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研究生:吳梅桂
研究生(外文):Mei-Kuei
論文名稱:精神分裂症患者服用克慮平導致的肥胖與心血管疾病相關危險因子之探討及透過減重飲食與規律性活動介入對其改善效果之研究
論文名稱(外文):The risk factors of cardiovascular disease and the effect of diet and physical activity program in clozapine-treated schizophrenic obesity
指導教授:李信達李信達引用關係王進崑王進崑引用關係
學位類別:博士
校院名稱:中山醫學大學
系所名稱:營養學研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:英文
論文頁數:118
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精神分裂症的盛行率約1%,該疾病主要是精神及社交功能的障礙,這類病患
必須長期靠藥物控制病情;第二代精神病藥物中的克慮平(clozapine)不只改善精
神分裂症患者的正向症狀也可以改善負向症狀及認知功能;許多研究證明克慮平
是所有抗精神病藥物中會使患者體重及身體質量指數(BMI)增加最多的藥物。一
般人均認為因服用抗精神病藥物導致肥胖的精神分裂症病人,其體位及生理變化
應該與一般非精神病的肥胖者是相同的,但研究結果發現,服用克慮平導致的肥
胖精神分裂症病人其腰臀比、血液中胰島素濃度及胰島素阻抗係數(HOMA index)
都明顯的比一般非精神病的肥胖者高,同時也發現該類病患其胰島素的敏感度、
總膽固醇、低密度脂蛋白膽固醇、類胰島素生長因子-1(IGF-1)等濃度、總膽固醇
/高密度脂蛋白膽固醇(TC/HDL-C)、低密度脂蛋白膽固醇/高密度脂蛋白膽固醇
(LDL-C/HDL-C)及類胰島素生長因子-1/類胰島素生長因子結合蛋白第三型的比
值 (IGF-1/IGFBP-3 molar ratio)也都明顯的比一般非精神病的肥胖者低,這些偏
高及偏低的數值均是造成心血管疾病的危險因子。為降低服用克慮平導致的肥胖
精神分裂症病人罹患心血管疾病之危險,因此透過減重飲食及規律性活動兩種方
式同時介入,為病患進行體重控制並分析其心血管疾病的危險因子的改善情形,
結果發現:經由減重飲食及規律性活動同時介入後,可以明顯的降低患者的體
重、身體質量指數、體脂肪百分比、腰圍及臀圍,除此之外還可以減少患者體內
三酸甘油酯,胰島素,類胰島素生長因子結合蛋白第三型等濃度及並增加類胰島
素生長因子-1/類胰島素生長因子結合蛋白第三型的比值,明顯的降低心血管疾
病的危險因子,因此要減少此類服用克慮平導致的肥胖精神分裂症患者體內心血
管疾病之危險因子-透過長期使用減重飲食及規律性活動兩者同時介入,是一種
既安全又有效,經濟又實惠的好方法。

Schizophrenia has a prevalence of 1 percent in all cultures and is equally
common in men and women. It is a devastating mental illness that impairs mental and
social functioning. Clozapine is effective in treating not only the positive symptoms
of schizophrenia, but also in reducing negative symptoms and cognitive deficits.
Several studies have reported significant weight gain with clozapine and the largest
weight gains seen with antipsychotic drug and had a significantly higher mean BMI
value and rate of obesity than patients treated with other SGAs. Obese patients with
schizophrenia being treated with clozapine (OSC) and non-psychiatric obese (OB) are
often assumed to share the same physiological changes in obesity. In fact, the obese
patients with schizophrenia being treated with clozapine was different from
non-psychiatric obese in physiological change. Although the anthropometric
parameters in the OB and OSC groups were similar, in the OSC group the
waist-to-hip ratio (WHR), insulin levels and HOMA index were significantly higher,
while insulin sensitivity, cholesterol, low-density lipoprotein (LDL) cholesterol,
TC/HDL-C, LDL-C/HDL-C, IGF-1 and IGF-1/IGFBP-3 molar ratio were lower, than
those of the OB group. Significant weight gain can lead to health complications such
as cardiovascular disease, hypertension, dyslipidemia, stroke, gallbladder disease,
osteoarthritis, sleep apnea, respiratory problems, certain cancers, and type 2 diabetes.
Compliance with prescribed antipsychotic medication is low and weight gain
contributes to psychotropic non-compliance. The intervention program of dietary
control and regular physical activity in obese patients with schizophrenia being
treated with clozapine can showed a significant decrease in body weight, BMI, body
fat percentage, and waist and hip girths. In addition, participating patients showed
improved metabolic profiles of triglyceride, insulin, IGFBP-3 levels, and the IGF-1 to
IGFBP3 molar ratio. In conclusion, the obese patients with schizophrenia being
treated with clozapine was different from non-psychiatric obese in physiological
3
change. The obese patients with schizophrenia being treated with clozapine group was
characterized by impaired glucose–insulin homeostasis, abnormal lipid profiles and
hormonal changes in the GH-IGF-IGFBP axis and in leptin. By way of the program of
dietary control and regular physical activity can significantly reduce body weight and
improve metabolic profiles of insulin, triglyceride, and IGFBP-3 among obese inpatients
taking clozapine for the treatment of schizophrenia.

Contents
Chinese Abstract……………………………………..……………..………………….……..1
English Abstract…………………………………………………..….……………..2
Chapter 1:
Literature review…...................……………………….....................................…4
Purposes…..………………………………………………………………….….…51
Chapter 2:
Glucose-insulin homeostasis, lipid profiles and GH-IGF-IGFBP axis in
clozapine-treated schizophrenic obesity versus non-psychiatric obesity…....53
2-1. Chinese Abstract………………………………………………………..….54
2-2. English Abstract……………………………………………………………56
2-3. Introduction…………………………………………………..……………58
2-4. Materials and Methods……………………………………………………59
2-5. Result……………………………………………………………………….63
2-6. Discussion……………………………………………………….………….64
2-7. Reference…………………………………………………………..……….70
Chapter 3:
Outcomes of obese, clozapine-treated inpatients with schizophrenia placed
on a six-month diet and physical activity program…………………….……..79
3-1. Chinese Abstract…………………………………………………….……..80
3-2. English Abstract………………………………………………………..…. 81
3-3. Introduction…………………………………………….………………….82
3-4. Materials and Methods……………………..……………………………..84
3-5. Result…………………………………………………………………….…88
3-6. Discussion…………………………………….………………………….…91
3-7. Conclusion…………………………………………………………………95
3-8. Reference………………………………………..……………………….…97
Chapter 4:
Summarize findings, conclusion and perspective: the risk factors of
cardiovascular disease and the effect of diet and physical activity program
in clozapine-treated schizophrenic obesity……………..………………….…..107
Appendixes………………………………………………………………….….…113
Appendix 1. Informed consent (baseline)……………...…...………….……..114
Appendix 2. Informed consent (intervention)…...…...……………………...115
Appendix 3. Approval Institutional Review Board of the Yu-Li Veterants
Hospital………………………..………………..…….…….…....117

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