【作者】 张岩；

【导师】 王彦君；

【作者基本信息】 吉林大学 ， 临床医学硕士（内科学）（专业学位）， 2019， 硕士

【摘要】 目的:观察与分析口服降糖药达格列净联合胰岛素对2型糖尿病患者各临床指标的影响,评价其临床疗效及安全性,为2型糖尿病的治疗方案提供更多更佳的选择。方法:收集2017年6月至2017年12月于吉林大学第二医院内分泌科就诊的符合纳入标准的2型糖尿病患者,随机分为达格列净组和对照组。达格列净组采用达格列净10mg,每日一次口服,联合胰岛素治疗;对照组仅使用胰岛素治疗。嘱两组患者均按照糖尿病饮食,适量运动,保持情绪稳定,遵医嘱根据血糖情况调整胰岛素剂量,使两组患者空腹血糖与餐后2小时血糖均稳定在血糖控制目标范围内。随访至12周时记录观察指标并将达格列净组随机分为亚组1(应用达格列净至12周后停用,之后仅使用胰岛素治疗),亚组2(继续应用达格列净至24周),并继续随访对照组、亚组1、亚组2至24周时记录观察指标。在各时间点观察指标如下:空腹血糖、餐后2小时血糖、糖化血红蛋白、体质指数、空腹胰岛素、甘油三酯、总胆固醇、胰岛素使用剂量、有无低血糖事件发生等指标,计算胰岛素敏感指数和胰岛素抵抗指数。结果:本研究中完成随访的患者共120例,其中对照组60例,达格列净组60例。随访至12周时收集两组相关临床指标:两组患者一般临床资料及各观察指标在基线时无统计学差异(p>0.05)。对照组和达格列净组的空腹血糖、餐后2小时血糖、糖化血红蛋白在12周随访点较基线下降(p<0.05),但两组组间比较无统计学差异(p>0.05)。对照组的体质指数在12周随访点较基线无统计学差异(p>0.05),达格列净组的体质指数在12周随访点较基线下降(p<0.05),且与对照组相比有统计学差异(p<0.05)。对照组和达格列净组的胰岛素敏感指数在12周随访点均较基线上升(p<0.05),且达格列净组上升幅度更大(p<0.05)。对照组和达格列净组的胰岛素抵抗指数在12周随访点均较基线下降(p<0.05),且达格列净组下降幅度更大(p<0.05)。对照组和达格列净组的甘油三酯、总胆固醇在12周随访点均较基线下降(p<0.05),但两组组间比较无统计学差异(p>0.05)。对照组胰岛素使用剂量在12周随访点较基线相比无统计学差异(p>0.05),达格列净组胰岛素使用剂量在12周随访点较基线下降(p<0.05),且与对照组相比有统计学意义(p<0.05)。从开始观察至12周随访点,对照组和达格列净组患者低血糖发生率组间比较无统计学差异(p>0.05)。随访至12周后,将达格列净组随机分为亚组1(30例),亚组2(30例),继续随访对照组、亚组1、亚组2患者至24周,收集三组相关临床指标:三组患者一般临床资料及各观察指标在基线时无统计学差异(p>0.05)对照组、亚组1和亚组2的空腹血糖、餐后2小时血糖、糖化血红蛋白在各随访点均较基线下降(p<0.05),但各组之间比较无统计学差异(p>0.05)。对照组的体质指数在各随访点较基线均无统计学差异(p>0.05),亚组1和亚组2的体质指数在各随访点均较基线下降(p<0.05),且与对照组相比有统计学差异(p<0.05),但亚组1和亚组2之间无统计学差异(p>0.05)。对照组、亚组1和亚组2的胰岛素敏感指数在各随访点均较基线上升(p<0.05),亚组1和亚组2在各随访点胰岛素敏感指数上升幅度大于对照组(p<0.05),亚组2的胰岛素敏感指数在24周随访点较12周随访点上升(p<0.05),且与亚组1相比有统计学差异(p<0.05)。对照组、亚组1和亚组2的胰岛素抵抗指数在各随访点均较基线下降(p<0.05),亚组1和亚组2在各随访点胰岛素抵抗指数下降幅度大于对照组(p<0.05),亚组2的胰岛素抵抗指数在24周随访点较12周随访点下降(p<0.05),且与亚组1相比有统计学差异(p<0.05)。对照组、亚组1、亚组2的甘油三酯、总胆固醇在各随访点均较基线下降(p<0.05),且24周随访点下降幅度大于12周随访点(p<0.05),但各组组间无统计学差异(p>0.05)。对照组胰岛素使用剂量在24周随访点较基线下降(p<0.05),亚组1和亚组2胰岛素使用剂量在各随访点均较基线下降(p<0.05),且与对照组相比有统计学差异(p<0.05);亚组2胰岛素使用剂量在24周随访点较12周随访点进一步下降(p<0.05),且与亚组1相比有统计学差异(p<0.05)。从开始观察至24周随访点,对照组、亚组1和亚组2患者低血糖发生率组间比较无统计学差异(p>0.05)。结论:1、对于2型糖尿病患者,达格列净联合胰岛素治疗2型糖尿病的疗效优于仅使用胰岛素治疗,能在平稳控制血糖的基础上明显减少胰岛素使用剂量,起到减重的效果,可改善胰岛素抵抗并在一定程度上修复胰岛细胞功能,且安全性良好。2、对于2型糖尿病患者,给予达格列净联合胰岛素治疗至24周与仅治疗12周相比,可进一步改善胰岛细胞功能且减少胰岛素使用剂量,其他各项指标无明显差异。更多还原

【Abstract】 Objective: To observe and analyze the effect on combination therapy with dapagliflozin and insulin on clinical indexes of patients with type 2 diabetes,and to evaluate its efficacy and safety,in order to provide more and better options for the treatment of type 2 diabetes mellitus.Method: To collect the clinical data of patients with type 2 diabetes who met the inclusion criteria from the endocrinology department of the Second Hospital of Jilin University from June 2017 to December 2017.They were randomly divided into two groups,dapagliflozin group and control group.Dapagliflozin group was treated with dapagliflozin(10 mg once daily)in combination with insulin therapy.The control group was treated with insulin only.Two groups of the patients were advised to follow the diet of diabetes mellitus,exercise moderately,maintain emotional stability and adjust insulin dose according to the doctor’s advice,so that the fasting plasma glucose and 2h plasma glucose in both groups were stable within the target of glycemic control.After the 12-week follow-up point,the observations were recorded and the dapagliflozin group was randomly divided into subgroup 1(only insulin therapy was used with dapagliflozin no longer used after the 12-week follow-up point),subgroup 2(continued with dapagliflozin to 24 weeks).We continued to follow up the observation indexes recorded in the control group,subgroup 1 and subgroup 2 to 24 weeks.The indicators were observed at each time point as follows: fasting plasma glucose,2h plasma glucose,glycosylated hemoglobin A1 c,Body Mass Index,fasting insulin,triglyceride,total cholesterol,insulin dose and the hypoglycaemic events.The homeostasis model assessment-insulin sensitivity index and homeostasis model assessment-insulin resistance index were calculated.Result: A total of 120 patients in this study were followed up,60 in the dapagliflozin group and 60 in the control group.We collected the clinical indicators of the two groups at the 12-week follow-up point.There was no statistical difference between the two groups at the baseline(p>0.05).The fasting plasma glucose,2h plasma glucose and glycosylated hemoglobin A1 c in the control group and the dapagliflozin group decreased at the 12-week follow-up point from baseline(p<0.05),but there was no statistical difference between two groups(p>0.05).There was no statistical difference in Body Mass Index at the 12-week follow-up point from baseline in the control group(p>0.05),while the Body Mass Index of the dapagliflozin group decreased from baseline at the 12-week follow-up point(p<0.05),and the result was statistically significant compared with the control group(p<0.05).The homeostasis model assessment-insulin sensitivity index increased in both the control group and the dapagliflozin group at the 12-week follow-up point compared to the baseline(p<0.05),and the increase was even greater in the dapagliflozin group(p<0.05).The homeostasis model assessment-insulin resistance index decreased in both the control group and the dapagliflozin group at the 12-week follow-up point compared to the baseline(p<0.05),and the decrease was even greater in the dapagliflozin group(p<0.05).The triglyceride and total cholesterol of the control group and the dapagliflozin group were lower than the baseline at the 12-week follow-up point(p<0.05),but there was no statistical difference between the two groups(p>0.05).There was no statistical difference in insulin dose between the control group and the baseline at the 12-week follow-up point(p>0.05),the insulin dose in the dapagliflozin group decreased from baseline at the 12-week follow-up point(p<0.05),and the result was statistically significant compared with the control group(p<0.05).From the beginning of observation to the 12-week follow-up point,there was no statistical difference in the incidence of hypoglycemia between the control group and dapagliflozin group(p>0.05).At the 12-week follow-up point,the dapagliflozin group was randomly divided into subgroups 1(30 cases)and subgroups 2(30 cases).Patients in the control group,subgroup 1 and subgroup 2 were followed up for 24 weeks to collect relevant clinical indicators.There was no statistical difference between the three groups at the baseline(p>0.05).The fasting plasma glucose,2h plasma glucose and glycosylated hemoglobin A1 c in the control group,subgroup 1 and subgroup 2 decreased from baseline at all follow-up points(p<0.05),but there was no statistical difference between the groups(p>0.05).There was no statistical difference in Body Mass Index between the control group and the baseline at all follow-up points(p>0.05).Subgroup 1 and subgroup 2 showed a decrease in Body Mass Index at all follow-up points(p<0.05),with a statistical difference compared with the control group(p<0.05),but there was no statistical difference between subgroup 1 and subgroup 2(p>0.05).The homeostasis model assessment-insulin sensitivity index of the control group,subgroup 1 and subgroup 2 increased at each follow-up point compared with the baseline(p<0.05).At each follow-up point,the increase of the homeostasis model assessment-insulin sensitivity index in subgroup 1 and subgroup 2 was greater than that in the control group(p<0.05).The homeostasis model assessment-insulin sensitivity index in subgroup 2 at the 24-week follow-up point was statistically higher than that at the 12-week follow-up point(p<0.05),the difference was statistically significant compared with that in subgroup 1(p<0.05).The homeostasis model assessment-insulin resistance index of the control group, subgroup 1 and subgroup 2 decreased at each follow-up point compared with the baseline(p<0.05).At each follow-up point,the decrease of the homeostasis model assessment-insulin resistance index in subgroup 1 and subgroup 2 was greater than that in the control group(p<0.05).The homeostasis model assessment-insulin resistance index in subgroup 2 at the 24-week follow-up point was statistically lower than that at the 12-week follow-up point(p<0.05),the difference was statistically significant compared with that in subgroup 1(p<0.05).The triglyceride and total cholesterol in the control group,subgroup 1 and subgroup 2 were all lower than the baseline at each follow-up point(p<0.05),and the triglyceride and total cholesterol at the 24-week follow-up point were lower than that at the 12-week follow-up point(p<0.05),but there was no statistical difference between the groups(p>0.05).The insulin dose in the control group was lower than the baseline at the 24-week follow-up point(p<0.05).The insulin dose in subgroup 1 and subgroup 2 decreased from the baseline at each follow-up point(p<0.05),and there was a statistical difference compared with the control group(p<0.05).The insulin dose of subgroup 2 decreased at the 24-week follow-up point compared with the 12-week follow-up point(p<0.05),and there was a statistical difference compared with subgroup 1(p<0.05).From the beginning of observation to the 24-week follow-up point,the incidence of hypoglycemia in the control group,subgroup 1 and subgroup 2 was compared,and there was no statistical difference between the groups(p>0.05).Conclusion: For the patients with type 2 diabetes,dapagliflozin combined with insulin is superior to insulin alone in the treatment of type 2 diabetes.On the basis of stable control of blood sugar,it can significantly reduce the dose of insulin and play a role in weight loss.It can improve insulin resistance and repair islet cell function to a certain extent with,and the security is good.For the patients with type 2 diabetes,compared with only 12 weeks of treatment,the combination of dapagliflozin and insulin for 24 weeks can further improve the function of islet cells and reduce the dose of insulin injection,but there is no significant difference in other indicators.更多还原