The Physiological Variations of Plasma Glucose Concentrations in Healthy, Non-Diabetic Children: Use of Continuous Glucose Sensors Nelly Mauras, Roy Beck, Katrina Ruedy, Andrea Booth, Stuart Weinzimer, and the Diabetes Research in Children Network (DirecNet) Study Group.

Clinical Centers Barbara Davis Center for Childhood Diabetes, Denver, CO Nemours Children’s Clinic, Jacksonville, FL Stanford University Medical Center, Stanford, CA University of Iowa, Iowa City, IA Yale University Medical Center, New Haven, CT Coordinating Center Jaeb Center for Health Research, Tampa, FL

Background Characterization of the diurnal variations in plasma glucose in normal children is critical for the interpretation of glucose values using continuous glucose sensors in pathological states, such as diabetes and hypoglycemic conditions. Preliminary reports and anecdotal data suggest that non-diabetic children have low sensor glucose levels, especially at night (Weinzimer SA, et al, Diabet Technol Ther 2003).

Objective To determine the accuracy of 2 glucose sensors, the Continuous Glucose Monitoring System (CGMS - Medtronics/Minimed) and the Glucowatch® G2TM Biographer (GW2B-Cygnus) in healthy, non diabetic children while examining the 24h pattern of glucose concentrations.

Inclusion Criteria healthy boys and girls ages 7 to 17 years normal HbA1C no first degree relatives with diabetes BMI between 10th and 90th percentile normal Hematocrit no skin abnormalities contraindicating sensor use

Procedures All patients were admitted to each center’s CRC An iv catheter was placed after numbing skin for reference blood glucose determinations every hour during the day (7AM to 9PM) and every 1/2 hour overnight (9:30PM to 6:30AM).

Glucowatch Biographer Measures blood glucose from interstitial fluid via reverse iontophoresis.

CGMS Measures blood glucose via a glucose oxidase based electrochemical sensor. CGMS

GW2B Accuracy Summary Statistics Total 11:00PM-6:00AM 6:30AM -10:30PM Paired data points 487 286 201 Absolute difference (median) 13 13 13 (mg/dl) (25, 75th percentiles) (6,23) (6,24) (7,21) %Values within 10 mg/dl 40% 41% 40% %Values within 20 mg/dl 70% 66% 74%

CGMS Accuracy Summary Statistics Total 11:00PM-6:00AM 6:30AM -10:30PM Paired data points 668 307 361 Absolute difference (median) 17 18 16 (mg/dl) (25, 75th percentiles) (8,29) (8,29) (7,29) %Values within 10 mg/dl 34% 32% 36% %Values within 20 mg/dl 58% 56% 60%

Low glucose readings by sensors GW2B CGMS 108 139 Values <60 mg/dl 7/108 1/139 Isolated readings Coincided with reference glucose 33/108 14/139 Paired value had reference glucose >70 mg/dl 33/33 14/14

Glucose values measured by reference lab, CGMS and GW2B sensors

Glucose values measured by reference lab, CGMS and GW2B sensors

Mean and range serum glucose concentrations (mg/dL) measured by reference lab in healthy children (N=15) Time of Day Glucose (mg/dL)

Summary In healthy non-diabetic children wearing continuous glucose sensors: the median absolute difference in glucose concentrations between the GW2B and reference glucose concentrations is 13 mg/dl, with 40% of values within 10mg/dl of the reference value for CGMS the median absolute difference is 17 mg/dl with 34% of values within 10mg/dl of the laboratory reference.

Conclusions Our data support that: 1) neither the GW2B nor CGMS is accurate enough to provide normative glycemia profiles for non-diabetic children 2) previous reports of low sensor glucose values in non-diabetic children may represent inaccurate glucose measurements 3) serum glucose concentrations in non-diabetic children are tightly controlled.