The epidemic of childhood obesity has led to the emergence of a cluster of cardiovascular risk factors, known as the metabolic syndrome, in nearly 9 percent of US teens;This K23 award investigates the development of the metabolic syndrome among early adolescents, with a focus on the mechanism of changes in adiponectin levels and visceral fat in relation to tobacco exposure, building on previous publications and pilot studies. The proposal provides Dr. Cook with a rigorous didactic and mentored training program in clinical research, focusing on the development during adolescence of the metabolic syndrome and its components. The didactic curriculum includes targeted training in courses, seminars and two offsite training programs, providing background and experience that bridge basic and clinical research. Dr. Cook : will obtain essential clinical research experience by conducting 2 interlocking projects under the guidance of an experienced, multi-disciplinary mentoring team. The overarching theme of the.research plan is to study precursors of obesity, diabetes, and cardiovascular risk factors during adolescence. During this critical biological period of physiologic change in body composition and insulin resistance, an individual establishes lifelong habits of diet, activity, and tobacco .use. Study 1 will build and follow a community cohort of above- average-weight 9-10 yr olds with various degrees of household smoke exposure. Cotinine, a metabolite of nicotine, will be used to quantify and track duration of tobacco exposure. This study will examine] longitudinal changes in key factors, such as adiponectin and total/central body fat, in relation to tobacco exposure during the critical period of puberty. These analyses may identify precursors to changes in the cardiovascular risk factors of the metabolic syndrome (dyslipidemia, elevated blood pressure, impaired glucose/insulin metabolism). Study 2 will be a cross-sectional metabolic substudy of subjects recruited from the larger cohort in Study 1, including individuals with high smoke exposure (passive of actiive) and no smoke exposure. They will undergo MR! for visceral fat measurement and a frequently sampled glucose tolerance test to determine insulin resistance. Ultimately, we propose to test the hypothesis that adolescence is a vulnerable period that stabjishes the course of future cardiovascular disease in adults, /^better understanding of early stages of cardiovascular disease will allow us to optimize both prevention and intervention strategies in future studies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (M1))
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Silsbee, Lorraine M
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University of Rochester
Schools of Dentistry
United States
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Balagopal, Prabhakaran Babu; de Ferranti, Sarah D; Cook, Stephen et al. (2011) Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation 123:2749-69
Cook, Stephen; Kavey, Rae Ellen W (2011) Dyslipidemia and pediatric obesity. Pediatr Clin North Am 58:1363-73, ix
Foltz, Jennifer L; Cook, Stephen R; Szilagyi, Peter G et al. (2011) US adolescent nutrition, exercise, and screen time baseline levels prior to national recommendations. Clin Pediatr (Phila) 50:424-33
Levy-Marchal, Claire; Arslanian, Silva; Cutfield, Wayne et al. (2010) Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 95:5189-98
Gracious, Barbara L; Cook, Stephen R; Meyer, Ashley E et al. (2010) Prevalence of overweight and obesity in adolescents with severe mental illness: a cross-sectional chart review. J Clin Psychiatry 71:949-54
Klein, Jonathan D; Sesselberg, Tracy S; Johnson, Mark S et al. (2010) Adoption of body mass index guidelines for screening and counseling in pediatric practice. Pediatrics 125:265-72
Kelishadi, Roya; Cook, Stephen R; Amra, Babak et al. (2009) Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis 204:538-43
Cook, Stephen; Auinger, Peggy; Huang, Terry T-K (2009) Growth curves for cardio-metabolic risk factors in children and adolescents. J Pediatr 155:S6.e15-26
Skelton, Joseph A; Cook, Stephen R; Auinger, Peggy et al. (2009) Prevalence and trends of severe obesity among US children and adolescents. Acad Pediatr 9:322-9
Rossi, Brooke; Sukalich, Sara; Droz, Jennifer et al. (2008) Prevalence of metabolic syndrome and related characteristics in obese adolescents with and without polycystic ovary syndrome. J Clin Endocrinol Metab 93:4780-6

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