The increasing prevalence of obesity in this country has grave public health implications due to associated diseases and complications. Despite increasing evidence that obesity is a genetic disorder with inherent abnormalities in insulin-stimulated fuel metabolism, virtually nothing is known about the nature of early metabolic defects and the antecedents of obesity-related complications in children at high risk for adult obesity. In the present study, we will examine these questions by performing comprehensive metabolic and clinical assessments in lean and obese preadolescent children of parents who are both affected with abnormal obesity. The euglycemic, hyperinsulinemic clamp technique will be used in combination with stable isotopic tracer infusions and indirect calorimetry to identify defects in insulin-stimulated glucose, amino acid and lipid metabolism. The hyperglycemic clamp will be used to detect alterations in glucose-stimulated insulin responses. Results in the high risk children will be compared with those in lean preadolescents of nonobese parents, subjects who are normally exquisitely sensitive to insulin and who have the lowest insulin responses to glucose. Metabolic defects in the at risk population will be related to alterations in fat distribution assessed by MRI techniques. Each group will be prospectively followed into adolescence in order to determine the evolution of the metabolic abnormalities and how they are related to accumulation and distribution of body fat and the development of changes in blood pressure and circulating lipids. In summary, these studies will provide new important data on the mechanisms underlying the development of obesity in humans.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028016-02
Application #
3329641
Study Section
Special Emphasis Panel (SRC (05))
Project Start
1991-06-01
Project End
1996-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Galderisi, Alfonso; Giannini, Cosimo; Weiss, Ram et al. (2018) Trajectories of changes in glucose tolerance in a multiethnic cohort of obese youths: an observational prospective analysis. Lancet Child Adolesc Health 2:726-735
Tricò, Domenico; Natali, Andrea; Mari, Andrea et al. (2018) Triglyceride-rich very low-density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents. Diabetes Obes Metab 20:2905-2910
Tricò, Domenico; Caprio, Sonia; Rosaria Umano, Giuseppina et al. (2018) Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort. Hepatology 68:1376-1390
Caprio, Sonia; Perry, Rachel; Kursawe, Romy (2017) Adolescent Obesity and Insulin Resistance: Roles of Ectopic Fat Accumulation and Adipose Inflammation. Gastroenterology 152:1638-1646
Tricò, Domenico; Di Sessa, Anna; Caprio, Sonia et al. (2017) Oxidized Derivatives of Linoleic Acid in Pediatric Metabolic Syndrome: Is Their Pathogenic Role Modulated by the Genetic Background and the Gut Microbiota? Antioxid Redox Signal :
Goffredo, Martina; Santoro, Nicola; Tricò, Domenico et al. (2017) A Branched-Chain Amino Acid-Related Metabolic Signature Characterizes Obese Adolescents with Non-Alcoholic Fatty Liver Disease. Nutrients 9:
Weiss, Ram; Santoro, Nicola; Giannini, Cosimo et al. (2017) Prediabetes in youth - mechanisms and biomarkers. Lancet Child Adolesc Health 1:240-248
Tricò, Domenico; Prinsen, Hetty; Giannini, Cosimo et al. (2017) Elevated ?-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents. J Clin Endocrinol Metab 102:2473-2481
Hoang, Don; Broer, Niclas; Sosa, Julie A et al. (2017) Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion. Ann Surg 266:1075-1083
Cropano, Catrina; Santoro, Nicola; Groop, Leif et al. (2017) The rs7903146 Variant in the TCF7L2 Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing ?-Cell Function and Hepatic Insulin Sensitivity. Diabetes Care 40:1082-1089

Showing the most recent 10 out of 92 publications