Depression and Insulin Resistance in Adolescents

项目摘要/摘要 2型糖尿病(T2D)是一种慢性疾病，伴有严重健康并发症的高风险 如心血管和外周血管疾病、中风、失明和肾功能衰竭。令人震惊的崛起 T2D在青少年和青壮年中的表现构成了巨大的公共卫生负担。 胰岛素抵抗(IR)是T2D的主要生理前兆。因此，针对目标的预防工作是可以修改的 IR的危险因素有可能显著降低发生T2D的风险。抑郁症状 通常首次出现在青春期，与青少年和成人的IR有关，预测成人发病 T2D，并导致T2D死亡率和发病率的增加，超出 抑郁症与肥胖症。抑郁症状和胰岛素抵抗之间联系的潜在机制是 不清楚。从理论上讲，抑郁症状通过促进应激诱导的行为(改变饮食， 降低体能)和上调生理应激机制(皮质醇、神经肽Y)。心理治疗 抑郁症可以改善成人的胰岛素抵抗，但改善抑郁症状是否能预防 T2D高危青少年胰岛素抵抗的进展。 这项建议的目的是：1)评估6周认知行为(CB)抑郁的效果。 预防组与6周标准护理健康教育(HE)组在减少抑郁症状方面的比较 和改善有T2D风险的青春期女孩的IR；2)评估与应激相关的行为和 调节抑郁症状减少与抑郁之间关系的生理因素 改善IR；以及3)试点交付基于正念的压力减轻(MBSR)小组以 青少年、女孩有患T2D的风险。少年派劳伦·舒梅克博士是一位儿童临床心理学家，他 青少年发育/精神病理学、饮食行为和儿童肥胖/肥胖背景- 相关的健康合并症特别适合于推进本提案中的目标。在K99阶段，Dr。 Shomaker将接受培训，以增强她在以下方面的专业知识：1)在 青少年，II)IR的测量，以及III)心血管健康的评估。Shomaker博士已经 组建了一支强大的指导和顾问团队，在儿童肥胖和IR的随机对照试验(RCT)方面具有专业知识 导师：玛丽安·塔诺夫西-克拉夫，博士，杰克·亚诺夫斯基，医学博士，博士)，CB抑郁症干预(Eric Stices，博士， Marjan Holloway博士)、心血管健身(孔陈博士)、应激生理学(Zofia Zukowska医学博士、 博士)、高级统计分析(Cara Olsen，博士)和MBSR(Kirk Brown，博士)。拟建的K99/R00 应用程序是推动Shomaker博士过渡到独立医生最终目标的理想工具 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， 以及心理社会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.