Diabetes Control and Complications Trial (DCCT) Results indicate that most youth with T1DM should be treated intensively in order to reduce the risk of progression of retinopathy and the development of microalbuminuria.

The Problem Translation of DCCT recommendations for treatment of youth with T1DM was expected to be especially challenging, since adolescents in that study had both higher HbA1c levels and an increased risk for severe hypoglycemia compared to adults.

One of the Solutions? The introduction of continuous glucose monitoring systems has provided pediatric practitioners with new tools to meet the special challenges presented by treatment of T1DM in children and adolescents.

DirecNet The Diabetes Research in Children Network was developed to test the clinical utility of continuous glucose monitoring in children with T1DM.

Creation of DirecNet Cooperative agreement through National Institute of Child Health and Human Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) RFA released February 22, year research grants awarded August 2001

Centers in DirecNet Coordinating Center –Jaeb Center for Health Research, Tampa, FL Clinical Centers –University of Colorado: Denver, CO –Children’s Hospital of Iowa: Iowa City, IA –Nemours Children’s Clinic: Jacksonville, FL –Stanford University: Stanford, CA –Yale University: New Haven, CT

Organizational Structure Steering Committee Clinical Centers Coordinating Center NIH Chairman

Organizational Structure Steering Committee Protocol Development Project Management Oversight DSMB

DirecNet’s Vision To develop standard study protocols and the research infrastructure to test clinically important questions regarding use of currently approved devices and new glucose monitoring systems, as they come online, in children with T1DM.

Inpatient Accuracy Study Principal Aim: To assess the accuracy of the Medtronic MiniMed CGMS and the GlucoWatch Biographer II vs gold standard plasma glucose measurements in children with T1DM Lead Investigator: Bruce Buckingham, M.D., Stanford

Study Design Subjects: 90 patients with T1DM in 3 age groups 1-6 yrs 7-11 yrs 12-17yrs 26 hr CRC admission 1-2 CGMS 1-2 GWB II Gold Standard plasma glucose via IV catheter

Daily Glucose Variations Procedure Regular meals and insulin doses GS glucose q30-60 min

Meal Induced Hyperglycemia Test Procedure 75 g liquid CHO meal Delayed pre-meal bolus GS glucose q 5min x 60 min

Insulin Induced Hypoglycemia Test Procedure IV Insulin units/kg Oral or IV glucose given if plasma glucose <60mg/dl GS glucose q 5min

Progress to Date 73 patients have completed study Recruitment to be completed in November First manuscript to be completed by February, 2003

Other DirecNet Inpatient Studies In Progress: CGMS and GWB II performance and 26hr GS glucose levels in healthy, non-diabetic children aged 7-17 yrs Future Studies: Use of this protocol to test new devices as they become available

DirecNet Outpatient Study (Protocol in Development) Lead Investigator: Peter Chase, M.D. U of Colorado Design: Randomized Clinical Trial 200 children with T1DM aged 7-17 yrs Experimental Group: SMBG + Sensor Control Group: SMBG Outcomes: A1c, hypoglycemia, psychosocial Innovative electronic data capture

Personal Note We have assembled an outstanding group of centers and will develop a portfolio of research protocols that will allow rapid translation of advances in glucose sensor technology to the management of children and adolescents with diabetes.