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| 研究生： |
呂瑾立 Lu, Chin-Li |
|---|---|
| 論文名稱： |
第一型糖尿病之流行病學特徵以及嚴重低血糖併發症對罹患心血管疾病風險及全死因死亡率的影響 Epidemiological Characteristics and The Effect of Severe Hypoglycemia on the Risks of Cardiovascular Disease and All-cause Mortality in Patients with Type 1 Diabetes Mellitus |
| 指導教授： |
李中一
Li, Chung-Yi |
| 學位類別： |
博士 Doctor |
| 系所名稱： |
醫學院 - 公共衛生學系 Department of Public Health |
| 論文出版年： | 2016 |
| 畢業學年度： | 104 |
| 語文別： | 英文 |
| 論文頁數： | 96 |
| 中文關鍵詞： | 第一型糖尿病 、發生率 、嚴重低血糖 、心血管疾病 、全死因死亡率 、流行病學 |
| 外文關鍵詞： | Type 1 diabetes, Incidence, Severe hypoglycemia, Cardiovascular disease, All-cause mortality |
| 相關次數： | 點閱：92 下載：13 |
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過去一、二十年，第一型糖尿病的發生率在大部分西方國家都呈現快速增加的趨勢。「衛生假說」是當前解釋第一型糖尿病發生率變化的重要假說之一。雖然大部分第一型糖尿病都在病人年紀很輕的時候被診斷出來，但是有關亞洲國家兒童的第一型糖尿病及其重要的併發症「嚴重低血糖事件」的發生率，卻鮮少有文獻報告過。嚴重低血糖是血糖控制過程中一個主要的絆腳石。嚴重低血糖的發生是否對於後續的全死因死亡率或心血管疾病的發生率有長期的負面影響？其影響是否呈現劑量效應關係？仍然沒有定論。
本研究有關歷年兒童第一型糖尿病發生率的報告，是從2003到2008年的台灣健保資料庫中擷取而得。我們從重大傷病檔中取得因第一型糖尿病而被登錄重大傷病名單的新診斷個案資料，輔以內政部人口統計資料，計算出兒童第一型糖尿病的發生率和臨床特性。並且透過生態研究設計，檢驗了第一型糖尿病與居住地區兒童人口密度和都市化程度的相關性。此外，我們針對2003年到2011年的第一型糖尿病盛行病例世代，透過平均6.2年的追蹤時期，我們在卜瓦松分布的前提下，估計了這些病患嚴重低血糖的發生率和發生頻率，並探討了其可能的危險因子。我們更進一步的探討嚴重低血糖的發生對於全死因死亡率和心血管疾病發生率的影響。我們在巢式病例對照研究的設計中，採用發生機率密度取樣的配對法，探討在死亡或發生心血管疾病的一年前、一到三年前或三到五年前有無經歷過嚴重低血糖事件，以及事件發生前五年內累計的嚴重低血糖發生次數，與全死因死亡率和心血管疾病發生率的相關性及劑量效應關係。我們另外並建立了兩個世代追蹤研究，一個採用固定時間區間的嚴重低血糖暴露資料；一個則將嚴重低血糖視為時間相依變項，採用不同時間重覆測量的嚴重低血糖暴露資料。在上述所有三種研究設計中，嚴重低血糖事件與全死因死亡率和心血管疾病發生率的相關性估計，都調整了初次診斷年齡、性別、社會經濟因素、以及糖尿病嚴重度指標的干擾效應。
本研究發現，2003到2008年間，台灣兒童第一型糖尿病發生率為每十萬人5.3人。較高的發生率與女性、年紀較長、以及居住在兒童人口密度較低的地區有關。糖尿病酮酸毒血症仍然是這類病人住院的主要診斷之一。嚴重低血糖的發生率為每100個人年發生2.80人次或6.03個事件。較高的嚴重低血糖發生率與女性、較長的年紀、以及較低的健保月投保薪資有關。另外，根據巢式病例對照研究的結果，全死因死亡率與死亡前1年內、1-3年內、3-5年內曾經發生嚴重低血糖事件顯著相關，但是心血管疾病發生率則只有跟發病前一年曾經發生嚴重低血糖事件顯著相關。發病或死亡前五年累計的嚴重低血糖發生次數越高，全死因死亡率及心血管疾病發生率越高。從另外兩個世代追蹤研究的結果看來，嚴重低血糖的發生與短期及長期內的全死因死亡率都顯著相關。不過，只有當我們把嚴重低血糖當作時間相依變數的研究下，嚴重低血糖依然與短期及長期內的全死因死亡率都顯著相關，而在只採用固定時間測量嚴重低血糖狀態的研究中，嚴重低血糖只與第3-4年追蹤期間的心血管疾病發生率顯著相關。
總結來說，台灣的兒童第一型糖尿病發生率與西方國家比起來相對較低。女性、初次診斷的年齡較大、以及收入較低，與較高的嚴重低血糖發生率有關。曾經發生嚴重低血糖與短期或長期內發生全死因死亡率的風險有關，與短期內發生心血管疾病的風險有關。嚴重低血糖事件累計發生次數越多，全死因死亡率和心血管疾病發生率越高。臨床醫療人員與第一型糖尿病病患在進行血糖控制時，應多費心預防嚴重低血糖事件的發生率。
The incidence rate of Type 1 diabetes (T1DM) increased rapidly in most Western countries during last decades. Hygiene hypothesis is one of the major hypotheses explaining the variation of incidence rate. Most T1DM is diagnosed at young age, but the population incidence of childhood T1DM and the major complication, severe hypoglycemia, were rarely reported in Asian. Severe hypoglycemia is the major obstacle in glycemic controls. Whether there is a long-term association and a dose-gradient relationship between severe hypoglycemia and subsequent risks of all-cause mortality and cardiovascular disease (CVD) incidence is still inconclusive.
We retrieved our data from Taiwan’s National Health Insurance Research Database (NHIRD) from 2003 to 2008 to report annual incidence rate of childhood T1DM. By counting the newly-diagnosed T1DM registered in the list of Catastrophic Illness Database in NHIRD and using the population statistics from Taiwan’s government, we reported the incidence rate and clinical features of childhood T1DM, and examined the association of the incidence rate of T1DM with child-population density and urbanization level of living areas in an ecological study. Besides, a T1DM cohort was followed from 2003 to 2011, with a mean follow-up period of 6.2 years, to estimate the incidence rate and frequency of severe hypoglycemia under the assumption of Poisson distribution. The possible risk factors for the incidence of severe hypoglycemia in T1DM cases were examined. Furthermore, by taking all-cause mortality and cardiovascular disease (CVD) incidence as separate outcomes, we employed incidence density sampling matching method to conduct two nested case-control studies, in which the exposure status of severe hypoglycemia in three time-windows (1-year, 1-3 years, and 3-5 years) prior to the two adverse outcomes were determined and associated with the risks of all-cause mortality and CVD incidence. The dose-gradient effect of severe hypoglycemia within 5 years was also investigated. In addition, we also conducted two cohort studies, one with a fixed-time exposure status of severe hypoglycemia, and the other one with time-dependent exposure status of severe hypoglycemia. The independent effect of severe hypoglycemia on all-cause mortality and CVD incidence were assessed in the three aforementioned three studies, with adjustment or matched for age at first diagnosis, sex, socioeconomic factors, and severity of diabetes.
The childhood incidence rate was 5.3 per 105 persons in Taiwan from 2003 to 2008. An increased incidence rate of T1DM was associated with female sex, older age, and lived in the areas with lowest child-population density. Diabetic ketoacidosis was still the most important cause for hospitalization. The incidence rate of severe hypoglycemia in T1DM was 2.80 persons per100 person-years (PYs) and 6.03 episodes per 100 PYs. An increased incidence rate of severe hypoglycemia was associated with female sex, older age, and lower monthly-income based insurance premium. Moreover, according to results of the nested case-control design, the risk of all-cause mortality was associated with history of severe hypoglycemia occurred in 1-year, 1-3 years, and 3-5 years prior to death, but the risk of CVD incidence was only associated with history of severe hypoglycemia occurred in the previous year. A higher frequency of severe hypoglycemia occurred within 5 years was associated with a higher risk of all-cause mortality and CVD incidence. The prior history of severe hypoglycemia was associated with both short-term and long-term risks of all-cause mortality in the two cohort studies. On the other hand, severe hypoglycemia was found to be associated with CVD incidence in the cohort study with time-dependent exposure status of severe hypoglycemia, but only significantly associated with the risk of CVD incidence in 3-4 year of follow-up in the cohort design with fixed-time exposure status of severe hypoglycemia.
In conclusion, the incidence rate of childhood T1DM in Taiwan was relatively low compared to most Western countries. Among patients with T1DM, female sex, older age of first diagnosis, and lower income level were associated with an increased risk of severe hypoglycemia. Prior history of severe hypoglycemia was associated with both short-term and long-term risk of all-cause mortality and short-term adverse effect on CVD incidence. Higher frequency of severe hypoglycemia attack was associated with elevated risks of all-cause mortality and CVD incidence. Clinicians and patients with T1DM should put emphasis on the prevention of severe hypoglycemia while managing glycemic control.
1. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. The Lancet. 2014;383(9911):69-82.
2. Group DP. Incidence and trends of childhood Type 1 diabetes worldwide 1990-1999. Diabet. Med. 2006;23(8):857-866.
3. Kawasaki E, Matsuura N, Eguchi K. Type 1 diabetes in Japan. Diabetologia. 2006;49(5):828-836.
4. Li XH, Li TL, Yang Z, et al. A nine-year prospective study on the incidence of childhood type 1 diabetes mellitus in China. Biomed. Environ. Sci. 2000;13(4):263-270.
5. Huen KF, Low LC, Wong GW, et al. Epidemiology of diabetes mellitus in children in Hong Kong: the Hong Kong childhood diabetes register. J. Pediatr. Endocrinol. Metab. 2000;13(3):297-302.
6. Panamonta O, Laopaiboon M, Tuchinda C. Incidence of childhood type 1 (insulin dependent) diabetes mellitus in northeastern Thailand. J. Med. Assoc. Thai. 2000;83(8):821-824.
7. Lee WW, Ooi BC, Thai AC, et al. The incidence of IDDM in Singapore children. Singapore Med. J. 1998;39(8):359-362.
8. Lin WH, Wang MC, Wang WM, et al. Incidence of and mortality from Type I diabetes in Taiwan from 1999 through 2010: a nationwide cohort study. PLoS One. 2014;9(1):e86172.
9. Jiang YD, Chang CH, Tai TY, Chen JF, Chuang LM. Incidence and prevalence rates of diabetes mellitus in Taiwan: analysis of the 2000-2009 Nationwide Health Insurance database. J. Formos. Med. Assoc. 2012;111(11):599-604.
10. Variation and trends in incidence of childhood diabetes in Europe. EURODIAB ACE Study Group. Lancet. 2000;355(9207):873-876.
11. Gardner SG, Bingley PJ, Sawtell PA, Weeks S, Gale EA. Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis. The Bart's-Oxford Study Group. BMJ. 1997;315(7110):713-717.
12. Writing Group for the DERG, Orchard TJ, Nathan DM, et al. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA. 2015;313(1):45-53.
13. Lind M, Svensson A-M, Kosiborod M, et al. Glycemic control and excess mortality in type 1 diabetes. N. Engl. J. Med. 2014;371(21):1972-1982.
14. Miller RG, Secrest AM, Sharma RK, Songer TJ, Orchard TJ. Improvements in the life expectancy of type 1 diabetes the Pittsburgh Epidemiology of Diabetes Complications Study Cohort. Diabetes. 2012;61(11):2987-2992.
15. Secrest AM, Becker DJ, Kelsey SF, LaPorte RE, Orchard TJ. All-Cause Mortality Trends in a Large Population-Based Cohort With Long-Standing Childhood-Onset Type 1 Diabetes: The Allegheny County Type 1 Diabetes Registry. Diabetes Care. 2010;33(12):2573-2579.
16. Arias E. United States Life Tables, 2011. National Vital Statistics Reports. Vol 64: U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES; 2015.
17. Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin. Exp. Immunol. 2010;160(1):1-9.
18. Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science. 2002;296(5567):490-494.
19. Parslow RC, McKinney PA, Law GR, Bodansky HJ. Population mixing and childhood diabetes. Int. J. Epidemiol. 2001;30(3):533-538; discussion 538-539.
20. Miller LJ, Pearce J, Barnett R, Willis JA, Darlow BA, Scott RS. Is population mixing associated with childhood type 1 diabetes in Canterbury, New Zealand? Soc. Sci. Med. 2009;68(4):625-630.
21. Rytkonen M, Moltchanova E, Ranta J, et al. The incidence of type 1 diabetes among children in Finland--rural-urban difference. Health Place. 2003;9(4):315-325.
22. Bruno G, Spadea T, Picariello R, et al. Early life socioeconomic indicators and risk of type 1 diabetes in children and young adults. J. Pediatr. 2013;162(3):600-605 e601.
23. Kaila B, Taback SP. The effect of day care exposure on the risk of developing type 1 diabetes: a meta-analysis of case-control studies. Diabetes Care. 2001;24(8):1353-1358.
24. Holmqvist BM, Lofman O, Samuelsson U. A low incidence of Type 1 diabetes between 1977 and 2001 in south-eastern Sweden in areas with high population density and which are more deprived. Diabet. Med. 2008;25(3):255-260.
25. Rewers A, Chase H, Mackenzie T, et al. PRedictors of acute complications in children with type 1 diabetes. JAMA. 2002;287(19):2511-2518.
26. Daneman D. Type 1 diabetes. The Lancet. 2006;367(9513):847-858.
27. Giorda CB, Ozzello A, Gentile S, et al. Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study. Acta Diabetol. 2015:1-9.
28. Donnelly LA, Morris AD, Frier BM, et al. Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study. Diabet. Med. 2005;22(6):749-755.
29. Pedersen-Bjergaard U, Pramming S, Heller SR, et al. Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection. Diabetes Metab. Res. Rev. 2004;20(6):479-486.
30. Leese GP, Wang J, Broomhall J, et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Diabetes Care. 2003;26(4):1176-1180.
31. Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44 Suppl 2:S14-21.
32. Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann. Intern. Med. 2004;141(6):421-431.
33. Stettler C, Allemann S, Jüni P, et al. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: Meta-analysis of randomized trials. Am. Heart J. 2006;152(1):27-38.
34. Goff DC, Jr., Gerstein HC, Ginsberg HN, et al. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am. J. Cardiol. 2007;99(12A):4i-20i.
35. Wright RJ, Frier BM. Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab. Res. Rev. 2008;24(5):353-363.
36. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. Ophthalmology. 1995;102(4):647-661.
37. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N. Engl. J. Med. 2000;342(6):381-389.
38. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 2005;353(25):2643-2653.
39. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N. Engl. J. Med. 1993;329(14):977-986.
40. Writing Team for the Diabetes C, Complications Trial/Epidemiology of Diabetes I, Complications Research G. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA. 2003;290(16):2159-2167.
41. Group AC, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2008;358(24):2560-2572.
42. Duckworth W, Abraira C, Moritz T, et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. N. Engl. J. Med. 2009;360(2):129-139.
43. Allen C, LeCaire T, Palta M, Daniels K, Meredith M, D’Alessio DJ. Risk factors for frequent and severe hypoglycemia in type 1 diabetes. Diabetes Care. 2001;24(11):1878-1881.
44. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J. Am. Coll. Cardiol. 2009;53(3):298-304.
45. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36(5):1384-1395.
46. Frier BM. Defining hypoglycaemia: what level has clinical relevance? Diabetologia. 2009;52(1):31-34.
47. American Diabetes A. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37 Suppl 1:S14-80.
48. Cryer PE. Severe hypoglycemia predicts mortality in diabetes. Diabetes Care. 2012;35(9):1814-1816.
49. Amiel SA, Dixon T, Mann R, Jameson K. Hypoglycaemia in Type 2 diabetes. Diabet. Med. 2008;25(3):245-254.
50. Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N. Engl. J. Med. 2013;369(4):362-372.
51. Fredheim S, Johansen A, Thorsen S, et al. Nationwide reduction in the frequency of severe hypoglycemia by half. Acta Diabetol. 2014;52(3):591-599.
52. Control D, Group CTR. Hypoglycemia in the diabetes control and complications trial. Diabetes. 1997;46(2):271-286.
53. Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group. Am. J. Med. 1991;90(4):450-459.
54. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853.
55. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 2009;360(2):129-139.
56. Genuth SM, Backlund JY, Bayless M, et al. Effects of prior intensive versus conventional therapy and history of glycemia on cardiac function in type 1 diabetes in the DCCT/EDIC. Diabetes. 2013;62(10):3561-3569.
57. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:b4909.
58. Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N. Engl. J. Med. 2010;363(15):1410-1418.
59. Hsu PF, Sung SH, Cheng HM, et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care. 2013;36(4):894-900.
60. Khunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care. 2015;38(2):316-322.
61. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012;35(9):1897-1901.
62. Goto A, Arah OA, Goto M, Terauchi Y, Noda M. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ. 2013;347.
63. Group UKHS. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007;50(6):1140-1147.
64. Gruden G, Barutta F, Chaturvedi N, et al. Severe hypoglycemia and cardiovascular disease incidence in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetes Care. 2012;35(7):1598-1604.
65. Gimenez M, Lopez JJ, Castell C, Conget I. Hypoglycaemia and cardiovascular disease in Type 1 Diabetes. Results from the Catalan National Public Health registry on insulin pump therapy. Diabetes Res. Clin. Pract. 2012;96(2):e23-25.
66. Fahrmann ER, Adkins L, Loader CJ, et al. Severe hypoglycemia and coronary artery calcification during the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study. Diabetes Res. Clin. Pract. 2015;107(2):280-289.
67. Seaquist ER, Miller ME, Bonds DE, et al. The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study. Diabetes Care. 2012;35(2):409-414.
68. Giménez M, Gilabert R, Monteagudo J, et al. Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with type 1 diabetes. Diabetes Care. 2011;34(1):198-203.
69. Fährmann ER, Adkins L, Loader CJ, et al. Severe hypoglycemia and coronary artery calcification during the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study. Diabetes Res. Clin. Pract. 2015;107(2):280-289.
70. Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care. 2011;34 Suppl 2(Supplement 2):S132-137.
71. Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care. 2010;33(6):1389-1394.
72. Bedenis R, Price AH, Robertson CM, et al. Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the Edinburgh Type 2 Diabetes Study. Diabetes Care. 2014;37(12):3301-3308.
73. Yakubovich N, Gerstein HC. Serious cardiovascular outcomes in diabetes: the role of hypoglycemia. Circulation. 2011;123(3):342-348.
74. Boucai L, Southern WN, Zonszein J. Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities. Am. J. Med. 2011;124(11):1028-1035.
75. Lu JF, Hsiao WC. Does universal health insurance make health care unaffordable? Lessons from Taiwan. Health Aff. (Millwood). 2003;22(3):77-88.
76. Cheng TM. Taiwan's new national health insurance program: genesis and experience so far. Health Aff. (Millwood). 2003;22(3):61-76.
77. Lu CL, Shen HN, Chen HF, Li CY. Epidemiology of childhood Type 1 diabetes in Taiwan, 2003 to 2008. Diabet. Med. 2014;31(6):666-673.
78. Liu CY, Hung, Y.T., Chuang, T.L., Chen, Y.J., Weng, W.S., Liu, J.S., Liang, K.Y. Incorporating Development Stratification of Taiwan Townships into Sampling Design of Large Scale Health Interview Survey. Journal of Health Management. 2006;4(1):1-22.
79. Ginde AA, Blanc PG, Lieberman RM, Camargo CA, Jr. Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr. Disord. 2008;8(1):4.
80. Young BA, Lin E, Von Korff M, et al. Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am. J. Manag. Care. 2008;14(1):15-23.
81. Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care. 2000;23(10):1516-1526.
82. Harron KL, McKinney PA, Feltbower RG, et al. Incidence rate trends in childhood type 1 diabetes in Yorkshire, UK 1978-2007: effects of deprivation and age at diagnosis in the South Asian and non-South Asian populations. Diabet. Med. 2011;28(12):1508-1513.
83. Schober E, Rami B, Waldhoer T, Austrian Diabetes Incidence Study G. Steep increase of incidence of childhood diabetes since 1999 in Austria. Time trend analysis 1979-2005. A nationwide study. Eur. J. Pediatr. 2008;167(3):293-297.
84. Karvonen M, Pitkaniemi M, Pitkaniemi J, Kohtamaki K, Tajima N, Tuomilehto J. Sex difference in the incidence of insulin-dependent diabetes mellitus: an analysis of the recent epidemiological data. World Health Organization DIAMOND Project Group. Diabetes Metab. Rev. 1997;13(4):275-291.
85. Svensson J, Carstensen B, Mortensen HB, Borch-Johnsen K, Danish Study Group of Diabetes in C. Gender-associated differences in Type 1 diabetes risk factors? Diabetologia. 2003;46(3):442-443.
86. Angus VC, Waugh N. Hospital admission patterns subsequent to diagnosis of type 1 diabetes in children : a systematic review. BMC Health Serv. Res. 2007;7:199.
87. Peery AI, Engelke MK, Swanson MS. Parent and teacher perceptions of the impact of school nurse interventions on children's self-management of diabetes. J. Sch. Nurs. 2012;28(4):268-274.
88. McKinney PA, Okasha M, Parslow RC, et al. Early social mixing and childhood Type 1 diabetes mellitus: a case-control study in Yorkshire, UK. Diabet. Med. 2000;17(3):236-242.
89. Fear NT, McKinney PA, Patterson CC, Parslow RC, Bodansky HJ. Childhood Type 1 diabetes mellitus and parental occupations involving social mixing and infectious contacts: two population-based case-control studies. Diabet. Med. 1999;16(12):1025-1029.
90. Staines A, Bodansky HJ, McKinney PA, et al. Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density. Int. J. Epidemiol. 1997;26(6):1307-1313.
91. Miller LJ, Willis JA, Pearce J, Barnett R, Darlow BA, Scott RS. Urban-rural variation in childhood type 1 diabetes incidence in Canterbury, New Zealand, 1980-2004. Health Place. 2011;17(1):248-256.
92. Gimenez M, Conget I. Comment on: Gruden et al. Severe hypoglycemia and cardiovascular disease incidence in type 1 diabetes: the EURODIAB prospective complications study. Diabetes Care 2012;35:1598-1604. Diabetes Care. 2012;35(12):e88; author reply e89.
93. Bolli GB. Hypoglycaemia unawareness. Diabetes Metab. 1997;23 Suppl 3:29-35.
94. Gold AE, MacLeod KM, Frier BM. Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care. 1994;17(7):697-703.
95. Wright RJ, Newby DE, Stirling D, Ludlam CA, Macdonald IA, Frier BM. Effects of acute insulin-induced hypoglycemia on indices of inflammation: putative mechanism for aggravating vascular disease in diabetes. Diabetes Care. 2010;33(7):1591-1597.
96. Joy NG, Hedrington MS, Briscoe VJ, Tate DB, Ertl AC, Davis SN. Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals. Diabetes Care. 2010;33(7):1529-1535.
97. Zhou Z. Survival Bias Associated with Time-to-Treatment Initiation in Drug Effectiveness Evaluation: A Comparison of Methods. Am. J. Epidemiol. 2005;162(10):1016-1023.
98. Levesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ. 2010;340(mar12 1):b5087-b5087.
99. Dekker FW, de Mutsert R, van Dijk PC, Zoccali C, Jager KJ. Survival analysis: time-dependent effects and time-varying risk factors. Kidney Int. 2008;74(8):994-997.
100. Greenland S, Thomas DC. On the need for the rare disease assumption in case-control studies. Am. J. Epidemiol. 1982;116(3):547-553.
101. Flanders WD, Louv WC. The exposure odds ratio in nested case-control studies with competing risks. Am. J. Epidemiol. 1986;124(4):684-692.
校內：2018-02-17公開校外：2018-02-17公開