【作者】 杨青；

【导师】 陈少华； 李曙远；

【作者基本信息】 山东大学 ， 内科学， 2013， 硕士

【摘要】 背景：流行病学研究显示,2型糖尿病(type2diabetes mellitus, T2DM)约占糖尿病总体人群的90-95%,以胰岛素分泌不足、敏感性降低及其引起的能量代谢紊乱伴高血糖症为特点,可导致眼、肾、神经、血管等组织慢性进行性病变。nesfatin-1是一种新型摄食相关胃肠调节肽,2006年由Oh-Ⅰ等第一次报导。近期研究发现除调节摄食外,nesfatin-1还可产生时间、剂量以及胰岛素依赖的降糖作用,且与T2DM患者体内代谢紊乱有关,可能参与其病情的发生、发展。阿卡波糖是α-糖苷酶抑制剂,可抑制小肠刷状缘对葡萄糖的吸收,降低餐后血糖峰值,是临床常用降糖药物。既往资料指出,阿卡波糖还对T2DM患者脂代谢异常有明显改善作用,但试验结果略有差异。考虑到阿卡波糖通过调节肠道吸收发挥作用,我们猜测其是否可以影响机体内胃肠调节肽——nesfatin-1的分泌,进而改善T2DM患者能量代谢,延缓其病情及或并发症的进展,目前相关报道尚无。本文通过分析T2DM患者服用阿卡波糖12周后血清nesfatin-1水平及糖、脂代谢指标的变化,探讨其在T2DM能量代谢紊乱中的作用,为早期防治糖尿病及其并发症提出新的思路。目的：1、研究阿卡波糖对T2DM患者血清nesfatin-1水平的影响。2、进一步验证阿卡波糖对T2DM患者糖、脂代谢的影响。方法：本试验共纳入符合标准的T2DM患者60例。采用SPSS软件将所有患者随机分为2组：试验组除原降糖方案外另给予阿卡波糖口服,对照组则继续原降糖方案进行空白对照。两组患者基线资料无显著性差异。试验前对原降糖药物剂量进行调整,当空腹血糖(fasting plasma glucose, FPG)、餐后2h血糖(2-hour postprandial blood glucose,2hPG)分别控制在6～8、8～10mmol/L后进入试验期。试验周期12周。采用酶联免疫吸附法检测2组患者试验前后血清nesfatin-1水平；收集所有纳入患者试验前后一般临床资料、糖脂代谢指标。以多项基本指标、不良反应进行安全评价。结果：1、试验组、对照组治疗前后nesfatin-1水平及糖、脂代谢指标变化的分析：(1)试验组血清nesfatin-1水平较前明显上升(P<0.01)；糖脂代谢方面,试验组FPG、2hPG、糖化血红蛋白(glycosylated hemoglobin, HbA1c)及稳态模型胰岛素抵抗指数(homeostasis model assessment of insulin resistance, HOMA-IR)均较前有显著降低(P<0.05或P<0.01),总胆固醇(total cholesterol, TC)、体质量指数(body mass index, BMI)及甘油三酯(triglyceride, TG)较前亦有明显下降(P<0.01或P<0.05)。其他指标变化无统计学意义。(2)对照组治疗前后血清nesfatin-1水平无显著性差异。血糖方面,对照组2hPG在治疗后有明显下降(P<0.01)。各脂代谢指标治疗前后变化则无统计学意义。2、两组患者治疗后指标变化的分析：采用协方差分析对两组患者各指标变化进行对比后发现,试验组nesfatin-1升高水平与对照组相比有统计学差异(P<0.05)。在改善糖、脂代谢方面试验组亦明显优于对照组,试验组FPG、2hPG、空腹胰岛素(fasting plasma insulin, FPI)、 HOMA-IR、HbA1c下降情况与对照组相比有显著性差异(P<0.01或P<0.05)；TG、TC变化亦较对照组有统计学差异(P<0.01或P<0.05)。其余检测指标变化无统计学意义。结论：给予阿卡波糖治疗的试验组血清nesfatin-1水平显著升高,糖脂代谢指标亦有明显下降。提示阿卡波糖可对T2DM患者血清nesfatin-1水平及糖脂代谢产生调节作用,从而改善其内部代谢紊乱状态,可能在延缓T2DM病情的发生、进展中发挥重要作用。更多还原

【Abstract】 Background:Type2diabetes mellitus (T2DM) is a metabolic disorder that is characterized by high levels of blood glucose as a result of insulin resistance and relative insulin deficiency. Epidemiologic studies have revealed that T2DM patients account for more than90%of all diabetics. Nesfatin-1is a new type of feeding-related gastrointestinal regulatory peptides, which was firstly reported in2006by Oh-Ⅰ. et al. The recent studies showed that nesfatin-1can cause Ca2+influx by activating the L-type Ca2+pathway on the cell membrane of islet β, which will further produce the time-, dose-and insulin-dependent hypoglycemic effects. Meanwhile, the fluctuation of nesfatin-1in type2diabetics had been conjectured participate in the regulation of metabolism disorder of the patients. Acarbose is a kind of α-glucosidase inhibitor, which is commonly-used in clinical at present. The hypoglycemic mechanism of it is delaying the glucose absorption into the brush border of small intestine and reducing the postprandial blood glucose peak. According to the previous researches, acarbose could regulate the lipid metabolism of T2DM patients in addition to its hypoglycemic effects. However, the results obtained differ in different experiments. Considering acarbose influences the absorption of intestines, we speculated that it might also affect the plasma nesfatin-1levels-a gastrointestinal regulatory peptides of T2DM patients, although there is no relative supporting yet. This paper explored the effects of acarbose on energy metabolism by analyzing the changes of plasma nesfatin-1levels and glycolipid metabolic in T2DM patients after taking acarbose for12weeks. It provided a new idea for the early prevention and treatment of diabetes mellitus, as well as its complications.Objective:1. To investigate the effects of acarbose on the plasma nesfatin-1levels of the T2DM patients.2. To further identify the effects of acarbose on the glycolipid metabolism of the T2DM patients.Methods:A total of60patients who met the inclusion criteria were selected for this experiment. The involved patients were divided into2groups using SPSS software: the test group was required to take acarbose in addition to its previous oral hypoglycemic agents (OHA); the control group was only required to take OHA. There was no significant difference of baseline levels between the two groups. Dose adjustment for previous OHA was conducted in front of the treatment. After fasting plasma glucose (FPG) and2-hour postprandial blood glucose (2hPG) of the patients were maintained at6～8and8～10mmol/L respectively, the patients entered the test period. The experiment kept12weeks. The plasma nesfatin-1levels of patients were measured using the ELISA method. The general clinical data and glycolipid metabolic indicators were collected at the same time. The experiment safety was evaluated based on several basic clinical indexes and adverse events.Results:1. Analysis of the changes of plasma nesfatin-1levels and glycolipid metabolism before and after the treatment:(1) The plasma nesfatin-1levels of test group were significantly increased after the treatment (P<0.01). With regard to the glycolipid metabolism, the FPG,2hPG, glycosylated hemoglobin (HbAlc), homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), triglyceride (TG) and total cholesterol (TC) were all dramatically decreased in test group after the treatment (P<0.01or P<0.05). The changes of other indicators were not statistically significant.(2) The plasma nesfatin-1levels of control group had no significant change before and after the treatment. With regard to the glycolipid metabolism, the2hPG of control group was significantly decreased (P<0.01), while the lipid metabolic indicator had no significant change.2. Comparison analysis of the treatment effects between the test group and the control group:After covariance analysis, it was observed that in test group, the changes of plasma nesfatin-1levels were significantly different when compared with the controls (P<0.05). The glycolipid metabolic parameters of test group were remarkably better than that of control group. The changes of FPG,2hPG, fasting plasma insulin (FPI), HOMA-IR, HbAlc, TG and TC of test group were dramatically different when in comparison with the control group (P<0.01or P<0.05). Other changes of indicators had not statistically significant.Conclusions:The plasma nesfatin-1levels and glycolipid metabolic indicators of test group, who was treated with acarbose except for OHA, were significantly changed when compared with controls. All of this is indicating that acarbose has a regulation effect on plasma nesfatin-1levels and glycolipid metabolism of T2DM patients. It might be improving the internal metabolism and playing an important role in delaying the development of T2DM, as well as its complications. This study provided a new idea for the clinical treatment of diabetes mellitus.更多还原