GENETIC AND PHENOTYPIC FEATURES OF NIDDM IN FAMILIES

一般认为，非胰岛素依赖型糖尿病的病因 糖尿病(NIDDM或II型糖尿病)是多因素的。总体而言 NIDDM的发展被认为是由于 多种环境和遗传因素的相互作用。有以下情况的人 NIDDM，以及那些容易患NIDDM的人，尽管不是普遍的 体内胰岛素有效性受损(或胰岛素抵抗)。 似乎既有遗传因素也有环境因素 治疗胰岛素抵抗。胰腺B细胞功能受损(减少 胰岛素分泌)在糖尿病的发病机制中也起着重要作用 NIDDM，也可能受到遗传和环境的影响 各种因素。导致大多数疾病的特定基因异常 NIDDM仍有待确认。然而，在少数情况下， NIDDM出现在相对较早的年龄(通常定义为 确诊时大于或等于25年)或受影响的多个家庭 成员在连续的世代中，特定的基因异常 已经找到了。其中包括胰岛素受体的突变，即 胰岛素原分子，胰岛素原向胰岛素和胰岛素的转化过程 葡萄糖激酶，是新陈代谢的第一个环节 胰腺B细胞中的葡萄糖因此对葡萄糖信号有贡献 用来分泌胰岛素。虽然高血糖的发展是 所有形式的糖尿病的共同点，标准 临床、流行病学和临床研究工具已经被 广泛用于测定糖尿病的病理生理学可以 用来描述血糖稳态异常的类型 (表型)存在于个人或家庭中的，即 主要的问题是胰岛素作用的缺陷，改变了 胰岛素或胰岛素原结构或胰岛素分泌缺陷。 根据具体异常的性质，这种研究可以 允许识别血糖调节中的一些缺陷，而不需要 存在明显的糖尿病。在这个项目中，我们将开展 过夜空腹血糖和胰岛素的测定 口服和静脉注射葡萄糖耐量的浓度和研究 (包括胰岛素抵抗指数) 在25岁之前起病的多代NIDDM。 对于这些目的具有潜在信息量的族 从我们妊娠中心的糖尿病参与者和 儿童纪念医院的内分泌和糖尿病临床 和西北医学院基金会。如果这些初步的 研究表明，在一个特定的家庭中，有一种独特的模式、安排 将被用于检查候选基因的突变。

It is generally believed that the etiology of non-insulin-dependent diabetes mellitus (NIDDM or Type II DM) is multifactorial. In general terms, the development of NIDDM is thought to occur as a result of the interaction of multiple environmental and genetic factors. Persons with NIDDM, and those predisposed to NIDDM commonly, though not universally have impaired insulin effectiveness (or insulin resistance) in vivo. There appear to be both genetic and environmental factors which account for insulin resistance. Impaired pancreatic B-cell function (diminished insulin secretion) also plays an important role in the pathogenesis of NIDDM and may also be influenced by both genetic and environmental factors. The specific genetic abnormalities which contribute to most NIDDM remain to be identified. However, in a few instances where the NIDDM has appeared at a relatively early age (usually defined as less than or equal to 25 years at diagnosis) or affected multiple family members in successive generations, specific genetic abnormalities have been found. These have included mutations in insulin receptors, the proinsulin molecule, the processing of proinsulin to insulin and in glucokinase, the enzyme that is the first link in the metabolism of glucose in the pancreatic B-cell thus contributing to the glucose signal for secretion of insulin. Although the development of hyperglycemia is the common denominator of all forms of diabetes mellitus, the standard clinical, epidemiological and clinical research tools that have been widely used to determine the pathophysiology of diabetes mellitus can be used to characterize the kind of abnormality in glucose homeostasis (phenotype) that is present in an individual or family, i.e., whether the predominate problem is one of defective insulin action, an alteration of insulin or proinsulin structure or defective insulin secretion. Depending on the nature of the specific abnormality, such studies may permit the identification of some defects in glucoregulation without the presence of overt diabetes. In this project we will carry out measurements of overnight fasting plasma glucose and insulin concentrations and studies of oral and intravenous glucose tolerance (including an index of insulin resistance) among members of families with multi generational NIDDM with onset of diabetes before 25 years of age. Families that are potentially informative for these purposes have been identified from among our Diabetes in Pregnancy Center participants and the Endocrinology and Diabetes Clinics of Children's Memorial Hospital and Northwestern Medical Faculty Foundation. If these preliminary studies suggest a distinct pattern within a given family, arrangements will be made to check for mutations in candidate genes.