綜合以上的實驗結果顯示,以中頻率 15 Hz、固定強度 10 mA 電
針人體足三里穴三十分鐘能夠增強第二型糖尿病病人的血糖值的降
低、改善胰島素阻抗性,並且使得游離脂肪酸有下降的趨勢。這個結
果也印證了動物實驗中電針的療效,在人類治療上亦有其作用。至於
對第二型糖尿病的長期療效,則有賴長期的臨床實驗來印證。血糖值
的下降、胰島素阻抗性的改善及游離脂肪酸的下降趨勢三者間的關
聯,則有賴分子生物學實驗介入及採用 Glucose clamp 測試胰島素抗
性來達成。
參考文獻
5 Chacko E. Culture and therapy: Complementary strategies for the treatment of type-2 diabetes in an urban setting in kerala, india.
Soc Sci Med. 2003;56(5):1087-1098.
6 Lee MS, Lee MS, Lim HJ, Moon SR. Survey of the use of
complementary and alternative medicine among korean diabetes mellitus patients. Pharmacoepidemiol Drug Saf.
2004;13(3):167-171.
7 Dunning T. Complementary therapies and diabetes. Complement Ther Nurs Midwifery. 2003;9(2):74-80.
8 Argaez-Lopez N, Wacher NH, Kumate-Rodriguez J, et al. The use of complementary and alternative medicine therapies in type 2 diabetic patients in mexico. Diabetes Care.
2003;26(8):2470-2471.
9 皇甫謐:針灸甲乙經卷十一(晉),中國醫學大成(三十四),上海科學 技術出版社,上海 1990:pp.82.
10 黃維三:針灸科學,第二版,國立編譯館,台北 1989:pp. 532.
12 張世良、林昭庚、謝慶良、張淳堆、鄭瑞棠:針灸治療糖尿病之文獻 探討。中華針灸醫學會雜誌 2002;11: 37-43.
13 Chang SL, Lin JG, Chi TC, Liu IM, Cheng JT. An insulin-dependent hypoglycaemia induced by electroacupuncture at the zhongwan (CV12) acupoint in diabetic rats. Diabetologia.
1999;42(2):250-255.
14 Mo X, Chen D, Ji C, Zhang J, Liu C, Zhu L. Effect of electro-acupuncture and transcutaneous electric nerve
stimulation on experimental diabetes and its neuropathy. Chen Tzu Yen Chiu. 1996;21(3):55-59.
15 Wang L. Clinical observation on acupuncture treatment in 35 cases of diabetic gastroparesis. J Tradit Chin Med. 2004;
24(3):163-165.
16 Matthew J. Orland. Diabetes Mellitus. In:Manual of Medical Therapeutics.28th,Eds Gregory A. Ewald and Clark R.,
Mckenzie,Little, Brown and Company, Boston 1995;pp. 437-463.
17 Frank GC. Dietatry guidelines for type 2 diabetes. A tool box for nurse practitioners. Adv Nurse Pract. 2004;12(8):39-46.
18 Plank J, Bock GM. Drug treatment of type 2 diabetes. Wien Med Wochenschr. 2003;153(21-22):452-458.
19 Berger W. Incidence of severe side effects during therapy with sulfonylureas and biguanides. Horm Metab Res Suppl.1985;
15:111-115.
20 Hoffmann IS, Roa M, Torrico F, Cubeddu LX, Ondansetron and metformin-induced gastrointestinal side effects. Am J Ther.
2003;10(6):447-451.
21 Stades AM, Heikens JT, Erkelens DW, Holleman F, Hoekstra JB.
Metformin and lactic acidosis: Cause or coincidence? A review of case reports. J Intern Med. 2004; 255(2):179-187.
22 [Anonymous]. Rosiglitazone and pioglitazone: New preparations.
two new oral antidiabetics both poorly assessed. Prescrire Int. 2002; 11(62):170-176.
23 Toyota T, Ueno Y.: Clinical effect and side effect of troglitazone. Nippon Rinsho. 2000; 58(2):376-382.
24 Katahira H, Ishida H.: Indication and side effect of alpha glucosidase inhibitor. Nippon Rinsho. 2002; 60(9):399-408.
25李鳳玲:針灸治療糖尿病的概況。中國針灸 1994;14:165-167。
32 Guyton AC. Hall JE. Textbook of medical physiology, ninth Ed.
W.B. Saunders Co. 1996;pp. 855-864.
33 Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s biochemistry, twenty fifth Ed. McGraw-Hill Book Co.
2000;pp.190-198.
34 Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s biochemistry, twenty fifth Ed. McGraw-Hill Book Co.
2000;pp.268-271.
35 Ganong WF. Review of medical physiology. Twentieth Ed.
McGraw-Hill Book Co. 2001;pp.322-343.
36 Hadley ME. Endocrinology, fifth Ed. Prentice hall international Inc. 2000;pp.268-271.
37 Rhodes CJ, White MF. Molecular insights into insulin action and secretion. Eur J Clin Invest 2002;32(suppl.3):3-13.
38 Ganong WF. Review of medical physiology. Twentieth Ed.
McGraw-Hill Book Co. 2001;pp.290-302.
39 Timothy O,Tu TN;Zimmerman BR:Hyperlipidemia and Diabetes Mellitus.Mayo Clinic Proceedings 1998;73:969-76.
40 Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI. Insulin resistance and risk for stroke. Neurology 2002;59:809-815.
41 American Diabetes Association. Consensus development conference on insulin resistance. Diabetes Care
1998;21:310-314.
42 Bergman RN,Finegood DT,Ader M. Assessment of insulin sensitivity in vivo. Endocrine Review 1985;6:45-86.
43 DeFronzo RA,Tobin JD,Andres R. Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol 1979;237:E241.
44 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and cell function form fasting plasma glucose and insulin
concentrations in man. Diabetologia 1985;28:412-419.
45 Boden G. Effects of free fatty acids (FFA) on glucose metabolism.
Significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes 2003; 111(3):121-124.
46 Sivan E, Boden G. Free fatty acids, insulin resistance, and pregnancy. Curr Diab Rep. 2003; 3(4):319-322.
47 Saad MJ, Folli F, Kahn JA, Kahn CR. Modulation of insulin receptor, insulin receptor substrate-1, and
phosphatidylinositol 3 kinase in liver and muscle of
dexamethasone-treated rats. J Clin Invest 1993;92:2065-2072.
48 Holmang A, Bjorntorp P. The effects of cortisol on insulin sensitivity in muscle. Acta Physiol Scand 1992;144:425.
49 Epps-Fung MV, Williford J, Wells A, Hardy RW. Fatty acid-induced insulin resistance in adipocytes. Endocrinology
1997;138:4338-4345.
50 Lupi R, Dotta F, Marselli L, Guerra SD, Masini M, Santangelo C, atane G, Boggi U, Piro S, Anello M, Bergamini E, Mosca F, Mario UD, Prato SD, Marchetti P. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets. Evidence that β-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes 2002;51:1437-1442.
51 Reaven P. Metabolic syndrome.J Insur Med. 2004; 36(2):132-142.
52 Jermendy G, Hetyesi K, Biro L, Hidvegi T. Prevalence of the metabolic syndrome in hypertensive and/or obese subjects.
Diabet Med. 2004; 21(7):805-806.
53 Alebiosu CO, Odusan BO. Metabolic syndrome in subjects with type-2 diabetes mellitus. J Natl Med Assoc. 2004; 96(6):817-821.
54 Reaven GM. Role of insulin resistance in human disease.Diabetes 1988;37:1595-1607.
55 Third report of the National Cholesterol Education Program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults.Final report.Circulation
2002;106:3143-3421.
56 Fritschi C, Richlin D. The metabolic syndrome--early action to decrease risks for cardiovascular disease. AAOHN J. 2004;
52(8):320-322.
57 Cheng JT, Liu IM, Tzeng TF, Tsai CC, Lai TY. Plasma glucose-lowering effect of beta-endorphin in
streptozotocin-induced diabetic rats. Hormon Metab Res 2002;34:570-576.
58 張世良、林昭庚、謝慶良、鄭瑞棠、張次郎:2Hz 電針不同俞穴降血 糖之比較研究。中醫藥雜誌 2002;13(2):111-117.
59 鄭裕文、張世良: Mechanism of Improving Insulin Resistance by Electroacupuncture。中國醫藥大學中西醫結合研究所碩士論文 2003.
60 宋立軍:針灸治療糖尿病臨床研究。中國針灸 1995;2(2):42.
61 林志剛:針藥結合治療 II 型糖尿病療效觀察。福建中醫藥 2000;31:19-20.
69 Liao YY. Seto K. Saito H. Kawakami M. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress. American Journal of Chinese Medicine. 1980;
8(4):354-66.
70 Shapira MY. Appelbaum EY. Hirshberg B. Mizrahi Y. Bar-On H. Ziv E. A sustained, non-insulin related, hypoglycaemic effect of electroacupuncture in diabetic Psammomys obesus.
Diabetologia. 2000; 43(6):809-13.
在基礎的動物實驗中發現電針可藉由內生性嗎啡 (endogenous opioid peptides) 與受
體結合,促進胰島素 (insulin) 分泌而調降血糖,且有改善胰島素敏感度作用與血中
在基礎的動物實驗方面,將正常實驗動物及 STZ 誘發糖尿病的動物以 prednisolone
40 mg/kg i.p. 30 min 誘導為胰島素阻抗的狀態,隨機分為對照組、電針組、藥物組
及針藥並用組,正常實驗動物進行各組前後 HOMA 值的比較及糖耐量試驗
(Glucose tolerance test,GTT) 的比較,而 STZ 的糖尿病動物在各組進行胰島素挑戰
試驗 (Insulin challenge test,ICT) 之比較,並檢測各組之 FFA、TG、Cholesterol 的
含量,在正常實驗動物各組前後 HOMA 值的比較中,以 naloxone 1 mg/kg i.v.阻斷
組處置前後 HOMA、β-endorphin 及 FFA、TG、Cholesterol 值的變化,以比較三
組對糖尿病人之影響。本研究主要結合電針與藥物的作用優點,期能較單獨使用藥
物有較佳的增敏作用,或提前增敏的作用,進而縮短療程、減少藥物的使用劑量及
副作用發生。完成此一研究除了針藥並用的動物實驗基礎探討外,能進一步落實先
前動物實驗之觀察於臨床。
附錄二 受試者同意書 中 國 醫 藥 大 學 附 設 醫 院
受試者同意書
試驗主題:
針藥並用改善胰島素敏感度之研究
執行單位:中西醫結合研所及相關之 醫療院所。
電話:04-22053366-1604/1647
試驗主持人:
張世良
職稱:助理教授協同主持人:
林榮宗、林振蔚
職稱:醫師緊急聯絡人:張世良 緊急聯絡電話:0936-321863 自願受試者姓名: 病歷號:
性別: 年齡:
通訊地址:
電話:
5.
評估及統計方法: HOMA、β-endorphin 及 FFA、TG、Cholesterol 值 的變化皆於中西所實驗室進行檢驗分析。組間以 One Way ANOVA 檢定,同組前後均值的比較則採 self-paired t test。(三)參與試驗可能獲得之效益:
針藥併用或單獨使用,理論上有降血糖改善胰島素敏感度及改
善血脂代謝的作用,針藥併用應有較佳的效果。
(七)本人已詳閱上列各項資料,有關本臨床試驗計畫之疑問也經試驗主
持人詳
細予以解釋,瞭解整個實驗的狀況,並經過充份的考慮後,本人同 意接受
為此次臨床試驗之自願受試驗者。
自願受試驗者簽名(或法定代理人): 日期:
身分證號碼: 電話:
見 證 人: 與受試者關係:
身分證號碼: 電話:
附錄三 中國醫藥大學附設醫院人體試驗委員會人體試驗計劃同意書
Abstract
A Randomized Controlled Clinical Trial in the Treatment of Type II Diabetes Mellitus with Electroacupuncture
Diabetes mellitus ranks among the top ten causes of mortality throughout the world. The managements of NIDDM patients are diet control, physical exercise and medicines. Among patients using oral antidiabetic drugs who initially achieve adequate blood glucose control, secondary failures may occur that warrant insulin therapy. Some studies reveal that physical exercise may increase glucagons and adrenaline secretion, which could raise the plasma glucose. Alternative therapies received attention for these reasons. Some animal model studies reveal that electroacupuncture applying on specific acupoints, such as Zhongwan and Zusanli, may reduce plasma glucose level and improve insulin resistance.
We undertook a randomized, single blind, sham group controlled study to evaluate the effect of electroacupuncture with middle frequency (15 Hz) and fixed intensity (10 mA) on human Zusanli acupoint for 30 minutes. A total of 26 NIDDM patients were enrolled in this study. They were randomly devided into 2 groups. There were 13 patients in the experimental group.
The main outcome was changes of laboratory parameter before and after electroacupuncture.
In the experimental group, the plasma glucose level was 166.8±26.6 mg/dL before electroacupuncture and 125.6±24.3 mg/dL after electroacupuncture (p<0.05). The HOMA index was 4.9±2.5 before electroacupuncture and 2.8±1.8 after electroacupuncture (p<0.05). In the control group, the plasma glucose level was 166±35 mg/dL before treatment and 162.6±32.9 mg/dL after treatment (NS). The HOMA index was 4.7±3.8 before treatment and 5.1±4.2 after treatment (NS). The percentage decrease of the plasma free fatty acid level was -10.5% in the experimental group and 46.2% in the control group.(p<0.05). In conclusion, applying electroacupuncture on human Zusanli acupoint can enhance the plasma glucose level decrease, lower insulin resistance and lower percentage decrease of plasma free fatty acid level.
Keyword: NIDDM, Electroacupuncture, Zusanli, Insulin resistance
謝 辭
僅 以 此 文 感 謝 行 政 院 國 家 科 學 委 員 會 提 供 研 究 計 劃 (NSC 94-2320-B-039-024) 經費,同時也感謝張世良博士及其研究助理團隊 提供的指導及協助,使本研究能順利完成。