Puberty is a risk factor for increased incidence of childhood diabetes, for deteriorating metabolic control, and for increased prevalence of microvascular complications. Moreover, in patients with cystic fibrosis, insulin requiring diabetes develops around the time of puberty. It is now known that puberty is associated with resistance to insulin's action on glucose metabolism. Whether this insulin resistance primarily involves glucose oxidation or glucose storage is not known, and its mechanism(s) remains unknown. Furthermore, it is not known what the consequences of this insulin resistance are on protein, lipid and energy metabolism. The goals of this project are to characterize how puberty alters the hormonal control of energy metabolism in normal man, to define the mechanism(s) responsible for pubertal insulin resistance, and to investigate the consequences of insulin resistance and/or hyperinsulinemia on protein accretion and increased growth that is characteristic of puberty. To accomplish this, the technique of sequential hyperinsulinemic-euglycemic clamp will be used in conjunction with stable isotope tracers to study glucose, leucine (protein), glycerol/palmitate (lipid) turnover kinetics in vivo, and the role of insulin in regulating these pathways. Total net rates of glucose and fat oxidation will be calculated from indirect calorimetric measurements of gaseous exchange.
The specific aims are 1) to determine whether pubertal insulin resistance is limited to glucose or involves protein and fat metabolism, by a cross-sectional study of normal prepubertal, pubertal and postpubertal subjects. 2) To quantitate the relative contributions of glucose oxidation versus glucose storage to the overall decrease in insulin action. 3) To examine whether decrease insulin stimulation of glucose uptake is dependent on increased FFA availability and oxidation. 4) To evaluate whether increased GH during puberty is responsible for decreased insulin action. 5) To study whether pubertal increase in testosterone level plays a role in insulin resistance. Short normal children and patients with delayed puberty will be studied prospectively for aims 4 and 5, respectively. An understanding of the normal physiologic changes in hormonal regulation of energy metabolism that occur during puberty is essential for a thorough evaluation of the pathophysiologic alterations that lead to disease states.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Metabolism Study Section (MET)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hosp Pittsburgh/Upmc Health Sys
United States
Zip Code
Kim, Joon Young; Tfayli, Hala; Michaliszyn, Sara F et al. (2018) Impaired Lipolysis, Diminished Fat Oxidation, and Metabolic Inflexibility in Obese Girls With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 103:546-554
Kim, Joon Young; Nasr, Alexis; Tfayli, Hala et al. (2017) Increased Lipolysis, Diminished Adipose Tissue Insulin Sensitivity, and Impaired ?-Cell Function Relative to Adipose Tissue Insulin Sensitivity in Obese Youth With Impaired Glucose Tolerance. Diabetes 66:3085-3090
Michaliszyn, Sara F; Lee, SoJung; Bacha, Fida et al. (2017) Differences in ?-cell function and insulin secretion in Black vs. White obese adolescents: do incretin hormones play a role? Pediatr Diabetes 18:143-151
Kim, Joon Young; Michaliszyn, Sara F; Nasr, Alexis et al. (2016) The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test Heralds Biomarkers of Type 2 Diabetes Risk in Obese Youth. Diabetes Care 39:1431-9
Michaliszyn, Sara F; Mari, Andrea; Lee, SoJung et al. (2014) ?-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes. Diabetes 63:3846-55
Burns, Stephen F; Lee, SoJung; Bacha, Fida et al. (2014) Pre-diabetes in overweight youth and early atherogenic risk. Metabolism 63:1528-35
Hughan, Kara S; Bonadonna, Riccardo C; Lee, SoJung et al. (2013) ?-Cell lipotoxicity after an overnight intravenous lipid challenge and free fatty acid elevation in African American versus American white overweight/obese adolescents. J Clin Endocrinol Metab 98:2062-9
de las Heras, Javier; Rajakumar, Kumaravel; Lee, SoJung et al. (2013) 25-Hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes. Diabetes Care 36:2048-53
Lee, SoJung; Boesch, Chris; Kuk, Jennifer L et al. (2013) Effects of an overnight intravenous lipid infusion on intramyocellular lipid content and insulin sensitivity in African-American versus Caucasian adolescents. Metabolism 62:417-23
Sjaarda, Lindsey; Lee, SoJung; Tfayli, Hala et al. (2013) Measuring ?-cell function relative to insulin sensitivity in youth: does the hyperglycemic clamp suffice? Diabetes Care 36:1607-12

Showing the most recent 10 out of 72 publications