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

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

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

380

400

2:00 PM 3:00 PM 4:00 PM 5:00 PM 6:00 PM 7:00 PM 8:00 PM 9:00 PM 10:00PM

11:00 PM 12:00AM

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 10:00AM

11:00AM

12:00PM

1:00 PM 2:00 PM

gluc

ose

(mg/

dl)

Procedure•Regular meals and insulin doses•GS glucose q30-60 min

Meal Induced Hyperglycemia Test

100

120

140

160

180

200

220

240

260

280

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320

340

360

4:55 PM 5:09 PM 5:24 PM 5:38 PM 5:52 PM 6:07 PM 6:21 PM

glu

cose

(m

g/d

l)

Procedure

•75 g liquid CHO meal

•Delayed pre-meal bolus

•GS glucose q 5min x 60 min

Insulin Induced Hypoglycemia Test

40

60

80

100

120

8:24 AM 8:42 AM 9:00 AM 9:18 AM

gluc

ose

(mg/

dl)

Procedure

•IV Insulin 0.05-0.1 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 ColoradoDesign:• 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.