(3.230.76.48) 您好!臺灣時間:2021/04/12 15:50
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:鄭明旭
研究生(外文):Ming-Hsu Cheng
論文名稱:以健保資料庫探討第二型糖尿病人使用Acarbose與失智症之相關性
論文名稱(外文):Acarbose Treatment and the Risk of Dementia in Type 2 Diabetic Patients: A Nationwide Cohort Study
指導教授:唐高駿唐高駿引用關係藍祚運藍祚運引用關係
指導教授(外文):Gau-Jun TangTzuo-Yun Lan
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫務管理研究所
學門:商業及管理學門
學類:醫管學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:46
中文關鍵詞:失智症第二型糖尿病飯後高血糖血糖波動
外文關鍵詞:DementiaType II Diabetes MellitusPostprandial GlucoseGlucose Excursion
相關次數:
  • 被引用被引用:0
  • 點閱點閱:361
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:60
  • 收藏至我的研究室書目清單書目收藏:0
研究背景與目的:
失智症是腦部疾病的其中之一,此疾病會導致認知功能逐漸地退化,並使個人的日常生活受到影響。失智症的危險因子包含,高血壓、高膽固醇、糖尿病、代謝症候群、肥胖和抽菸等。
過去研究顯示,血糖波動會造成腦部神經受損,尤其在大腦皮質和海馬迴,因為血糖波動變大會增加自由基的產生,導致神經元受損和澱粉樣蛋白前驅蛋白(amyloid precursor protein)的堆積造成神經的傷害。眾所周知,所有種類之口服降血糖藥均可改善第二型糖尿病人之血糖值,其中Acarbose(α-glucosidase inhibitor)可減少碳水化合物吸收進而改善飯後高血糖並減少血糖波動與其他口服降血糖藥有所不同。因此,本研究運用分析健保資料庫之資料來探討第二型糖尿病患使用Acarbose與失智症的相關性。
研究方法:
本研究為回溯性世代研究,資料來源為台灣的全民健康保險研究資料庫,於2000年至2005年間篩選6,950位60歲以上被診斷為糖尿病人之新發個案,定義診斷日期為研究的指標日期(index date)。本研究分為兩組,一組使用 Acarbose治療,另一組沒有使用Acarbose治療,兩組均持續追蹤1年、3年、5年。以存活分析中的Kaplan-Meier Curve、Log-Rank Test以及Cox比例危險模型來分析結果。
研究結果:
總共2,907符合收案條件並納入本研究,Acarbose組969人,非Acarbose組1,938人。Acarbose組平均4.96年的觀察中,發生失智症(含老年性癡呆症、阿茲海默症、血管型失智症)事件共有17件(1.8%),非Acarbose組平均4.95年的觀察中,發生失智症事件共有49件(2.5%)。在Acarbose組發生阿茲海默症事件共有2件(0.2%),非Acarbose組,發生阿茲海默症事件共有5件(0.3%)。在Acarbose組發生血管型失智症事件共有16件(1.7%),非Acarbose組,發生血管型失智症事件共有47件(2.4%)。以Kaplan-Meier方法分析看出,兩組隨著時間的進行,其存活機率遞減的速度差異不大;而log rank檢定p值為0.190,統計學上無顯著差異。在COX regression的分析,未校正其他危險因子前,Acarbose組相較於非Acarbose組的失智症(含老年性癡呆症、阿茲海默症、血管型失智症)風險比(Hazard ratio)為0.69(95%CI[0.40-1.20]),統計學上無顯著差異。經校正後,風險比(Hazard ratio)為0.67(95%CI[0.38-1.17]),仍然在統計學上無顯著差異。
研究結論:
本研究結果得知,針對第二型糖尿病患者且年齡大於60歲,使用Acarbose組與非Acarbose組,兩組發生失智症風險是相當。本研究仍有許多限制因素,未來需有更多的研究證實,第二型糖尿病患者使用Acarbose可減少發生失智症的風險。

Background:
Dementia is one of brain diseases and causes cognitive function regression gradually. Meanwhile, dementia also affects a person’s daily life. The risk factor of dementia included hypertension, hyperlipidemia, diabetes mellitus, metabolic syndrome, obesity and smoking. etc. Previous studies have shown results that glucose excursions lead to brain neuronal damage, especially in cerebral cortex and hippocampus in terms of high glucose excursions level leads to increase free radical and accumulation of amyloid precursor protein in damaged neuronal. All of oral antidiabetic (OAD) agents could improve glucose level and Acarbose, α-glucosidase inhibitor, delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. Currently, there were a few studies to discuss Acarbose in treating dementia. Our study aims to understand that the relationship of Acarbose and the risk of dementia in T2DM patients.
Method:
A retrospective cohort study and utilize Nation Health Insurance(NHI) database from 2000 to 2005 representing 1 million sampling from whole population in Taiwan. The study subjects included newly diagnosed T2DM patients within use Acarbose or other OADs, older than 60 years from 2000 to 2005 and never use OAD or diagnosed dementia before 2000. The primary outcome was dementia after the start of follow up. The results were analyzed using Cox proportional hazard regression.
Results:
Among 2,907 patients with newly diagnosed T2DM patients identified during 2000 to 2005, 969(33%) were treated with Acarbose, 1,938(67%) were treated with non-Acarbose. During 5 years(Acarbose: median 4.96 years, Non-Acarbose median 4.95 years ) of follow up, 17 patients(1.8%) who had received Acarbose treatment developed dementia as compared to 49 patients(2.5%) who never used Acarbose therapy. The crude hazard ratio(HR) and adjusted HR were 0.69(95%CI[0.40-1.20]) and 0.67(95%CI[0.38-1.17]) , respectively.
Conclusion:
In patients with T2DM aged over 60 years without preexisting dementia, the stratified analysis indicated no increased risk of dementia in Acarbose patients. (all P =0.190). Additional randomized controlled trials are warranted to confirm our results.

目錄
致謝 I
摘要 II
Abstract IV
目錄 VI
表目錄 VII
圖目錄 VIII
第一章 緒論 1
第一節 前言 1
第二節 背景分析 2
第三節 研究目的 2
第二章 文獻探討 1
第一節 失智症之病因與分類 1
第二節 糖尿病之病因與分類 2
第三節 失智症與糖尿病相關性研討之探討 4
第三章 研究方法 6
第一節 研究設計 6
第二節 研究變相及操作定義 10
第三節 資料處理流程 12
第四節 統計方法 14
第四章 研究結果 16
第一節 基本資料分析 16
第二節 存活分析 21
第五章 討論 29
第一節 基本資料 29
第二節 失智症事件與其影響因子之關係探討 36
第三節 降血糖藥物的用藥醫囑性 38
第四節 研究設計討論 39
第六章 研究限制 41
第七章 結論與建議 42
參考文獻 43

表目錄
表1 Acarbose藥品健保代碼(衛生福利部食品藥物管理署) 7
表2 國際疾病分類代碼 8
表3 主要研究變相操作定義 11
表4 疾病共變因子 12
表5 基本資料和過去疾病分布 19
表5 基本資料和過去疾病分布(續) 20
表6 次分析-Acarbose組/非Acarbose組與發生失智症的機會結果比較(連續5年的追蹤) 23
表7 次分析-Acarbose組/非Acarbose組與發生失智症的機會結果比較(連續1,3,5年的追蹤) 25
表8 次分析-Acarbose組/非Acarbose組與發生失智症的機會結果比較(年齡與性別) 28

圖目錄
圖1 研究流程 17
圖2 Kaplan-Meier曲線分析 Acarbose組/非Acarbose組與失智症之關聯性 22
圖3 2016年美國臨床內分泌醫師協會糖尿病指引( American Association of Clinical Endocrinologists 2016) 32
圖4 2012年 國際糖尿病聯盟糖尿病指引(IDF Diabetes Treatment Algorithm 2012) 33
圖5 2015年中華民國糖尿病照護指引 34
圖6 Acarbose作用機轉 35





參考文獻

A.Ceriello, E.Falleti, E.Motz, C.Taboga, L.Tonutti, Z.Ezsol, et al. (1998). Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus(the possible role of oxidative stress. Horm Metab Res, 30 (3), P. 146-149.
Abbatecola A.M. , Rizzo M.R., Barbieri M., Grella R., Arciello A., Laieta M.T., et al. (2006). Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology, 67 (2), P. 235-240.
Alzheimer’s Disease International. (2013). Dementia statistics. 擷取自 http://www.alz.co.uk/research/statistics
Berr C., Wancata J., & Ritchie K. (2005). Prevalence of dementia in the elderly in Europe. European Neuropsychopharmacology, 15, P. 463-471.
Biessels G.J., Staekenborg S., Brunner E., Brayne C., & Scheltens P. (2006). Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol, 5, P. 64-74.
Biessels G.J., Brunner E., Staekenborg S., & Brayne C. (2006). Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol, 5 (2), P. 113.
Burns A, & Iliffe S. (2009). Dementia. British Medical Journal (Clinical Research Edition), 338.
Bynum J. P. W., Rabins P. V., Weller W., Niefeld M., Anderson G. F., & Wu A. W. . (2004). The Relationship between a Dementia Diagnosis, Chronic Illness, Medicare Expenditures, and Hospital Use. Journal of the American Geriatrics Society, 52, P. 187-194.
Catindig J.A., Venketasubramanian N., Ikram M.K., & Chen C. (2012). Epidemiology of dementia in Asia: insights on prevalence, trends and novel risk factors. J Neurol Sci, 321, P. 11-16.
Ceriello A., Quagliaro L., Piconi L., Assaloni R., Da Ros R., Maier A., et al. (2004). Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes, 53 (3), P. 701-710.
Coutinho M., Gerstein H.C., Wang Y., & Yusuf S. (1999). The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care, 22 (2), P. 233-240.
Crane P.K., Walker R., & Hubbard R.A. (2013). Glucose Levels and Risk of Dementia. N Engl J Med, 369, P. 540-548.
de Galan B.E., Zoungas S., Chalmers J., Anderson C., Dufouil C., Pillai A., et al. (2009). Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia, 52 (11), P. 2328-2336.
Dementia Fact sheet N°362. (2012). 擷取自 http://www.who.int/mediacentre/factsheets/fs362/en/
E. M. Ebly, I. M. Parhad, & D. B. Hogan. (1994). Prevalence and types of dementia in the very old: Results from the Canadian Study of Health and Aging. Neurology, 44 (9), P. 1593.
Esposito K., Nappo F., Marfella R., Giugliano G., Giugliano F,, Ciotola M., et al. (2002). Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation, 106 (16), P. 2067-2072.
García-Pérez LE., Alvarez M., Dilla T., Gil-Guillén V., & Orozco-Beltrán D. (2013). Adherence to therapies in patients with type 2 diabetes. Diabetes Ther, 4 (2), P. 175-194.
Gradman T.J., Laws A., Thompson L.W., & Reaven G.M. (1993). Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin-dependent diabetes mellitus. J Am Geriatr Soc, 41 (12), P. 1305-1312.
Hanefeld M., Cagatay M., Petrowitsch T., Neuser D., Petzinna D., & Rupp M. (2004). Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J, 25 (1), P. 10-16.
Hanefeld M., Chiasson J.L., Koehler C., Henkel E., Schaper F., & Temelkova-Kurktschiev T. (2004). Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke, 35 (5), P. 1073-1078.
Holman R.R., Cull C.A., & Turner R.C. (1999). A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care, 22 (6), P. 960-964.
Hsinlin T. Cheng, Jacqueline R. Dauch, John M. Hayes, Brandon M. Yanik, & Eva L. Feldman. (2012). Nerve growth factor/p38 signaling increases intraepidermal nerve fiber densities in painful neuropathy of type 2 diabetes. Neurobiol Dis, 45 (1), P. 280-287.
International Diabetes Federation. (2015). 2015 IDF Atlas Taiwan Report. IDF Annual Report.
J.S.Wang, S.D.Lin, W.J.Lee, S.L.Su, Lee I. T, S.T.Tu, et al. (2011). Effects of Acarbose Versus Glibenclamide on Glycemic Excursion and Oxidative Stress in Type 2 Diabetic Patients Inadequately Controlled by Metformin: A 24-Week, Randomized, Open-Label, Parallel-Group Comparison. Clin Ther, 33, P. 1932-1942.
Jhoo J.H., Kim K.W., Huh Y., Lee S.B., Park J.H., Lee J.J., et al. (2008). Prevalence of dementia and its subtypes in an elderly urban korean population: results from the Korean Longitudinal Study on Health And Aging (KLoSHA). Dement Geriatr Cogn Disord 26: 270–276. 26, P. 270-276.
JiangYi-Der, ChangChia-Hsuin, Tong-Yuan Tai, Jung-Fu Chen, & Lee-Ming Chuang. (2012). Incidence and prevalence rates of diabetes mellitus in Taiwan: Analysis of the 2000–2009 Nationwide Health Insurance database. Journal of the Formosan Medical Association, 111, P. 599-604.
Kerti L. , Witte A.V., Winkler A., Grittner U., Rujescu D., & Floel A. (2013). High glucose levels associated with lower memory and reduced hippocampal microstructure. Neurology, 81, P. 1746-1752.
Lin C.H., & Sheu W.H. (2013). Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med, 273 (1), P. 102-110.
Lobo A., Launer L.J., Fratiglioni L., Andersen K., Di Carlo A., Breteler M.M., et al. (2000). Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology, 54 (11), P. 4-9.
Lu FP, Lin KP, & Kuo HK. (2009). Diabetes and the risk of multi-system aging phenotypes: A systematic review and meta-analysis. Plos One, 4, P. 1-12.
M.Ikeda, R.Fukuhara, K.Shigenobu, K.Hokoishi, N.Maki, A.Nebu, et al. (2004). Dementia associated mental and behavioural disturbances in elderly people in the community: findings from the first Nakayama study. Journal of neurology, neurosurgery, and psychiatry, 75.
Meneilly G.S., Cheung E., Tessier D., Yakura C., & Tuokko H. (1993). The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J Gerontol, 48, P. 117-121.
Monnier L., Mas E., Ginet C., Michel F., Villon L., Cristol J.P., et al. (2006). Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA, 295 (14), P. 1681-1687.
Mortby M.E., Janke A.L., Anstey K.J., Sachdev P.S., & Cherbuin N. (2013). High Normal Blood Glucose is Associated with Decreased Brain Volume and Cognitive Performance in the 60s: The PATH through Life Study. PLoS One, 8 (9), P. 1-9.
Naor M., Steingrüber H.J., Westhoff K., Schottenfeld-Naor Y., & Gries A.F. (1997). Cognitive function in elderly non-insulin-dependent diabetic patients before and after inpatient treatment for metabolic control. J Diabetes Complic, 11, P. 40-46.
Petersen R.C., Roberts R.O., Knopman D.S., Geda Y.E., Cha R.H., Pankratz V.S., et al. (2010). Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study of Aging. Neurology, 75, P. 889-897.
Plassman B.L., Langa K.M., Fisher G.G., Heeringa S.G., Weir D.R., Ofstedal M.B., et al. (2008). Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med, 148, P. 427-434.
Profenno L. A., Porsteinsson A. P., & Faraone S. V. (2010). Meta-analysis of Alzheimer’s disease risk with obesity, diabetes and related disorders. Biol. Psychiatry, 67, P. 505-512.
Rachmani R., Bar-Dayan Y., Levi Z., Ronen Z., Slavachevsky I., & Ravid M. (2004). The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study. Diabetes Obes Metab, 6 (1), P. 63-68.
ransdellPierson. (2014). German database study hints diabetes drug cuts Alzheimer’s risk. 擷取自 http://www.reuters.com/article/us-alzheimers-prevention-actos-idUSKBN0FJ0VJ20140714
S.E. Nissen, & K. Wolski. (2007). Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med (356), P. 2457-2471.
Santilli F., Formoso G., Sbraccia P., Averna M., Miccoli R., Di Fulvio P., et al. (2010). Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus. J Thromb Haemost, 8 (4), P. 828-837.
Standl E., Schnell O., & Ceriello A. (2011). Postprandial Hyperglycemia and Glycemic Variability Should we care? Diabetes Care, 34 (2), P. 120-127.
Statistical Yearbook of Interior. (2013). Statistical Yearbook of Interior. 擷取自 http://sowf.moi.gov.tw/stat/year/elist.htm
Strachan M.W., Reynolds R.M., Marioni R.E., & Price J.F. (2011). Cognitivefunction, dementia and type 2 diabetes mellitus in the elderly. Nat Rev Endocrinol, 7, P. 108-114.
Williams S.B., Goldfine A.B., Timimi F.K., Ting H.H., Roddy M.A., Simonson D.C., et al. (1998). Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation, 97 (17), P. 1695-1701.
Wu Y.T., Lee H.Y., Norton S., Chen C., Chen H., He C., et al. (2013). Prevalence studies of dementia in mainland china, Hong Kong and Taiwan: a systematic review and meta-analysis. PLoS One, 8, P. e66252.
Yaffe K., Falvey C.M., & Hamilton N. (2013). Association Between Hypoglycemia and Dementia in a Biracial Cohort of Older Adults wit Diabetes Melitus. JAMA Intern Med, 173, P. 1300-1306.
Yan WW, Chen GH, Wang F, et al. Long-term acarbose administration alleviating the impairment of spatial learning and memory in the SAMP8 mice was associated with alleviated reduction of insulin system and acetylated H4K8. Brain Res.2015;1603:22–31.
Zhang Y., Xu Y., Nie H., Lei T., Wu Y., Zhang L., et al. (2012). Prevalence of dementia and major dementia subtypes in the Chinese populations: a meta-analysis of dementia prevalence surveys, 1980–2010. J Clin Neurosci, 19, P. 1333-1337.
林建良、許惠恒、沈宜靜 (2013).二甲雙胍類降血糖藥物「Metformin」: 過去 、現在與未來.內科學誌,24,P. 477-486。
國家衛生研究院 (2011年8月29日).國家衛生研究院電子報419期,擷取自 http://enews.nhri.org.tw/enews_list_new3.php?volume_indx=419&enews_dt=2011-08-29
國家衛生研究院 (2009年6月18日).國家衛生研究院電子報第307期,擷取自 http://enews.nhri.org.tw/enews_list_new2_more.php?volume_indx=307&showx=showarticle&article_indx=7194
陳欣 (2007).我國失智症盛行率及其病患醫療利用和死亡情形探討(碩士論文).台北:國立陽明大學衛生福利研究所。
葉炳強、劉珣瑛(1993)。癡呆症的診斷,癡呆症患者的認識與照顧。
劉景寬(1997a)。忘了我是誰:失智症及其在台灣的現況(上)。健康世界,142(262),123-124。
劉景寬(1997b)。忘了我是誰:失智症及其在台灣的現況(下)。健康世界,143(263),122-125。
卓良珍(1998)。如何預防老年癡呆症。社會福利,(134),42-48。

連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔