The proposed K23 career development and research plans will prepare Edmond P. Wickham 111, M.D., for a productive career as an independent clinical investigator focusing on the role of traditional and non-traditional cardiovascular risk factors in the vascular dysfunction frequently present in overweight and obese adolescents. The candidate seeks to combine his unique training in Pediatrics, Internal Medicine, and Endocrinology to examine the relationships among adiponectin multimers, circulating progenitor cell number and function, and endothelial function in adolescents. The candidate will complete formal didactic training in study design, biostatistics, and public health resulting in a Masters of Public Health degree. He will integrate this classroom training with the completion of a multi-disciplinary research protocol under the guidance of a diverse team of mentors, each with exceptional research and training records. The proposed studies will test the hypothesis that in adolescents, adiponectin (with particular emphasis on the high molecular weight [HMW] isoform) contributes to endothelial dysfunction, in part through its effects on circulating progenitor cell (CPC) number and function. To test this hypothesis, the candidate will measure traditional cardiovascular risk factors (blood pressure, waist circumference, lipids, glucose), insulin resistance (using glucose and insulin values during an oral glucose tolerance test), inflammatory cytokines, adiponectin multimers, CPC number (CD34+ cells determined by flow cytometry), and flow-mediated dilation (FMD) of the brachial artery in 30 normal-weight, 30 overweight, and 100 obese adolescents ages 11-18. Baseline measures will be repeated in 60 of the obese adolescents after 12-weeks of participation in a family-based, structured weight management program. Additionally, in vitro CPC studies (quantification of colony forming units [CFUHill] and CPC incorporation during a tubule formation assay) will be performed on cells isolated from 30 obese adolescents (ages 14-18) with the metabolic syndrome (MetS) and 30 normal-weight children. Finally, in a subset of 20 adolescents (10 obese-MetS, 10 normal-weight), a second tubule formation assay will be performed in the presence of human recombinant adiponectin to determine the effects of adiponectin on CPC function.

Public Health Relevance

Obese adolescents are at increased risk of developing significant health problems including diabetes mellitus, elevated cholesterol, and elevated blood pressure;each of which is associated with an increased risk of cardiovascular disease. Adiponectin, a hormone released by fat cells, may play an important role in the early blood vessel changes that ultimately lead to heart disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HD053742-01A2
Application #
7662117
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Winer, Karen
Project Start
2009-07-10
Project End
2014-06-30
Budget Start
2009-07-10
Budget End
2010-06-30
Support Year
1
Fiscal Year
2009
Total Cost
$134,568
Indirect Cost
Name
Virginia Commonwealth University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Bean, M K; Ingersoll, K S; Powell, P et al. (2018) Impact of motivational interviewing on outcomes of an adolescent obesity treatment: results from the MI Values randomized controlled pilot trial. Clin Obes 8:323-326
Le, Trang N; Celi, Francesco S; Wickham 3rd, Edmond P (2016) Thyrotropin Levels Are Associated with Cardiometabolic Risk Factors in Euthyroid Adolescents. Thyroid 26:1441-1449
Browning, Matthew G; Bean, Melanie K; Wickham, Edmond P et al. (2015) Cardiometabolic and Fitness Improvements in Obese Girls Who Either Gained or Lost Weight during Treatment. J Pediatr 166:1364-9
Wickham 3rd, Edmond P; DeBoer, Mark D (2015) Evaluation and Treatment of Severe Obesity in Childhood. Clin Pediatr (Phila) 54:929-40
Bean, M K; Powell, P; Quinoy, A et al. (2015) Motivational interviewing targeting diet and physical activity improves adherence to paediatric obesity treatment: results from the MI?Values randomized controlled trial. Pediatr Obes 10:118-25
Franco, R Lee; Privett, Stacey H; Bowen, Mary K et al. (2015) Sympathetic Activity Assessed during Exercise Recovery in Young Obese Females. J Pediatr 167:378-83.e1
Ning, Yi; Yang, Shibing; Evans, Ronald K et al. (2014) Changes in body anthropometry and composition in obese adolescents in a lifestyle intervention program. Eur J Nutr 53:1093-102
Vanguri, Poornima; Brengman, Matthew; Oiticica, Claudio et al. (2014) Laparoscopic gastric plication in the morbidly obese adolescent patient. Semin Pediatr Surg 23:24-30
Vanguri, Poornima; Lanning, David; Wickham, Edmond P et al. (2014) Pediatric health care provider perceptions of weight loss surgery in adolescents. Clin Pediatr (Phila) 53:60-5
Franco, R Lee; Bowen, Mary K; Arena, Ross et al. (2014) Sex differences in pulmonary oxygen uptake kinetics in obese adolescents. J Pediatr 165:1161-5

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