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(申请人提供)：由于儿童肥胖症的流行，糖尿病前期和糖尿病在儿科人群中的发病率正在上升。流行病学研究表明，儿童时期的糖尿病前期与成年后患2型糖尿病的风险较高有关。由于患有前驱糖尿病的儿童是一组高危人群，他们可能会从早期的识别和干预中受益，因此人们对儿科人群中先前在成人中验证的生物标志物的使用越来越感兴趣。这项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，包括血红蛋白A1c(HbA1c)，以及用于在超重和肥胖的儿童队列中识别葡萄糖耐量进展(从正常到糖尿病前期或从糖尿病前期到糖尿病)的新型代谢生物标志物。此外，还将进行一项喂养研究，以检查与糖耐量异常相关的代谢生物标记物的变异性，以响应大量营养素的饮食组成。这项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能纵向预测超重/肥胖儿童的糖耐量(从正常到糖尿病前期或从糖尿病前期到糖尿病)的进展。具体目标#2a：确定新的代谢指标，纵向预测超重/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)和胰岛素抵抗的进展。具体目标#2b：在超重/肥胖的青少年人群中，评估与糖耐量异常相关的代谢生物标志物的变异性，以响应高碳水化合物和高多不饱和脂肪饮食。新陈代谢组学在人类疾病风险方面的应用是美国国立卫生研究院医学研究路线图的一个主要重点。虽然越来越多的代谢组学研究已经在成人中进行，但很少有研究在儿童中进行。这将是评估一套全面的常规和新型生物标记物用于识别患有胰岛素敏感性和糖耐量状态进展的青少年的预测能力的首批纵向研究之一。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进行的独特的多学科合作，并将提供与未来儿科筛查政策相关的重要信息，对青春期糖尿病前期/2型糖尿病发病机制的洞察，以及关于特定饮食干预及其对代谢体处于危险状态的影响的信息。