【作者】 刘霞；

【导师】 张永莉；

【作者基本信息】 延安大学 ， 内科学（专业学位）， 2015， 硕士

【摘要】 目的:观察利拉鲁肽与胰岛素泵联合应用对非初诊2型糖尿病患者在控制血糖水平及减轻体重等方面治疗前后的改善情况。评估两药联合作用于非初诊2型糖尿病患者的临床效果,以期寻找更有效的降糖方案及合适的临床剂量,为提高治疗非初诊2型糖尿病患者的临床效果并减轻药物的不良反应提供理论和实验依据。方法:1.选择2013年1月~2015年1月在延安大学附属医院东关分院综合内科及榆林市中医医院北方医院内分泌科收治的45例非初诊2型糖尿病患者,所有患者均进行糖尿病饮食、适量运动,研究期间禁用其它降糖药物及影响诺和力活性成分的药物。2.选取此45例患者随机分为两组,对照组21例,实验组24例。对照组:在饮食运动的基础上给予胰岛素泵治疗,根据血糖调节胰岛素剂量;实验组:在对照组的基础上,加用利拉鲁肽按0.6 mg/d渐递增至1.2 mg/d治疗。3.分别对比两组患者在治疗前及治疗3个月后的空腹血糖(FPG)、餐后2小时血糖(PBG2h)、糖化血红蛋白(HbA1c)、空腹C-肽(CP)、餐后1小时C-肽(1hCP)、空腹胰岛素、餐后1小时胰岛素、β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)、血脂(TC、TG、HDL、LDL)、血压、体重、体重指数(BMI)、腰臀比(WHR)、同型半胱氨酸(Hcy)、尿微量白蛋白(mAlb)。并且记录两组治疗中低血糖反应次数、胃肠道、肝功能损害等的不良反应;评价分析两组治疗前后胰岛β细胞功能和胰岛素抵抗改善情况。4.统计学分析使用SPSS22.0软件统计包进行相关数据统计学处理,计量资料采用(x__±s)表示,组间比较采用t检验,组间计数资料采用四格表x2检验。检验标准:α=0.05,P<0.05为差异有统计学意义。结果:1.两组基线资料的比较,两组入选病例在治疗前从性别、年龄、fpg、pbg2h、hba1c、cp、1hcp、空腹胰岛素、餐后1小时胰岛素、homa-β、homa-ir、tc、tg、hdl、ldl、血压、体重、bmi、whr、hcy、malb、alt、ast、ggt均差异不显著(p>0.05)。2.两组治疗前后血糖、糖化血红蛋白的比较:实验组治疗前后的比较fpg(11.97±3.59vs6.29±1.22)、2hbpg(16.34±5.62vs7.36±2.17)、hba1c(11.97±4.59vs5.46±1.67),差异显著(p<0.05);对照组治疗前后的比较:fpg(11.29±3.82vs6.97±1.19)、2hbpg(16.86±5.17vs7.34±2.62)、hba1c(12.46±3.67vs5.57±1.59),差异显著(p<0.05);实验组与对照组治疗后均可以有效控制fpg、2hpbg、hba1c,差异不显著(p>0.05)。3.两组胰岛素、c肽及β细胞功能方面相关参数的比较:实验组治疗前后的比较:cp(1.93±1.13vs3.08±0.98)、1hcp(2.30±1.63vs6.86±1.64)、空腹胰岛素(8.70±0.85vs24.17±2.35)、餐后1小时胰岛素(24.87±2.23vs66.58±2.08)、homa-ir(4.17±1.50vs2.34±1.23)、homa-β(16.57±11.50vs34.76±9.79),差异显著(p<0.05)。对照组治疗前后的比较:cp(1.98±0.98vs2.43±1.13)、1hcp(2.86±1.64vs6.30±1.63)、空腹胰岛素(9.15±0.15vs18.20±1.22)、餐后1小时胰岛素(23.95±1.31vs46.55±2.11)、homa-ir(4.20±0.23vs2.77±1.50)、homa-β(16.80±10.97vs23.17±8.43),差异不显著(p>0.05);实验组与对照组治疗后,实验组可以有效的改善cp、1hcp、空腹胰岛素、餐后1小时胰岛素、homa-ir、homa-β,降低胰岛素用量,差异显著(p<0.05)。3.两组体重、bmi及whr的比较:实验组治疗前后在改善体重、bmi及whr的比较:(83.63±11.22vs76.38±15.33)、(29.20±3.09vs25.01±3.12)(1.03±0.07vs0.85±0.06),差异显著(p<0.05);对照组治疗前后在改善体重、bmi及whr的比较:(79.38±15.33vs82.63±10.23)(29.01±3.12vs29.54±3.10)(1.05±0.06vs1.06±0.07),差异不显著(p>0.05)。实验组与对照组治疗后比较,实验组可以有效的改善体重、bmi及whr,差异显著(p<0.05)。4.两组血脂方面相关参数的比较:实验组治疗前后在改善血脂方面相关参数的比较:tc(5.47±1.42vs4.37±1.39)、tg(4.59±3.09vs3.15±3.46)、hdl(1.15±0.49vs1.87±0.30)、LDL(3.34±1.23vs2.68±1.33)差异显著(P<0.05)。对照组治疗前后在改善血脂方面相关参数的比较:TC(5.72±1.39vs5.52±1.43)、TG(4.18±3.46vs 4.15±3.13)、HDL(1.07±0.30vs1.16±0.53)、LDL(3.68±1.33vs1.16±0.53),差异不显著(P>0.05)。实验组与对照组治疗后比较,实验组可以有效的降低TC、TG、LDL,增高HDL,差异显著(P<0.05)。5.两组收缩压、Hcy、mAlb的比较:实验组治疗前后收缩压、Hcy、mAlb的比较:(134.31±13.12vs130.5±9.67)、(11.97±5.59vs8.46±4.67)、(50.42±8.55vs48.41±8.05),差异显著(P<0.05);实验组治疗前后舒张压的比较,(75.31±10.13vs75.24±10.02)差异不显著(P>0.05)。对照组治疗前后收缩压、舒张压、Hcy、mAlb的比较:(130.5±9.67vs132.31±12.13)、(75.43±10.52vs75.47±10.13)、(12.46±4.67vs13.57±4.53)、(51.23±8.54vs51.41±8.26),差异不显著(P>0.05)。实验组和对照组在治疗后,舒张压均无明显改变,实验组可有效控制收缩压、Hcy、mAlb,差异显著(P<0.05)。6.两组不良反应的比较:治疗期间对照组有5例患者发生低血糖反应,发生率为23.81%;实验组有1例患者出现低血糖反应,占总例数4.17%,差异显著(P<0.05)。治疗过程中实验组24例患者中有8例患者曾出现过恶心、腹泻症状,占33.33%,有3例不能耐受退出;有4例患者曾出现过便秘症状,占16.67%;有1例患者出现流感样症状(4.17%/24)退出实验组,而对照组未见上述症状,故实验组出现上述不良症状的次数明显高于对照组,差异显著(P<0.05)。两组治疗前后ALT、AST、GGT均未见异常改变。结论:1.无论胰岛素泵单用还是利拉鲁肽与胰岛素泵联合应用治疗非初诊2型糖尿病患者均可以平稳控制血糖、降低HbA1c。2.利拉鲁肽与胰岛素泵两药联合应用可以减少胰岛素剂量,明显改善β细胞功能,改善胰岛素抵抗。3.利拉鲁肽与胰岛素泵联合应用可以降低体重、血压、血脂。4.利拉鲁肽与胰岛素泵联合应用比单独应用胰岛素泵更能减少低血糖反应的发生率。更多还原

【Abstract】 Objectives:To observe the insulin pump and liraglutide combining with insulin pump the application of the first diagnosis in patients with type 2 diabetes in improving the situation of controling blood sugar levels and weight lossing before and after treatment.Assess on the combination of two drugs, clinical effect of patients who was not first type 2 diabetes. In order to find a more effective hypoglycemic and appropriate clinical doses, for clinically further to improve the clinical effect of in patients with not first diagnosed type 2 diabetes and reduce the drug adverse reactions to provide theoretical and experimental basis. Methods:1.Choose from January 2013 to January 2013 at department of Comprehensive Internal Medicine of Dongguan branch Hospital Affiliated to Yan’an university and TCM hospitals in the north of Yulin city hospital endocrinology of 45 patients of not first diagnosed type 2 diabetes.All patients have to eat diabetes diet, exercise, during the study period to disable the other oral glucose-lowering drugs and impact force active ingredient related.2.Select the 45 patients were randomly divided into two groups, one group is control group of 21 cases,the other group is experimental group of 24 cases Control group. The control group is only given insulin pump treatment, according to the adjustment of blood insulin dose.The experimental group is basis on insulin pump therapy to give liraglutide of 0.6 mg/d gradually increased to 1.2 mg/d.3.Respectively, compared two groups of patients before starting treatment and intervention treatment after 3 months of fasting plasma glucose(FPG), blood sugar 2 hours after meal(PBG2h), glycosylated hemoglobin(Hb A1c), fasting c-peptide(CP), 1 hour postprandial c-peptide(1h CP), fasting insulin, insulin 1 hour after the meal, beta cell function, insulin resistance(HOMA- beta), insulin resistance index(HOMA IR), blood lipid(TC, TG, HDL, LDL, blood pressure, body weight, body mass index(BMI), waist hip ratio(WHR), homocysteine(Hcy), trace albumin(m Alb). And record low blood glucose reaction times,gastrointestinal adverse reactionsin, liver function damage and so on in two groups of treatment; evaluation analysis of two groups before and after treatment islet beta cell function and improve insulin resistance.4.Statistical analysis Use SPSS22.0 statistical software package for statistical processing, measurement data using(x__±s), comparing between group use t test, counting information between groups use four tables x2 test. Inspection standard: α = 0.05, P < 0.05 was significant difference. Results:1.The comparison of two groups of baseline data, two groups of selected cases before treatment by gender, age, FPG, PBG2 h, Hb A1 c, CP, 1h CP, fasting insulin, 1 hour after the meal, HOMA-beta, HOMA IR, TC, TG, HDL, LDL, blood pressure, body weight, BMI, WHR, Hcy, m Alb and ALT、AST、GGT have no difference(P > 0.05).2. The experimental group before and after treatment the comparison of related parameters in oral glucose-lowering: FPG(11.97±3.59 vs6.29 ± 1.22), 2h BPG(16.34 ±5.62 vs7.36±2.17) and Hb A1c(11.97±4.59vs5.46±1.67),the difference is significant(P<0.05).The comparison of related parameters control in the aspect of hypoglycemic: FPG(11.29±3.82vs6.97±1.19), 2h BPG(16.86±5.17vs7.34±2.62) and Hb A1c(12.46±3.67vs5.57±1.59), the difference is significant(P<0.05).The experimental group and control group after treatment can effectively control the FPG, 2h PBG, Hb A1 c, it is no significant difference(P>0.05).Two groups of insulin, C-peptide and beta-cell function in the comparison of related parameters:the experimental group before and after treatment in the aspect of improve beta-cell function related parameters comparison: CP(1.93 ± 1.13 vs3.08 ± 0.98), 1h CP(2.30 ± 1.63 vs6.86 ± 1.64), fasting insulin(8.70 ± 0.85 vs24.17 ± 2.35), 1 hour after a meal insulin(24.87 ± 2.23 vs66.58 ± 2.08), HOMA-IR(4.17 ± 1.50 vs2.34 ± 1.23) and HOMA- beta(16.57 ± 11.50 vs34.76 ± 9.79), the difference is significant(P < 0.05). The control group before and after treatment in the aspect of improve beta-cell function related parameters comparison: CP(1.98±0.98vs2.43± 1.13),1h CP(2.86±1.64 vs6.30± 1.63), fasting insulin(9.15±0.15 vs18.20± 1.22), 1 hour after a meal insulin(23.95±1.31 vs46.55± 2.11), HOMA IR(4.20±0.23 vs2.77± 1.50)and HOMA- beta(16.80±10.97vs23.17±8.43), it is no difference(P>0.05).The experimental group and control group after treatment, the experimental group can effectively improve CP, 1h CP, fasting insulin, 1 hour after the meal insulin HOMA-IR, HOMA-beta and reduce the dosage of insulin, it is has difference(P < 0.05).3. The comparison of two groups of body weight, BMI and WHR:the experimental group before and after treatment in improving the body weight, BMI and WHR comparison:(83.63±11.22 vs76.38±15.33),(29.20±3.09vs25.01±3.12),(1.03±0.07 vs0.85 ±0.06), it is has significant difference(P< 0.05).The control group before and after treatment in improving the body weight, BMI and WHR comparison:(79.38± 15.33 vs.82.63 ±10.23),(29.01 ±3.12 vs29.54 ±3.10),(1.05 ±0.06 vs1.06 ± 0.07), it is has no difference(P>0.05).The experimental group compares with control group after treatment, the experimental group can effectively improve body weight, BMI and WHR, it is has significant difference(P < 0.05).4.The comparison of two groups of blood fats aspect related parameters:the experimental group before and after treatment the comparison of related parameters in the aspect of improving blood lipids: TC(5.47±1.39vs5.47±1.42), TG(4.59±3.09vs3.15±3.46), HDL(1.15±0.49vs1.87±0.30), LDL(3.34±1.23vs2.68±1.33),it is has significant difference(P< 0.05).The control group before and after treatment the comparison of related parameters in the aspect of improving blood lipids: TC(5.72±1.39 vs5.52±1.43), TG(4.18±3.46vs4.15± 3.13), HDL(1.07±0.30vs1.16±0.53), LDL(3.68 ±1.33 vs1.16±0.53), it is has no difference(P>0.05).The experimental group compares with control group after treatment, the experimental group can effectively reduce TC, TG, LDL, raise HDL, it is has significant difference(P < 0.05).5.The comparison of two groups of systolic blood pressure, Hcy, m Alb:the experimental group before and after treatment the comparison of systolic blood pressure, Hcy, m Alb(134.31 ±13.12 vs130.5±9.67),(11.97±5.59vs8.46±4.67),(50.42±8.55vs48.41±8.05),P<0.05, there is significant difference.The experimental group before and after treatment the comparison of diastolic blood pressure,(75.31 ±10.13 vs75.24 ±10.02),P﹥0.05, there is no significant difference.The control group before and after treatment systolic blood pressure, diastolic blood pressure, and the comparison of Hcy,m Alb,(130.5±9.67vs132.31±12.13),(75.43±10.52vs75.47±10.13),(12.46±4.67vs13.57±4.53),(51.23±8.54vs51.41±8.26), P>0.05,it is has no difference.The experimental group and control group after treatment, no significant changes in diastolic blood pressure,but the experimental group can effectively control the systolic blood pressure, Hcy and m Alb, there is significant difference(P < 0.05).6.Two groups of adverse reactions of comparison: during treatment 5 patients of the control group have a low blood glucose reaction, the incidence is 23.81%; 1 patients of the experimental group appears hypoglycemia, accounting of4.17%, it is significant difference(P < 0.05).During in treatment’process 8 patients of the experimental group have been nausea, diarrhea, accounted for 33.33%, 3 case of intolerance to exit; Four patients have been constipation symptoms, 16.67%; 1 case of patients with influenza-like symptoms(4.17% / 24) out of the experimental group, while the control group don’t have the above symptoms, therefore, the experimental group in the number of adverse symptoms was obviously higher than that of control group, it is significant difference(P < 0.05).ALT, AST, GGT of the two groups before and after treatment have no obvious abnormal. Conclusion:1.Insulin pump alone and the liraglutide combing with insulin pump therapy can control blood sugar,significantly lower Hb A1 c values in patients with not first diagnosed type 2 diabetes.2.Liraglutide combing with insulin pump therapy can reduce insulin dose, significantly improve beta-cell function and the insulin resistance.3.Liraglutide combing with insulin pump therapy can reduce the body weight and insulin resistance.4.Liraglutide combing with insulin pump therapy can more reduce the incidence of hypoglycemia than insulin pump therapy.更多还原