GENETICS OF TYPE II DIABETES MELLITUS AND OBESITY

宾夕法尼亚州兰开斯特县的旧秩序阿米什人最初只有几百人，现在人口超过200人。这个人群是一个定义明确的，基因同质的高加索人群，有非常大的兄弟姐妹，高度的血缘关系，家谱记录良好。本研究的目的是招募非胰岛素依赖型糖尿病（NIDDM）的大型多重家系，并对其进行表型表征，以便在全基因组范围内寻找这种异质性和多基因疾病的易感基因。到目前为止，已经研究了一千多个主题。这些人来自80个两代和三代家庭，构成一个扩展的谱系和超过2000对兄弟姐妹。在首次连续招募的258名受试者中，如果他们有一级亲属患有糖尿病，则16.2%患有糖尿病，而如果没有一级亲属患有糖尿病，则仅为6.5% （RR 2.5; p</-0.01, 95% CI 1.2-5.0）。表型特征包括家族史和病史、人体测量（身高、体重、腰围、臀部、脂肪量）、75克口服葡萄糖耐量试验、血红蛋白A1c和血脂。在本报告期间，研究人员分析了1640种胰岛素和1036种瘦素，以进一步表征这些已知的葡萄糖代谢血清标志物的表型。几种不同类型的参数和非参数分析，包括受影响的兄弟姐妹对和系谱成员对分析正在进行中。仅限核心实验室；没有住院日或门诊。

The Old Order Amish of Lancaster County, Pennsylvania initially numbered in the hundreds, and are now a population of over 200. This population is a well-defined, genetically homogeneous Caucasian population with very large sibships, a high degree of consanguinity, and well documented genealogies. The goal of this study is to recruit and phenotypically characterize large multiplex pedigrees with noninsulin dependent diabetes mellitus (NIDDM) for a genome-wide search for susceptibility genes for this heterogeneous and polygenic disorder. To date, over a thousand subjects have been studied. These individuals are from 80 two- and three-generation families constituting one extended pedigree and over 2000 sib pairs. Of the first consecutive 258 subjects recruited, 16.2% had diabetes if they had a first degree relative with diabetes, compared to only 6.5% if there was no first degree relative with diabetes (RR 2.5; p</-0.01, 95% CI 1.2-5.0). Phenotypic characterization includes family and medical history, anthropometry (height, weight, waist, hip, fat mass), 75 gram oral glucose tolerance test, hemoglobin A1c, and lipids. During the current reporting period, 1640 insulins and 1036 leptins were analyzed to further characterize phenotypically these known serum markers of glucose metabolism. Several different types of parametric and nonparametric analyses including affected sib pairs and pedigree member pair analysis are in process. CORE LABORATORY ONLY; NO INPATIENT DAYS OR OUTPATIENT VISITS.