臺灣博碩士論文加值系統

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

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