参芪复方与胰岛素联用对2型糖尿病患者β细胞功能、氧化应激及血GLP-1水平影响的临床观察及机制研究

【作者】 张新霞；

【导师】 谢春光；

【作者基本信息】 成都中医药大学 ， 中医内科学， 2013， 博士

【摘要】 本论文分为糖尿病的理论探讨和临床研究两个部分。第一部分理论探讨本论文的理论探讨从祖国医学的角度,对糖尿病的认识、病因病机、辨证论治体系进行了阐述。第二部分临床研究目的研究需使用胰岛素治疗的2型糖尿病(T2DM)患者加用参芪复方后胰岛β细胞功能是否有一定的改善,同时观察它对氧化应激及血GLP-1等的影响以探讨参芪复方可能的作用机制。对象及方法单用胰岛素治疗的2型糖尿病患者随机分为试验组和对照组,试验组使用胰岛素和参芪复方,对照组单用胰岛素,研究期为12周。于基线和研究结束时分别进行口服葡萄糖耐量试验(OGTT)+C肽释放试验(100g标准馒头餐),测量血糖、C肽、GLP-1(均为0小时、0.5小时、2小时)；HbAlc;空腹胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白一胆固醇(HDL-c).低密度脂蛋白一胆固醇(LDL-c).游离脂肪酸(NEFA).总的超氧化物歧化酶(T-SOD).丙二醛(MDA)、可溶性E-选择素(sE-selectin)、可溶性血管细胞黏附分子-1(sVCAM-1)；疑血酶原时间(PT)、活化部分凝血活酶时间(APTT)纤维蛋白原(Fib)、血红蛋白、肝肾功等。△CP30/△G30评估早相C肽的分泌。计算HOMA-β、HOMA-IR以分别反映胰岛β细胞功能和胰岛素抵抗。结果42位患者进入研究,40位完成研究。基线时,两组患者的一般资料及观测指标经过统计学分析均无统计学差异(p>0.05),研究结束时,试验组临床总疗效、中医症状、体征积分均优于对照组。无论是试验组还是对照组的各点的血糖均有明显降低,HbAlc亦有明显降低分别为[(10.97±1.23vs7.71±1.01)%,p<0.05]。试验组试验后与试验前相比0.5hC肽[(0.86±0.42vs1.59±0.54)nmol/L,p=0.000],△CP30/△G30(0.07±0.48vs0.53±0.51,p=0.01)均明显升高,对照组无明显变化；试验组试验后与对照组试验后相比0.5hC肽[(1.22±0.43vs1.59±0.54)nmol/L,p=0.023],△CP30/△G30(0.27±0.22vs0.53±0.51,p=0.04),表明试验组试验后0.5hC肽、△CP30/△G30与对照组相比改善明显且差异有统计学意义。试验组与试验前相比0hGLP-1[(219.88±100.14vs266.17±105.63)pg/mL,p=0.000],0.5hGLP-1[(260.67±104.25vs333.94±114.48)pg/mL,p=0.000],2hGLP-1[(211.21±91.85vs245.91±113.32)pg/mL,p=0.001]有升高且差异有统计学意义,对照组无明显变化。试验组试验后与对照组试验后相比OhGLP-1[(227.02±100.15vs266.17±105.63)pg/mL, p=0.315],差异无统计学意义；0.5hGLP-1[(245.98±101.48vs333.94±114.48)pg/mL, p=0.014],差异有统计学意义；2hGLP-1[(211.53±97.08vs245.91±113.32)pg/mL, p=0.309]差异无统计学意义。试验组T-SOD明显升高、MDA. sE-select in、sVCAM-1明显下降。PT.APTT.Fib对照组试验前后无统计学差异,试验组试验前后差异有统计学意义,且试验组试验后与对照组试验后相比差异有统计学意义。试验组的TG.LDL-C均有下降。HDL-c无明显变化,NEFA明显降低[(242.85±252.21vs566.80±476.33)ng/mL,p=0.000],对照组的血脂无明显变化。HOMA-β、HOMA-IR无论是试验组还是对照组差异均无统计学意义。结论单使用胰岛素控制血糖的T2DM患者,通过12周的参芪复方的治疗可以明显改善这些患者的中医症状及体征、减轻体重、控制血糖、提高HbAlc的达标率、改善β细胞的分泌功能。这些作用部分与参芪复方能够使胰岛素抵抗减轻、脂代谢紊乱改善、凝血功能改善、餐后GLP-1分泌尤其是早相GLP-1增加、氧化应激减少、抗氧化作用提高及血管内皮功能改善有关。更多还原

【Abstract】 There are two parts in this paper.One part is reference review of diabetes,The other part is clinical research on the treatment for Shenqi Compound Extract combined with insulin therapy in type2diabetic patients.Reference reviewIn reference review part of this paper, from the perspective of traditional Chinese medicine, the understanding of diabetes, etiology and pathogenesis, syndrome differentiation and treatment system are described.clinical researchObjective:To investigate the effects of Shenqi Compound Extract combined with insulin therapy on islet B cell function,especially on early phase of insulin secretion, oxidative stress and on the secretion of glucagon-like peptide-1(GLP-1)in type2diabetic patients who need to use insulin therapy to control bloodglucose.Methods:Type2diabetic patients who need to use insulin therapy were selected. One is study group and the other is control group. The study group injected insulin and combined with Shenqi Compound Extract orally, the control group only used insulin.This study lasted for12weeks. At baseline and the end of the study,Oral glucose tolerance test(100g standards bread)+C-peptide release test was performed,respectively. Other indices such as plasma glucose,C-peptide,serum GLP-1(0h,0.5h,2h),and HbA1c,total cholesterol(TC),triglycerides(TG), high density lipoprotein cholesterol(HDL-ch) and low density lipoprotein cholesterol(LDL-ch),none stesterified fatty acid (NEFA),total superoxide dismutase(T-SOD),malondialdehyde(MDA),soluble E-selectin (sE-selectin),soluble vascular cell adhesion molecule-1(sVC AM-1),prothrombin time(PT),activated partial thromboplastin (APTT),fibrinogen(Fib),hemoglobin,liver and kidney function were detected. Use ΔCP30/ΔG30to evaluate the early phase of βcell function. Calculated HOMA-β, HOMA-IR to reflect the pancreatic beta cell function and insulin resistance(IR).Results:Fourty two patients were included in the study and fourty patients finished follow-up. At baseline, the two groups of patients with general information and observations through the statistical analysis were not statistically different (p>0.05).Either the study group or the control group of each point plasma glucose significantly decreased, HbAlc is also significantly decreased[(10.97±1.23vs7.71±1.01)%, p<0.05].After the study, compared with before the study,0.5hC-p of the study group increased[(0.86±0.42vs1.59±0.54)nmol/L,p=0.000] significantly Δ CP30/Δ G30of the study group increased (0.07±0.48vs0.53±0.51,p=0.01) significantly,too.In the control group these indices did not change significantly.0hGLP-1,0.5hGLP-1,2hGLP-1of the study group increased all. T-SOD activity of the study group were improved. Other indices of the study group,such as MDA levels,sE-selectin,sVCAM-1,TG、LDL-C were decreased significantly. NEFA decreased[(242.85±252.21vs566.80±476.33)ng/mL,p=0.000]too. No significant changes in the lipids of the control group. The level of PT,APTT of the study group had shorter than that of the control group. The level of Plasma TG,LDL-C,Fib of the study group were decreased. No significant changes in HDL-c.HOMA-B,HOMA-IR, regardless of the study group or the control group showed no significant difference.Conclusion:Single-use insulin to control blood sugar in type2diabetic patients,12weeks Shenqi Shenqi Compound Extract treatment can significantly improve the clinical symptoms and signs of these patients, control blood glucose,improve HbAlc compliance rate, improve Bcell function.Effects of Shenqi Compound Extract on these function in type2diabetic patients may relate to the improvement of IR,improvement of lipid metaboli-sm disorders, improvement of Coagulation function,increasing of postprandial GLP-1secretion, especially in the early phase of GLP-1secretion,decreasing in oxidative stress,improvement of the anti-oxidation, improvement of endothelial function.更多还原