DESCRIPTION (provided by applicant): Recently, an increasing number of cases of type 2 diabetes (T2DM) in children have become evident, a phenomenon which is thought to be related to widespread obesity, decreased physical activity, and other factors. The rising rates of diabetes among children represent a disturbing trend with significant implications for future health care costs to society. Currently, there are no widely accepted clinical recommendations for screening or managing this condition in the pediatric population. A program is being established by the NIH to address this emerging health problem by implementing an intervention trial to identify appropriate treatment of childhood T2DM. The Children?s Hospital of Philadelphia (CHOP) proposes to be a clinical site. Philadelphia is representative of urban America and has a large proportion of African-American and Hispanic high-risk minorities. The Diabetes Care Center (DCC) at CHOP currently follows over 1100 children with diabetes and diagnoses 30 new cases per year of T2DM. Given that the majority of children with T2DM suffer from obesity, with resultant insulin resistance, we hypothesize that improvement of peripheral insulin sensitivity will be the most effective treatment, both for glucose control and for the preservation of insulin secretion. The aims of this proposal are: 1) To evaluate glucose control of pediatric Type 2 diabetes patients on monotherapy with either a thiazolidinedione, a biguanide, or a sulfonylurea in a prospective double blind randomized trial. 2) To evaluate secondary outcome measures including insulin secretory function, insulin sensitivity glucose tolerance and body composition over time, in relation to treatment interventions, glucose control, and psychosocial functioning. 3) To evaluate glucose control on combination therapy with 2 oral agents in pediatric subjects with T2DM who have demonstrated inadequate glucose control (hemoglobin A1c>6.5) after 6 months on a single oral agent; 4) To establish and sustain a local network of partnerships with health care providers, health care systems, and community agencies in Philadelphia to support effective implementation of lifestyle changes critical to the management of childhood T2DM. and finally 5) To evaluates the impact of the local network on lifestyle modification on specific patient?s outcomes over time such as weight and BMI, psychological function, diet, and physical fitness. Aim 1 is completed after 6 months of the monotherapy. Subsequently, the patients are followed for 5 years. To achieve these aims, CHOP will build upon its existing resources within the DCC, the Nutrition Section, and Department of Psychiatry. New and existing partnerships will be forged and reinforced with members of the Philadelphia community to implement lifestyle changes.