Depression and Insulin Sensitivity in Adolescents

青少年的抑郁和胰岛素敏感性

• 批准号: 9494565
• 负责人: LAUREN BERGER SHOMAKER
• 金额: $ 55.32万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9494565
• 关键词: Accelerometer; Accounting; Address; Adolescence; Adolescent; Adolescent obesity; Adrenal Gland Hyperfunction; Adult; Affect; Aftercare; Aggressive course; Award; Behavior; Behavioral; Beta Cell; Cell physiology; Child; Circadian Rhythms; Cognitive; Communities; Comorbidity; Consultations; Control Groups; Data; Depressive disorder; Deterioration; Diabetes Mellitus; Diabetes prevention; Disadvantaged; Disease; Doctor of Philosophy; Eating; Ethnic group; Face; Failure; Family; Family history of; Female Adolescents; Goals; Health; Health education; Healthcare; High Prevalence; Human; Hydrocortisone; Insulin; Insulin Resistance; Intervention; Knowledge; Link; Longevity; Mediator of activation protein; Medicine; Mental Depression; Mission; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Output; Overweight; Pathogenesis; Physical activity; Physiological; Physiology; Play; Population; Prevention; Psychosocial Stress; Puberty; Public Health; Randomized Controlled Trials; Recording of previous events; Research; Risk; Risk Factors; Role; Scientist; Sleep; Sleep disturbances; Stress; Structure; Structure of beta Cell of islet; Symptoms; Testing; Time; United States National Institutes of Health; Work; cardiometabolic risk; cardiometabolism; child depression; cost effective; depressive symptoms; diabetes risk; early onset; effective intervention; ethnic diversity; experience; follow-up; girls; high risk; high-risk adolescents; improved; innovation; insulin secretion; insulin sensitivity; lifestyle intervention; moderate-to-vigorous physical activity; modifiable risk; multidisciplinary; physical inactivity; prevent; program costs; programs; prospective; psychosocial; racial and ethnic; response; sedentary; statistics; stress symptom; symptomatic improvement; theories; young adult

Project Summary/Abstract There has been rapid escalation of type 2 diabetes (T2D) rates in adolescents. Early-onset T2D (<20y) typically shows a more aggressive course than adult-onset T2D and disproportionately affects girls from disadvantaged, racial/ethnic groups. This group of girls also is at heightened risk for depression, and depression and T2D are linked. Depressive symptoms often manifest in adolescence and are a prospective risk factor for worsening of insulin sensitivity, the major physiological precursor—in combination with deterioration of pancreatic β-cell ca- pacity to secrete insulin—in the path to T2D. The effects of depression on poor insulin sensitivity remain even after accounting for adiposity. In theory, depressive symptoms may worsen insulin sensitivity through stress- induced behaviors (e.g., disinhibited eating, [physical inactivity], sleep disturbance) and stress-induced phys- iological causal mechanisms (e.g., hypercortisolism). The central theme of our proposal is that intervening to reduce depressive symptoms in adolescents at-risk for T2D may offer an innovative, targeted approach to ame- liorate insulin resistance and to, consequently, preserve β-cell function and lessen T2D risk. In preliminary data from an NIH K99/R00 Award, the PI found initial evidence that a 6-week cognitive-behavioral group decreased depressive symptoms and prevented worsening of insulin sensitivity 1 year later in overweight and obese girls with moderate depressive symptoms and a family history of T2D, in comparison to a 6-week health education control group. Directly extending these findings, the aims of this R01 proposal are: 1) to assess the efficacy of a 6-week cognitive-behavioral depression group vs. a 6-week health education control group for improving insulin sensitivity and preserving β-cell function in racially/ethnically diverse adolescent girls at-risk for T2D with mod- erate depressive symptoms over a 1-year follow-up; 2) to evaluate changes in eating, [physical activity], and sleep as behavioral explanatory mediators underlying the relationship between decreases in depressive symp- toms and improvements in insulin sensitivity and β-cell function over 1 year and 3) to test changes in cortisol awakening response, diurnal cortisol rhythm, and total daily cortisol output as physiological mechanisms explain- ing the relationship between decreases in depressive symptoms and improvements in insulin sensitivity and β- cell function over 1 year. We have assembled a strong, multidisciplinary team of scientists with expertise in depression, obesity, eating (PI: Lauren Shomaker, PhD), [child and adolescent insulin sensitivity and secre- tion] (Co-I: Kristen Nadeau, MD, MS), [puberty, precursors of early-onset T2D] (Co-I: Megan Kelsey, MD, MS), and statistics (Co-I: Sangeeta Rao, PhD), as well as consultation from experts on [ambulatory physical activity monitoring (Andrea Kriska, PhD, MS)], sleep medicine (Kenneth Wright Jr, PhD), [and adolescent depression (Eric Stice, PhD)]. Our long-term goal is to identify feasible, cost-effective public health solutions that have high potential for effective dissemination in communities at-risk for cardiometabolic disease and to understand the mechanisms by which alleviating psychosocial stress facilitates more positive health outcomes.

项目总结/摘要 青少年2型糖尿病（T2 D）发病率迅速上升。早发性T2 D（<20岁）通常 显示出比成人发病的T2 D更具侵略性的过程，并且不成比例地影响来自弱势群体的女孩， 种族/民族团体。这组女孩患抑郁症的风险也很高，抑郁症和T2 D是 有联系抑郁症状通常在青春期出现，是抑郁症恶化的潜在风险因素。 胰岛素敏感性是主要的生理指标，结合胰腺β细胞癌的恶化， 分泌胰岛素的能力--在2型糖尿病的发病过程中。抑郁症对胰岛素敏感性差的影响仍然存在 再加上肥胖症从理论上讲，抑郁症状可能会通过压力使胰岛素敏感性恶化- 诱发行为（例如，饮食不受抑制，[身体活动不足]，睡眠障碍）和压力引起的物理- 生物学因果机制（例如，皮质醇增多症）。我们建议的中心主题是， 减少有T2 D风险的青少年的抑郁症状可能提供一种创新的，有针对性的方法， 减轻胰岛素抵抗，从而保护β细胞功能并降低T2 D风险。初步数据显示， 从NIH K99/R 00奖，PI发现初步证据表明，6周的认知行为组下降， 抑郁症状，并防止超重和肥胖女孩1年后胰岛素敏感性恶化 中度抑郁症状和T2 D家族史，与6周健康教育相比 对照组直接扩展这些发现，本R 01提案的目的是：1）评估 6-认知行为抑郁组与健康教育对照组在改善胰岛素水平方面的比较 敏感性和保留β细胞功能在种族/民族多样化的青春期女孩的风险为T2 D与中度， 在1年的随访中评估抑郁症状; 2）评估饮食、[体力活动]和 睡眠作为行为解释性介质，是抑郁症状减少与抑郁症之间关系的基础， 1年内胰岛素敏感性和β细胞功能的改善和3）测试皮质醇的变化 觉醒反应，昼夜皮质醇节律，和每日皮质醇总输出作为生理机制解释- 研究抑郁症状的减轻与胰岛素敏感性和β- 细胞功能1年以上。我们组建了一支强大的多学科科学家团队，他们拥有以下方面的专业知识： 抑郁症，肥胖，饮食（PI：劳伦Shomaker，博士），[儿童和青少年胰岛素敏感性和分泌， [青春期，早发性T2 D的前兆]（Co-I：Megan凯尔西，MD， MS）和统计学（Co-I：Sangeeta Rao，PhD），以及[门诊体检]专家的咨询 活动监测（Andrea Kriska，PhD，MS）]，睡眠医学（Kenneth Wright Jr，PhD），[和青少年 抑郁症（Eric Stice，PhD）]。我们的长期目标是确定可行的、具有成本效益的公共卫生解决方案 在心脏代谢疾病高危社区有效传播的潜力很大， 了解减轻心理压力的机制有助于取得更积极的健康成果。