Depression and Insulin Resistance in Adolescents

项目概要/摘要 2型糖尿病（T2 D）是一种慢性疾病，伴有严重健康并发症的风险增加 例如心血管和外周血管疾病、中风、失明和肾衰竭。惊人增多 在青少年和年轻人中T2 D的表现构成了巨大的公共卫生负担。 胰岛素抵抗（IR）是T2 D的主要生理前体。因此，针对可改变的 IR的风险因素有可能显著降低发展为T2 D的风险。抑郁症状 通常在青春期首次出现，与青少年和成人的IR相关，可预测成人发病 2型糖尿病，并导致2型糖尿病死亡率和发病率的风险增加，超出了 抑郁症伴肥胖症抑郁症状和IR之间联系的潜在机制是 不清楚抑郁症状理论上通过促进压力诱导的行为（改变饮食， 降低健身）和上调生理应激机制（皮质醇，神经肽Y）。心理治疗 抑郁症可以改善成年人的IR，但尚不确定改善抑郁症状是否可以预防 有T2 D风险的青少年的IR进展。 本研究的目的是：1）评估为期6周的认知行为（CB）抑郁症的影响 预防组与为期6周的标准护理健康教育（HE）组在减少抑郁症状方面的比较 和改善处于T2 D风险中的青春期女孩的IR; 2）评估与压力相关的行为和 介导抑郁症状减少的潜在关系的生理因素， IR的改善; 3）以正念为基础的减压（MBSR）小组的试点交付， 青少年女孩有患T2 D的风险。私家侦探劳伦·肖梅克博士是一位儿童临床心理学家， 青少年发育/精神病理学、饮食行为和儿童肥胖/肥胖的背景- 相关的健康共病特别适合于推进本提案中的目标。在K99阶段，博士。 Shomaker将接受培训，以提高她在以下方面的专业知识：1）进行随机对照试验（RCT）， 青少年，ii）测量IR，和iii）评估心血管健康。肖马克医生 组建了一个强大的指导和顾问团队，他们在儿童肥胖和IR的RCT方面具有专业知识（合作， 导师：Marian Tanofsy-Kraff，博士，Jack Yanovski，医学博士，博士），CB抑郁干预（Eric Stice，博士， Marjan霍洛威，博士），心血管健康（Kong Chen，博士），压力生理学（Zofia Zukowska，医学博士， 高级统计分析（Cara Olsen，PhD）和MBSR（Kirk Brown，PhD）。建议的K99/R 00 应用程序是理想的工具，以促进博士Shomaker的最终目标过渡到一个独立的 职业生涯侧重于青少年心理社会发展和身体健康之间的相互联系， 以及社会心理因素和身体健康之间联系的潜在机制。

PROJECT SUMMARY/ABSTRACT Type 2 diabetes (T2D) is a chronic disease accompanied by heightened risk for severe health complications such as cardiovascular and peripheral vascular disease, stroke, blindness, and renal failure. The alarming rise in the manifestation of T2D among adolescents and young adults poses an enormous public health burden. Insulin resistance (IR) is a major physiological precursor to T2D. Thus, prevention efforts targeting modifiable risk factors for IR have the potential to diminish the risk of developing T2D significantly. Depressive symptoms often first appear during adolescence, are associated with IR in adolescents and adults, predict adult-onset T2D, and contribute to increased risk for T2D mortality and morbidity, beyond the interrelationship of depression with obesity. The mechanisms underlying the link between depressive symptoms and IR are unclear. Depressive symptoms theoretically induce IR by promoting stress-induced behaviors (altered eating, lowered fitness) and upregulating physiological stress mechanisms (cortisol, neuropeptide Y). Psychotherapy for depression improves IR in adults, but it is uncertain whether ameliorating depressive symptoms prevents progression of IR in adolescents at risk for T2D. The aims of this proposal are: 1) to assess the effects of a 6-wk cognitive-behavioral (CB) depression prevention group vs. a 6-wk standard-of-care health education (HE) group on reducing depressive symptoms and improving IR in adolescent girls at risk for T2D; 2) to assess the stress-related behavioral and physiological factors that mediate the relationship underlying decreases in depressive symptoms and improvements in IR; and 3) to pilot delivery of a mindfulness-based stress reduction (MBSR) group to adolescents girls at risk for T2D. The PI, Dr. Lauren Shomaker, is a child clinical psychologist whose background in adolescent development/psychopathology, eating behavior, and pediatric obesity/obesity- related health co-morbidities is uniquely suited to advance the aims in this proposal. During the K99 phase, Dr. Shomaker will obtain training to enhance her expertise in: 1) conduct of randomized controlled trials (RCTs) in adolescents, ii) measurement of IR, and iii) assessment of cardiovascular fitness. Dr. Shomaker has assembled a strong mentoring and consultant team with expertise in RCTs for pediatric obesity and IR (Co- Mentors: Marian Tanofsy-Kraff, PhD, Jack Yanovski, MD, PhD), CB depression interventions (Eric Stice, PhD, Marjan Holloway, PhD), cardiovascular fitness (Kong Chen, PhD), stress physiology (Zofia Zukowska, MD, PhD), advanced statistical analysis (Cara Olsen, PhD), and MBSR (Kirk Brown, PhD). The proposed K99/R00 application is the ideal vehicle to promote Dr. Shomaker's ultimate goal of transitioning to an independent career focused upon the interconnections between adolescent psychosocial development and physical health, and the putative mechanisms underlying the links between psychosocial factors and physical well-being.