Conventional and Metabolomic Predictors of Pediatric Prediabetes & Insulin Resist

儿童糖尿病前期的常规和代谢组学预测因子

• 批准号: 8843502
• 负责人: Joyce Lee
• 金额: $ 56.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843502
• 关键词: Adolescence; Adolescent; Adult; American; Biological Markers; Biometry; Carbohydrates; Cardiovascular Diseases; Child; Childhood; Clinical; Cross-Sectional Studies; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diet; Dietary Intervention; Early Intervention; Early identification; Epidemic; Epidemiologic Studies; Epidemiology; Etiology; Functional disorder; Future; Glycosylated hemoglobin A; Growth; Health; Human; Impaired fasting glycaemia; Incidence; Individual; Insulin; Insulin Resistance; Intake; Interdisciplinary Study; Intervention; Lead; Link; Longitudinal Studies; Macronutrients Nutrition; Measures; Medical Research; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Overweight; Pathogenesis; Pattern; Performance; Policies; Population; Prediabetes syndrome; Prevalence; Preventive Intervention; Puberty; Research Personnel; Research Project Grants; Risk; Risk Factors; Science; Time; Youth; cohort; diabetes risk; disorder risk; feeding; glucose tolerance; high risk; human disease; impaired glucose tolerance; insight; insulin sensitivity; interest; metabolomics; novel; nutrition; obesity in children; performance tests; polyunsaturated fat; primary care setting; response; screening; trend

DESCRIPTION (provided by applicant): Rates of prediabetes and diabetes are increasing in the pediatric population, due to the epidemic of childhood obesity. Epidemiologic studies have linked prediabetes in childhood with a higher risk of type 2 diabetes in adulthood. Because children with prediabetes represent a high-risk group of individuals who may benefit from early identification and intervention, there is increasing interest in the use of biomarkers previously validated in adults for pediatric populations. The proposed study will evaluate the longitudinal test performance of an array of conventional biomarkers of glycemia, including Hemoglobin A1c (HbA1c), and novel metabolomic biomarkers for identifying progression of glucose tolerance (normal to prediabetes or prediabetes to diabetes) in an overweight and obese pediatric cohort. In addition, a feeding study will also be conducted to examine variability in metabolomic biomarkers associated with abnormal glucose tolerance in response to macronutrient diet composition. The specific aims of this study are the following: Specific Aim #1: Assess whether conventional biomarkers of glycemia longitudinally predict progression of glucose tolerance (normal to prediabetes or prediabetes to diabetes) in a cohort of overweight/obese children. Specific Aim #2a: Identify novel metabolomic measures that longitudinally predict progression of glucose tolerance (normal to prediabetes or prediabetes to diabetes) and insulin resistance in a cohort of overweight/obese children. Specific Aim #2b: Evaluate the variability in metabolomic biomarkers associated with abnormal glucose tolerance in response to high carbohydrate and high polyunsaturated fat diets in an overweight/obese adolescent population. Application of the science of metabolomics to human disease risk is a major focus of the NIH's Roadmap for Medical Research. Although an increasing number of metabolomic studies have been conducted in adults, few studies have been conducted in children. This will be one of the first longitudinal studies to evaluate the predictive capacity of a comprehensive set of conventional and novel biomarkers for identifying adolescents with insulin sensitivity and progression of glucose tolerance status. The proposed research project represents a unique multidisciplinary collaboration of investigators with expertise in pediatric obesity and diabetes, diabetes epidemiology, metabolomics, human nutrition, and biostatistics, and will provide important information relevant for future pediatric screening policy, insights into the pathogenesis of prediabetes/type 2 diabetes during adolescence, and information on specific dietary interventions and their impact on the metabolomic 'at risk' profile.

描述（由申请人提供）：由于儿童肥胖症的流行，儿童中糖尿病前期和糖尿病的发病率正在增加。流行病学研究已将儿童期糖尿病前期与成年后患 2 型糖尿病的较高风险联系起来。由于患有糖尿病前期的儿童是可能受益于早期识别和干预的高危人群，因此人们越来越关注将先前在成人中验证过的生物标志物用于儿科人群。拟议的研究将评估一系列常规血糖生物标志物的纵向测试性能，包括糖化血红蛋白 (HbA1c) 和新型代谢组生物标志物，用于识别超重和肥胖儿童的糖耐量进展（正常到糖尿病前期或糖尿病前期到糖尿病）队列。此外，还将进行一项喂养研究，以检查与宏量营养素饮食成分反应的异常葡萄糖耐量相关的代谢组生物标志物的变异性。本研究的具体目标如下： 具体目标#1：评估传统的血糖生物标志物是否纵向预测超重/肥胖儿童队列中糖耐量的进展（从正常到糖尿病前期或从糖尿病前期到糖尿病）。具体目标#2a：确定新的代谢组学测量方法，纵向预测超重/肥胖儿童队列中糖耐量（正常到糖尿病前期或糖尿病前期到糖尿病）和胰岛素抵抗的进展。具体目标#2b：评估超重/肥胖青少年群体中与高碳水化合物和高多不饱和脂肪饮食引起的糖耐量异常相关的代谢组生物标志物的变异性。将代谢组学科学应用于人类疾病风险是美国国立卫生研究院医学研究路线图的一个主要重点。尽管越来越多的代谢组学研究在成人中进行，但在儿童中进行的研究却很少。这将是首批纵向研究之一，旨在评估一套全面的传统和新型生物标志物的预测能力，用于识别青少年的胰岛素敏感性和葡萄糖耐量状态的进展。拟议的研究项目代表了具有儿科肥胖和糖尿病、糖尿病流行病学、代谢组学、人类营养和生物统计学专业知识的研究人员的独特的多学科合作，并将为未来的儿科筛查政策、深入了解前驱糖尿病/糖尿病类型的发病机制提供重要信息。青春期 2 型糖尿病，以及有关特定饮食干预措施及其对代谢组“危险”状况影响的信息。