• Theses


Evaluation of Coronary Artery Disease Patients with and without Type II Diabetes by Using Dynamic MR Perfusion of Pancreas and Proton MR Spectroscopy of Muscle and Liver

Advisor : 施庭芳


第二型糖尿病的致病機制是十分複雜的,胰島素分泌的缺陷 (secretory defect) 以及周邊胰島素阻抗 (insulin resistance) 為疾病成因的兩大特點;要發展成第二型糖尿病,兩個缺陷必須同時存在。胰島素阻抗常是第二型糖尿病的早期特徵,而分泌機能失常則是由初期胰島素抵抗,進展成為第二型糖尿病的重要因子。因此,要有效治療第二型糖尿病,除了降低胰島素抵抗、改進對胰島素的敏感度,也必須朝著增強beta 細胞的生存、以及預防其分泌機能失常來努力。 就臨床的診斷、治療和預防的目的來看,要了解胰島素分泌的功能,多半由血液中insulin的濃度來判斷,我們無法得知胰臟中正常beta 細胞的數量或是功能;另一方面,臨床上也沒有影像檢查技術或方法,能夠量測胰島的血流或是能預測其存活度(viability),除非是用組織切片或開刀取出組織等侵入性的方法。過去有人利用老鼠實驗證明胰島的血流(islet blood flow)變差確實與第二型糖尿病相關,然而要在人體專一性測量胰島的血流是不可能的,只能利用間接的方式來測量;因此,我們希望能利用非侵入性的磁振造影動態灌注技術來發展出影像診斷的方法及參數,用來預測或代表胰臟的組織與功能。 另一方面,周邊胰島素阻抗主要的場所在肝臟、肌肉和脂肪組織,因此胰島素阻抗會導致肥胖與脂肪不正常堆積。一般而言,肝臟、肌肉的阻抗性會出現在脂肪組織之前,所以在胰島素阻抗的初期,病人並未出現明顯肥胖時,體內的肝臟與肌肉可能已經先出現不正常的脂肪堆積。為了了解體內肌肉及肝臟的脂肪堆積情形,我們利用氫磁振頻譜技術來量測這些地方的脂肪濃度,希望藉此了解,第二型糖尿病人體內脂肪的分布情形是否與臨床相關、在形成糖尿病之前與之後是否不同。 所謂代謝症候群(metabolic syndrome)是指糖尿病、肥胖、高血壓、以及粥狀動脈硬化(atherosclerosis)的集合並探討之間的關連。因此,探討在冠狀動脈粥狀硬化的病人族群當中,合併有第二型糖尿病或無糖尿病者之間的差異是有必要的。我們研究的目的是利用磁振造影技術來找出確定診斷為冠狀動脈粥狀硬化的病人合併有第二型糖尿病或無糖尿病者之間,胰臟的組織灌注與肌肉及肝臟的脂肪堆積情形是否存在不同。 在胰臟的組織灌注方面,我們的研究結果顯示在控制了病人的年齡、BMI、以及心血管狹窄的嚴重度之後,同為冠狀動脈狹窄者,併有第二型糖尿病病人的胰臟動態灌注明顯比非糖尿病病人差;在磁振頻譜分析方面,我們的研究結果顯示第二型糖尿病病人有較高濃度的肌肉細胞內脂肪且與血糖控制好壞相關,長時間曝露在高血糖的狀況下會造成肌肉細胞內脂肪堆積;最後,雖然我們的研究結果並未顯示第二型糖尿病病人有較高濃度的肝臟細胞內脂肪,但是我們也證實了肝臟細胞內脂肪濃度與高血脂症及血中三酸甘油脂明顯相關,肝臟的磁振頻譜檢查應能協助臨床上脂肪肝的檢測。

Parallel abstracts

The pathophysiology of type 2 diabetes is complex and still partially unknown. The defect of insulin secretion and the peripheral insulin resistance are both necessary in the development of type 2 diabetes. Insulin resistance appears early in the course of the disease, but the secrete defect is the key factor in the transformation from the initial stage into type 2 diabetes. Thus as potential therapeutic implications are considered, it is not only important to reduce the insulin resistance and improve the insulin sensitivity but also promote the beta-cell survival and keep it from secretory dysfunction. In clinical application of diagnosis, treatment and prevention, we measure the serum insulin concentration in order to access the function of insulin secretion. We could not measure the beta-cell mass or islet blood flow in the pancreas directly by any of the present image modality. The islet blood flow or its viability could only be accessed by tissue proof from biopsy or operation. Only animal study had been mentioned and the data in human is to be obtained. Thus, it is important to develop a method to measure the in vivo pancreatic blood flow or tissue perfusion by a non-invasive and reproducible method in human subjects. We apply MR dynamic-perfusion technique on the pancreas to access the relationship between the tissue perfusion and its function. On the other hand, as insulin resistance acts on the liver, muscle and adipose tissue, it results in abnormal fat deposition in these structures. Insulin resistance of the liver and muscle often appears earlier than the adipose tissue, thus liver and muscle may pile up abnormal fat in the initial stage before patients become overt obese. We apply MR spectroscopy technique to measure the lipid component in the liver and muscle in order to evaluate the relationship between the distribution of lipid and clinical information of type 2 diabetes. The metabolic syndrome emphasized the association between DM, obesity, hypertension and atherosclerosis. Thus we aim to investigate the difference of MR perfusion of pancreas and proton MR spectroscopy of muscle and liver between subjects, who are documented CAD, with and without type 2 diabetes. Among subjects with documented CAD, the obtained data demonstrate that 1) the MR perfusion of pancreas in subjects with type 2 diabetes is significantly decreased than in subjects without diabetes, even after adjusted with their age, BMI, and severity of CAD; 2) the intramyocellular lipid is found higher in subjects with type 2 diabetes than in subjects without diabetes and is also higher in subjects with poor blood sugar control than in subjects with better control; 3) although higher intrahepatocellular lipid is not shown in the subjects with type 2 diabetes, the well correlation between the intrahepatocellular lipid and the serum TG makes the feasibility of clinical utility of liver MRS in the detection of fatty liver.


1. A. Misra, S. Sinha, M. Kumar, N. R. Jagannathan and R. M. Pandey. Proton magnetic resonance spectroscopy study of soleus muscle in non-obese healthy and Type 2 diabetic Asian Northern Indian males: high intramyocellular lipid content correlates with excess body fat and abdominal obesity. Diabet. Med 2003;20:361-7
2. Alexandra E. Butler, Juliette Janson, Susan Bonner-Weir, Robert Ritzel, Robert A. Rizza, and Peter C. Butler. Beta-Cell Deficit and Increased beta-Cell Apoptosis in Humans With Type 2 Diabetes. Diabetes 2003;52:102–110
4. Atef N, Portha B, Penicaud L: Changes in islet blood flow in rats with NIDDM. Diabetologia 1994;37:677–680
5. Boden G, Lebed B, Schatz M, Homko C, Lemieux S. Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes 2001; 50:1612– 1617.
6. Boesch C, Slotboom J, Hoppeler H, Kreis R. In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy. Magn Reson Med 1997; 37:484–493.