臺灣博碩士論文加值系統

研究背景與動機：糖尿病與癌症是兩種不同形式的慢性病，且影響全球民眾健康，尤其是第2型糖尿病與癌症之間有許多錯綜複雜的共同危險因子。口服降血糖藥物為第2型糖尿病之主要治療方式，其中一類為Thiazolidinedione(TZDs)。該類藥物接二連三發生不良事件，最近美國FDA再發佈『使用糖尿病藥物(Actos®，愛妥糖)超過一年以上，可能會增加罹患膀胱癌的風險』，震驚全球醫界，更讓新陳代謝科醫師及病患陷入恐慌。目前關於使用TZDs類藥物與罹患癌症風險之大型具全國代表性研究仍然不多，尤其利用亞洲人口數據探討糖尿病患者使用TZDs藥物與癌症發生之相關性研究，更是付之闕如。
研究目的：以健保資料庫探討第2型糖尿病患者服用TZDs藥物與罹患膀胱癌、大腸癌及其他癌症之相關性。
研究方法：資料來源為全民健保2005年之承保抽樣歸人檔資料庫，本研究申購2002-2009年共100萬人進行分析。研究對象為使用降血糖TZDs類藥物且ICD-9-CM主診斷、次診斷及第三診斷碼為250.00~250.93之糖尿病患者，年齡大於40歲。本研究樣本八年共27,382人，其中男性患者為14,748人，女性為12,634人。以卡方檢定與二元邏輯斯及多項式邏輯斯進行分析。
研究結果：本研究發現性別、年齡、糖尿病病齡、疾病嚴重度、TZDs使用期長短及就醫層級別影響糖尿病患者服用TZDs藥物罹患大腸癌、膀胱癌或其他癌症風險。顯示男性年齡50歲以上隨著年齡增加罹患大腸癌或膀胱癌風險性成正相關，其勝算比為年齡40-49歲之2至9倍以上。糖尿病病齡1-2年者且TZDs使用期3年以上者比未滿1年有高於1倍以上之風險比。大多數罹患癌症者選擇醫學中心就醫。疾病嚴重程度重度者比輕度高達3-4倍以上風險罹患癌症。
結論：第2型糖尿病服用TZDs類藥物3年以上有高風險罹患膀胱癌、大腸癌或其他癌症，高齡者及疾病嚴重程度重度者為高危險群。建議衛生署是否考慮將TZDs類藥物下架或將高齡使用TZDs類藥物3年以上者給予免費膀胱癌篩檢及定期追蹤，以確保民眾用藥安全及降低健保醫療費用支出。

Background: Diabetes and cancer are common chronic diseases with tremendous impact on health worldwide.Type 2 diabetes and cancer have many common risk factors complicated. Oral hypoglycemic drugs for type 2 diabetes, is the primary treatment, one of drugs is the Thiazolidinedione (TZDs). Adverse events occurred one after another of these drugs. The U.S. Food and Drug Administration (FDA) is informing the public that“use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer”, shocked the world medical, making panic with endocrinologist and patients. Current association between TZDs use and cancer onset among patients with diabetes, a large nationally representative study is still small. Especially in the Asian diabeties data with taking TZDs and cancer related research, it is missing.
Objectives: To explore association between TZDs use and bladder cancer, colorectal cancer or other cancers onset among patients with type 2 diabetes by National Health Insurance (NHI) database.
Methods: A random sample of 1,000,000 people insured by the NHI in 2005 was created by the National Health Research Institute for academic research.To study on National Health Insurance database from 2002-2009. Study for the use of hypoglycemic drugs TZDs and ICD-9-CM primary diagnosis, secondary diagnosis, and the third diagnosis code 250.00- 250.93 of diabetes, with greater than 40 years of age. The results of 27,382 patients, of which 14,748 were males, 12,634 were females. By Chi-square test , binary logistic and multinomial logistic analysis.
Results: The study found that gender, age, duration of diabetes, severity of diabetes, TZDs use and hospital level influence patients with diabetes taking TZDs risk of colorectal cancer , bladder cancer and other cancers. Showed that males with age over 50 years as the age increases the risk of bladder cancer or colorectal cancer is positively related and the odds ratio of 2 to 9 times for the age of 40-49 years. Duration of diabetes 1-2 years and TZDs period of 3 years than those with less than one year are more than one times higher than the risk ratio. Most patients with cancer choose Medical Center for cancer treatment. Those with severity of disease and severe up to 3-4 times more than the mild risk of cancer.
Conclusion: Type 2 diabetes taking TZDs drugs for 1-2 years have high risk of suffering from bladder cancer, colorectal cancer and other cancers, elderly and disease severity were severe for the high risk group. Recommended that the Department of Health is considering TZDs withdrawal or to be used TZDs drugs were given over 3 years free bladder cancer screening and regular follow-up to ensure public safety and reducing medication health insurance expenses.

中文摘要 i
英文摘要 iii
誌謝 v
目錄 vi
表目錄 viii
圖目錄 ix
第一章 緒論 1
第一節 研究背景與動機 1
第二節 研究重要性 4
第三節 研究目的 5
第二章 文獻探討 6
第一節 糖尿病流行病學、診斷與分類 6
第二節 第2型糖尿病藥物治療 11
第三節 TZDs藥品之簡介 17
第四節 糖尿病與癌症相關性研究 19
第五節 TZDs與其他降血藥物和癌症相關研究 22
第六節 罹患癌症之相關因素 25
第七節 文獻小結 30
第三章 研究方法 31
第一節 研究架構 31
第二節 研究設計與流程 33
第三節 研究對象與資料來源 35
第四節 操作型定義 36
第五節 分析方法 40
第四章 研究結果 42
第一節 糖尿病患者使用TZDs之描述性統計 42
第二節 卡方檢定之獨立性檢定 49
第三節 TZDs藥物罹患癌症類別探討 58
第四節 邏輯斯迴歸分析 60
第五章 討論 68
第一節 影響使用TZDs藥物罹患大腸癌或膀胱癌 68
第二節 影響使用TZDs藥物罹患其他癌症 70
第六章 結論與建議 74
第一節 結論 74
第二節 建議 76
第三節 研究限制 78
參考文獻 79

【英文文獻】
ADA. (2004). Insulin Administration. Diabetes care 27, S106-109.
ADA. (2010). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 33, s62-s69.
Akhter, J. (1997). The American Diabetes Association''s Clinical Practice Recommendations and the developing world. Diabetes Care, 20(6), 1044-1045.
Arrow, K. J. (1963). Uncertainty and the Welfare Economics of Medical Care. America Economics Review, 53, 941-973.
Bao, B., Wang, Z., Li, Y., Kong, D., Ali, S., Banerjee, S., & Sarkar, F. (2011). The complexities of obesity and diabetes with the development and progression of pancreatic cancer. Biochim Biophys Acta, 1815(2), 135-146.
Barone, B. B., Yeh, H. C., Snyder, C. F., Peairs, K. S., Stein, K. B., Derr, R. L., & Brancati, F. L. (2008). Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus:
A Systematic Review and Meta-analysis. JAMA, 300(23), 2754-2764.
Boyle, J. P., Honeycutt, A. A., & Narayan, K. M. (2001). Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the US. . Diabetes Care, 24, 1936-1940.
Brauer, P. M., McKeown-Eyssen, G. E., & Jazmaji, V. (2002). Familial aggregation of diabetes and hypertension in a case-control study of colorectal neoplasia. Am J Epidemiol. , 156, 702-713.
CDC. (1997). Centers for Disease Control and Prevention.
Chang, C. H., Lin, J. W., Wu, L. C., Lai, M. S., Chuang, L. M., & Chan, K. A. (2011). Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus. Hepatology, 1-44.
Chang, H. Y., Hsu, C. C., Pan, W. H., Liu, W. L., Cheng, J. C., Tseng, C. H., & Hurng, B. S. (2010). Gender differences in trends in diabetes prevalence from 1993 to 2008 in Taiwan. Diabetes Research and Clinical Practice, 90(3), 358-364.
Chang, K. J., Kuo, W. H., & Wang, M. Y. (2008). The Epidemiology of Breast Cancer in Taiwan. J. Chinese Oncol. Soc., 24(2), 85-93.
Chaudhry, R., Goel, V., & Sawka, C. (2001). Breast cancer survival by teaching status of the initial treating hospital. Canadian Medical Association Journal, 164(2), 183-188.
Chou, P., Tung, T. H., Li, C. L., Chuang, S. Y., Heng, L. C., & Yang, N. P. (2002). Epidemiology of Diabetes Mellitus in Taiwan. Taiwan J Public Health, 21(2), 83-96.
Chustecka, Z. (2010). Links Between Diabetes and Cancer-ADA/ACS Consensus Report. Cancer.
Ciaradi, T. P., Gilmore, A., & Olefsky, J. M. (1990). In vitro studies on the action of CS-045 a new antidiabetic agent. Metabolism, 39, 1056-1062.
Cock, T. A., Houten, S. M., & Auwerx, J. (2004). Peroxisome proliferator-activated receptor- : too much of good thing causes harm. EMBO Reports, 5, 142-147.
Cristofanilli, M., Yamamura, Y., & Kau, S. W. (2005). Thyroid hormone and breast carcinoma: Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma. Cancer, 103, 1122-1128.
DeCensi, A., Puntoni, M., Goodwin, P., Cazzaniga, M., Gennari, A., & Bernardo Bonanni, S. G. (2010). Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis. Cancer Prevention Research, 3(11), 1451-1461.
Eddi, R., Karki, A., Shah, A., DeBari, V., & DePasquale, J. R. (2011). Association of Type 2 Diabetes and Colon Adenomas Journal of Gastrointestinal Cancer.
El-Serag, H. B., Hampel, H., & Javadi, F. (2006). The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. . Clin Gastroenterol Hepatol., 4(3), 369-380.
Extermann, M. (2006). Comorbidity and Cancer American Society of Clinical Oncology (pp. 294-296).
Extermann, M. (2007). Interaction Between Comorbidity and Cancer. Cancer control., 14(1), 13-22.
Extermann, M., Overcash, J., Lyman, G. H., Parr, J., & Balducci, L. (1998). Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. , 16, 1582-1587.
Extermann, M., Yoder, J., & Overcash, J. (2003). Influence of concomitant medications metabolized by cytochrome P-450 on toxicity from chemotherapy. Presented at the 8th International Conference on Geriatric Oncology. Rome, Italy.
FDA. (2000). Summary of Safety-Related Drug Labeling Changes Approved By FDA July 2000. MedWatch Safety Information 2000 Retrieved from http://www.fda.gov/medwatch/safety/2000/jul00.htm#avandi.
FDA. (2001). Summary of Safety-Related Drug Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) July 2001. MedWatch Safety Information 2001. Retrieved from http://www.fda.gov/medwatch/safety/ 2001/feb01.htm#avandi.
FDA. (2002). Summary of Safety-Related Drug Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) January 2002. MedWatch Safety Information 2002. Retrieved from http://www.fda.gov/medwatch/ SAFETY/2002/jan02.htm#actos.
FDA. (2011). FDA Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer. Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm259150.htm.
Ferrarra, A., Lewisames, J. D., Quesenberry, C. P., Pengt, T., Stromb, B. L., S. K., V. D. E., & Habel, L. A. (2011). Cohort Study of Pioglitazone and Cancer Incidence in Patients With Diabetes. Diabetes Care, 34, 923-929.
Franco, O. H., Steyerberg, E. W., Hu, F. B., Mackenbach, J., & Nusselder, W. (2007). Associations of diabetes mellitus with total life expectancy and life expectancy with and without cardiovascular disease. Arch Intern Med., 167(11), 1145-1151.
Friberg, E., Orsini, N., Mantzoros, C. S., & Wolk, A. (2007). Diabetes mellitus and risk of endometrial cancer:a meta-analysis. Diabetologia 50, 1365-1374.
Galli, A., Ceni, E., & Crabb, D. W. (2004). Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPAR independent mechanisms. Gut, 53, 1688-1697.
Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., & Yee, D. (2010). Diabetes and cancer: a consensus report. [Consensus Development Conference]. CA Cancer J Clin, 60(4), 207-221. doi: 10.3322/caac.20078
Gonza''lez-Pe''rez, A., & Garci''a , L. A. (2005). Prostate cancer risk among men with diabetes mellitus (Spain). Cancer Causes and Control, 16, 1055-1058.
Govindarajan, R., Ratnasinghe, L., Simmons, D. L., Siegel, E. R., Midathada, M. V., Kim, L., & Lang, N. P. (2007). Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol, 25(12), 1476-1481. doi: 10.1200/JCO.2006.07.2777
Hall, W., Jani, A., Ryu, J., Narayan, S., & Vijayakumar, S. (2005). The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer. Prostate Cancer and Prostatic Diseases, 8, 22-30.
Han, S., Rivera, H. N., & Roman, J. (2005). Peroxisome proliferator-activated receptor-gamma ligands inhibit alpha5 integrin gene transcription in non-small cell lung carcinoma cells. Am J Respir Cell Mol Biol, 32, 350-359.
Hanjalic-Beck, A., Gabriel, B., Schaefer, W., Zahradnik, H.-P., Schories, M., Tempfer, C., & Denschla, D. (2010). Metformin versus acarbose therapy in patients with polycystic ovary syndrome (PCOS): a prospective randomised double-blind study. Gynecological Endocrinology, 26(9), 69-697.
Harris, B. (2011). Thiazolidinedione Retrieved 11/27, 2011, from http://en. wikipedia.org/wiki/Thiazolidinedione.
Hassan, M. M., Curley, S. A., Li, D., Kaseb, A., Davila, M., Abdalla, E. K., & Vauthey, J. N. (2010). Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. [Research Support, N.I.H., Extramural]. Cancer, 116(8), 1938-1946. doi: 10.1002/cncr.24982.
Inzucchi, S. E. (2002). Oral antihyperglycemic therapy for type 2 diabetes. JAMA, 287(2), 360-372.
James, D. L., Ferrara, A., Peng, T., Hedderson, M., B. Bilker, W., Charles P. Quesenberry, J., & Strom, B. L. (2011). Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone Interim report of a longitudinal cohort study. Diabetes Care 34, 916-922.
Jarrar, M. H., & Baranova, A. (2007). PPARgamma activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGFbeta signalling. J Cell Mol Med, 11, 71-87.
King, H., Aubert, R. E., & Herman, W. H. (1998). Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care, 21, 1414–1431.
Koro, C., Barrett, S., & Qizilbash, N. (2007). Cancer risks in thiazolidinedione users compared to other anti-diabetic agents. [Comparative Study Research Support, Non-U.S. Gov''t]. Pharmacoepidemiol Drug Saf, 16(5), 485-492. doi: 10.1002/pds.1352.
Krone, C., & Ely, J. (2005). Controlling hyperglycemia as an adjunct to cancer therapy. Integr Cancer Ther, 4, 25-31.
Lai, S.-W., Liao, K.-F., Chen, P.-C., Tsai, P.-Y., Hsieh, D. P. H., & Chen, C.-C. (2011). Antidiabetes Drugs Correlate With Decreased Risk of Lung Cancer: A Population-Based Observation in Taiwan. Clinical Lung Cancer. doi: doi:10.1016/j.cllc.2011.10.002.
Larsson, S. C., Mantzoros, C. S., & Wolk, A. (2007). Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer, 121(4), 856-862.
Larsson, S. C., Orsini, N., & Wolk, A. (2005). Diabetes Mellitus and Risk of Colorectal Cancer: A Meta-Analysis. J Natl Cancer Inst 97, 1679-1687.
Le, M. L., Wilkens, L. R., & Kolonel, L. N. (1997). Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Res., 57, 4787-4794.
Lee-Feldstein, A., Anton-Culver, H., & Feldstein, P. J. (1994). Treatment differences and other prognostic factors related to breast cancer survival: Delivery systems and medical outcomes. Journal of the American Medical Association, 271(15), 1163-1168.
Lee, M. Y., Lina, K., Hsiaoa, P. J., & Shina, S. J. (2011). The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients. Metabolism in press.
Liao, K. F., Lai, S. W., Li, C. L., & Chen, W. C. (2011). Diabetes Mellitus Correlates With Increased Risk of Pancreatic Cancer: A Population-based Cohort Study in Taiwan. Journal of Gastroenterology and Hepatology.
Lyles, B. E., Akinyeke, T. O., Moss, P. E., & Stewart, L. V. (2009). Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARgamma-dependent and PPARgamma- independent pathways. Cell Cycle, 8(2), 268 - 277.
Ma, J., Li, H., & Giovannucci, E. (2008). Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer:a long-term survival analysis. Lancet Oncol, 9, 137-1047.
Monami, M., Lamanna, C., Balzi, D., Marchionni, N., & Mannucci, E. (2009). Sulphonylureas and cancer: a case-control study. [Research Support, Non-U.S. Gov''t]. Acta Diabetol, 46(4), 279-284. doi: 10.1007/s00592-008-0083-2.
Narayan, K. M., Boyle, J. P., Thompson , T. J., Sorensen, S. W., & Williamson, D. F. (2003). Lifetime risk for diabetes mellitus in the United States. JAMA, 290(14), 1884-1890.
Nathan, D. M., Buse, J. B., & Davidson, M. B. (2009). Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia, 52, 17-30.
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B. (2009). Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care,32, 193-203.
NICE. (2010). Type 2 diabetes: the management of type 2 diabetes (partially updated by CG87) from http://www.nice.org.uk/CG87.
Nicolucci, A. (2010). Epidemiological aspects of neoplasms in diabetes. Acta Diabetol Lat, 47, 87–95.
Nwankwo, J. O., & Robbins, M. E. (2001). Peroxisome proliferator-activated receptor- gamma expression in human malignant and normal brain, breast and prostate-derived cells. Prostaglandins Leukot Essent Fatty Acids, 64, 241-245.
Papanas, N., Maltezos, E., & Mikhailidis, D. P. (2009). Metformin: diamonds are forever. Expert Opin Pharmacother, 10, 2395-2397.
Piccinni, C., Domenico, M., Giulio, M., & Elisabetta, P. (2011). Assessing the Association of Pioglitazone Use and Bladder Cancer Through Drug Adverse Event Reporting. Diabetes Care, 34, 1369-1371.
Pollak, M. (2009). Energy metabolism, cancer risk, and cancer prevention. Recent Results Cancer Res, 181, 51-54.
Psarakis, H. M. (2006). Clinical Challenges in Caring for Patients With Diabetes and Cancer. Diabetes Spectrum 19(3), 157-162.
Ramos-Nino, M. E., Maclean, C. D., & Littenberg, B. (2007). Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System. [Research Support, N.I.H., Extramural]. BMC Med, 5, 17. doi: 10.1186/1741-7015-5-17.
Sato, H., Ishihara, S., Kawashima, K., Moriyama, N., Suetsugu, H., Kazumori, H., & Kinoshita, Y. (2000). Expression of peroxisome proliferator-activated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists. British Journal of cancer Epidemiol Biomarkers Prev, 83, 1394-1400.
Smith, D. W. (1996). Cancer mortality at very old age. Cancer Causes and Control, 77, 1367-1372.
Somon, D., & Balkau, B. (2010). Diabetes mellitus, hyperglycaemia and cancer. Diabetes & metabolism, 36(3), 182-191.
Stattin, P., Björ, O., Ferrari, P., Lukanova, A., Lenner, P., Lindahl, B., & Kaaks, R. (2007). Prospective Study of Hyperglycemia and Cancer Risk. Diabetes Care 30, 561-567.
Stocks, T., Rapp, K., Bjørge, T., Manjer, J., Ulmer, H., Selmer, R., & Stattin, P. (2009). Blood Glucose and Risk of Incident and Fatal Cancer in the Metabolic Syndrome and Cancer Project (Me-Can): Analysis of Six Prospective Cohorts. PLoS Medicine, 6(2), e1000201.
Suh, N., Wang, Y., Williams, C., R, R., Gilmer, T., Willson, T., & Sporn, M. (1999). A new ligand for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), GW7845, inhibits rat mammary carcinogenesis. Cancer Res, 59, 5671-5673.
Svacina, S. (2011). Is there any relation between diabetes therapy and cancer risk? Vnitr Lek, 57(9), 760-763.
Tolman, K. G., Fonseca, V., Dalpiaz, A., & Tan, M. H. (2007). Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease. DIABETES CARE, 30(3), 734-743.
Tseng, C. H. (2011). Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. [Research Support, Non-U.S. Gov''t]. Diabetologia, 54(8), 2009-2015. doi: 10.1007/s00125-011-2171-z
Tsubouchi, Y., Sano, H., Kawahito, Y., Mukai, S., Yamada, R., Kohno, M., & Kondo, M. (2000). Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis. . Biochem Biophys Res Commun, 270, 400-405.
Vigneri, P., Frasca, F., & Sciacca, L. (2009). Diabetes and cancer. Endocr Relat Cancer, 16, 1103-1123.
Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., & Vigneri, R. (2009). Diabetes and cancer. Endocrine-Related Cancer, 16, 1103-1123.
Wang, F., Herrington, M., Larsson, J., & Permert, J. (1995). Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. Molecular Cancer, 2, 1-5.
Wideroff, L., Gridley, G., Mellemkjaer, L., Chow, W., Linet, M., Keehn, S., & Olsen, J. H. (1997). Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst, 89, 1360-1365.
Zumkeller, W. (2001). IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour growth? J Clin Pathol: Mol Pathol, 54, 285-288.
 
【中文文獻】
丁彥伶(2009)，健保藥費慢性病及重大傷病占最大宗熱門話題健保費都用到哪裡了？，全民健康保險雙月刊，14-17。
中央健康保險局(2005)，糖尿病專業醫療服務品質報告，Retrieved from http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=7&webdata_id=848。
行政院衛生署(2002)，91年國人主要死因資料，Retrieved from http://www.doh.gov.tw/statistic/index.htm。
行政院衛生署(2011)，藥品許可證查詢，Retrieved from http://www.nhi.gov.tw/webdate/webdate.asp?menu=1&menu_id=7&webdate_id=848。
行政院衛生署統計室(2010)，99年主要死因分析，Retrieved from http://www.doh.gov.tw/CHT2006/DM/DM2_2.aspx?now_fod_list_no=11962&class_no=440&level_no=4。
李彩蓮(2011)，藥品安全性比有效性更重要，藥師週刊，1729期，第3版。
林世崇(2010)，糖尿病治療的新策略，台灣醫界，53(9)，458-465。
章殷超、溫在弘、賴美淑(2009)，利用地理資訊系統探討肝癌病患就醫地理可近性與醫院選擇間之相關性，台灣衛誌，28(6)，517-529。
陳建仁、陳國東(1997)，非胰島素依賴型糖尿病盛行率與危險因子，中華衛誌，16(4)，291-308。
謝博生(2006)，第二型糖尿病病人使用胰島素增敏劑Thiazolidinediones藥物之爭議，台灣醫學，10(1)，98-104。