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

基本信息

批准号：
8629297
负责人：
Joyce Lee
金额：
$ 64.47万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/8629297
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 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 public health relevance response screening trend

项目摘要

PROJECT SUMMARY 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.

项目概要由于儿童期的流行，儿童中糖尿病前期和糖尿病的发病率正在增加肥胖。流行病学研究表明，儿童期糖尿病前期与儿童患 2 型糖尿病的风险较高有关。成年期。因为患有前驱糖尿病的儿童是一个高危人群，他们可能会受益于早期识别和干预，人们对使用先前在成人儿童人群。拟议的研究将评估阵列的纵向测试性能传统的血糖生物标志物，包括糖化血红蛋白 (HbA1c) 和新型代谢组学用于识别葡萄糖耐量进展的生物标志物（正常到糖尿病前期或糖尿病前期到糖尿病）在超重和肥胖的儿科队列中。此外，还将进行喂养研究以检查与大量营养素反应的葡萄糖耐量异常相关的代谢组生物标志物的变异性饮食构成。本研究的具体目的如下：具体目标#1：评估传统的血糖生物标志物是否纵向预测血糖的进展一组超重/肥胖儿童的葡萄糖耐量（正常到糖尿病前期或糖尿病前期到糖尿病）。具体目标#2a：确定纵向预测血糖进展的新型代谢组学指标一组人群中的耐受性（糖尿病前期正常或糖尿病前期正常）和胰岛素抵抗超重/肥胖儿童。具体目标#2b：评估与异常血糖相关的代谢组生物标志物的变异性超重/肥胖者对高碳水化合物和高多不饱和脂肪饮食的耐受性青少年人口。将代谢组学科学应用于人类疾病风险是 NIH 路线图的一个主要重点医学研究。尽管越来越多的代谢组学研究在成人中进行，但很少有已经在儿童中进行了研究。这将是评估的第一个纵向研究之一用于识别青少年的一套全面的传统和新型生物标志物的预测能力与胰岛素敏感性和葡萄糖耐量状态的进展有关。拟议的研究项目代表由具有儿童肥胖和糖尿病专业知识的研究人员组成的独特的多学科合作，糖尿病流行病学、代谢组学、人类营养和生物统计学，并将提供重要信息与未来儿科筛查政策相关，深入了解糖尿病前期/2 型糖尿病的发病机制青春期期间的具体饮食干预措施及其对代谢组影响的信息风险概况。