application) In adults, type 2 diabetes represents a group of polygenic disorders with abnormalities in insulin sensitivity, insulin secretion, and hepatic glucose production. Recently, there have been increased reports of what appears to be type 2 diabetes in the pediatric population. This increase in type 2 diabetes in children has occurred amidst an environment of increasing insulin resistance, as noted by 1) the pubertal stage of many affected individuals, 2) the parallel increase in obesity within the pediatric population, 3) the parallel increase in sedentary lifestyle features, and 4) the frequent presence of acanthosis nigricans. However, all individuals with insulin resistance do not have type 2 diabetes. Little data is available on the pathophysiology of impaired glucose tolerance and type 2 diabetes in children and adolescents. In order to prove that type 2 diabetes in adolescents is characterized by severe insulin resistance and defects in B-cell function, adolescents with Type 2 diabetes followed at Children's Memorial Hospital will undergo a thorough history, physical examination, an oral gluocse tolerance and, in a subset of participants, a frequently sampled intravenous glucose tolerance test. In order to prove that adolescents with acanthosis nigricans and varying degrees of glucose tolerance are characterized by severe insulin resistance and defects in B-cell function, a group of adolescents with acanthosis nigricans will be recruited. Each will have a thorough history and targeted physical, and an oral glucose tolerance test to assess insulin sensitivity, insulin secretion, and glucose tolerance. A subset of these will also undergo a modified IVGTT as well. In order to prove that adolescents with insulin resistance have evidence of risk factors for later cardiovascular disease, a group of individuals with low insulin sensitivity will have cardiovascular studies to evaluate for pediatric antecedents of cardiovascular disease. A better understanding of the pathophysiology of type 2 diabetes and its development in adolescents, will enable us to predict which preventive and therapeutic interventions will be successful in hopes of improving the morbidity and mortality associated with type 2 diabetes and/or severe insulin resistance.
| Brickman, Wendy J; Huang, Jie; Silverman, Bernard L et al. (2010) Acanthosis nigricans identifies youth at high risk for metabolic abnormalities. J Pediatr 156:87-92 |
| Brickman, Wendy J; Binns, Helen J; Jovanovic, Borko D et al. (2007) Acanthosis nigricans: a common finding in overweight youth. Pediatr Dermatol 24:601-6 |
