Year: 2014
Type: article
Study design: Observational Study
Abstract: Diabetes and cancer are common diseases whose incidence is increasing globally, with a tremendous impact on health worldwide. In 2010, the prevalence rates of diabetes and prediabetes among individuals aged 18 years and older in China were 11.6% (113.9 million individuals) and 50.1% (439.4 million), respectively.1 Because of the rapid economic development and lifestyle change in China, as well as increased longevity,2 diabetes has become a major public health problem and cancer has become the leading cause of death in China.3 Epidemiologic evidence suggests a link between diabetes and the increased risk of many forms of cancer.4, 5 However, little is known about the detailed characterization of aspects of diabetes (onset age, diabetes duration, therapy, and degree of glycemic control) in relation to cancer risk, especially in the Chinese population, and these issues can be better addressed in well-conducted and appropriately designed prospective observational studies. In 2010, we launched a nationwide large prospective cohort study in China, namely the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study.6 The REACTION study was conducted in 25 local communities selected from 12 rural and 13 urban areas stratified according to geographic region, degree of urbanization, and economic development status. Because there is a large variation in cancer incidence between different regions of China, the sampling strategy considered the representativeness of the general population of China. In total, 284 460 eligible subjects aged 40 years and older consented to participate in the study, 260 738 (91.7%) completed a personal interview and 271 404 (95.4%) and 248 557 (87.4%) provided blood and urine sample, respectively. Altogether, 259 657 participants completed the personal interview and were enrolled in the study in 2010–11.7 Characteristics of the cohort show several important concerns. First, the study population had a high prevalence of diabetes. Based on results of glucose tolerance tests, the prevalence of diabetes and prediabetes was 20.89% (24.03% in men and 19.03% in women) and 24.98% (24.58% in men and 24.19% in women), respectively, among Chinese aged 40 years and older. However, fewer than 50% of participants with diabetes from this community-based survey were aware of this diagnosis, in accordance with findings of the 2010 general population-based survey by the China Noncommunicable Disease Surveillance Group.1 Second, the prevalence rates of obesity and overweight were 15.17% and 38.51%, respectively. A growing body of evidence suggests that obesity and weight gain are associated with increased risk of certain malignancies. Furthermore, strong associations of obesity with both insulin resistance and type 2 diabetes have been consistently demonstrated over a number of decades. The high prevalence of obesity undoubtedly has increased the incidence of diabetes, and likely that of cancers as well. Further analysis indicated that both general and abdominal obesity were associated with elevated prevalent cardiovascular diseases and will likely correlate with 10-year coronary heart disease risk, regardless of the presence or absence of insulin resistance.8 Third, the cross-sectional results from REACTION baseline survey indicated that, compared with those with normal glucose metabolism, men with diabetes had a significantly lower adjusted prevalence ratio (PR) of gastric cancer (PR 0.38; 95% confidence interval [CI] 0.16–0.89), whereas women with diabetes had significantly higher adjusted PRs of cancer of all sites (PR 1.36; 95% CI 1.20–1.56) and of cancers of the breast (PR 1.56; 95% CI 1.21–2.00), endometrium (PR 1.58; 95% CI 1.16–2.15), and thyroid (PR 1.53; 95% CI 1.03–2.27).7 The REACTION cohort benefits from several strengths: the large study population is representative of various geographical regions of China and offers adequate statistical power; it has a strong leadership and research team, with well-established infrastructure and study instrumentation; detailed risk factor data are collected by personal interview; comprehensive physical and biochemical measurements are made at baseline, including anthropometric parameters, fasting and 2-h glucose and insulin, and lipid profiles; and there is proper collection and storage of baseline blood and urine samples for future biomarker research. The study provides a platform with rich resources for investigators from different fields to examine important research questions concerning both diabetes and cancer. Using baseline cross-sectional data, the REACTION group has investigated a variety of risk factors for diabetes and other metabolic diseases. Reports thus far have shown associations of ages at menarche and at menopause with cardiovascular disease, diabetes, and osteoporosis,9 associations between sleep duration, daytime nap duration, and osteoporosis varying by sex, menopause and sleep quality,10 associations of green tea and rock tea consumption with risk of impaired fasting glucose and impaired glucose tolerance,11 and an association between serum uric acid levels and cardiovascular disease.12 Several inflammatory cytokines have been reported to be associated with the urinary albumin-to-creatinine ratio or hypertension in the Chinese population.13, 14 Using the community-based survey data, the REACTION group also established several diagnostic criteria, including HbA1c cut-off points, for the diagnosis of diabetes and prediabetes in a middle-aged and elderly Han population from northwest China,15 a Chinese risk score model for identifying postprandial hyperglycemia without an oral glucose tolerance test,16 and optimal waist circumference cut-off values for identifying metabolic risk factors in middle-aged and elderly subjects in Shandong Province of China.17 The major challenge of the study lies in the follow-up of the large cohort. Because the tumor registry system is not well established in some areas of China, verification of cancer diagnosis may be challenging for some cases. The REACTION study will shed light on the roles of hyperglycemia and hyperinsulinemia in cancer development and whether there are modifying effects of antidiabetic therapy (especially metformin and glargine) on the association of diabetes and cancer. The 3-year follow-up study began in April 2014, with results expected in late 2015. 糖尿病和恶性肿瘤已成为全球发病率逐年升高的常见疾病,并对全世界范围的人群健康产生巨大影响。2010年,年龄在18周岁及以上的中国人群的糖尿病及糖尿病前期的患病率分别为11.6%(113900000人)和50.1%(439400000人)1。随着经济的发展和生活方式的改变以及寿命的延长2,糖尿病在中国已成为一个重要的公共卫生问题,而恶性肿瘤也成为了导致中国人死亡的首要因素3。流行病学研究证据提示糖尿病与多种恶性肿瘤风险升高相关4, 5。然而,在中国人群中尚无关于糖尿病具体特征如发病年龄、病程、治疗、血糖控制水平等与恶性肿瘤风险关系的研究,这些问题可以通过良好设计并实施的前瞻性观察研究得到更好的解答。2010年我们在全国范围内进行了一项名为中国糖尿病患者恶性肿瘤风险评估纵向研究(Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal,REACTION)的大型前瞻性队列研究6。 REACTION研究在根据地理位置、城市化程度、经济发展水平进行分层后筛选出的12个乡村地区及13个城市地区进行。鉴于中国不同地区癌症发病率的显著差异,所采用的样本抽取方法考虑到了中国普通人群的代表性。最终,284460名年龄在40周岁及以上的社区居民符合标准并同意参加研究,其中260738名(91.7%)居民完成了个人问卷调查,271404名(95.4%)及248557名(87.4%)居民分别提供了血液和尿液样本。在2010至2011年间共有259657名志愿者完成了个人问卷调查并被纳入到研究中7。从队列人群的基线特征中可以看出一些关键问题。首先,研究人群具有较高的糖尿病患病率,在40周岁及以上的中国人群中,以糖耐量试验为诊断标准,糖尿病及糖尿病前期的患病率分别为20.89%(男性24.03%,女性19.03%)和24. 89%(男性24.58%,女性24.19%)。然而糖尿病知晓率却不到50%,这与2010年中国非传染性疾病监测组进行的人群普查结果相符1。第二,肥胖和超重的发生率分别是15.7%和38.51%。越来越多的证据表明,肥胖和体重增加与某些恶性肿瘤风险升高相关。另外,肥胖与胰岛素抵抗及糖尿病的密切关联在近十年来不断被证实。肥胖发生率不断升高无疑导致糖尿病及恶性肿瘤发病率的升高。本研究进一步分析显示,无论胰岛素抵抗存在与否,均匀型肥胖和中心型肥胖均与心血管疾病患病率升高相关,并可能与10年冠状动脉性心脏病风险相关8。第三,根据REACTION研究基线水平调查得出的横断面研究结果表明,校正各类混杂因素后,与糖代谢正常的人群相比,男性糖尿病患者的胃癌患病率(PR 0.38;95% CI 0.16–0.89)显著降低,而女性糖尿病患者所有的恶性肿瘤患病率(PR 1.36;95%CI 1.20–1.56)以及乳腺癌患病率(PR 1.56;95% CI 1.21–2.00)、子宫内膜癌患病率(PR 1.58;95% CI 1.16–2.15)、甲状腺癌患病率(PR 1.53;95% CI 1.03–2.27)则显著升高7。 REACTION队列研究具有如下优势:大样本人群,足以代表中国不同地区的情况并提供了足够的数据分析效能;该研究拥有强大的领导团体及研究团队,精良的基础设施和测试设备;个人问卷调查采集了具体的风险因素;在基线水平制定了详细的物理及生化指标,包括人口学参数、空腹及餐后2小时血糖和胰岛素、脂代谢水平等;恰当收集和保存了基线的血液及尿液标本以备后续对生物标记物的研究测定。该研究为各领域研究糖尿病及恶性肿瘤相关的重要问题的工作者提供了一个资源丰富的平台。通过对基线横断面数据的分析,REACTION研究组探讨了糖尿病及其他代谢性疾病的一系列危险因素。报道揭示了月经初潮及停经年龄与心血管疾病、糖尿病及骨质疏松之间的关联9,不同的性别、停经情况和睡眠质量下的睡眠时间、白天小睡时间与骨质疏松的关系10,绿茶、红茶的饮用与空腹葡萄糖调节受损及葡萄糖耐量受损的关系11,以及血清尿酸水平与心血管疾病之间的关系12。据报道一些炎症细胞因子与中国人群的尿白蛋白/肌酐比值或高血压相关13, 14。通过对社区人群数据的分析,REACTION研究组也建立了一些诊断标准,包括在中国西北地区中老年汉族人群中寻找糖化血红蛋白对糖尿病及糖尿病前期的诊断切点15,替代糖耐量试验识别中国人餐后高血糖的风险评分模型16,以及在中国山东省中老年人群中诊断代谢综合征的腰围最佳切点17。 该研究最主要的挑战是对这一大型队列研究人群的随访工作。因为肿瘤登记系统在中国某些区域的建立并不完善,所以对某些病例恶性肿瘤诊断的验证并非易事。REACTION研究将有助于阐明高血糖及高胰岛素血症在恶性肿瘤发展过程中的作用以及降糖治疗(尤其是二甲双胍和甘精胰岛素)是否对糖尿病和恶性肿瘤的关系产生影响。3年的随访研究于2014年4月开始,预计在2015年底得出结果。
Source: Journal of Diabetes
Authors: Guang Ning, Zachary Bloomgarden
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1891874652