摘要
背景
糖尿病是一种常见的慢性终身性疾病,致残率、死亡率仅次于肿瘤和心血管疾病,居第3位。随着经济的发展和生活方式的改变,糖尿病发病率逐年升高,其中95%左右为2型糖尿病(T2DM)。据世界卫生组织预测,到2025年,全球成人糖尿病患者将增至3亿,新增病例将主要集中在中国、印支次大陆及非洲等发展中国家,可见糖尿病的患病形势将持续恶化,成为严重的公共卫生问题。
2型糖尿病的特点是胰岛素抵抗伴随胰岛素相对不足,或胰岛素分泌缺陷伴有或不伴有胰岛素抵抗,表现为慢性高血糖和高胰岛素血症,主要危害是其慢性并发症,如心脏、血管、肾脏、视网膜及神经等病变。2型糖尿病是由遗传因素与环境因素共同作用于个体而导致的多因素遗传性疾病。其中环境因素的影响更为重要,糖尿病本身并不遗传,遗传的是个体对糖尿病的易感性,这种易感性须通过环境因素的作用导致个体发病。以往研究关注了年龄、吸烟和饮酒与糖尿病的关系。大量流行病学及临床资料表明,肥胖、2型糖尿病、高脂血症、高血压等常合并存在。研究表明,血压与糖尿病存在关联,血压水平与血糖水平呈正相关。同时国内外研究发现,血脂异常与2型糖尿病患病存在关联性。
近年来,随着人类基因组计划的完成和功能基因组学研究的开展,一系列T2DM的相关易感基因被发现,并引起人们的关注。相关的易感基因有：瘦素基因、血管紧张素转换酶基因、钙蛋白酶基因、白介素6基因、肿瘤坏死因子α (TNF-α)及本文中的脂联素基因和胰岛素受体基因等众多易感基因。
相关研究表明,糖尿病的患病率存在种族差异。以往研究显示彝族高血压患病率最低,由于2型糖尿病同血压存在显著性关联,提示彝族人群2型糖尿病患病率水平可能较低。凉山彝族自治州位于四川省西南部,面积为6.01万平方公里,辖17个县(市)。境内居住有彝、汉、蒙、藏、回等10多个世居民族,总人口415.5万人,其中彝族人口近200万,占凉山地区总人口的43.6%,是我国最大的彝族聚居区。该人群生活地处偏远高山,遗传上相对隔离。同时一部分彝族农民移居到城市,这就为开展移民流行病学研究提供了难得的自然现场。
目的
本研究以彝族和汉族人群为研究对象,开展移民流行病学研究,以期了解凉山地区彝族和汉族人群糖尿病患病率,并且通过比较彝族农民、移民和汉族人群2型糖尿病患病率及其关联因素,找出影响糖尿病患病的可能的危险因素,为2型糖尿病的防制提供依据。
方法
本研究以四川凉山(包括西昌市、金阳县、昭觉县、布拖县、喜德县、德阳县、宁南县)彝族和汉族人群为研究对象,开展现况研究。共调查彝族人群2878人,(其中彝族农民1549人,彝族移民1329人)和汉族人群2150人。现场进行问卷调查并测量血压、身高和体重,同时采集被调查者空腹血样,检测血糖、血脂等生化指标。为了进一步探讨脂联素基因和胰岛素受体基因与彝族人群、汉族人群2型糖尿病的关联性,从现场调查数据库抽取所有2型糖尿病的病例作为病例组,按照种族的不同分为彝族病例和汉族病例两组,根据病例数从数据库里随机选择彝族和汉族两组健康对照者,分别与病例在年龄和性别上进行频数匹配。应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对病例组和对照组两候选基因型进行检测。
结果
彝族农民T2DM患病率为4.33%(男性：6.15%,女性2.89%)。彝族移民T2DM患病率为9.03%(男性：11.31%,女性：5.81%)。汉族人群T2DM患病率为7.58%(男性：7.34%,女性：7.83%)。T2DM总患病率彝族农民最低,彝族移民最高。女性调查对象中,彝族农民女性T2DM患病率最低,汉族女性最高。男性调查对象中,彝族农民男性最低,彝族移民男性最高。比较彝族农民、移民和汉族居民不同性别T2DM患病率,彝族农民女性T2DM患病率最低,彝族移民男性T2DM患病率最高。彝族农民和移民T2DM患病率男性均显著高于女性,汉族人群男性和女性T2DM患病率基本一致。彝族农民、彝族移民和汉族人群T2DM年龄标化患病率分别为4.01%、8.88%和6.22%,三组间差异存在显著性。彝族移民男性T2DM年龄标化患病率为10.35%,显著高于彝族农民男性和汉族男性。彝族农民女性T2DM年龄标化患病率为2.41%,显著低于另外两组人群女性。三组人群不同性别间比较,彝族农民女性T2DM年龄标化患病率最低,与其他5组比较,差异具有显著性。彝族农民、彝族移民和汉族人群T2DM年龄／性别标化患病率分别为4.26%、8.41%和6.08%,彝族农民和移民间比较存在显著性差异。
多因素分析显示,彝族人群中与T2DM关联的因素有性别、年龄、血压、饮酒、TG,其中饮酒为保护因素。与彝族农民T2DM关联的因素有性别、年龄、血压、BMI、饮酒和TG,饮酒同样为保护因素。彝族移民中有意义的因素有年龄、血压、HDL-c、移居时间及原著地生活时间。汉族人群中,仅发现年龄和HDL-c与T2DM的关联性。研究彝族农民女性亚组中,未发现与T2DM关联的因素。
本研究彝族和汉族人群中,两人群均符合H-W平衡。结果未发现目标SNP(脂联素基因第二外显子+45T/G多态性与胰岛素受体基因第八外显子NsiI多态性)与2型糖尿病的关联。目标SNPs之间以及与其他环境因素交互作用分析显示,胰岛素受体基因第八外显子NsiI多态性(显性模型)与TG的交互作用存在统计学显著性。
结论
彝族农民2型糖尿病患病水平低于全国同期水平(9.7%)。移居城镇后,生活方式城镇化,2型糖尿病患病率显著增高,高于汉族人群水平。本研究发现,年龄、性别、血压、血脂、体重和饮酒与2型糖尿病存在关联。本研究未证实脂联素基因第二外显子+45T/G以及胰岛素受体基因第八外显子NsiI多态性与彝族和汉族研究人群2型糖尿病存在显著关联。
Background
Diabetes is a kind of common and chronic lifelong disease. As a cause of disability and mortality, diabetes ranks third, just below cancer and cardiovascular disease. The prevalence of diabetes is increasing with the development of the economy and the change of life style. In China, about95%diabetes patients develop type2diabetes mellitus. According to the prediction of the WHO, there will be about300million patients with diabetes all over the world by2025, most of which will be in China, the subcontinent of India and Africa. Owing to this situation, we can draw the conclusion that the worsening situation of diabetes is becoming a serious public health problem. Type2diabetes, symptoms of which are chronic high blood glucose and hyperinsulinemia, results from insulin resistance with relatively low insulin production, or from the body's failure to produce insulin with or without insulin resistance. Type2diabetes can cause many chronic complications, such as cardiovascular disease, chronic renal failure, diabetic retinopathy and nerve injury. This polygenetic disease is caused by the interaction of genetic and environmental factors, in which the latter are more important. Diabetes itself is not transmitted to next generation. The one transmitted is the susceptibility of diabetes, which causes the disease with the effect of environmental factors. Previous studies paid attention to the relationship between age/smoke and diabetes. Many epidemiological and clinical results show that obesity, type2diabetes, hyperlipidemia and hypertension always co-exist. Research shows that blood pressure is associated with diabetes, with a positive correlation between blood pressure and blood glucose levels. Foreign and domestic studies have found an find the association between normal serum lipids and type2diabetes.
Recently, with the completion of the human genome project and the development of functional genomics, a set of susceptibility gene loci were found, abstracting the attention of researchers. Such loci are the genes for leptin, angiotensin converting enzyme, calpain, interleukin-6, TNF-a and the target genes of the current research, the adipoQ gene and insulin receptor gene, etc.
Related studies have indicated that prevalences of diabetes are different among different races. The hypertension prevalence in the Yi people is the lowest in China. Since diabetes is associated with hypertension, we could infer that the prevalence of diabetes in the Yi people is probably low as well. The Liangshan Yi autonomous prefecture is located in south-western Sichuan province, with0.601million square kilometers and17counties. There are Yi, Han, Meng, Zang, Hui and other ethnic people living in this area, with a total population of41.55million. With20million Yi people in this area (43.6%), the Liangshan Yi prefecture has the largest population of Yi in China. The Yi people live in remote mountain areas with genetic isolation. Recent decades, some emigrate to towns and cities, offering an important natural field for migration epidemiology research.
Objective
The current migrantion epidemiologic research carried out in Yi and Han people to understand prevalence of diabetes in Yi and Han people in liangshan area. This study focused on the prevalence and risk factors for diabetes in the Yi and Han people in the Liangshan Yi prefecture. By comparison of prevalence and risk factors among Yi farmers, Yi migrants and Han people, this study may provide some suggestions to prevent T2DM.
Methods
This is a cross-sectional study on T2DM in Yi and Han people in the Liangshan area (including Xichang, Jinyang, Zhaojue, Butuo, Xide, Deyang and Ningnan), Sichuan, China. A sample of2878Yi people (Yi farmers:1549, Yi migrants:1329) and2150Han people were selected. Questionnaire survey, anthropometric measurement and blood test were carried out. For the further purpose to explore the association between adipoQ/insulin receptor genes and type2diabetes in Yi and Han people. All the type2diabetes patients were for the case group, and healthy controls were randomly and frequently matched by race, age and sex. PCR-RFLP was used to test the target gene in case and control group.
Results
The prevalence of T2DM in Yi farmers is4.33%(male:6.15%, female:2.89%), and that of Yi migrant is9.03%(male:11.31%, female:5.81%). The prevalence of T2DM in Han people is7.58%(male:7.34%, female:7.83%). Yi farmers have the lowest total prevalence of T2DM and Yi migrants have the highest prevalence. Among female participants, Yi farmers have the lowest prevalence and Han people have the highest. For males, it is lowest in Yi farmers and highest in Yi migrants. Yi farmer females have the lowest prevalence and Yi migrant males have the highest. For Yi farmers and migrants, the prevalence of T2DM in males is higher than in females. In Han people, the prevalence is not significantly different between males and females. The age standardized prevalences among Yi farmers, Yi migrants and Han people(4.01%,8.88%and6.22%respectively) are significantly different. The standardized prevalence in Yi migrant male is10.35%, significantly higher than in Yi farmer and Han people males. The prevalence in Yi farmer females is2.41%, significantly lower than in the other two groups. Comparison made in different groups by race and sex shows that the standardized prevalence T2DM in female Yi farmers is the lowest, and is significantly different from the other five groups. The age-and sex-standardized prevalences among Yi farmers, Yi migrants and Han people are4.26%,8.41%and6.08%, respectively and the significant difference is observed between Yi farmers and migrants. Multivariate analysis shows that age, sex, hypertension and abnormal TG level are the risk factors for type2diabetes, and in Yi people drink is a protective factor. The associated factors in Yi farmers are age, sex, hypertension, BMI, drink and TG, and drink is a protective factor as in Yi people. For Yi migrant, age, blood pressure and HDL-c lower level are the risk factors for type2diabetes, as well as time before and after emigration. In Han people, only age and HDL-c are associated with T2DM. In Yi farmer females, no associated factors are found.
Conclusions
The prevalence of T2DM in Yi farmers is lower than the national level in the same period. After emigration, with the life style urbanization, the prevalence of type2diabetes goes up significantly and becomes even higher than in Han people. Age, sex, blood pressure, blood lipid, body weight and drink are associated with T2DM. Association between the target SNPs and T2DM in the research group is not significant.
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