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

青少年 2 型糖尿病的治疗方案（当今）

• 批准号: 7605860
• 负责人: Siripoom V McKay
• 金额: $ 29.11万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605860
• 关键词: Acanthosis Nigricans; Adolescent; Adult; Aerobic; Affect; Behavior; Behavior Therapy; Beta Cell; Body Composition; C-reactive protein; Cardiovascular system; Cell physiology; Child; Childhood; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Diabetic Angiopathies; Diagnosis; Disease; Double-Blind Method; Economic Burden; Economics; End Point; Environmental Risk Factor; Epidemic; Ethnic group; Failure; Family; Family history of; Functional disorder; Funding; Genetic; Geographic Locations; Glycosylated hemoglobin A; Grant; Health Care Costs; Hemoglobin; Hypertension; Incidence; Individual; Institution; Insulin Resistance; Label; Life Style; Lipids; Measurement; Measures; Medical; Metabolic syndrome; Metformin; Microalbuminuria; Minority; Modification; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Outcome Measure; Ovarian; Overweight; Patients; Pattern; Pediatrics; Physical activity; Population; Puberty; Publishing; Quality of life; Randomized; Randomized Clinical Trials; Range; Relative (related person); Research; Research Personnel; Resources; Risk; Safety; Source; Surrogate Markers; Syndrome; Time; Today; Treatment Failure; United States National Institutes of Health; Upper arm; Week; Youth; abstracting; base; burden of illness; cardiovascular risk factor; cost; cost effectiveness; early onset; experience; fitness; glycemic control; illness length; improved; insulin sensitivity; middle age; nutrition; prevent; programs; prospective; psychological outcomes; response; rosiglitazone; social; type 2 diabetes in children; urban area

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. ABSTRACT 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. I. HYPOTHESIS 1) Patients treated with metformin plus rosiglitizone will fail their primary therapy later than those on metformin alone. Failure is defined as Hemoglobin A1c8% for 6 months. 2) Patients treated with metformin plus intensive lifestyle modification will fail later than those on metformin alone. II. SPECIFIC AIMS 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; compae 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. III. BACKGROUND AND SIGNIFICANCE Type 2 Diabetes Mellitus (T2DM) has dramatically increased throughout the world in many ethnic groups and among people with diverse social and economic backgrounds. Over the last decade, the increase in the number of children and youth with T2DM has been labeled an "epidemic". Before the 1990's, it was rare for most pediatric centers to have patients with T2DM. By 1994, T2DM patients represented up to 16% of new cases of diabetes in children in urban areas, and by 1999, depending on geographic location, the range of percent of new cases due to T2DM was between 8-45% and disprpoortionately represented in minority populations. T2DM in children and youth, as in adults, is due to the combination of insulin resistance and relative beta cell ailure. It appears that there are a host of genetic and environmental risk factors for insulin resistance and limited beta cell reserve. The epidemic of pediatricT2DM is coincident with the rise in the number of children who are overweight or at risk for overweight and with a decrease in the physical activity pattern of youth. There has been a strong association between T2DM and the onset of puberty, a positive family history of T2DM, and elelements of the metabolic syndrome such as acanthosis nigricans and polycystic ovarian syndrome (PCOS). Despite the dramatic increase in the number of cases of T2DM in pediatric populations, there have been no published large-scale studies investigating the pathophysiology, treatment, and complications of these disorders in children and youth. The long-term complications and costs associated with T2DM make such studies imperative. Between 1997 and 2002, the estimated cost of diabetes with regard to direct medical cost increased from $44 billion to $92 billion, and the total cost icnreased from $98 billion to $132 billion. The vast majority of monies are spent on the long-term complications of this disorder. Since the long-term microvascular and cardiovascular complications relate to duration of diabetes and to control of glycemia, it could be hypothesized that the increasing number of children and youth diagnosed with T2DM, if not effectively treated, could dramatically add to the economic burden of this disease over the ensuing decades. The pharmacologic therapies for this study, which include using metformin alone and metformin in combination with rosiglitazone, were chosen because metformin is approved in pediatrics and because theoretically both of these agents improve insulin sensitivity. Additional agents were not chosen because the estimated number of patients available for recruitment would not support a trial with more than three arms. As the epidemic of T2DM in children and youth is relatively recent, there is little controlled evidence regarding the use of lifestyle modification to improve insulin sensitivity and glycemic control, induce wieght loss, or affect other outcome measures, such as dyslipideia and hypertension, in pediatric patients with T2DM.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 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。 抽象的 过去十年中，儿童 2 型糖尿病的发病率急剧增加。 由于发病较早，病程较长，这些儿童的医疗费用将会增加；他们还可能比中年诊断出的人有更多的并发症。 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，目前已发表的经验很少。 该试验将确定 3 种治疗方法中哪一种对于维持血糖控制最有效。 尽管试验时间不够长，无法评估这 3 个组之间的并发症是否存在显着差异，但仍将测量与并发症相关的替代标志物（例如血脂、C 反应蛋白、微量白蛋白尿）。 这是一项前瞻性、部分双盲、随机临床试验，有 3 个治疗组：单用二甲双胍、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 A1c 或连续 6 个月或更长时间 =8%。 在跑步的 2 至 6 个月内，每 1 至 4 周就会见到一次受试者。 随机化后，受试者将在第一年每 2 个月接受一次检查，随后几年每 3 个月接受一次检查。 此外，生活方式组的受试者将在前 6 个月内每周与 PAL（体育活动和营养负责人）会面一次，在后 6 个月内每两周一次，此后每月一次。 终点测量将在随机、6 个月、24 个月和研究结束时进行。 一、假设 1) 使用二甲双胍联合罗格列酮治疗的患者比单独使用二甲双胍治疗的患者主要治疗失败的时间晚。 失败定义为血红蛋白 A1c8% 持续 6 个月。 2) 使用二甲双胍加强化生活方式改变治疗的患者比单独使用二甲双胍治疗的患者失败的时间要晚。 二. 具体目标 TODAY 试验的主要目的是比较三个治疗组在血糖控制的基础上按时治疗失败的疗效。 次要目标是：比较和评估三个治疗组的安全性；比较三种治疗方法对 T2DM 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、心血管危险因素、微血管并发症、生活质量和心理结果；评估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。 三． 一、背景及意义 2 型糖尿病 (T2DM) 在世界各地的许多种族群体以及具有不同社会和经济背景的人群中急剧增加。 在过去的十年中，患有 T2DM 的儿童和青少年数量的增加被贴上了“流行病”的标签。 20 世纪 90 年代之前，大多数儿科中心很少有 T2DM 患者。 到 1994 年，T2DM 患者占城市地区儿童糖尿病新发病例的 16%，到 ​​1999 年，根据地理位置，T2DM 新发病例的百分比范围在 8-45% 之间，并且在少数民族人口。 与成人一样，儿童和青少年的 T2DM 是由胰岛素抵抗和相对 β 细胞疾病共同造成的。 胰岛素抵抗和β细胞储备有限似乎有许多遗传和环境风险因素。 儿童 T2DM 的流行与超重或有超重风险的儿童数量的增加以及青少年体力活动模式的减少同时发生。 T2DM 与青春期开始、T2DM 阳性家族史以及黑棘皮病和多囊卵巢综合征 (PCOS) 等代谢综合征要素之间存在密切关联。 尽管儿科人群中 T2DM 病例数量急剧增加，但尚未发表大规模研究来调查儿童和青少年这些疾病的病理生理学、治疗和并发症。 与 T2DM 相关的长期并发症和费用使得此类研究势在必行。 1997年至2002年间，糖尿病的直接医疗费用估计从440亿美元增加到920亿美元，总费用从980亿美元增加到1320亿美元。 绝大多数资金都花在了这种疾病的长期并发症上。 由于长期微血管和心血管并发症与糖尿病病程和血糖控制有关，因此可以假设，越来越多的被诊断患有 T2DM 的儿童和青少年如果得不到有效治疗，可能会大大增加这一群体的经济负担。在接下来的几十年里，疾病不断蔓延。 选择本研究的药物疗法包括单独使用二甲双胍和二甲双胍与罗格列酮联合使用，因为二甲双胍已在儿科获得批准，而且理论上这两种药物都能改善胰岛素敏感性。 没有选择其他药物，因为估计可招募的患者数量不支持三组以上的试验。 由于 T2DM 在儿童和青少年中的流行相对较新，因此很少有对照证据表明使用生活方式改变来改善儿科患者的胰岛素敏感性和血糖控制、诱导体重减轻或影响其他结果指标，例如血脂异常和高血压。 T2DM 患者。