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 #2 a: 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 #2 b: 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.

Public Health Relevance

This proposed research project 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/obese pediatric cohort, and a feeding study will be conducted to examine variability in metabolomic biomarkers related to macronutrient diet composition, providing valuable information about the predictors and determinants of abnormal glucose tolerance.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01HD074559-01A1
Application #
8629297
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Giacoia, George
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109