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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 莊立民(Lee-Ming Chuang) | |
dc.contributor.author | Chih-Hung Lin | en |
dc.contributor.author | 林志弘 | zh_TW |
dc.date.accessioned | 2021-06-13T15:17:32Z | - |
dc.date.available | 2011-10-07 | |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-11 | |
dc.identifier.citation | 1.Fong DS, Aiello L, Gardner TW, et al. Retinopathy in Diabetes. Diabetes Care 2004;27:s84-s7.
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Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus. Circulation 2005;111:3489-93. 8.Association AD. Standards of Medical Care in Diabetes—2011. Diabetes Care 2011;34:S11-S61. 9.Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801-9. 10.Brownlee M. The Pathobiology of Diabetic Complications. Diabetes 2005;54:1615-25. 11.Hauschka PV, Mann KG, Price P, Termine JD. Report of the Ad Hoc Committee on Nomenclature and Standards for Bone Proteins and Growth Factors. J Bone Miner Res 1986;1:485-6. 12.Hakala BE, White C, Recklies AD. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 1993;268:25803-10. 13.Shackelton LM, Mann DM, Millis AJ. Identification of a 38-kDa heparin-binding glycoprotein (gp38k) in differentiating vascular smooth muscle cells as a member of a group of proteins associated with tissue remodeling. J Biol Chem 1995;270:13076-83. 14.Rehli M, Krause SW, Andreesen R. Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 1997;43:221-5. 15.Rejman JJ, Hurley WL. Isolation and characterization of a novel 39 kilodalton whey protein from bovine mammary secretions collected during the nonlactating period. Biochem Biophys Res Commun 1988;150:329-34. 16.Fusetti F, Pijning T, Kalk KH, Bos E, Dijkstra BW. Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39. J Biol Chem 2003;278:37753-60. 17.Renkema GH, Boot RG, Au FL, et al. Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages. Eur J Biochem 1998;251:504-9. 18.Rathcke CN, Vestergaard H. YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm Res 2006;55:221-7. 19.Johansen JS, Jensen BV, Roslind A, Nielsen D, Price PA. Serum YKL-40, a new prognostic biomarker in cancer patients? Cancer Epidemiol Biomarkers Prev 2006;15:194-202. 20.Johansen JS, Lottenburger T, Nielsen HJ, et al. Diurnal, weekly, and long-time variation in serum concentrations of YKL-40 in healthy subjects. Cancer Epidemiol Biomarkers Prev 2008;17:2603-8. 21.De Ceuninck F, Gaufillier S, Bonnaud A, Sabatini M, Lesur C, Pastoureau P. YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes. Biochem Biophys Res Commun 2001;285:926-31. 22.Recklies AD, White C, Ling H. The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem J 2002;365:119-26. 23.Nishikawa KC, Millis AJ. gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. Exp Cell Res 2003;287:79-87. 24.Boot RG, van Achterberg TA, van Aken BE, et al. Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler Thromb Vasc Biol 1999;19:687-94. 25.Malinda KM, Ponce L, Kleinman HK, Shackelton LM, Millis AJ. Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells. Exp Cell Res 1999;250:168-73. 26.Ling H, Recklies AD. The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha. Biochem J 2004;380:651-9. 27.Recklies AD, Ling H, White C, Bernier SM. Inflammatory cytokines induce production of CHI3L1 by articular chondrocytes. J Biol Chem 2005;280:41213-21. 28.Rathcke CN, Johansen JS, Vestergaard H. YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance. Inflamm Res 2006;55:53-9. 29.Nielsen AR, Erikstrup C, Johansen JS, et al. Plasma YKL-40: a BMI-independent marker of type 2 diabetes. Diabetes 2008;57:3078-82. 30.Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H. YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care 2009;32:323-8. 31.Brix JM, Hollerl F, Koppensteiner R, Schernthaner G, Schernthaner GH. YKL-40 in type 2 diabetic patients with different levels of albuminuria. Eur J Clin Invest 2011;41:589-96. 32.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70. 33.Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med 2001;344:1608-21. 34.Anderson KM, Odell PM, Wilson PWF, Kannel WB. Cardiovascular disease risk profiles. American Heart Journal 1991;121:293-8. 35.Rathcke CN, Raymond I, Kistorp C, Hildebrandt P, Faber J, Vestergaard H. Low grade inflammation as measured by levels of YKL-40: association with an increased overall and cardiovascular mortality rate in an elderly population. Int J Cardiol 2010;143:35-42. 36.Johansen JS, Bojesen SE, Tybjaerg-Hansen A, Mylin AK, Price PA, Nordestgaard BG. Plasma YKL-40 and total and disease-specific mortality in the general population. Clin Chem 2010;56:1580-91. 37.Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 1989;32:219-26. 38.Kucur M, Isman FK, Karadag B, Vural VA, Tavsanoglu S. Serum YKL-40 levels in patients with coronary artery disease. Coron Artery Dis 2007;18:391-6. 39.Tseng C-H. Prevalence and Risk Factors of Peripheral Arterial Obstructive Disease in Taiwanese Type 2 Diabetic Patients. Angiology 2003;54:331-8. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36985 | - |
dc.description.abstract | [研究背景]
糖尿病的大、小血管併發症,包括視網膜病變、腎病變、腦中風、週邊動脈阻塞疾病、神經病變及冠狀動脈心臟病等,均會對糖尿病患者造成重大影響。而就目前所知,第2型糖尿病本身,及其血管併發症的發生,可能都與人體內之慢性發炎狀態有關。YKL-40 為一40kD的凝集素(lectin)分子,會在各種急性或慢性發炎情況下上升。各個研究顯示:在第2型糖尿病患者血液中,YKL-40濃度較非糖尿病之對照組為高;並且,在第1型及第2型糖尿病患者的身上,血液中的YKL-40濃度與患者白蛋白尿的嚴重度亦呈現一正相關性。 本研究的目的,在於檢視第2型糖尿病患者血液內YKL-40濃度,與各項併發症,以及死亡率間之關係;並進一步評估其作為預後指標之潛力。 [方法] 本試驗的研究世代來自於先前對代謝疾病功能基因體及蛋白體學研究的參加者,收案期間自1996年7月至2003年6月,共包括232名男性及241名女性。參加者的平均年齡為61.71 9.67歲。臨床測量數據及生化檢驗結果來自收案時測量的數據。血漿中的YKL-40濃度則利用市售之ELISA套件進行測量。於測量前,血漿樣本均儲存於-80℃的環境中。整個研究世代追蹤至2008年12月31日為止,並記錄其生存狀態。參加者並根據YKL-40濃度的四分位數,分為四組(Q1: 11.29-52.92 ng/dl; Q2: 53.40-87.02 ng/dl; Q3: 87.20-150.71 ng/dl, and Q4: 151.69-417.35 ng/dl)。 [結果] 於四分組中,蛋白尿的盛行率分別為10.62%、16.24%、16.38%及32.48%(p<0.01)。在調整可能的混淆變項後,Q4組發生蛋白尿的勝算比為Q1組的2.63倍(95% CI: 1.00-6.28, p<0.05)。四分組的死亡率分別為12.61%、13.56%、29.66%及40.68%(p<0.01)。在調整可能的混淆變項後,Q4組的總死亡風險為Q1組之2.03倍(95% CI: 1.07-3.84, p<0.05)。而在先前沒有心血管疾病病史的受試者中,其血漿中YKL-40濃度高於中位數者(86.49 ng/dl),其因心血管疾病死亡的風險,為血漿中YKL-40濃度低於中位數者之3.45 (95% CI: 1.28-9.30, p<0.05)倍。 [結論] 與此一研究中,我們發現到了,當第2型糖尿病患者血漿內的YKL-40濃度越高,其蛋白尿、因所有原因或心血管疾病死亡的風險就越高。因此,後續的研究,應專注於YKL-40在糖尿病內皮功能失調的致病機轉角色上。 | zh_TW |
dc.description.abstract | Background Various micro- and macro-vascular diabetic complications cause major impacts on patients with diabetes. Plasma YKL-40 concentration had been found to correlate with severity of albuminuria in type 1 and type 2 diabetic patients. In this study, we evaluated the association among plasma concentration of YKL-40, PAOD, proteinuria and mortality in type 2 diabetic patients.
Methods The study cohort consisted of 232 male and 241 female type 2 diabetic patients who participated in previous study of functional genomic and proteomics in metabolic disorders from July, 1996 to June, 2003. The mean age was 61.71 9.67 years old Presence of proteinuria was determined by semi-quantitative Multistix test. Presence of peripheral arterial occlusive disease (PAOD) was determined by Ankle-brachial index (ABI). The plasma YKL-40 level was measured by a commercial ELISA assay with samples stored at -80℃. The cohort was followed subsequently till December 31st, 2008 with the vital status recorded. The participants were divided into 4 subgroups according to plasma YKL-40 quartile (Q1: 11.29-52.92 ng/dl; Q2: 53.40-87.02 ng/dl; Q3: 87.20-150.71 ng/dl, and Q4: 151.69-417.35 ng/dl). Results The prevalence of proteinuria in Q1 to Q4 were 10.62%, 16.24%, 16.38% and 32.48%, respectively (p<0.01). After adjusting possible confounding variables, the odds ratio of proteinuria for Q4 group was 2.63 (95% CI: 1.10-6.28, p<0.05) compared with Q1 group. The mortality rate of quartile groups were 12.61%, 13.56%, 29.66% and 40.68%, respectively (p<0.01). After adjusting possible confounding variables, the hazard ratio (HR) of all-cause mortality in Q4 group was 2.03 fold (95% CI: 1.07-3.84, p<0.05) higher compared with Q1 group. In subgroup analysis without history of previous admission due to cardiovascular diseases (CVDs), the HR for CVD-specific mortality in those YKL-40 above median (86.49 ng/dl) was 3.45 fold (95% CI 1.28-9.30, p<0.05) higher compared with those YKL-40 below median. Conclusion In our study, we demonstrated that elevation of plasma YKL-40 level in type 2 diabetic patients was correlated with increased risk of proteinuria, all-cause and CVD-specific mortality. Further study should focus on the pathological role of YKL-40 in diabetic endothelial dysfunction. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:17:32Z (GMT). No. of bitstreams: 1 ntu-100-P98421018-1.pdf: 678968 bytes, checksum: 0d900a7aa2517ef322b03dea85282a5d (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書....................................i
謝辭..............................................ii 中文摘要..........................................iii 英文摘要...........................................v 碩士論文內容 第一章 緒論........................................1 1.1 第2型糖尿病之血管併發症..........................1 1.2 YKL-40........................................2 1.3 YKL-40與糖尿病的關係............................3 1.4 研究假說及目的..................................4 第二章 研究方法及材料................................5 2.1 研究世代的組成及基本資料收集......................5 2.2 YKL-40濃度之測量................................5 2.3 併發症的測量及死亡個案之登錄......................6 2.4 統計分析.......................................6 第三章 結果.........................................8 3.1 研究世代之基本資料...............................8 3.2 血管併發症之分析.................................8 3.3 死亡率之分析....................................9 第四章 討論.........................................11 第五章 展望.........................................13 論文英文簡述.........................................14 參考文獻............................................24 附圖及附表 表1:YKL-40百分位分組之各組基本資料....................30, 31 表2:YKL-40百分位分組之血壓、血糖及血脂的控制狀況........32 表3:YKL-40百分位分組間,產生蛋白尿的勝算比.............33 表4:YKL-40百分位分組之總死亡風險比....................34 表5:YKL-40中位數分組之心血管疾病死亡風險比.............35 圖1:YKL-40之結構...................................36 引用自http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=23998 圖2:YKL-40於細胞處於發炎環境中可能表現之調控機轉........37 引用自Ling, et al. Biochem J 2004;380:651-9 圖3:第2型糖尿病患者與非糖尿病者血漿中YKL-40濃度之比較 (1).....38 引用自Rathcke, et al. Inflamm Res 2006;55:53-9. 圖4:第2型糖尿病患者與非糖尿病者血漿中YKL-40濃度之比較 (2).....38 引用自Nielsen, et al. Diabetes 2008;57:3078-82. 圖5:YKL-40百分位分組中,週邊動脈阻塞疾病及蛋白尿的盛行率...... 39 圖6:Kaplan-Meier curves of survival (all-cause)........ 40 圖7:Kaplan-Meier curves of survival (CVD-specific)......41 附錄 期刊論文(投稿中).........................................42 | |
dc.language.iso | zh-TW | |
dc.title | 第2型糖尿病患者血漿中YKL-40濃度與血管併發症之關聯性研究 | zh_TW |
dc.title | Association study of the plasma concentration of YKL-40 and vascular complications in patients with type 2 diabetes | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 余家利(Chia-Li Yu),吳寬墩(Kwan-Dun Wu) | |
dc.subject.keyword | YKL-40,第2型糖尿病,蛋白尿,週邊動脈阻塞疾病,存活分析, | zh_TW |
dc.subject.keyword | YKL-40,type 2 diabetes,proteinuria,PAOD,survival analysis, | en |
dc.relation.page | 67 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-11 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
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