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, 2001
• 5-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
NIH
Clinical
Centers
Steering
Committee
Chairman
Coordinating
Center
Organizational Structure
Steering
Committee
Project
Management
Protocol
Development
DSMB
Oversight
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
400
380
360
340
320
300
glucose (mg/dl)
280
260
240
220
200
180
160
140
120
100
80
60
40
2:00 PM 3:00 PM 4:00 PM 5:00 PM 6:00 PM 7:00 PM 8:00 PM 9:00 PM
10:00
PM
11:00 PM
12:00
AM
1:00 AM 2:00 AM 3:00 AM 4:00 AM 5:00 AM 6:00 AM 7:00 AM 8:00 AM 9:00 AM
10:00
AM
11:00
AM
12:00
PM
1:00 PM 2:00 PM
Meal Induced Hyperglycemia Test
360
340
320
300
glucose (mg/dl)
280
260
240
Procedure
220
•75 g liquid CHO meal
200
180
•Delayed pre-meal bolus
160
•GS glucose q 5min x 60 min
140
120
100
4:55 PM
5:09 PM
5:24 PM
5:38 PM
5:52 PM
6:07 PM
6:21 PM
Insulin Induced Hypoglycemia Test
Procedure
•IV Insulin 0.05-0.1 units/kg
•Oral or IV glucose given if plasma glucose
<60mg/dl
•GS glucose q 5min
120
glucose (mg/dl)
100
80
60
40
8:24 AM
8:42 AM
9:00 AM
9:18 AM
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.