GLUCOSE AND INSULIN ABNORMALITIES IN FANCONI ANEMIA

范可尼贫血的血糖和胰岛素异常

• 批准号: 7375937
• 负责人: Anna Petryk
• 金额: $ 0.36万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375937
• 关键词: GLUCOSE; INSULIN; ABNORMALITIES; FANCONI; ANEMIA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies have demonstrated an association between Fanconi anemia (FA) and diabetes mellitus (DM). Swift et al (Science 1972) reported an increased prevalence of diabetes in relatives of children with FA. More recently, Wajnrajch et al (Pediatrics 2001) reported abnormalities in oral glucose tolerance testing (OGTT) in 25% of patients with FA with 72% of patients manifesting resistance to insulin action; however, the patients were not stratified based on pre- or post-BMT or androgen therapy. Androgens, BMT and stress can be associated with abnormalities in OGTT. The authors also correlated these abnormalities with complementation group and found a trend toward insulin resistance in the complementation group FA-G. However, it is the mutation for FA-C that lies in the region encoding a protein thought to be associated with type 2 DM, not FA-G (Rothschild et al, Genomics 1995). Therefore, we plan to further define the insulin and glucose abnormalities in FA through insulin-modified frequently sampled iv glucose tolerance test (FSIGT) in addition to OGTT to provide pathophysiologic information about insulin secretion and sensitivity. We will also be able to determine the contribution of androgens and complementation groups to the insulin and glucose abnormalities. These results will enable us to better predict the FA patients who will develop diabetes. This knowledge has become important now that many more children with FA are living into adulthood. If an association with a complentation group is found, we could then hypothesize that the heterozygous parents and possibly siblings would be at increased risk for DM as well.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。以往的研究已经证明范可尼贫血（FA）和糖尿病（DM）之间的关联。Swift等人（Science 1972）报告了FA儿童亲属中糖尿病的患病率增加。最近，Wajnrajch et al（Pediatrics 2001）报告了25%的FA患者口服葡萄糖耐量试验（OGTT）异常，72%的患者表现出胰岛素抵抗;然而，未根据BMT或雄激素治疗前或治疗后对患者进行分层。雄激素、骨髓移植和压力可能与OGTT异常有关。作者还将这些异常与互补组相关联，并发现在互补组FA-G中有胰岛素抵抗的趋势。然而，FA-C的突变位于编码被认为与2型DM相关的蛋白质的区域，而不是FA-G（Rothschild等，Genomics 1995）。因此，我们计划通过胰岛素修饰的频繁采样的静脉葡萄糖耐量试验（FSIGT），除了OGTT进一步定义FA的胰岛素和葡萄糖异常，提供有关胰岛素分泌和敏感性的病理生理信息。我们还将能够确定雄激素和互补基团对胰岛素和葡萄糖异常的贡献。这些结果将使我们能够更好地预测FA患者将发展为糖尿病。随着越来越多患有FA的儿童进入成年期，这些知识变得非常重要。如果发现与互补组相关，我们可以假设杂合子父母和可能的兄弟姐妹患糖尿病的风险也会增加。