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.
引文
1. WHO Technical Report Series No.844. Prevention of diabetes mellitus. Report of a WHO Study Group. Geneva:World Heath Organization, 1994.
2. 李立明主编.流行病学.第五版,北京:人民卫生出版社,2003,418-428.
3. 李立明.流行病学进展.北京:北京医科大学出版社,2002:64-88.
4. 冯波,李栩,黄亦文等.上海市浦东新区社区人群糖尿病状况和相关因素分析.中华糖尿病杂志,2004,12(3):187.
5. 金其林,宋晓敏,伍佩英等1社区人群糖尿病及代谢综合征的流行病学调查.实用诊断与治疗杂志,2005,19(5):342.
6. 阎立芹,孙玉娥,刘晓辉1大连市金州区糖尿病的流行病学调查分析.辽宁医学杂志,2004,18(3):168.
7. 贲松涛,金迎,齐今吾等.沈阳地区NIDDM和糖耐量减低流行病学调查研究.中国医科大学学报,1997,26(1):38.
8. 袁申元,朱良湘,胡虹莺等.北京地区20682人群糖尿病筛查及1566人OGTT的研究.中华内分泌代谢杂志,1997,13(2):69.
9. 潘长玉,陆菊明,田慧等.首都钢铁公司成年人糖尿病患病率的调查.中华医学杂志,1995,75(7):409.
10.潘孝仁,李光伟,刚勇等.糖耐量低减的特征及其与冠心病发生的关联.中华内分泌代谢杂志,1989,5(1):20.
11.潘长玉,金文胜.2型糖尿病流行病学.中华内分泌代谢杂志,2005,21(5):增录5S1-5S5.
12. Zimmet P, Alberti K, Shaw J. Global and societal implication of the diabetes epidemic. Nature,2001,414(6865):782-787.
13.中华人民共和国卫生部疾病控制司.中国糖尿病防治指南.2004.
14. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. National diabetes fact sheet,2003.
15.武阳丰,谢高强,李莹,赵连成,周北凡.中国部分中年人群糖尿病患病率、知晓率、治疗率及控制率现况调查,2005,26(8):564-568.
16. Cockram C, Alberti G, Allgot B, Aschner P, Dwyer T, Haffner S, Mbanya JC, McLaughlin C, Mohan V. Diabetes and cardiovascular disease:time to act. Report of the International Diabetes Federation (IDF), Brussels, 2001.
17. Knowler WC, Coresh J, Elston RC, Freedman BI, Iyengar SK, Kimmel PL, Olson JM, Plaetke R, Sedor JR, Seldin MF. The Family Investigation of Nephropathy and Diabetes(FIND):Design and methods. J Diabetes Complications,2005,19(1):1-9.
18. Procopiou M, Philippe J. The metabolic Syndrome and type 2 diabetes: epidemiological figures and country specificities. Ceregrovase Dis,2005,20(Suppl 1):S2-S8.
19. Marcovecchio M, Mohn A, Chiarelli F. Type 2 diabetes mellitus in children and adolescents. J Endocrinol Invest,2005,28(9):853-863.
20. Martin S, Martin E, Klug C, Weinauer F, Landgraf R, Rapp S. Diabetes study in Bavaria:known risk factors correlate with an increased level of HbAlc. Dtsh Med Wochenschr,2007,132(24):1315-1320
21.陈兴宝,唐玲,陈慧云等.2型糖尿病并发症对患者治疗费用的影响评估.中国糖尿病杂志,2003,11(4)
22.胡善联,刘国恩,许樟荣等.我国糖尿病流行病学和疾病经济负担研究现状.中国卫生经济,2008,27(8):5
23. Mainous AG, Majeedd A, Koopman RJ, Baker R, Everett CJ, Tilley BC, Diaz VA. Acculturation and diabetes among Hispanics:evidence from the 1999-2002 National Health and Nutrition Examination Survey. Public Health Rep,2006,121(1):60-66.
24. Uitewaal PJ, Manna DR, Bruijnzeels MA, Hoes AW, Thomas S. Prevalencc of type 2 diabetes mellitus. Other cardiovascular risk factors, and cardiovascular disease in Turkish and Moroccan immigrants in north west Europe:a systematic review. Prev Med,2004,39(6):1068-1076.
25. Tsumaura K, Hayashi T, Suematsu C, et al. Daily alcohol consumption and the risk of type 2 diabetes in Japanese men:the Osaka Health Survey. Diabetes Care,1999,22(9):1432.
26. Perry IJ, Wannamethee SG, Walker MK, et al. Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men. BMJ,1995,310:560.
27.广东省糖尿病流行病学调查协作组.吸烟、饮酒的糖尿病危险性分析.广东医学,2001,22(6):459-4621.
28.王红霞,梁秀芬,张玉敏.我国2型糖尿病的流行病学及危险因素研究.内蒙古医学杂志,2006,38(2):156-1591.
29.吴先萍,扬维中,杨小明,等.2型精尿病危险因素的病洲对照研究.中国慢性病预防与控制,2000,8(6)-262.
30.刘尊永,程锦泉,彭吉等.深圳市居民糖尿病危险因子与2型糖尿病发病关系的分析.中华预防医学杂志,2000,34(4):232.
31.袁申元,朱良湘,胡虹莺,等.北京地区20682人群糖尿病筛查及1566人OGTT的研究.中华内分泌代谢杂志,1997,13(2):69.
32. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996,271:10697-10703.
33. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apMl (AdiPose Most abundant Gene transcript). Biochem Biophys Res Commun 1996,221:286-289.
34. Saito K, Tobe T, Minoshima S, Asakawa S, Sumiya J, Yoda M, Nakano Y, Shimizu N, Tomita M. Organization of the gene for gelatin-binding protein (GBP28). Gene 1999,229:67-73.
35. Schaffler A, Langmann T, Palitzsch KD, Scholmerich J, Schmitz G. Identification and characterization of the human adipocyte apM-1 promoter. Biochim Biophys Acta 1998,1399:187-197.
36. Vionnet N, Hani E-H, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Lepretre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P. Genome wide search for type 2 diabetes-susceptibility genes in French whites:evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome Iq21-q24. Am J Hum Genet 2000,67:1470-1480.
37. Statnick MA, Beavers LS, Conner LJ, Corominola H, Johnson D, Hammond CD, Rafaeloff-Phail R, Seng T, Suter TM, Sluka JP, Ravussin E, Gadski RA, Caro JF. Decreased expression of apMl in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res 2000,1:81-88.
38. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999,257:79-83.
39. Vasseur F, Meyre D, Froguel P. Adiponectin, type 2 diabetes and the metabolic syndrome:lessons from human genetic studies. Expert Rev Mol Med 2006,8:1-12.
40. Viktor A. Potapov, Dimitry A. Chistiakov, Anna Dubinina, Minara S. Shamkhalova, Marina V. Shestakova, Valery V. Nosikov. Adiponectin and Adiponectin Receptor Gene Variants in Relation to Type 2 Diabetes and Insulin Resistance-Related Phenotypes. The Review of Diabetic Studies 2008,5(1):28-37.
41. Hanis CL, Bertin TK. Identification of a insulin receptor exon-8 Nsil polymorphism using the polymerase chain reaction. Nucleic Acid Research, 1991,5918:5923..
42. Schrader A. P, Zee R Y, Morris B J. Association analyses of NsiI RFLP of human insulin receptor gene in hypertensives [J]. Clin Genet,1996, 49(2):74-78.
43.林从容,吴可贵.胰岛素受体基因第8外显子多态性与原发性高血压病的关系.高血压杂志,1999,7(4).
44.王瑞连,朱梅佳.胰岛素受体基因多态性与脑梗死关系的研究进展.神经疾病与精神卫生,2006,6(1).
45. Zimmet P, Alberti K, Shaw J. Global and societal implication of the diabetes epidemic. Nature,2001,414 (6865):782-787.
46. Knowter WC, Pettitt DJ, Sadd M, Bennett PH. Diabetes mellitus in the Pina Indians:incidence, risk factors and pathogenesis. Diabetes Metab Rev,1990,6(1):1-27.
47. Branead FL, Whelton PK, Kuller LH, Klag MJ. Diabetes mellitus, race, and socioeconomic status:a population-based study. Ann Epidemiol, 1996,6(1):67-73.
48.中国2000年人口普查资料.中国统计出版社,2000.
49.单广良.中国协和医科大学博士论文,1998.
50.全国1991年高血压抽样调查领导小组.业务技术指导组.全国1991年高血压抽样调查数据册1993,10.
51. He J, Tell Gs, Tang YC, et al. Effect of migrant on blood pressure:the Yi People Study. Epidemiology.1991 Mar,2(2):87-98.
52.李立明主编.流行病学.第六版,北京:人民卫生出版社,2008,409.
53.中国高血压防治南修订委员会.高血压水平的定义和分类.修订版.中国高血压防治指南,2005:17.
54. 《中国成人血脂异常防治指南》制订联合委员会.中国成人血脂异常防治指南.人民卫生出版社,2007,13.
55. Wenying Yang, Juming Lu, Jianping Weng, et al. Prevalence of Diabetes among Men and Women in China. N Engl J Med 2010; 362:1090-1101
56.上海市糖尿病研究协作组.上海地区十万人口糖尿病调查报告.中华医学杂志,1980,60(6):323.
57.全国糖尿病防治协作组调查研究组.全国14省市30万人口中糖尿病调查报告.中华内科杂志,1981,20(11):678.
58.全国糖尿病防治协作组.1994年中国糖尿病患病率及其危险因素.中华内科学杂志.1997,36(6):384.
59.王克安,李天麟,向丁红,等.中国糖尿病流行特点研究.中华流行病学杂志,1998,19(5):282.
60.王陇德.中国居民营养与健康状况调查报告之一2002年综合报告.北京:人民卫生出版社,2005:57-60.
61. Abubakari AR, Lauder W, Jones MC, et al. Prevalence and time trends in diabetes and physical inactivity among adult West African populations: The epidemic has arrived. Public Health,2009 Sep,11.
62. NEEL JV. Diabetes mellitus:a "thrifty" genotype rendered detrimental by "progress"?. Am J Hum Genet,1962,14:353-362.
63. Tattersall RB, Fajans SS. Prevalence of diabetes and glucose intolerance in 199 offspring of thirth-seven conjugal diabetic parents. Diabetes.1975,24(5):452-462.
64.陈玉,周玲,徐耀初等.2型糖尿病与遗传和环境因素相互关系的研究.中华预防医学杂志.2002,36(3):191-194.
65. Molyneaux L, Constantino M, Yue D. Strong family history predicts a younger age of onset for subjects diagnosed with type2 diabetes. Diabetes Obes Metab.2004,6(3):187-194.
66. Hadi Harati, Farzad Hadaegh, Navid Saadat et al. Population-based incidence of Type 2 diabetes and its associated risk factors:results from a six-year cohort study in Iran. BMC Public Health.2009, 186(9):2458-2463.
67. Hae-Rang Chung, Rafael P6rez-Escamilla, Risk factors of type 2 diabetes among Korean adults:The 2001 Korean national health and nutrition examination survey. Nutrition Research and Practice.2009;3(4):286-294.
68.胡英华,李光伟,潘孝仁,等.大庆糖尿病患病率调查及21纪我国糖尿病发病情况预测.中华内科杂志,1993,32(3):173.
69.刘茂玲,刘礼锦,邹宇华.2型糖尿病危险因素的交互作用研究.中国慢性病预防与控制,2008,16(2):136.
70.庄祥云译.糖尿病的性别差异.日本医学介绍,2001,22(9):411-412.
71.程巧云,李景风,卫成.社区居民Ⅱ型糖尿病及相关因素调查.中国公共卫生,2005,21(8):1014-1015.
72. Musaiger AO, AL-Mannai MA. Social and lifestyle factors associated with diabetes in the adult Bahraini Population. J Biosoc Sci.2002,34(2): 277-281.
73. Everhart JE, Pettitt DJ, Bennett PH, et al. Duration of obesity increases the incidence of NIDDM. Diabetes,1992,41(2):235-240.
74.胡传峰,李立明.2型糖尿病体质因素流行病学研究进展.中国糖尿病杂志,2001,1(9):52-54.
75. Perez-Bravo F, Carrasco E, Santos JL, et al. Prevalence of type2 diabetes and obesity in rural Mapuche population from Chile. Nutrition,2001, 17(3):236-238.
76.任青娟.河北医科大学硕士学位论文.2008.
77.刘国红.2型糖尿病的流行病学特征.湖北预防医学杂志,2003,14(1):4.
78.王松.大学生德育知行分离现象产生的原因及对策.科技信息,2009(6)
79.柯登地.教师知行分离问题初探.上海师范大学学报,2007,36(1):120-124.
80.张明,方鹏骞.已婚男性长途卡车司机艾滋病风险行为分析.中国艾滋病性病,2008,14(5):511-512.
81. Pekkanen J, Tuomilehto J, Uutela A, et al. Social class, health behaviour, and mortality among men and women in eastern Finland. BMJ,1995,311 (7005): 589-593.
82. Choiniere R, Lafontaine P, Edwards A C. Distribution of cardiovascular disease risk factors by socioeconomic status among Canadian adults [J]. Can Med Assoc J,2000,162:S13-24.
83. Brunner E J, Marmot M G, Nanchahal K, et al. Social inequality in coronary risk:central obesity and the metabolic syndrome. Evidence from the Whitehall II study. Diabetologia,1997,40(11):1341-1349.
84. Drewnowski A, Specter S E. Poverty and obesity:the role of energy density and energycosts. Am J Clin Nutr,2004,79(1):6-16.
85. Dallongeville, Bernard Ruidavets, Dominique Cottel, et al. Household Income Is Associated With the Risk of Metabolic Syndrome in a Sex-Specific Manner. Diabetes care,2005,28(2):409-415.
86. Darmon N A, Briend, Drewnowski A. Energy-dense diets are associated with lower diet costs:a community study of French adults. Public Health Nutr, 2004,7(1):21-27.
87. Sarlio-Lahteenkorva S, Lahelma E, The association of body mass index with social and economic disadvantage in women and men. Int J Epidemiol, 1999,28(3):445-449.
88.潘孝任,李光伟,胡英华,王继兴,杨文英,安作新,刘娟,曹辉碧,胡泽溪,庞成言,张辉,郑辉,王金平,姜希贵,姜亚云.饮食和运动干预治疗对糖尿病发病率的影响:530例糖耐量低减人群六年前瞻性观察,中华内科杂志.1995,34(2):108-112.
89. Lindstrom J, Louheranta A, Mannelin M, Rastas M, Salminen V, Eriksson J, Uusitupa M, Tuomilehto J. The Finish Diabetes Prevention Study (DPS):lifestyle intervention and 3-year result on diet and physical activity. Diabetes Care,2003,26(12):3230-3236.
90. Boule NG, Kenny GP, Haddad E, Wells GA, Sigal RJ, Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia,2003,46(8):1071-1081.
91. Baba S. Diabetes. Elsevier Science B. V.,1994,777p.
92. NaKai N, etal. Exercise training prevents maturation-induced decrease in insulin sensitivity. J Appl physiol,1996,80(6):1963.
93. Ikemoto S. Expression of an insulin-responsive glucose transporter(GLUT4)Minigene in transgenic mice:Effect of exercise and role in glucose hemeostasis. Pro Natl Aad Sci.USA 1995,92:865.
94. Borghouts LB, Keizer HA. Exercise and insulin sensitivity:a review. Int J Sports Med,2000,21(1):1-12.
95. Corcoran MP, Lamon-Fava S, Fielding RA. Skeletal muscle lipid deposition and insulin resistance:effect of dietary acids and exercise. Am J Clin Nutr,2007,85(3):662-677.
96. Lee JS, Bruce CR, Tunstall RJ, Cameron-smith D, Hugel H, Hawley JA. Interaction of exercise and diet on GLUT-4 protein and gene expression in type 1 and type 2 rat skeletal muscle. Acta Physiol Scand,2002, 175(1):37-44.
97. Terada S, Yokozeki T, Kawanaka K, Ogawa K, Higuchi M, Ezaki 0, Tabata I. Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle. J Appl Physiol,2001,90(6): 2019-2024.
98. King H, Kriska AM. Prevention of type Ⅱdiabetes by physical training. Diabetes Care,1992,15(11):1794-1799.
99. Farlane IA, Gill GV, Finnegan D, Pinkeny J. Diadetes in a high secure hospital. Postgrad Med J,2004,80(939):35-37.
100. Hu G, Lindstrom J, Valle TT, Eriksson JG, Jousilahti P, Silventionen K, Qiao Q, Tuomilehto J. Physical activity, body mass index and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch Inter Med,2004,164(8):892-896.
101. King H, Kriska AM. Prevention of obesity and type 2 diabetes. Lipids, 2003,38(2):103-108.
102. Mansion JE, Nathan DM, Krolewski AS, Stampfer MJ, Willett WC, Hennekens CH. A prospective study of exercise and incidence of diabetes among US male physicians. JAMA,1992,268(1):63-67.
103. Rimm EB. Cigarette smoking and the risk of diabetes in women. Am J Pnblic Health,1993,83:211.
104.广东省糖尿病流行病学调查协作组.吸烟、饮酒的糖尿病危险性分析.广东医学,2001,22(6):459-4621.
105.王红霞,梁秀芬,张玉敏.我国2型糖尿病的流行病学及危险因素研究.内蒙古医学杂志,2006,38(2):156-1591.
106. Perry IJ, Wannamethee SG, Walker MK, et al. Prospective study of risk factors for development of non2insulin dependent diabetes in middle aged Briti shmen. BMJ,1995,310:560.
107. Ford ES, Malarcher AM, Herman WH, et al. Diabetes mellitus and cigarette smoking. Findings from the 1989 National Health Interview Survey. Diabetes Care,1994,17(7):688.
108. Targher G, Alberiche M, Zenere MB, et al. Cigarette smoking and insulinresistance in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab,1997,82:3619.
109. Rimm EB, Chan J, Stampfer MJ, et al. Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. BMJ,1995, 310:555.
110. Tsumaura K, Hayashi T, Suematsu C, et al. Daily alcohol consumption and the risk of type 2 diabetes in Japanese men:the Osaka Health Survey. Diabetes Care,1999,22(9):1432.
111.陈爱民,徐耀初,沈洪兵等.吸烟、饮酒因素与糖尿病关系的病例对照研究.中国公共卫生,1999,15(11):973.
112. Amini M, Afshin-Nia F, Bashardoost N, et al. Prevalence and risk factors of diabetes mellitus in the Isfahan city population (aged 40 or over) in 1993. Diabetes Res Clin Pract Dec 1997,38(3):185-190.
113. Bayo J, Latorre PM, Garcia F, et al. Risk factors associated with prevalence of non-insulin dependent diabetes mellitus in Lejona (Vizcaya). Med Clin (Barc) Nov 2,1996,107(15):572-577.
114. Philip AM, Braxton DM, Aodolfo AV, et al. Incidence of NIDDM and impaived glucose tolerance in hypertensive subjects. Diabetes,1993,42:154.
115.吴先萍,杨维中,杨小明等.2型糖尿病危险因素的病例对照研究.中国慢性病预防与控制,2000,8(6):262.
116.李伟光,张辉,潘孝仁等.原发性高血压为2型糖尿病的独立预测因素.中华内科学杂志,1994,33(10):654.
117. Ferrannini E, Buzzifli G, Bonadonuk R, et al. Insulin resistance in essential hypertension. N Engl J Med,1987,317(10):356.
118.唐晓君,卢仙娥,李革等.2型糖尿病危险因素分析.中国公共卫生,2004,20(1):74.
119.张秋梅,靳建鸣,管乐等.2型糖尿病患者高危因素分析.中国慢性病预防与控制,2003,11(2):61.
120. Man Z W, Zhu M, Noma Y, et al. Impaired beta2cell function and deposition if fat droplets in the pancreas as a consequence of hypertriglyceridemia in OL ETE rat, a model of spontaneous NIDDM. Diabetes,1997,46:1718-1724.
121.鲁一兵,缪珩,王华等.2型糖尿病危险因素的对因素logistic回归分析.中华流行病学杂志,2001,22(4):277.
122. MCGARRY J. Denis dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes. Diabetes,2002,51(1):7-18.
123. Bays HE, Dujovne CA, McGovern ME, et al. Comparison of once-daily, niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin(the ADvicor Versus Other Cholesterol-Modulating Agents Trial Evaluation). Am J Cardiol,2003,91:667-678.
124. Keech A, Simes RJ, Barter P, et al. for the FIELD Study Investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9759 people with type 2 diabetes mellitus:randomized controlled trial. Lancet,2005,366:1849-1664.