Depression and Insulin Resistance in Adolescents

描述（由申请人提供）：2型糖尿病（T2D）是一种慢性疾病，伴有严重健康并发症的风险增加，如心血管和外周血管疾病、中风、失明和肾衰竭。青少年和年轻人中T2D表现的惊人增加构成了巨大的公共卫生负担。胰岛素抵抗（IR）是T2D的主要生理前体。因此，针对IR的可改变风险因素的预防工作有可能显著降低发展为T2D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，预测成人发作的T2D，并导致T2D死亡率和发病率风险增加，超出了抑郁与肥胖的相互关系。抑郁症状和IR之间联系的潜在机制尚不清楚。理论上，抑郁症状通过促进应激诱导的行为（改变饮食，降低健康）和上调生理应激机制（皮质醇，神经肽Y）诱导IR。抑郁症的心理治疗可改善成人的IR，但尚不确定改善抑郁症状是否可预防T2D风险青少年IR的进展。该提案的目的是：1）评估为期6周的认知行为（CB）抑郁预防组与为期6周的标准护理健康教育（HE）组在减少T2D风险少女的抑郁症状和改善IR方面的效果; 2）评估压力-相关的行为和生理因素，介导的关系，潜在的减少抑郁症状和改善IR;和3）试点交付正念为基础的减压（MBSR）组的青少年女孩的风险为T2D。主要研究者Lauren Shomaker博士是一名儿童临床心理学家，其在青少年发育/精神病理学、饮食行为和儿童肥胖/肥胖相关健康共病方面的背景非常适合推进本提案中的目标。在K99阶段，Shomaker博士将接受培训，以提高她在以下方面的专业知识：1）在青少年中进行随机对照试验（RCT），ii）测量IR，iii）评估心血管健康。Shomaker博士组建了一个强大的指导和顾问团队，具有儿科肥胖和IR RCT的专业知识（共同导师：Marian Tanofsy-Kraff博士，Jack Yanovski博士，CB抑郁干预（埃里克·斯蒂斯，博士，马里安霍洛威，博士），心血管健康（Kong Chen，PhD）、应激生理学（Zofia Zukowska，MD，PhD）、高级统计分析（Cara Olsen，PhD）和MBSR（Kirk Brown，PhD）。拟议的K99/R00应用程序是促进Shomaker博士过渡到独立职业生涯的最终目标的理想工具，该目标侧重于青少年心理社会发展与身体健康之间的相互联系，以及心理社会因素与身体健康之间联系的假定机制。

DESCRIPTION (provided by applicant): 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 up regulating physiological stress mechanisms (cortisol, neuropeptide Y). Psychotherapy for depression improves IR in adults, but it is uncertain whether ameliorating depressive symptoms prevent 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.