Type 2 Diabetes in Youth: Beta Cell Preservation

描述(由申请人提供)： 此应用程序用于治疗儿童2型糖尿病 (T2 DM)来自S儿童医院的一支强大的调查干部 匹兹堡大学和匹兹堡大学。这些调查人员聚集在一起 在儿童糖尿病方面的长期专业知识传统(阿尔斯兰尼博士 和Becker)，2)研究儿童的胰岛素抵抗和分泌 (阿尔斯兰尼博士，PI)，3)行为医学和生活方式干预 儿童肥胖(Marcus和Vinditti博士)，4)体力活动和 生活方式干预(Kriska和Aaron博士)，5)慢性病流行病学 肥胖、2型糖尿病和糖尿病的疾病和大型干预试验 心血管疾病(刘易斯·库勒、克里斯卡和马库斯博士)和6) 为大型干预试验招募人员(珍妮特·邦克)基于我们的集体 实力，我们相信我们完全可以达到临床站点的目标 这项针对儿童2型糖尿病的多中心试验。 这位少年派，席尔瓦·阿尔斯兰尼，医学博士，一直处于“新兴”的前沿 儿童2型糖尿病的流行。她一直是美国国立卫生研究院的顾问， 疾病预防控制中心和美国糖尿病协会(ADA)。她是世界上 由八名成员组成的专家小组制定了美国反兴奋剂机构的共识立场 2儿童和青少年的糖尿病。她对儿童胰岛素的研究 抗药性和分泌性对理解 儿童2型糖尿病的危险因素。此外，还有 强大的机构基础设施来支持我们的应用程序，包括1) 儿科综合临床研究中心(席尔瓦·阿尔斯兰尼安主任， M.D.)，2)儿童糖尿病中心？匹兹堡S医院，3) NIH资助的肥胖营养研究中心(ONRC)(David Kelley，M.D.，PI)， 4)公共卫生研究生院，最后，5)多重 与不同学科的合作，包括国家计划 处境不利的青年。最后，以病人为本的PI的K24奖 研究补充了本RFA的目标之一，即培训和 培养年轻的临床医生-科学家。 我们的建议将调查青年2型糖尿病患者的干预策略 延缓胰岛细胞退化和保存胰岛β细胞的目标 功能。为此，我们建议使用随机临床试验设计， 3个武器：常规护理、行为生活方式和风险管理 干预，行为生活方式干预与双因素相结合 胰岛素增敏疗法。β细胞功能和胰岛素的测量 阻力将是人们感兴趣的主要结果。尿白蛋白排泄 颈动脉内膜-中层厚度将是 利息。我们还建议该RFA纳入辅助研究。 儿童2型糖尿病治疗干预的综合方法 糖尿病将成为预防成人发病率和 从童年早期就开始死亡。

DESCRIPTION (provided by applicant): This application for the treatment of type 2 diabetes mellitus in children (T2DM) is from a strong cadre of investigators from Children?s Hospital of Pittsburgh and the University of Pittsburgh. These investigators bring together a long-standing tradition of expertise in 1) childhood diabetes (Drs. Arslanian and Becker), 2) in investigating insulin resistance and secretion in children (Dr. Arslanian, PI), 3) in behavioral medicine and lifestyle intervention for childhood obesity (Drs. Marcus and Vinditti), 4) in physical activity and lifestyle interventions (Drs. Kriska and Aaron), 5) in epidemiology of chronic disease and large intervention trials of obesity, type 2 diabetes and cardiovascular disease (Drs. Lewis Kuller, Kriska and Marcus), and 6) in recruiting for large intervention trials (Janet Bonk). Based on our collective strength, we believe that we can fully meet the goals for a clinical site for this multicenter trial of type 2 diabetes mellitus in children. The PI, Silva Arslanian, M.D., has been at the forefront of the "emerging epidemic" of type 2 diabetes in children. She has been a consultant to the NIH, CDC, and the American Diabetes Association (ADA). She was one of the eight-member panel of experts who developed the ADA Consensus Position of type 2 Diabetes in Children and Adolescents. Her research in childhood insulin resistance and secretion has made important contributions to the understanding of risk factors for type 2 diabetes mellitus in children. In addition, there is a strong institutional infrastructure to support our application, including 1) the pediatric General Clinical Research Center (Director, Silva Arslanian, M.D.), 2) the Diabetes Center at Children?s Hospital of Pittsburgh, 3) the NIH-funded Obesity Nutrition Research Center (ONRC), (David Kelley, M.D., PI), 4) the Graduate School of Public Health, and lastly, 5) the multiple collaborations with different disciplines including national programs for disadvantaged youth. Finally, the K24 Award of the PI in patient-oriented research complements one of the objectives of this RFA which is to train and develop young clinician-scientists. Our proposal will investigate intervention strategies in youth with T2DM with the objective of delaying beta-cell deterioration and preserving beta-cell function. To this aim we propose to use a randomized clinical trial design with 3 arms: conventional care, behavioral lifestyle and risk management intervention, and behavioral lifestyle intervention combined with dual-agent insulin sensitizing therapy. Measures of beta-cell function and insulin resistance will be the primary outcome of interest. Urinary albumin excretion and carotid artery intima-media thickness will be the secondary outcomes of interest. We also propose that this RFA incorporate ancillary studies. A comprehensive approach to therapeutic interventions in children with type 2 diabetes mellitus will form the basis for prevention of adult morbidity and mortality starting early in childhood.