第二型糖尿病患者嚴重低血糖與癌症的探討

研究目的：目前已經知道第二型糖尿病與癌症有關，可能機轉包括高胰島素血症、高血糖、炎症反應、降血糖藥物。低血糖亦會造成發炎反應，但這種發炎反應，是否和癌症的生成有關，目前未知。本研究探討第二型糖尿病病人嚴重低血糖併發症與將來發生癌症是否有關係，並分析第二型糖尿病患者將來發生癌症的危險因子。研究方法及資料：使用全民健康保險研究資料庫的糖尿病人抽樣歸人檔進行13年(西元1999至2011年)的回溯性世代研究，共有116577個新診斷的第二型糖尿病患者。排除小於18歲以及先前已罹患癌症的患者，得到研究族群110999人，依是否曾經併發嚴重低血糖將研究族群分成兩組，比較此兩組在人口學變項、降血糖藥物、共病症方面的差異。接著將兩組進行1:2傾向分數配對(PSM: propensity score matching)，使兩組在人口學變項、降血糖藥物、共病症的差異減小後，再分析兩組13年的癌症罹患機率有無差別。最後，分析嚴重低血糖、各種人口學變項、降血糖藥物、共病症是否為第二型糖尿病患者罹患癌症的獨立危險因子。研究結果：嚴重低血糖者有4963人，為所有研究族群110999人的4.47%。年紀大者、女性、月收入及都市化程度較低者，嚴重低血糖的比率較大。曾經發生嚴重低血糖的組別，有較多的心血管疾病、慢性肺疾病、高血脂症、腎臟疾病、精神疾病，各種降血糖藥物使用的比率也較高。然而，未曾發生嚴重低血糖的組別卻有較高比率的慢性肝疾病。將嚴重低血糖組與非嚴重低血糖組進行1:2傾向分數配對，以Kaplan-Meier方法預估兩組13年的罹癌函數，嚴重低血糖組得到癌症的機率較高(Log-Rank test, p<0.001)。以Cox比例風險模式(cox proportional hazard model)來分析第二型糖尿病患者在各種變數下的罹癌風險:曾發生嚴重低血糖者相較於未發生者，其罹癌的風險為HR:1.70(95% CI:1.52-1.91, p<0.01);年齡每增加一歲，其罹癌的風險為HR:1.03(95% CI:1.02-1.03, p<0.01);男性相較於女性，其罹癌的風險為HR:1.41(95% CI:1.28-1.54, p<0.01);降血糖藥物不會增加第二型糖尿病患者罹癌的風險。結論與建議：根據我們的研究設計，嚴重低血糖是全癌的獨立危險因子，各種降血糖藥物不會使癌症的風險增加。當病人併發嚴重低血糖時，可能要注意將來潛在罹患癌症的風險。然而，嚴重低血糖與癌症的因果關係尚未確立，可能需要更多的研究來證實。

關鍵字

第二型糖尿病；嚴重低血糖；癌症

並列摘要

Objective：Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Possible mechanisms include hyperinsulinemia, hyperglycemia, inflammation, and anti-diabetic drugs. Hypoglycemia also causes inflammation. However, it is unknown whether this kind of inflammation will lead to cancer. We investigated the risk of all-site cancer in patients with type 2 diabetes with or without prior severe hypoglycemia. Methods and Materials：The study population derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1999-2011, comprised 116577 patients with newly diagnosed type 2 diabetes. After excluding patients with prior cancer, we selected subjects≧18 years old and divided them into two groups according to whether they had severe hypoglycemia(total study population: 110999 patients). We compared the differences between groups in demographic data, anti-diabetic drugs, and comorbidity. We designed a 13-year retrospective cohort study consisting of severe hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without severe hypoglycemia. We investigated the relationships of severe hypoglycemia with all-site cancer and try to find independent risk factors for all-site cancer in patients with type 2 diabetes. Results：There were 4963 patients(4.47%) with severe hypoglycemia among the total study population(110999 patients). Patients with severe hypoglycemia were older and had a higher percentage of female gender, lower monthly income, lower urbanization, cardiovascular disease, chronic lung disease, hyperlipidemia, renal disease, mental disorder, and anti-diabetic drugs prescription. However, patients without severe hypoglycemia had a higher percentage of chronic liver disease. During the 13-year retrospective cohort study(with and without sever hypoglycemia:1:2), Kaplan-Meier survival analysis of cumulative incidence of cancer showed patients with severe hypoglycemia had a higher risk of developing cancer(Log-Rank test, p<0.001). Results of Cox proportional hazard models revealed that severe hypoglycemia (HR:1.70, 95% CI:1.52-1.91, p<0.01), older age (HR:1.03 per 1 year, 95% CI:1.02-1.03, p<0.01), male gender (HR:1.41, 95% CI:1.28-1.54, p<0.01) were independent risk factors of all-site cancer. Anti-diabetic drugs would not increase the risk of cancer. Conclusion and Suggestion：According to our study design, severe hypoglycemia is an independent risk factor of all-site cancer. Anti-diabetic drugs would not increase the risk of cancer. More attention may be needed for patients with type 2 diabetes suffering from severe hypoglycemia. The influence of severe hypoglycemia on cancer warrants further investigation.

並列關鍵字

type 2 diabetes ； severe hypoglycemia ； cancer

參考文獻

1. IDF Diabetes Atlas 6th edition. 2013 ed. http://www.idf.org/diabetesatlas, International Diabetes Federation, 2013

2. Jiang Y-D, Chang C-H, Tai T-Y, Chen J-F, Chuang L-M: Incidence and prevalence rates of diabetes mellitus in Taiwan: Analysis of the 2000–2009 Nationwide Health Insurance database. Journal of the Formosan Medical Association = Taiwan yi zhi 2012;111:599-604

3. Li H-Y, Jiang Y-D, Chang C-H, Chung C-H, Lin BJ, Chuang L-M: Mortality trends in patients with diabetes in Taiwan: A nationwide survey in 2000–2009. Journal of the Formosan Medical Association = Taiwan yi zhi 2012;111:645-650

7. Cryer PE, Davis SN, Shamoon H: Hypoglycemia in diabetes. Diabetes care 2003;26:1902-1912

9. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R: Diabetes and cancer. Endocrine-related cancer 2009;16:1103-1123

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第二型糖尿病患者嚴重低血糖與癌症的探討

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