Epidemiologic Studies of Type 2 Diabetes in Normal Weight Adults

正常体重成人 2 型糖尿病的流行病学研究

• 批准号: 7739544
• 负责人: Mercedes Renee Carnethon
• 金额: $ 22.88万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-27 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739544
• 关键词: Adult; Affect; Age; Atherosclerosis; Autonomic nervous system; Behavioral; Blood Vessels; Body Weight; Body mass index; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Chronic; Clinical; Cohort Studies; Communities; Coronary artery; Data; Data Set; Development; Diabetes Mellitus; Disease; Epidemiologic Studies; Ethnic group; Event; Gender; Genes; Genetic; Genetic Models; Genetic Polymorphism; Genotype; Health; Heart; Heart Rate; Hypertension; Hypertriglyceridemia; Individual; Inflammation; Insulin; Kidney Diseases; Longitudinal Studies; Measurement; Medical; Meta-Analysis; Metabolic; Metabolic Diseases; Minority; Morbidity - disease rate; Nervous System Physiology; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Obesity; Overweight; PPARG gene; Participant; Persons; Phenotype; Prevalence; Prevention; Principal Investigator; Publishing; Race; Reporting; Research Design; Resources; Risk; Risk Factors; Role; Sampling; Single Nucleotide Polymorphism; Stratification; TCF7L2 gene; Testing; Time; Weight; cohort; depression; depressive symptoms; ethnic difference; experience; follow-up; gene environment interaction; genetic risk factor; inflammatory marker; mortality; novel; offspring; public health relevance; racial and ethnic; response; young adult

DESCRIPTION (provided by principal investigator): The metabolically obese normal weight (MONW) phenotype is a clustering of obesity-related metabolic disorders (e.g., type 2 diabetes [T2DM], hypertriglyceridemia, hypertension) in persons with normal body mass index (BMI). T2DM in normal weight persons is an intriguing and understudied representation of the MONW phenotype that affects between 5-15 percent of persons with T2DM. In response to PA-06-151 (Secondary Analyses in Obesity, Diabetes, Digestive and Kidney Disease), we propose to pool together data from multiple existing longitudinal cohort studies to conduct an epidemiologic study of demographic and clinical characteristics, behavioral factors, and candidate genes associated with the development of T2DM in normal weight participants. Using longitudinal follow-up for clinical events in each of the studies, we will compare the rates of cardiovascular complications between normal weight and overweight/ obese persons who experienced incident T2DM. The cohort studies included in this application are the Atherosclerosis Risk in Communities, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults, Framingham Offspring Study, Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis and genetic data from the Candidate Gene Association Resource project. The resulting pooled dataset will include a large, diverse (e.g., race/ethnic, gender, and age) sample of persons who can be classified at the time of incident T2DM as normal weight (BMI<25 kg/m2) or overweight/obese (BMI>25 kg/m2). Preliminary studies and published reports suggest that over 2600 cases of incident T2DM, and the largest sample of normal weight persons with incident T2DM to date (~10 percent of total with T2DM), will be available to carry out the following aims: 1) compare the prevalence or mean levels of baseline demographic and clinical characteristics between normal weight and overweight/obese participants with incident T2DM; 2) test whether the relation between genotype and incident T2DM is modified by weight status at the time T2DM is identified; 3) compare the cardiovascular morbidity and mortality rates between normal weight and overweight/obese persons with incidentT2DM. The successful completion of these studies can be expected to identify demographic and clinical characteristics associated with a higher likelihood of having T2DM despite being normal weight, and to determine whether three previously-identified novel risk factors for T2DM (i.e., inflammation, autonomic nervous system function, and depressive symptoms) are predictors of disease in the absence of obesity. By investigating the presence of an interaction between obesity and established genes for T2DM (PPARG, KCNJ11 and TCF7L2) in association with T2DM, we can begin to unravel the mechanisms by which these candidate genes are associated with T2DM. Findings from this study will extend beyond the small proportion of normal weight persons with T2DM to provide a better understanding of novel risk factors and genetic polymorphisms for T2DM and the role of obesity in clinical cardiovascular consequences of T2DM. PUBLIC HEALTH RELEVANCE: Type 2 diabetes (T2DM) is a serious chronic medical condition. Approximately 15 percent of persons with T2DM are normal weight according to body mass index measurements (BMI<25 kg/m2). Because of the small number of normal weight persons who have T2DM in any single study, we propose to pool together data from 6 existing epidemiologic studies to assemble a cohort of persons with incident T2DM. According to published estimates and preliminary studies, we expect to have over 2600 incident cases of T2DM. Using common measurements across studies and long-term follow up for illness and death, we will test whether established baseline clinical and demographic characteristics and candidate genes are more common in participants who are normal weight versus overweight/obese at the time of incident T2DM and whether rates of illness and death from cardiovascular diseases differ between the two groups. Findings from this study extend beyond the small proportion of normal weight persons with T2DM to provide a better understanding of risk factors other than overweight for T2DM and the cardiovascular consequences of T2DM.

描述（由首席研究者提供）：代谢肥胖的正常体重（MORW）表型是与正常体重指数（BMI）患者中与肥胖相关的代谢性疾病的聚类（例如，2型糖尿病[T2DM]，高甘油三酯血症，高糖尿病，高血压）。正常体重的人中的T2DM是对MONW表型的有趣且研究的表示，它影响了5-15％的T2DM患者。为了应对PA-06-151（肥胖，糖尿病，消化和肾脏疾病的次级分析），我们建议将来自多个现有纵向队列研究的数据汇集在一起​​，以进行人口统计学和临床​​特征，行为特征，行为因素以及与正常体重参与者T2DM相关的候选基因的流行病学研究。在每项研究中，使用纵向随访进行临床事件，我们将比较经历了发生T2DM的正常体重与超重/肥胖者之间的心血管并发症率。该应用程序中包括的队列研究是社区的动脉粥样硬化风险，心血管健康研究，年轻人的冠状动脉风险发展，弗雷明汉后代研究，杰克逊心脏研究，杰克逊心脏研究，动脉粥样硬化的多族裔研究以及候选人基因协会资源项目的遗传数据。由此产生的合并数据集将包括一个大型（例如种族/种族，性别和年龄）样本的样本，这些人可以在正常重量（BMI <25 kg/m2）或超重/肥胖症（BMI> 25 kg/m2）时被归类为正常重量（BMI <25 kg/m2）或超重/m2）。初步研究和发表的报告表明，迄今为止，有2600多个事件T2DM的病例和最大的正常体重患者样本（迄今为止T2DM的正常人重量）将可用于以下目的：1）比较正常体重和超重参与者之间正常体重和临床参与者之间的基线范围和临床特征的普遍性或平均水平，与Indistect Addist t2D进行了比较； 2）测试是否确定了T2DM时的重量状态来修改基因型和入射T2DM之间的关系； 3）比较正常体重与超重/肥胖者之间的心血管发病率和死亡率与IntistT2DM。可以预期，这些研究的成功完成将确定尽管体重正常，但与具有T2DM的可能性更高相关的人口和临床特征，并确定T2DM的三个先前鉴定的新型新型风险因素（即炎症，自主神经系统功能和抑郁症状）是否是缺乏肥胖症的疾病的预测。通过研究肥胖和已建立的T2DM基因之间存在相互作用（PPARG，KCNJ11和TCF7L2）与T2DM相关，我们可以开始揭示这些候选基因与T2DM相关的机制。这项研究的结果将超出具有T2DM的正常体重者比例的范围，以更好地了解T2DM的新型风险因素和遗传多态性，以及肥胖症在T2DM临床心血管后果中的作用。公共卫生相关性：2型糖尿病（T2DM）是一种严重的慢性病病。根据体重指数测量值（BMI <25 kg/m2），大约15％的T2DM患者的体重正常。由于在任何一项研究中具有T2DM的正常体重人数少，我们建议将来自现有的6个流行病学研究的数据汇总在一起，以组装有入射T2DM的人群。根据已发表的估计和初步研究，我们预计将有超过2600例T2DM事件。使用跨研究的常见测量以及疾病和死亡的长期随访，我们将测试既定的基线临床和人口统计学特征和候选基因在正常体重与超重/肥胖的参与者中是否更为普遍，而在事件发生T2DM时，疾病和死亡发生率和对心血管疾病的死亡率与两组之间的心血管疾病是否有所不同。这项研究的结果范围超出了T2DM的正常体重的一小部分，可以更好地了解T2DM超重和T2DM心血管后果以外的其他风险因素。