Cognitive-Behavioral Therapy and Exercise Training in Adolescents At-Risk for Type 2 Diabetes

项目摘要/摘要 青春期发病的2型糖尿病(T2D)的发病率迅速上升，尤其是女性 历史上处于不利地位的种族/民族群体。预防至关重要，因为青少年发病的T2D通常表现为 与成人发病相比，更具侵袭性的病程和有效的治疗选择仍然难以捉摸。标准- 对T2D预防的护理包括运动训练以改善胰岛素抵抗，这是一种关键的生理学 T2D的前身。尽管短期内有好处，但运动训练对青少年的效果并不明显。 面临T2D的风险。在相当一部分青少年中，抑郁可能是可以解释的。青春期是值得注意的 对于抑郁症的增加和体力活动的减少，特别是对肥胖的女性。年轻人的 随着时间的推移，抑郁症状可能会导致胰岛素抵抗的恶化，与BMI(公斤/平方米)无关 通过压力调节的途径，如减少体力活动和健康。此外，青春期抑郁症是 与体力活动和心肺功能的下降有关，即使在考虑了肥胖症之后， 抑郁预示着更多的人不坚持运动训练。这项提议的中心主题是 首先提供认知行为疗法(CBT)，然后进行干预的干预序列 其次，运动训练将为改善胰岛素抵抗提供有针对性的、有效的策略和 因此，降低有抑郁症状的T2D高危青少年女性的T2D风险。在前一次 NIH/NIDDK K99/R00随机对照试验(RCT)，我们发现CBT治疗6周组可减轻抑郁 在对患有中度抑郁的T2D高危青少年女性进行6周随访时，与 6周教育性健康教育对照组。患有重度抑郁的青少年被随机分配到 与对照组相比，CBT在1年内的空腹和2小时胰岛素水平较低。我们的初步数据表明，CBT的重点是 关于增加体育锻炼的频率/乐趣以对抗抑郁情绪部分解释了原因 减少抑郁降低了T2D风险。目前尚不清楚CBT是否与标准护理锻炼一样有效 训练，或者CBT和运动训练是否能最大限度地降低T2D风险 青春期女性有患T2D伴抑郁症状的风险。要解决这些差距，并直接在我们的 在之前的工作中，我们提出了一个四臂随机对照试验：(1)比较四个6周6周序列的疗效 改善N=300名患有T2D并伴有抑郁症状的高危青少年女性的胰岛素抵抗： (I)CBT运动，(Ii)运动CBT，(Iii)仅CBT(CBT继续CBT)，以及(Iv)仅运动 (ExerciseContinue Exercise)；(2)评估体力活动/健康状况，作为导致抑郁的中介因素- 胰岛素抵抗关联；以及(3)评估减轻抑郁的潜在机制 使用混合方法增加体力活动，改善体能和胰岛素抵抗 评估。研究结果将支持我们的长期目标，即确定可行的、经济有效的干预策略 有效传播给抑郁症状升高的T2D高危青少年的可能性很高。

Project Summary/Abstract There has been rapid escalation in adolescent-onset type 2 diabetes (T2D), particularly in females from historically disadvantaged racial/ethnic groups. Prevention is critical because adolescent-onset T2D often shows a more aggressive disease course than adult-onset, and effective treatment options remain elusive. Standard- of-care for T2D prevention includes exercise training to ameliorate insulin resistance, a key physiological precursor to T2D. Despite short-term benefits, exercise training shows insufficient effectiveness in adolescents at-risk for T2D. Depression may be explanatory in a considerable subset of teenagers. Adolescence is notable for increases in depression and decreases in physical activity, especially in females with obesity. Youths' depression symptoms contribute to worsening insulin resistance over time, independent of BMI (kg/m2), likely through stress-mediated pathways such as reduced physical activity and fitness. Also, adolescent depression is associated with decreased physical activity and cardiorespiratory fitness, even after accounting for adiposity, and depression predicts greater non-adherence to exercise training. The central theme of this proposal is that an intervention sequence of delivering cognitive-behavioral therapy (CBT) first, followed by intervening with exercise training second, will offer a targeted, efficacious strategy for improving insulin resistance and consequently, lowering T2D risk in adolescent females at-risk for T2D with depression symptoms. In a prior NIH/NIDDK K99/R00 randomized controlled trial (RCT), we found that 6-week group CBT decreased depression at 6-week follow-up in adolescent females at-risk for T2D with moderately elevated depression, compared to a 6-week didactic health education control group. Adolescents with elevated depression who were randomized to CBT had lower fasting and 2-hour insulin at 1-year vs. controls. Our preliminary data suggest that CBT's focus on enhancing frequency/enjoyment of physical activity to combat depressed mood partially explained why decreasing depression lowered T2D risk. It is not known if CBT is just as efficacious as standard-of-care exercise training, or whether CBT followed by exercise training results in a maximally potent alleviation of T2D risk in adolescent females at-risk for T2D with depression symptoms. To address these gaps and directly build on our prior work, we propose a four-arm RCT to: (1) Compare the efficacy of four 6-week6-week sequences for improving insulin resistance in N=300 adolescent females at-risk for T2D with elevated depression symptoms: (i) CBTexercise, (ii) exerciseCBT, (iii) CBT only (CBTcontinue CBT), and (iv) exercise only (exercisecontinue exercise); (2) Evaluate physical activity/fitness as mediators underlying the depression- insulin resistance association; and (3) Evaluate underlying mechanisms by which decreasing depression increases physical activity and improves fitness and insulin resistance using a mixed-methods process evaluation. Findings will support our long-term goal to identify feasible, cost-effective intervention strategies with high potential for effective dissemination to adolescents at-risk for T2D with elevated depression symptoms.