减重手术治疗2型糖尿病临床疗效评价与成本效果评估

发布时间：2018-01-03 09:38

本文关键词：减重手术治疗2型糖尿病临床疗效评价与成本效果评估　出处：《山东大学》2017年博士论文　论文类型：学位论文

【摘要】：研究背景随着人类生活水平的日益提高,继心血管病、肿瘤之后,糖尿病已成为第三大威胁人类健康的慢性疾病。其高医疗高花费、高致残、高致死的特征是目前世界各国共同面对的公共卫生问题。而在我国,糖尿病发展情况更为严峻。我国2型糖尿病患病率在过去的二十多年中呈爆炸式增长。1980年,我国男性的患病率不到5%;而2010年,我国糖尿病患病率约为11.6%。2015年,我国约有1.1亿名糖尿病患者,约占我国成年人总数的1/10。更为严重的是,我国近半数成年人处于糖尿病前期,约为5亿人。这不仅带来罹患2型糖尿病的风险,也带来罹患心血管病等其他疾病的风险。尽管近百年来在糖尿病治疗领域取得很大的进展,使一部分患者的体重下降,血糖达标,但遗憾的是,目前的传统治疗方法未能彻底治愈糖尿病,同时无法延缓糖尿病并发症的发生。近年来,减重手术在肥胖型2型糖尿病的治疗中取得了突破性进展。减重手术最初被用于治疗病态性肥胖,上世纪90年代观察到,减重手术除子明显减轻体重,还可以良好的控制血糖。随后在一项前瞻性研究性对照研究后发现并证实,术后患者不需要药物降糖并能长期保持血糖正常的例数明显高于非手术组,且与糖尿病相关的并发症发生率和病死率大大降低。在内科治疗病态性肥胖及2型糖尿病等代谢性疾病难以维持长期稳定的效果的情况下,减重手术经过数十年的发展已被证明是治疗病态性肥胖及2型糖尿病等代谢性疾病切实有效的方法,成为治疗糖尿病新阶段的专家共识。然而,现在阶段减重手术治疗2型糖尿病依然存在若干研究不足。首先,以亚洲人群为对象的,减重手术与非手术治疗2型糖尿病疗效的Meta分析缺乏。由于2型糖尿病与胰岛素抵抗相关,且不同人群表达的胰岛素抵抗指数不尽相同,因而减重手术针对不同人群可能产生的效果也不尽相同。所以针对于亚洲人群的减重手术与非手术治疗2型糖尿病疗效的Meta分析具有必要性。其次,作为应用最广泛且最被认可的两种减重手术术式——腹腔镜Roux-en-Y 胃旁路术(Laparoscopic Roux-en-Y Gastric Bypass,LRYGB)和腹腔镜胃袖状切除术(Laparoscopic Sleeve Gastrectomy,LSG)治疗2型糖尿病疗效评价的随机对照试验仍然不足。第三,基于倾向性评分法研究真实世界LRYGB和LSG治疗2型糖尿病的疗效评价缺乏。尽管随机对照试验具有组间可比性好、防止选择性偏倚、研究对象的诊断确切等一些优势,但由于其严格的纳入、排除标准,导致研究结果的代表性和外在的真实性受到一定的局限。因此将LRYGB和LSG治疗2型糖尿病的疗效评价应用于基于倾向性评分法还原的真实世界进行研究有必要性,但目前相关研究仍然缺乏。最后,LRYGB和LSG治疗2型糖尿病的成本效果评估缺乏。减重手术治疗2型糖尿病短期的临床效果评估已经被多项大型研究证实,但是从卫生经济学角度分析,与非手术治疗策略相比,减重手术治疗2型糖尿病在单位质量调整生命年的效果情况至今还未有研究。研究目的本研究基于Meta分析法、倾向性评分法、马尔科夫模型、首都医科大学附属北京世纪坛医院糖尿病外科治疗中心数据以及国家自然科学基金项目(71673169)的资助,进行了"减重手术治疗2型糖尿病临床疗效评价与成本效果评估"。本文通过进行(1)针对亚洲人群,减重手术与非手术治疗2型糖尿病临床疗效的Meta分析;(2)LRYGB和LSG治疗2型糖尿病的疗效评价——小型随机对照试验;(3)LRYGB和LSG治疗2型糖尿病的疗效评价——基于倾向性评分法的回顾性列队研究;(4)LRYGB和LSG治疗2型糖尿病的成本效果评估——基于马尔科夫模型的经济学评价,旨在比较在亚洲人群中,减重手术与非手术治疗2型糖尿病患者在血糖控制、体重控制和糖尿病缓解上的优劣以及其长期的成本效果,并进一步分析不同的手术术式(LRYGB和LSG)的疗效差异和成本效果差异,以此为手术人群的筛选及适应症的把握上提供线索,为治疗2型糖尿病的进一步发展贡献绵薄之力。研究资料与方法本研究针对于LRYGB和LSG治疗2型糖尿病疗效评价与成本效果评估,通过Meta分析、随机对照试验以及真实世界的队列研究对减重手术治疗2型糖尿病进行证据补充,为患者提供参考信息,也为治疗2型糖尿病的进一步发展提供数据。综述所述,研究方法可以归纳为:(1)对减重手术与非手术治疗2型糖尿病疗效的Meta分析,为评价减重手术治疗和非手术的常规治疗的方案选择提供参考;(2)通过小型随机对照试验进行LRYGB和LSG治疗2型糖尿病的疗效评价,有利于针对于LRYGB和LSG的手术术式选择证据补充;(3)通过基于倾向性评分法的回顾性列队研究进行LRYGB和LSG治疗2型糖尿病的疗效评价,有利于进一步在真实世界验证LRYGB和LSG治疗2型糖尿病的疗效差异性,为治疗糖尿病提供数据支持和指南依据;(4)基于马尔科夫模型对LRYGB和LSG治疗2型糖尿病的成本效果评估,为临床提供第一份关于减重手术治疗2型糖尿病的经济学评价,有利于证据的补足。研究主要结果根据以上的分析和讨论,本研究主要结论为:(1)通过文献综述可得,减重手术治疗2型糖尿病在国外有几十年的历史,而在我国只发展了十几年,还在起步阶段。而其控制血糖效果已得到研究者及越来越多的患者的认可,2014年发布的《中国肥胖和2型糖尿病外科治疗指南》,对减重手术治疗2型糖尿病进一步明确了其术前评估与准备及术后并发症等。尽管治疗效果较为显著,但针对我国人群,对于手术术式选择以及适应症把握上研究仍然较浅。(2)应用Meta分析法系统性评价了减重手术与非手术方式治疗亚洲人群2型糖尿病患者在血糖控制、体重控制、胆固醇浓度、甘油三酯以及糖尿病缓解率的疗效情况,结果显示,与非手术方法相比,当前常用的外科减重手术均能有效改善术后2型糖尿病患者的糖化血红蛋白、BMI、体重、LDL、HDL、CHOL、TRIG;且减重手术在2型糖尿病缓解率方面显著优于非手术治疗方式。(3)基于LRYGB和LSG治疗肥胖合并2型糖尿病患者的小型随机对照试验和回顾性队列在"真实世界"的验证,结果显示:对于我国患者,减重手术是在血糖控制、体重控制和糖尿病缓解等指标上治疗肥胖合并2型糖尿病的有效方法,且LRYGB和LSG两种术式的临床疗效并无统计学差异,与其他研究结果基本一致。另外,且LRYGB和LSG两种术式的临床疗效并无统计学差异,并各有其特点:LRYGB适用于体重较小且需依靠内分泌改善的患者;LSG对于低年龄、高体重、糖尿病程度较轻、术前胰岛素功能较完善的患者更为适用;而其安全性均值得信赖。(4)基于马尔科夫模型,将3种治疗2型糖尿病的方案,即LRYGB方案、LSG方案以及非手术治疗方案以1年为循环周期,运行直至80岁或者死亡,以对比三种方案单位成本的效果值。结果显示,LRYGB方案及LSG方案的成本效果比值远远高于初期投入最低的非手术治疗方案。因此我们认为,LRYGB与LSG均为高成本效果比的治疗方式,在单位成本上优于非手术治疗方式。而较为肥胖的患者更适合采用LSG手术进行治疗。政策建议(1)应进一步发展2型糖尿病外科治疗临床路径标准化。(2)应增强外科治疗2型糖尿病科普力度。(3)应促进公卫与临床相结合,加强团队合作。(4)在鼓励外科治疗的同时,应该进一步研究发展内科疗法。创新性与不足之处(1)创新之处:①基于倾向性评分法将回顾性数据利用模型进行1:1匹配,以将小型临床试验的结果带入"真实世界"进行验证,更一步证明研究的可靠性,为循证医学提供依据。②基于马尔科夫模型,模拟2型糖尿病患者不同的生存状态,并收集各个参数代入模型,以1年为循环周期,运行直至80岁或者死亡,以对比手术治疗方法和非手术治疗方案单位质量调整生命年的效果值。为我国减重手术治疗2型糖尿病的经济学评价进行补足。(2)不足之处本研究尚存在一定的局限性:①无论是随机对照试验还是基于倾向性评分法的匹配研究,样本量较小,且未能观察到长期结局;②旨在对减重手术治疗2型糖尿病的情况进行全方位的评估,但因为时间关系,未完成患者术后生命质量评价问卷调查。如果能收集到这部分主观评价相关数据并进一步进行研究,便可以更好的提升本研究的全面性,为循证医学提供较为充足的证据。
[Abstract]:Background: with the increasing standards of living, after cardiovascular disease, cancer, diabetes has become a chronic disease to human health third major threats. Its high medical cost, high morbidity, high mortality characteristics is currently facing the world public health problem. But in our country, the development of more diabetes severe. Prevalence rate was the explosive growth of.1980 over the past more than 20 years China's type 2 diabetes, Chinese male prevalence rate of less than 5%; and in 2010, the prevalence rate is about 11.6%.2015 years of diabetes in China, there are about 110 million diabetic patients in China, the total of Chinese adults 1/10. is more serious in China, nearly half of all adults in pre diabetes, about 500 million people. It not only brings the risk of developing type 2 diabetes, but also bring the risk of cardiovascular disease and other diseases. Although nearly a hundred years in the treatment of diabetes The field has made great progress, the proportion of patients with decreased body weight, blood glucose, but unfortunately, not the traditional treatment method of current cure diabetes, and can delay the occurrence of complications of diabetes. In recent years, bariatric surgery in obese have achieved a breakthrough in the treatment of type 2 diabetes in bariatric surgery was initially. For the treatment of morbid obesity, in 90s observed that bariatric surgery except for significant weight loss, but also can control blood glucose well. Then in a prospective study of comparative study and found that patients do not need drugs hypoglycemic and maintain normal blood glucose were significantly higher than in non surgery group for a long period of time, and diabetes related morbidity and mortality is reduced greatly. In the medical treatment of morbid obesity and type 2 diabetes and other metabolic diseases difficult to maintain long-term stable effect Under the condition of bariatric surgery after decades of development has been proved to be a method for the treatment of morbid obesity and type 2 diabetes and other metabolic diseases effectively, a new expert consensus stage for treatment of diabetes. However, the present stage of bariatric surgery in the treatment of type 2 diabetes still exists if dry research. First of all, to the Asian population as the object the curative effect of the treatment of type 2 diabetes, bariatric surgery and non surgery Meta analysis. Due to lack of type 2 diabetes and insulin resistance, and the expression of different groups of insulin resistance index is not the same, so the bariatric surgery for different people may have the effect is not the same. So for bariatric surgery and non surgery in Asia the curative effect in the treatment of type 2 diabetes Meta analysis is necessary. Secondly, as a two weight loss surgery is most widely used and most recognized: laparoscopic Roux-en-Y Gastric bypass (Laparoscopic Roux-en-Y Gastric Bypass, LRYGB) and laparoscopic sleeve gastrectomy (Laparoscopic Sleeve, Gastrectomy, LSG) randomized controlled trials to evaluate the efficacy of treatment of type 2 diabetes is still insufficient. Third, the lack of efficacy of propensity score method to study the real world of LRYGB and LSG in the treatment of type 2 diabetes. Although based on randomized controlled trials is comparable between groups, to prevent selective bias, the exact diagnosis research object and some other advantages, but because of its strict inclusion and exclusion criteria, the results lead to the representation and in reality is limited to a certain degree. Therefore, LRYGB and LSG in the treatment of type 2 diabetes curative effect evaluation based on reduction propensity score method of the real world is necessary to study, but the study is still lacking. Finally, cost effectiveness analysis of LRYGB and LSG in the treatment of type 2 diabetes lack . to evaluate the clinical effect of bariatric surgery for type 2 diabetes mellitus in short term has been a number of large studies, but from the view of health economics analysis, compared with the non operative treatment strategies, bariatric surgery for the treatment of type 2 diabetes in unit of quality adjusted life years the situation has not yet studied. This study based on Meta analysis, tendency score method, Markov model, Beijing Shijitan Hospital, CMU affiliated to the Capital Medical University diabetes surgery center data and National Natural Science Fund (71673169) funded the "cost effectiveness evaluation and clinical efficacy of the treatment of type 2 diabetes bariatric surgery assessment. This paper (1) for the Asian population, clinical analysis of the treatment of type 2 diabetes bariatric surgery and non operation of Meta; (2) the curative effect evaluation of LRYGB and LSG in the treatment of type 2 diabetes mellitus -- small randomized controlled trial; (3) LRYG The curative effect evaluation of B and LSG in the treatment of type 2 diabetes: a retrospective cohort study based on propensity score method; (4) to assess the cost effect of LRYGB and LSG in the treatment of type 2 diabetes mellitus -- Based on the economic evaluation of the Markoff model to compare in Asian populations, bariatric surgery and non surgical treatment in patients with type 2 diabetes blood sugar control on the quality, ease the weight control and diabetes and its long-term cost effectiveness, and further analysis of different operation type (LRYGB and LSG) differences in the efficacy and cost effectiveness, in order to provide clues for the screening of surgical population and indications of the master, for the further development of the treatment of type 2 diabetes contribute to research. Materials and methods this study for LRYGB and LSG in the treatment of patients with type 2 diabetes cost evaluation and effect evaluation, through the Meta analysis of randomized controlled trials and cohort of the real world Study on bariatric surgery for the treatment of type 2 diabetes evidence supplement, provide reference information for patients, to provide data for the further development of the treatment of type 2 diabetes. A review of the research methods, can be summarized as follows: (1) analysis of curative effect in the treatment of type 2 diabetes mellitus on bariatric surgery and non operation of Meta, provide a reference for the selection of conventional treatment evaluation of bariatric surgery and non surgery program; (2) evaluate the curative effect in the treatment of type 2 diabetes through small randomized controlled trials of LRYGB and LSG, is conducive to the choice of surgery for evidence of needle type LRYGB and LSG; (3) the curative effect based on propensity score method a retrospective cohort study and LRYGB LSG for the treatment of type 2 diabetes evaluation of efficacy is conducive to further verification of LRYGB and LSG in the real world for the treatment of type 2 diabetes, for the treatment of diabetes and provide data support according to the guidelines; (4) based on the Maldives Cost effectiveness evaluation model, treatment of type 2 diabetes on LRYGB and LSG, to provide the economic evaluation of type 2 diabetes clinical report on the first bariatric surgery, is conducive to the evidence of the complement. Main research results based on the above analysis and discussion, the main conclusions of this study are: (1) available through literature review, bariatric surgery treatment of type 2 diabetes has decades of history in foreign countries, while in China, only the development of more than ten years, is still in the initial stage. The effect of blood glucose control has been studied and recognized by more and more patients, released in 2014 "China obesity and type 2 diabetes guidelines for surgical treatment of >, bariatric surgery for type 2 diabetes further defined their preoperative evaluation and postoperative complications and preparation. Although the treatment effect is remarkable, but for our people, for the selection of surgical procedures and indications of grasp are still shallow. ( 2) application of Meta analysis system of evaluation and non surgical bariatric surgery for the Asian population of patients with type 2 diabetes in glycemic control, weight control, cholesterol, triglyceride and diabetes remission rate, the results show that, compared with non operative methods, the current commonly used surgical bariatric surgery to HbA1c, 2 patients diabetes after surgery can effectively improve the BMI, LDL, HDL, weight, CHOL, TRIG; and bariatric surgery in type 2 diabetes remission rate was significantly higher than those of non surgical treatment. (3) based on LRYGB and LSG in the treatment of obese patients with type 2 diabetes mellitus patients with small randomized controlled trials and retrospective cohort in the real world the verification results show that: in our patients, bariatric surgery is in glycemic control, weight control and diabetes remission effect method indicators such as the treatment of obesity with type 2 diabetes, and LRYGB and LSG two There was no significant difference between the clinical curative effect of surgery, consistent with the results of other studies. In addition, the clinical effect and there was no significant difference between the LRYGB and LSG of the two groups, and each has its own characteristics: LRYGB is suitable for small weight and need to rely on the endocrine of patients improved; LSG for the low age, high body weight, diabetes is light, preoperative insulin function better in patients with more suitable; the safety is dependable. (4) based on the Markoff model, the 3 kinds of treatment of type 2 diabetes, namely LRYGB scheme, LSG scheme and non operative treatment in a 1 year cycle, running until the age of 80 or death. In order to compare the three schemes of the unit cost of the value. The results show that the cost effect ratio of LRYGB scheme and LSG scheme is much higher than the initial investment of the nonoperative treatment of the lowest. So we think that LRYGB and LSG are high cost effect ratio rule Therapy, superior in unit costs of non operation treatment. Which is more suitable for obese patients with LSG surgery. Policy recommendations (1) should be further development of surgical treatment of type 2 diabetes clinical pathway standardized. (2) should enhance the surgical treatment of type 2 diabetes science efforts. (3) should promote the public who combined with clinic, to strengthen the team. (4) to encourage surgical treatment at the same time, further research should be the development of medical treatment. The innovation and deficiency of innovation: (1) the propensity score method based on retrospective data using a model of 1:1, the small clinical trial results into the "real the world" to verify the reliability further proof research, provide the basis for evidence-based medicine. Based on the Markoff model, simulation of different patients with type 2 diabetes survival status, and collect all the parameters into the model, in a 1 year cycle Run, until the age of 80 or death, compared to surgical treatment and non operative treatment unit of quality adjusted life years effect value. Economic evaluation for our country bariatric surgery for the treatment of type 2 diabetes supplement. (2) the deficiencies still exist some limitations: whether the propensity score matching study the method is based on randomized controlled trials, the small sample, and the failure to observe long-term outcome; to evaluate the full range of bariatric surgery in the treatment of type 2 diabetes, but because of the time, the evaluation of quality of life after surgery did not complete the questionnaire. If this part can collect related data and subjective evaluation further, they can better enhance the comprehensiveness of this study, provide enough evidence for evidence-based medicine.

【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R587.1;R656.6

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