Conventional and Metabolomic Predictors of Pediatric Prediabetes & Insulin Resist

描述（由申请人提供）：由于儿童肥胖症的流行，儿童人群中糖尿病前期和糖尿病的发病率正在增加。流行病学研究表明，儿童期糖尿病前期与成年后患2型糖尿病的风险较高有关。由于糖尿病前期儿童代表了一个高危人群，他们可能会从早期识别和干预中受益，因此人们越来越感兴趣地将先前在成人中验证的生物标志物用于儿科人群。这项拟议的研究将评估一系列常规生物标志物的纵向测试性能，包括血红蛋白A1 c（HbA 1c）和新的代谢组学生物标志物，用于确定超重和肥胖儿童队列中葡萄糖耐量的进展（正常至糖尿病前期或糖尿病前期至糖尿病）。此外，还将进行喂养研究，以检查与糖耐量异常相关的代谢组学生物标志物对大量营养素饮食组成的反应的变异性。本研究的具体目的如下：具体目的#1：评估是否常规生物标志物的纵向预测葡萄糖耐量（正常到前驱糖尿病或前驱糖尿病到糖尿病）的超重/肥胖儿童队列的进展。具体目标#2a：确定新的代谢组学指标，纵向预测葡萄糖耐量（正常到糖尿病前期或糖尿病前期到糖尿病）和胰岛素抵抗在超重/肥胖儿童队列的进展。具体目标#2b：评价超重/肥胖青少年人群中高碳水化合物和高多不饱和脂肪饮食对糖耐量异常相关的代谢组学生物标志物的变异性。代谢组学在人类疾病风险中的应用是NIH医学研究路线图的主要焦点。虽然越来越多的代谢组学研究已在成人中进行，很少有研究已在儿童中进行。这将是第一个纵向研究，以评估一套全面的传统和新型生物标志物的预测能力，以确定青少年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多学科合作，并将为未来的儿科筛查政策提供重要信息，深入了解青春期糖尿病前期/2型糖尿病的发病机制，以及关于特定饮食干预及其对代谢组学“风险”概况的影响的信息。

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.