臺灣博碩士論文加值系統

重症病人較容易有壓力型高血糖、全身性發炎反應、高同半胱胺酸血症等較嚴重的臨床症狀，維生素B-6營養狀況也有偏低的情形。
磷酸比哆醛為維生素B-6的活性化型式，因擔任糖質新生及肝醣分解過程的輔酶，故在醣類的代謝過程中扮演重要的角色。維生素B-6也因參與核酸、mRNA及蛋白質的合成，故在發炎反應產生大量細胞激素與發炎介質的情況下會增加體內磷酸比哆醛之利用。此外，維生素B-6為同半胱胺酸代謝過程中協助轉硫作用所需的輔酶。因此重症病人若有維生素B-6營養狀況缺乏的情況，可能會增加其血糖、發炎反應及血漿同半胱胺酸濃度。本研究目的是：1. 比較維生素B-6營養狀況正常與缺乏的重症病人其臨床狀況、血糖及發炎反應相關指標、血漿同半胱胺酸濃度的差異性；2. 探討維生素B-6營養狀況與血糖和發炎反應相關指標、血漿同半胱胺酸濃度的關係。本橫斷式研究共募集到彰化基督教醫院第二外科加護病房的34位重症病人。病人住加護病房第1天與第8天分別接受體位測量，飲食紀錄，疾病嚴重度 (APACHE II score)，臨床血液生化值 (如：白蛋白、血糖、血清胰島素、糖化血色素、C-反應蛋白等) 、維生素B-6營養狀況指標 [如：血漿磷酸比哆醛 (PLP)、比哆醛 (PL)、比哆酸 (4-PA)，紅血球PLP，尿液4-PA及轉胺酶活性係數 (EAST-AC, EALT-AC)]，發炎反應相關指標 (如：介白素-6、腫瘤壞死因子-α) 及血漿同半胱胺酸濃度的評估及分析。依據病人入加護病房第1天血漿PLP濃度區分為維生素B-6正常組 (PLP ≧ 20 nmol/L, n = 20) 與缺乏組 (PLP < 20 nmol/L, n = 14)。結果顯示正常及缺乏組病人入加護病房第1天皆處於高血糖狀況 (175.07 ± 16.02 vs. 161.25 ± 6.20 mg/dL)。缺乏組病人在第1天及第8天的血糖濃度無顯著變化，但正常組病人的第8天血糖值較第1天顯著降低37.5 mg/dL。兩組病人第8天胰島素濃度皆較第1天有微幅上升但並無顯著差異及變化。所有受試者的紅血球PLP改變量與血糖濃度改變量是顯著負相關 (β = -0.726, p = 0.029)。正常組病人第8天介白素-6濃度較第1天濃度有顯著下降，但血漿PLP、PL及4-PA濃度，紅血球PLP濃度、EALT-AC及EAST-AC皆與C-反應蛋白、介白素-6及腫瘤壞死因子-α無顯著相關性。正常組病人入加護病房第1天及第8天血漿同半胱胺酸濃度都顯著低於缺乏組病人。所有受試者之紅血球PLP濃度與血漿同半胱胺酸濃度呈現顯著負相關 (r = -0.268, p = 0.027)，但是血漿PA濃度 (r = 0.252, p = 0.038) 以及紅血球EALT-AC (r = 0.287, p = 0.018) 與血漿同半胱胺酸濃度呈現顯著正相關。本研究結果顯示當重症病人入加護病房第1天時若有足夠血漿磷酸比哆醛濃度，在第8天時會有較佳的血糖反應，較低的血漿同半胱胺酸濃度，及顯著下降的介白素-6濃度。但是血漿及紅血球PLP與血糖、同半胱胺酸及發炎反應相關指標的關係仍待進一步研究。

Critically ill patients are likely to have stress hyperglycemia, systemic inflammation, hyperhomocysteinemia, and compromised vitamin B-6 status. The biologically active form of vitamin B-6 is pyridoxal 5’-phosphate (PLP), which functions as a coenzyme in gluconeogenesis and glycogenolysis. Vitamin B-6 is also involved in the synthesis of nucleic acids, mRNA, and protein synthesis, thus the production of cytokines and inflammatory mediators during inflammatory responses might increase the use of PLP. In addition, PLP also acts as the coenzyme in the metabolism of homocysteine. Critically ill patients with compromised vitamin B-6 status may have higher blood glucose and inflammatory responses, and hyperhomocysteinemia. The purposes of this study were to compare the differences of blood glucose, inflammatory responses and plasma homocysteine concentration between adequate vitamin B-6 (PLP ≧ 20 nmol/L) and deficient (PLP &lt; 20 nmol/L) groups, and additionally to examine the relationship of vitamin B-6 status with blood glucose, inflammatory responses and plasma homocysteine concentration in critically ill surgical patients. This was a cross-sectional study. Thirty-four patients were recruited from the surgical intensive care unit (SICU) of Changhua Christian Hospital. Anthropometric and clinical measurements (i.e., blood glucose, serum albumin, insulin, glycated hemoglobin, C-reactive protein), severity of illness (APACHE II score), vitamin B-6 status [i.e., plasma PLP, pyridoxal (PL) and 4-pyridoxic acid (4-PA), erythrocyte PLP, erythrocyte alanine aminotransferase activity coefficient (EALT-AC) and erythrocyte aspartate aminotransferase activity coefficient (EAST-AC)], inflammatory response indicators [ie., interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)] and plasma homocysteine concentration were assessed and measured at the 1st and 8th day of admission to the SICU. Patients were allocated to either adequate (n = 20) or deficient (n = 14) vitamin B-6 groups according to their baseline plasma PLP level. Results showed that patients in the adequate and deficient groups were both having hyperglycemia (175.07 ± 16.02 vs. 161.25 ± 6.20 mg/dL, respectively) at the 1st day of admission. Patients with vitamin B-6 deficiency had no significant changes in blood glucose concentration (171.86 ± 29.69 mg/dL) at day 8; whereas there was a significant 37.5 mg/dL of blood glucose reduction in patients with adequate vitamin B-6 status at day 8. The change of erythrocyte PLP concentration was negatively correlated with the change of blood glucose concentration (β = -0.726, p = 0.029) in all subjects. Plasma IL-6 concentrations were significantly decreased at day 8 in patients with adequate vitamin B-6. Plasma PLP, PL and 4-PA, erythrocyte PLP, EALT-AC and EAST-AC did not significantly correlat with C-reactive protein, IL-6 and TNF-α in all subjects. Plasma homocysteine concentration was significantly reduced at day 8 in both groups. Erythrocyte PLP was negatively correlated with plasma homocysteine concentration (r = -0.268, p = 0.027), while plasma 4-PA (r = 0.252, p = 0.038) and erythrocyte EALT-AC (r = 0.287, p = 0.018) were significantly positively correlated with homocysteine concentration in all subjects. Critically ill patients with adequate vitamin B-6 status at admission have better blood glucose response and lower homocysteine and IL-6 concentrations at day 8. However, further studies are warranted to investigate the relationship between plasma PLP, erythrocyte PLP and blood glucose, inflammatory response and plasma homocysteine concentration.

壹、 摘要
中文摘要................................................1
Abstract................................................4
貳、 文獻回顧
一、重症病人之血糖變化..............................7
二、壓力型高血糖對於重症病人的影響..................8
三、重症病患維生素B-6的營養狀況....................10
四、維生素B-6與血糖控制............................11
五、維生素B-6與發炎反應............................12
六、維生素B-6與同半胱胺酸..........................14
參、 研究動機......................................18
肆、 研究目的......................................19
伍、 材料與方法
一、 研究設計......................................20
二、 研究對象......................................20
三、 研究方法
I. 臨床資料......................................21
II. 疾病嚴重程度..................................21
III. 體位測量......................................22
IV. 飲食紀錄......................................22
V. 血液及尿液採樣................................23
VI. 血液臨床檢驗值分析............................23
VII. 尿液臨床檢驗值分析............................24

VIII. 維生素B-6含量測定
1. 血漿磷酸比哆醛、比哆醛及比哆酸................25
2. 紅血球磷酸比哆醛..............................28
3. 尿液比哆酸....................................30
4. 紅血球天門冬胺酸轉胺酶活性係數................32
5. 紅血球丙胺酸轉胺酶活性係數....................34
IX. 其他生化值分析
1. 胰島素........................................37
2. 血漿同半胱胺酸................................37
3. 介白素-6......................................40
4. 腫瘤壞死因子-α................................40
四、 統計分析......................................42
陸、 結果
一、基本資料及體位測量..............................43
二、臨床生化檢驗指標................................44
三、發炎反應及同半胱胺酸濃度相關指標................45
四、維生素B-6營養狀況評估...........................46
五、維生素B-6營養狀況與生化指標之相關性.............47
六、其他臨床結果相關性分析..........................49
柒、 討論
一、重症病人維生素B-6營養狀況與血糖濃度.................50
二、重症病人維生素B-6營養狀況與發炎相關指標.............52
三、重症病人維生素B-6營養狀況與血漿同半胱胺酸濃度.......53
四、重症病人疾病嚴重程度與血糖濃度......................54
捌、 研究限制.......................................55
玖、 結論...........................................56
表一~表九............................................. 57
拾、 參考文獻...........................................66
附錄一 財團法人彰化基督教醫院臨床試驗許可書.............84
附錄二 人體試驗計畫接受試驗同意書.......................85
附錄三 受試者基本資料調查表.............................91
附錄四 APACHE II score評估表............................96
附錄五 血漿磷酸比哆醛、比哆醛及比哆酸標準品圖...........98
附錄六 血液樣本之血漿磷酸比哆醛、比哆醛及比哆酸圖譜.....99
附錄七 紅血球磷酸比哆醛標準品圖譜......................100
附錄八 血液樣本之紅血球磷酸比哆醛圖譜..................101
附錄九 尿液 4-比哆酸標準品圖...........................102
附錄十 尿液樣本之 4-比哆酸圖譜.........................103
附錄十一 血漿同半胱胺酸標準品圖譜......................104
附錄十二 血液樣本之血漿同半胱胺酸圖譜..................105

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