跳到主要內容

臺灣博碩士論文加值系統

(44.212.99.248) 您好!臺灣時間:2023/01/28 12:18
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:蕭景中
研究生(外文):Ching Chung Hsiao
論文名稱:移植後糖尿病對於腎臟移植病患預後的影響
論文名稱(外文):The impact of post transplantation diabetes mellitus on subsequent outcomes in patients receiving kidney transplantation
指導教授:劉碧華劉碧華引用關係
指導教授(外文):P. H. Liu
學位類別:碩士
校院名稱:長庚大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:63
中文關鍵詞:移植後糖尿病腎臟移植
外文關鍵詞:post transplantation diabetic mellitus移植後糖尿病
相關次數:
  • 被引用被引用:0
  • 點閱點閱:51
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
背景:腎臟移植是治療末期腎疾病的一個選擇,而腎臟移植後得到糖尿病會造成較差的移植腎及病人存活。台灣有著全世界最高的末期腎疾病發生率及盛行率,然而對於台灣移植後糖尿病的流行病學及對病人造成的影響研究卻不完全。因此,此研究最主要的目的是了解移植後糖尿病的發生率及對於病人預後的影響。

方法:利用台灣的健保資料庫,在西元1997至2011年,共有3,663名腎臟移植病人被納入研究,計算移植後糖尿病的累積發生率,並利用競爭風險存活分析,分別估計三組腎臟移植病人(無糖尿病、移植前已有糖尿病、及移植後糖尿病病人)不同預後的風險比(HR)及95%信賴區間(95% CI)。預後包括病患移植腎的失敗風險(移植後再進入透析)、主要心血管疾病(包括心臟衰竭、急性心肌梗塞、及腦中風)發生的風險、以及全死因死亡的風險,最後再針對不同的族群去做次族群分析。

結果:3,663名腎臟移植病人,有531人(14%)在腎臟移植前就有糖尿病,631人(17%)移植後產生糖尿病。移植後一年有7.2%病人得到糖尿病,移植後三年有11.5%病人得到糖尿病,移植後5年有15%病人得到糖尿病,移植後十年有23.4%病人得到糖尿病。相對於非糖尿病病人,移植後糖尿病病人及移植前已有糖尿病病人有較高的移植腎失敗風險(移植後糖尿病病人 HR 1.65,95% CI 1.47–1.85;移植前已有糖尿病病人HR 1.33,95% CI 1.18–1.50),有較高的主要心血管疾病風險(移植後糖尿病病人HR 1.51,95% CI 1.31–1.74;移植前已有糖尿病病人HR 1.64,95% CI 1.41–1.9),以及全死因死亡風險(移植後糖尿病病人HR 1.79,95% CI 1.59–2.01;移植前已有糖尿病病人HR 2.03,95% CI 1.81–2.18)。 相對於非糖尿病病人,移植後糖尿病病人及移植前已有糖尿病病人有較高的心血管相關死亡(移植後糖尿病病人HR 2.14,95% CI 1.43–3.20,p<0.001;移植前已有糖尿病病人HR 1.89,95% CI 1.25–2.86,p=0.002),惡性腫瘤相關死亡(移植後糖尿病病人HR 1.56,95% CI 1.18–2.07,p=0.002;移植前已有糖尿病病人HR 1.89,95% CI 1.25–2.86,p=0.027),以及感染相關死亡(移植後糖尿病病人HR 1.47,95% CI 1.14–1.90,p=0·003;移植前已有糖尿病病人HR 2.25,95% CI 1.77–2.84,p<0.001)。次族群分析發現移植後糖尿病病人增加重大心血管疾病及死亡的風險,主要在年齡小於五十五歲的族群,及較少共病症(包括心房顫動、肝硬化、心臟衰竭、或心肌梗塞)病人族群。
結論:移植後第一年得到糖尿病的發生率最高。而移植後糖尿病對於移植腎的存活、病患的重大心血管疾病風險、及死亡有不好的影響,且在年輕病患及較少共病症的病患特別明顯。 因此,針對移植後糖尿病需要更加積極且密切追蹤,以早期診斷、預防、與治療,延緩不良預後發生。
Background: Occurrence of post-transplant diabetes mellitus (PTDM) was reported to associate with worse patient and graft survival in kidney transplant recipients. Taiwan has the highest incidence and prevalence rates of dialysis initiation in the world. Nonetheless, data about the incidence and prevalence of PTDM in Taiwan is not well studied. The study aimed to survey the epidemiologic features of PTDM and its impact on subsequent patient and graft outcomes in Taiwan.
Methods: Between 1997 and 2011, 3663 kidney transplant recipients were recruited in the study from the Taiwan National Health Insurance Research Database (NHIRD). The hazard ratio (HR) and 95% confidence intervals (CI) between three interested groups (DM, PTDM, and non-DM) were calculated using Cox proportional hazards model with competing risk analysis. The primary outcomes were the occurrence of graft failure, major adverse cardiovascular events (MACE), all-cause mortality, and death with functioning graft. Mortality risks from cardiovascular diseases, cancer and infection for three interested groups were also calculated. Subgroup analysis were performed regarding age, sex and different comorbidity status.
Results: PTDM developed in 17% (631/3663) of kidney transplant recipients. The one-, three-, five-, and ten-year cumulative incidence of PTDM after transplantation was 7.2%, 11.5%, 15%, and 23.4%, respectively. DM and PTDM were associated with significantly higher risks of graft failure (DM: HR 1.33, 95% CI 1.18–1.50 ; PTDM: HR 1.65, 95% CI 1.47–1.85), MACE (DM: HR 1.64, 95% CI 1.41–1.9 ; PTDM: HR 1.51, 95% CI 1.31–1.74), and all-cause mortality (DM: HR 2.03, 95% CI 1.81–2.18; PTDM: HR 1.79, 95% CI 1.59–2.01) compared with non-DM group. The risk of cardiovascular disease-associated mortality (DM: HR 1.89, 95% CI 1.25–2.86, p=0.002; PTDM: HR 2.14, 95% CI 1.43–3.20, p<0.001), cancer-associated mortality (DM: HR 1.89, 95% CI 1.25–2.86, p=0.027; PTDM: HR 1.56, 95% CI 1.18–2.07,p=0.002), and infection-associated mortality (DM: HR 2.25, 95% CI 1.77–2.84, p<0.001; PTDM: HR 1.47, 95% CI 1.14–1.90, p=0·003) was significantly higher in patients with DM and PTDM compared with non-DM group. In subgroup analysis, the increased risks of MACE and mortality from PTDM were mainly seen in patients with younger age and those without associated comorbidities including atrial fibrillation (AF), cirrhosis, congestive heart failure (CHF), and myocardial infarction (MI).
Conclusions: In the present study, PTDM was associated with poor graft and patient survival. The survival disadvantages of MACE and mortality from PTDM were mainly observed in patients aged less than 55 years. Further studies to prevent and predict PTDM are warranted.
指導教授推薦書
口試委員會審定書
致謝 ..iii
中文摘要 .iv
英文摘要 .vi
Chapter 1 Introduction ... 1
Chapter 2 Method ... 6
2.1 資料來源 ... 6
2.2 研究設計 ... 8
2.3 研究定義及目標 .... 9
2.4 統計分析 . 12
Chapter 3 Results………..19
3.1 研究族群特徵 ...... 19
3.2 腎臟移植前後的糖尿病發生率 ...... 21
3.3 移植後糖尿病 PTDM 的危險因子. 22
3.4 DM/PTDM/non-DM 組別對於移植腎失敗,主要心血管事件及
死亡的風險 .... 23
3.5 DM/PTDM/non-DM 族群的心血管疾病死亡風險,惡性腫瘤死
亡風險及感染死亡風險 .... 25
3.6 次族群分析 ... 26
Chapter 4 Conclusion and discussion ...... 27
4.1 討論 .. 27
4.2 研究限制 . 32
4.3 結論 .. 33
參考書目 34
圖表…………………38

圖目錄
Figure 1. The flow chart of patient selection process ... 38
Figure 2. Definition of three groups(DM ,PTDM, and non-DM group).. 39
Figure 3. Temporal trends of DM rates prior and after transplantation ... 40
Figure 4. Cumulative incidence rates of death-censored graft failure in
DM, PTDM, and non-DM groups .... 41
Figure 5. Cumulative incidence rates of MACE in DM, PTDM, and
non-DM groups ..... 42
Figure 6. Cumulative incidence rates of survival in DM, PTDM, and
non-DM groups ..... 43



表目錄
Table 1. Demographical characteristic in patients with kidney
transplantation by diabetes status……………………………………….44
Table 2. Risk of PTDM among 3,132 Patients without DM prior to
transplantation…………………………………………………………...47
Table 3. Risk of graft failure, MACE, all-cause mortality, and death with
functioning graft in kidney transplant recipients stratified by diabetes
status…………………………………………………………………….48
Table 4. Hazard ratios for cancer, cardiovascular diseases, and
infection-related death in kidney transplant recipients stratified by
diabetes status…………………………………………………………...49
Table 5. Subgroup analyses for the risk of interested outcomes………...50
Table 6. Risk of graft failure, MACE, and all-cause mortality in kidney
transplant recipients stratified by diabetes status in a detailed manner....51
2918-2929, doi:10.1111/j.1523-1755.2005.00774.x (2005).
2 Schoolwerth, A. C. et al. Chronic kidney disease: a public health problem that needs a public health action plan. Prev Chronic Dis 3, A57 (2006).
3 Saran, R. et al. US Renal Data System 2018 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis 73, A7-A8, doi:10.1053/j.ajkd.2019.01.001 (2019).
4 Tsai, H. I. & Yu, H. P. A review of nationwide population study of organ transplantation in Taiwan. Acta Anaesthesiol Taiwan 54, 70-74, doi:10.1016/j.aat.2016.05.003 (2016).
5 Cosio, F. G., Hickson, L. J., Griffin, M. D., Stegall, M. D. & Kudva, Y. Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes. Am J Transplant 8, 593-599, doi:10.1111/j.1600-6143.2007.02101.x (2008).
6 Sharif, A. & Baboolal, K. Risk factors for new-onset diabetes after kidney transplantation. Nat Rev Nephrol 6, 415-423, doi:10.1038/nrneph.2010.66 (2010).
7 Hjelmesaeth, J., Asberg, A., Muller, F., Hartmann, A. & Jenssen, T. New-onset posttransplantation diabetes mellitus: insulin resistance or insulinopenia? Impact of immunosuppressive drugs, cytomegalovirus and hepatitis C virus infection. Curr Diabetes Rev 1, 1-10, doi:10.2174/1573399052952604 (2005).
8 Davidson, J. et al. New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation 75, SS3-24, doi:10.1097/01.TP.0000069952.49242.3E (2003).
9 Bergrem, H. A. et al. Undiagnosed diabetes in kidney transplant candidates: a case-finding strategy. Clin J Am Soc Nephrol 5, 616-622, doi:10.2215/CJN.07501009 (2010).
10 Sharif, A. et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant 14, 1992-2000, doi:10.1111/ajt.12850 (2014).
11 Yates, C. J., Fourlanos, S., Hjelmesaeth, J., Colman, P. G. & Cohney, S. J. New-onset diabetes after kidney transplantation-changes and challenges. Am J Transplant 12, 820-828, doi:10.1111/j.1600-6143.2011.03855.x (2012).
12 Kasiske, B. L., Snyder, J. J., Gilbertson, D. & Matas, A. J. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 3, 178-185 (2003).
13 Kuo, H. T., Sampaio, M. S., Vincenti, F. & Bunnapradist, S. Associations of pretransplant diabetes mellitus, new-onset diabetes after transplant, and acute rejection with transplant outcomes: an analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database. Am J Kidney Dis 56, 1127-1139, doi:10.1053/j.ajkd.2010.06.027 (2010).
14 Cosio, F. G. et al. Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney Int 62, 1440-1446, doi:10.1111/j.1523-1755.2002.kid582.x (2002).
15 Cole, E. H., Johnston, O., Rose, C. L. & Gill, J. S. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin J Am Soc Nephrol 3, 814-821, doi:10.2215/CJN.04681107 (2008).
16 Matas, A. J. et al. Posttransplant diabetes mellitus and acute rejection: impact on kidney transplant outcome. Transplantation 85, 338-343, doi:10.1097/TP.0b013e318160ee42 (2008).
17 Joss, N., Staatz, C. E., Thomson, A. H. & Jardine, A. G. Predictors of new onset diabetes after renal transplantation. Clin Transplant 21, 136-143, doi:10.1111/j.1399-0012.2006.00580.x (2007).
18 Chien, Y. S. et al. Incidence and risk factors of new-onset diabetes mellitus after renal transplantation. Transplant Proc 40, 2409-2411, doi:10.1016/j.transproceed.2008.06.034 (2008).
19 Cheng, C. Y. et al. Risk Factors in and Long-Term Survival of Patients with Post-Transplantation Diabetes Mellitus: A Retrospective Cohort Study. Int J Environ Res Public Health 17, doi:10.3390/ijerph17124581 (2020).
20 Chen, Y.-C. et al. Taiwan’s National Health Insurance Research Database: administrative health care database as study object in bibliometrics. 86, 365-380, doi:10.1007/s11192-010-0289-2 (2011).
21 Wu, C. S., Lai, M. S., Gau, S. S., Wang, S. C. & Tsai, H. J. Concordance between patient self-reports and claims data on clinical diagnoses, medication use, and health system utilization in Taiwan. PloS one 9, e112257, doi:10.1371/journal.pone.0112257 (2014).
22 Hsieh, C. Y., Chen, C. H., Li, C. Y. & Lai, M. L. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. Journal of the Formosan Medical Association = Taiwan yi zhi 114, 254-259, doi:10.1016/j.jfma.2013.09.009 (2015).
23 Cheng, C. L., Chien, H. C., Lee, C. H., Lin, S. J. & Yang, Y. H. Validity of in-hospital mortality data among patients with acute myocardial infarction or stroke in National Health Insurance Research Database in Taiwan. Int J Cardiol 201, 96-101, doi:10.1016/j.ijcard.2015.07.075 (2015).
24 Kao, W. H. et al. Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan. Pharmacoepidemiol Drug Saf 27, 1060-1066, doi:10.1002/pds.4267 (2018).
25 Austin, P. C., Jembere, N. & Chiu, M. Propensity score matching and complex surveys. Stat Methods Med Res 27, 1240-1257, doi:10.1177/0962280216658920 (2018).
26 Austin, P. C. & Stuart, E. A. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 34, 3661-3679, doi:10.1002/sim.6607 (2015).
27 Austin, P. C., Lee, D. S. & Fine, J. P. Introduction to the Analysis of Survival Data in the Presence of Competing Risks. Circulation 133, 601-609, doi:10.1161/CIRCULATIONAHA.115.017719 (2016).
28 Schultz, L. R., Peterson, E. L. & Breslau, N. Graphing survival curve estimates for time-dependent covariates. Int J Methods Psychiatr Res 11, 68-74, doi:10.1002/mpr.124 (2002).
29 McCaffrey, D. F. et al. A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Statistics in Medicine 32, 3388-3414, doi:10.1002/sim.5753 (2013).
30 Shivaswamy, V., Boerner, B. & Larsen, J. Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes. Endocr Rev 37, 37-61, doi:10.1210/er.2015-1084 (2016).
31 Jenssen, T. & Hartmann, A. Post-transplant diabetes mellitus in patients with solid organ transplants. Nat Rev Endocrinol 15, 172-188, doi:10.1038/s41574-018-0137-7 (2019).
32 Nampoory, M. R. et al. Inferior long-term outcome of renal transplantation in patients with diabetes mellitus. Med Princ Pract 11, 29-34, doi:10.1159/000048657 (2002).
33 Boudreaux, J. P. et al. The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients. Transplantation 44, 376-381, doi:10.1097/00007890-198709000-00010 (1987).
34 Revanur, V. K. et al. Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clin Transplant 15, 89-94 (2001).
35 Porrini, E. et al. Impact of metabolic syndrome on graft function and survival after cadaveric renal transplantation. Am J Kidney Dis 48, 134-142, doi:10.1053/j.ajkd.2006.04.078 (2006).
36 Wauters, R. P. et al. Cardiovascular consequences of new-onset hyperglycemia after kidney transplantation. Transplantation 94, 377-382, doi:10.1097/TP.0b013e3182584831 (2012).
37 Cosio, F. G. et al. New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int 67, 2415-2421, doi:10.1111/j.1523-1755.2005.00349.x (2005).
38 Sumrani, N. B. et al. Diabetes mellitus after renal transplantation in the cyclosporine era--an analysis of risk factors. Transplantation 51, 343-347, doi:10.1097/00007890-199102000-00014 (1991).
39 Lim, W. H., Wong, G., Pilmore, H. L., McDonald, S. P. & Chadban, S. J. Long-term outcomes of kidney transplantation in people with type 2 diabetes: a population cohort study. Lancet Diabetes Endocrinol 5, 26-33, doi:10.1016/S2213-8587(16)30317-5 (2017).
40 Eide, I. A. et al. Mortality risk in post-transplantation diabetes mellitus based on glucose and HbA1c diagnostic criteria. Transpl Int 29, 568-578, doi:10.1111/tri.12757 (2016).
41 Eide, I. A. et al. Associations Between Posttransplantation Diabetes Mellitus and Renal Graft Survival. Transplantation 101, 1282-1289, doi:10.1097/TP.0000000000001259 (2017).
42 Miles, A. M. et al. Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation 65, 380-384, doi:10.1097/00007890-199802150-00014 (1998).
43 Sharif, A., Moore, R. & Baboolal, K. Influence of lifestyle modification in renal transplant recipients with postprandial hyperglycemia. Transplantation 85, 353-358, doi:10.1097/TP.0b013e3181605ebf (2008).
44 Chakkera, H. A., Weil, E. J., Pham, P. T., Pomeroy, J. & Knowler, W. C. Can new-onset diabetes after kidney transplant be prevented? Diabetes Care 36, 1406-1412, doi:10.2337/dc12-2067 (2013).
45 Wissing, K. M., De Meyer, V. & Pipeleers, L. Balancing Immunosuppressive Efficacy and Prevention of Posttransplant Diabetes-A Question of Timing and Patient Selection. Kidney Int Rep 3, 1249-1252, doi:10.1016/j.ekir.2018.08.013 (2018).
46 Hjelmesaeth, J. et al. Tapering off prednisolone and cyclosporin the first year after renal transplantation: the effect on glucose tolerance. Nephrol Dial Transplant 16, 829-835, doi:10.1093/ndt/16.4.829 (2001).
47 Rizzari, M. D. et al. Ten-year outcome after rapid discontinuation of prednisone in adult primary kidney transplantation. Clin J Am Soc Nephrol 7, 494-503, doi:10.2215/CJN.08630811 (2012).
48 Pirsch, J. D. et al. New-Onset Diabetes After Transplantation: Results From a Double-Blind Early Corticosteroid Withdrawal Trial. Am J Transplant 15, 1982-1990, doi:10.1111/ajt.13247 (2015).
49 Serrano, O. K. et al. Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes From the University of Minnesota. Transplantation 101, 2590-2598, doi:10.1097/TP.0000000000001756 (2017).
50 Teutonico, A., Schena, P. F. & Di Paolo, S. Glucose metabolism in renal transplant recipients: effect of calcineurin inhibitor withdrawal and conversion to sirolimus. J Am Soc Nephrol 16, 3128-3135, doi:10.1681/ASN.2005050487 (2005).
51 Veroux, M. et al. Conversion to sirolimus therapy in kidney transplant recipients with new onset diabetes mellitus after transplantation. Clin Dev Immunol 2013, 496974, doi:10.1155/2013/496974 (2013).
52 Park, S. C. et al. Effect of transient post-transplantation hyperglycemia on the development of diabetes mellitus and transplantation outcomes in kidney transplant recipients. Transplant Proc 47, 666-671, doi:10.1016/j.transproceed.2014.11.053 (2015).
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