.After treatment, the clinical efficacy of each group was evaluated.Fasting insulin(FINS),insulin(2 hINS),fasting C-peptide(FCP),2 h C-peptide(2 hCP),islet B cell functional level(HOMA-B) and insulin resistance index(HOMA-IR) were measured before and after treatment.Fasting blood glucose(FPG),total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were compared before and after treatment in each group.Blood urea nitrogen(BUN),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum creatinine(Scr) and inflammatory factors serum interleukin-6(IL-6),C-reactive protein(CRP) and tumor necrosis factor(TNF-α) levels were measured before and after treatment in each group.Adverse events occurred during treatment were recorded.Results:Compared with before treatment, the total effective rate was 95.0% in group A,91.7% in group B and 88.3% in group C after treatment, the difference was not statistically significant(P>0.05).After treatment, the levels of FINS,2 hINS,FCP,2 hCP and HOMA-B in each group were significantly increased, while those of HOMA-IR were significantly decreased(P<0.05).The levels of HOMA-B in group A were significantly higher than those in group B and group C(P<0.05).After treatment, the HbAlc, FPG,TG and LDL-C levels in each group were significantly decreased(P<0.05),there was no significant difference between groups(P>0.05).After treatment, the levels of CRP,IL-6 and TNF-α in each group were significantly reduced(P<0.05),there was no significant difference between groups(P>0.05).Before and after treatment, the levels of ALT,AST,BUN and Scr in each group were not significantly different(P>0.05).The incidence of hypoglycemia and other adverse reactions in group A was 6.7%,which was significantly lower than 23.3% in group B and 25.0% in group C(P<0.05).Conclusion:Compared with traditional oral hypoglycemic agents, sitagliptin can significantly improve patients’ blood glucose status without increasing the occurrence of hypoglycemia and gastrointestinal adverse reactions, and has the function of protecting islet B cells.It may be a better choice for combined treatment with insulin.更多还原