TREATMENT OPTIONS FOR TYPE 2 DIABETES IN ADOLESCENTS AND YOUTH (TODAY)

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 中心，不一定是研究者的机构。 儿童2型糖尿病的发病率在过去十年中急剧增加。 由于发病较早，因此疾病持续时间较长，这些儿童的医疗保健费用将增加;他们也可能比中年人诊断出的并发症更多。 关于维持2型糖尿病儿童正常血糖和预防并发症的最佳治疗方法，几乎没有发表过经验。 本试验将确定3种治疗方法中哪一种在维持血糖控制方面最有效。 虽然试验时间不足以评估这3组之间的并发症是否存在显著差异，但将测量与并发症相关的替代标志物（例如，血脂谱、C反应蛋白、微量白蛋白尿）。 这是一项前瞻性、部分双盲、随机化临床试验，有3个治疗组：二甲双胍单药治疗、二甲双胍加强化生活方式治疗（行为矫正计划）。 主要终点是失败时间，定义为血红蛋白A1 c ≥ 8%，连续6个月或更长时间。 在运行的2-6个月期间，每1 - 4周一次观察受试者。 随机化后，受试者将在第一年每2个月接受一次访视，在随后几年每3个月接受一次访视。 此外，生活方式组的受试者将在前6个月每周一次与PAL（体力活动和营养负责人）会面，在第2个6个月每2周一次，此后每月一次。 将在随机化、6个月、24个月和研究结束时进行终点测量。 TODAY试验的主要目的是比较三个治疗组在基于血糖控制的至治疗失败时间方面的疗效。 次要目标是：比较和评价三个治疗组的安全性;比较三种治疗对T2 DM病理生理学的影响，包括β细胞功能和胰岛素抵抗、身体成分、营养、体力活动和有氧健身、心血管风险因素、微血管并发症、生活质量和心理结局;评价个人和家庭行为对治疗反应的影响;并比较三个治疗组的相对成本效益。

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. The incidence of type 2 diabetes in children has increased dramatically in the past decade. With earlier onset and thus longer duration of disease these children will have increased health care costs; they may also have more complications than someone diagnosed in middle age. There is little published experience on the best treatment to maintain normal glycemia and prevent complications in children with type 2 diabetes. This trial will determine which of 3 treatments is most effective in maintaining glycemic control. Although the trial will not be long enough to assess if there is a significant difference in complications between these 3 arms, surrogate markers associated with complications will be measured (e.g., lipid profile, C-reactive protein, microalbuminuria). This is a prospective, partially double-blinded, randomized clinical trial with 3 treatment arms: metformin alone, metformin plus intensive lifestyle treatment (behavior modification program). The primary endpoint is time to failure defined as hemoglobin A1c> or =8% for 6 or more consecutive months. Subjects will be seen every 1 to 4 weeks during the 2-6 months of the runnin. After randomization, subjects will be seen every 2 months in the first year and every 3 months in subsequent years. In addition, subjects in the lifestyle arm will meet with a PAL (physical activity and nutrition leader) once a week for the first 6 months, every 2 weeks in the 2nd 6 months and monthly thereafter. Endpoint measurements will be done at randomization, 6 months, 24 months and end of study. The primary objective of the TODAY trial is to compare the efficacy of the three treatment arms on time to treatment failure based on glycemic control. The secondary aims are to: compare and evaluate the safety of the three treatment arms; compare the effects of the three treatments on the pathophysiology of T2DM with regards to beta cell function and insulin resistance, body composition, nutrition, physical activity and aerobic fitness, cardiovascular risk factors, microvascular complications, quality of life, and psychological outcomes; evaluate the influence of individual and family behaviors on treatment response; and compare the relative cost effectiveness of the three treatment arms.