探討消化性潰瘍患者接受迷走神經切斷術後發生第二型糖尿病及肝硬化之風險

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 醫學院 > 臨床醫學研究所 > 博碩士論文 > Item 310903500/59003

請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/59003

題名:	探討消化性潰瘍患者接受迷走神經切斷術後發生第二型糖尿病及肝硬化之風險 Risk of subsequent type 2 diabetes and liver cirrhosis in peptic ulcer patients underwent truncal vagotomy
作者:	吳汐淇;Shih-Chi Wu
貢獻者:	臨床醫學研究所博士班
關鍵詞:	消化性潰瘍;迷走神經切斷術;第二型糖尿病;肝硬化;peptic ulcer;vagotomy;type 2 diabetes;liver cirrhosis
日期:	2019-07-17
上傳時間:	2019-11-11 09:19:52 (UTC+8)
出版者:	中國醫藥大學
摘要:	研究顯示迷走神經在身體代謝恆定、免疫、神經系統及發炎反應調節方面扮演重要角色.另外,由分出枝的迷走神經媒介的神經訊號可藉由”炎性反射”機轉來調控前驅發炎反應及免疫功能.因此迷走神經功能不全或被切斷會導致”炎性反射”異常並影響身體之恆定. 另一方面, 迷走神經亦可調節血液中血糖濃度,研究亦顯示迷走神經切斷術會抑制胰高血糖素樣?-1(GLP-1)的分泌. 因此可合理推論迷走神經和第二型糖尿病應有相當之關聯. 除此之外, 肝臟迷走神經系統亦可調節肝臟星狀細胞(hepatic stellate cells)，而肝臟星狀細胞則和肝臟生長、再生,以及肝硬化相關, 由此可見迷走神經在身體扮演之重要角色. 然而,有關迷走神經及迷走神經切斷術的研究卻常出現和原先理論(炎性反射)分歧的結果. 舉例而言,在一個肺臟發炎的老鼠實驗中, 顯示刺激迷走神經並未達到如預期的有益效果. 另外, 在一個人類風濕性關節炎的實驗顯示, 迷走神經切斷術並未如預期的增加風濕性關節炎的風險, 而對於急性發炎部分, 在人類身上並未看到如同老鼠切斷迷走神經後一樣的結果我們對此分歧的結果感到興趣,認為有可能是因為老鼠和人類係屬不同類物種之故. 這也是“老鼠醫學” 和”人類醫學”相異之處. 由於倫理的考量,吾人不可能在平常人體上實驗迷走神經切斷術來得到數據. 我們發現複雜性消化性潰瘍病人接受迷走神經切斷術的族群, 相當合適作為研究迷走神經和身體恆定,及其他全身性疾病如第二型糖尿病和肝硬化. 在排除了幽門螺旋桿菌感染的病人族群後, 於迷走神經切斷術和第二型糖尿病的研究顯示,消化性潰瘍病人較非消化性潰瘍病人有較高的第二型糖尿病風險 (危險比=1.43, 95%信賴區間=1.40~1.47, p <0.001). 比較迷走神經切斷術、簡單縫合術、及以藥物治療未接受手術者三種族群, 接受迷走神經切斷術的病人有最低的第二型糖尿病風險 (危險比=0.48, 95% 信賴區間=0.41-0.56, p <0.001). 在排除了幽門螺旋桿菌感染的病人族群後,於迷走神經切斷術和肝硬化的研究顯示,消化性潰瘍病人較非消化性潰瘍病人有較高的肝硬化風險 (危險比=2.79, 95%信賴區間=2.66-2.93, p <0.001). 比較迷走神經切斷術、簡單縫合術、及以藥物治療未接受手術者三種族群, 接受迷走神經切斷術的病人有最低的第二型糖尿病風險 (危險比=0.46, 95% 信賴區間=0. 0.33-0.64, p <0.001). 在此系列研究中, 消化性潰瘍病人較非消化性潰瘍病人有較高的第二型糖尿病和肝硬化風險. 而接受迷走神經切斷術的病人則有較低的風險. 此現象或可歸因於在消化性潰瘍病人迷走神經活性增加所導致之故. 鑒於目前醫界處理消化性潰瘍穿孔大多皆以簡單縫合術合併術後藥物治療, 我們的研究或可提供處理此類病人不同之思考方向. 另外,尋找生物標記來定量迷走神經活性,亦有其重要性. Studies have showed that the vagus nerve was associated with metabolic homeostasis and had close relations with the immune and nervous systems that are essential in the regulation of inflammation. In addition, the efferent vagus nerve-mediated cholinergic signaling regulated proinflammatory responses and immune function via the” inflammatory reflex”. Therefore, dysfunction in vagus nerve or vagotomy might cause perturbation in this reflex that have impacts on systemic homeostasis. On the other hand, the serum glucose level is modulated partly mediated by vagus nerve, and study showed vagotomy is associated with suppression of glucagon-like peptide-1(GLP-1) secretion, indicating possible correlation between vagal system and type 2 diabetes. Moreover, the hepatic vagus nervous system have an impact on modulation of hepatic stellate cells (HSCs), in which the HSCs play important roles in liver development, regeneration, and liver fibrosis. However, studies showed inconsistent result to the notable inflammatory reflex theory. For example, a rodent study showed no beneficial effects of vagus nerve stimulation after pulmonary inflammation, while a human study showed vagotomy for acute inflammation in rodents was not mirrored in human rheumatoid arthritis, and vagotomy had no specific effect on the risk of developing rheumatoid arthritis in humans. We assume that these diverse outcome might be due to difference in species. We are interested in this issue and try to assess the role of vagotomy and vagus nerve in human. Yet, it is impractical to obtain experimental data of vagal nerve severance in humans. We found that complicated peptic ulcer patients undergoing truncal vagotomy (i.e., vagal nerve severance) may be used to study the relationship between the hepatic vagal nervous system and diabetes, as well as liver cirrhosis. In the first study for vagotomy and type 2 diabetes, after carefully collect data and exclude patients with helicobacter pylori infection, we found that the overall diabetes incidence was higher in patients with peptic ulcer than those without peptic ulcer (15.87 vs. 12.60 per 1000 person-years) by an adjusted hazard ratio (aHR) of 1.43 [95% confidence interval (CI) = 1.40-1.47] based on the multivariable Cox proportional hazards regression analysis (competing risk). Comparing ulcer patients with truncal vagotomy and simple suture/hemostasis or those without surgical treatment, the aHR was the lowest in the vagotomy group (0.48, 95% CI = 0.41-0.56). In the second study for vagotomy and liver cirrhosis, after carefully collect data and exclude patients with helicobacter pylori infection, we found that peptic ulcer patients were with higher incidence of liver cirrhosis than those without peptic ulcer (2.63 vs. 0.96 per 1000 person-years) and with a 2.79-fold adjusted hazard ratio (95% CI = 2.66-2.93) based on the multivariable Cox proportional hazards regression analysis. Comparing with different peptic ulcer management strategies, the aHR value for subsequent liver cirrhosis risk was the lowest in vagotomy group (HR = 0.46, 95% CI = 0.33-0.64). Consequently, we found that there were higher incidence of type 2 diabetes and cirrhosis in peptic ulcer patients and those who received simple suture procedure. In addition, vagotomy decreased the risk of subsequent type 2 diabetes and liver cirrhosis in complicated peptic ulcer patients. This result might be attributed to the alleviation of vagal hyperactivity in complicated peptic ulcer patients. Our finding may, at least in part, suggest a consideration for current surgical treatment in such patients. Moreover, search for biomarkers or indicators for a precise quantified measurement of vagal activity is of importance.
顯示於類別:	[臨床醫學研究所] 博碩士論文

文件中的檔案:

檔案	大小	格式	瀏覽次數
index.html	0Kb	HTML	51	檢視/開啟

在CMUR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....