Use of The FreeStyle Navigator TM Continuous Glucose Monitoring System in Children on Glargine- based Multiple Daily Injection Therapy Stuart Weinzimer 1, Dongyuan Xing 2, Michael Tansey 3, Rosanna Fiallo-Scharer 4, Nelly Mauras 5, Tim Wysocki 5, Roy Beck 2, William Tamborlane 1, Katrina Ruedy 2, Darrell Wilson 6, and the Diabetes Research in Children Network (DirecNet) Study Group 1 New Haven, CT; 2 Tampa, FL; 3 Iowa City, IA; 4 Denver, CO; 5 Jacksonville,FL; 6 Stanford, CA

Introduction: Real-time continuous glucose monitoring (CGM) can potentially revolutionize the treatment of type 1 diabetes (T1D) in children. The Diabetes Research in Children Network previously showed that pump-treated youth with T1D using the FreeStyle Navigator lowered HbA1c and increased time spent in target range. We hypothesized that the use of multiple daily injection (MDI) regimens, which offer less flexibility than pumps, may limit the effectiveness of CGM to improve glycemic control. Our objective was to determine whether youth utilizing glargine-based MDI would benefit from daily use of the Navigator. Methods: Following use of a masked Navigator for 4-7d to characterize baseline glycemic control, 27 subjects (mean age 11.0  3.9y, mean diabetes duration 4.0  3.1y) with T1D using basal-bolus MDI therapy with glargine were asked to use the Navigator daily for 26 wks. Results: 23 subjects completed both the 13- and 26-week visits. Sensor use decreased slightly from median 121 hours per week at weeks 1-4 to 101 at weeks (p=0.07), and continued to decline to 48 by weeks (p<0.001 c/w wks 1-4). Mean A1c decreased from baseline to 13 weeks (7.9  1.0% to 7.3  0.9%, p=0.004), but rose again by 26 weeks (7.6  1.2%, p=0.17 from baseline). Subjects and parents reported overall high levels of satisfaction with the Navigator, and subjects showed improved quality of life with the Navigator. Conclusions: Real-time CGM with the Navigator is feasible and tolerable in pediatric patients using basal-bolus MDI and associated with reduced HbA1c and improved quality of life over a 3 month period. Future pediatric trials of CGM should include both MDI- and pump-treated patients and should concentrate on obstacles to continued sensor use. Abstract

Background Real-time continuous glucose monitoring devices (CGM) are a potentially powerful tool in the management of type 1 diabetes (T1D) For successful adoption into clinical practice, they must be accurate, comfortable to wear, and easy to use, particularly in children Previous studies of CGM in children have focused primarily on children utilizing insulin pump therapy; it is unknown whether this type of technology will be tolerated and effective in children using intensive multiple injection regimens, who may be unaccustomed or unwilling to wear and/or use continuous devices

Study Aim The purpose of this pilot study was to examine the effectiveness and tolerability of a continuous glucose monitor (Abbott Navigator) in children with type 1 diabetes using intensive glargine-based multiple daily injection (MDI) regimens

Research Design & Methods 27 children with T1D (4-17 yr old) using glargine-based MDI wore the Navigator as an outpatient for 1 week but were blinded to sensor data Subjects then wore the Navigator (unblinded) as an outpatient for 13 weeks Devices were downloaded weekly to subjects’ home computers and subjects were contacted frequently (q1- 4wk) in order to monitor Navigator use Questionnaires were completed at baseline and 13 weeks Outcome measures included: glycemic control, glucose variability, and tolerability (as assessed by questionnaire scores)

Study Subjects * RAIA = Rapid-Acting Insulin Analog (Aspart or Lispro) N 27 (23 completed) Age 11.0 ± 3.9 yr Female 14 (52%) Caucasian 25 (93%) Mean HbA1c 7.9 ± 1.0% Mean T1D duration 4.0 ± 3.1 yr MDI Regimen Glargine + RAIA* Glargine + RAIA* + NPH Glargine + RAIA* + Reg 21 (78%) 5 (16%) 1 ( 4%)

FreeStyle Navigator™ Continuous Glucose Monitoring System Measures interstitial glucose levels Requires calibration using fingerstick blood glucose at 10, 12, 24 and 72 hours after insertion After a 10-hr warm-up, provides glucose readings every 60 seconds for up to 120 hours Operating range mg/dL Displays a trend arrow indicating glucose rate of change Alarms for actual or impending high or low glucose levels

Results – Glycemic Control HbA1c (%) Baseline A1c ≤ 7.5% Baseline A1c > 7.5% BaselineWeek 7Week 13 ** p = 0.03 * p = 0.02 * ** The p-values shown were for comparisons of 9-13 wk vs. baseline.

Results – Glycemic Targets 20% 30% 40% 50% 60% 70% 80% 90% Baseline A1c ≤ 7.5% Baseline A1c > 7.5% BaselineWks 1-4Wks 5-8Wks 9-13 Percentage sensor Glucose Values In Target Range ( mg/dL) p = 0.36 p = 0.68 The p-values shown were for comparisons of 9-13 wk vs. baseline.

Questionnaires * Lower score denotes less fear (possible range 15-75) † Lower score denotes higher quality of life (possible range 0-112) ** completed by subjects ≥ 9 years of age § Higher score denotes greater satisfaction (possible range 1-5) Baseline13 Weeks Hypoglycemia Fear * Patients ** 31 ± 1031 ± 8 Parents41 ± 10 PedsQL † Patients ** 31 ± 1126 ± 12 Parents37 ± 1137 ± 14 CGM Satisfaction § Patients ** 3.5 ± 0.5 Parents3.8 ± 0.4

Results – Glucose Variability Mean Amplitude of Glycemic Excursion (MAGE, mg/dL) BaselineWks 1-4Wks 5-8Wks 9-13 Baseline A1c ≤ 7.5% Baseline A1c > 7.5% * The p-values shown were for comparisons of 9-13 wk vs. baseline. p = 0.17 * p = 0.004

Conclusions Use of the Navigator CGM was associated with an improvement in glycemic control without an accompanying rise in hypoglycemia Glycemic variability decreased with use of the Navigator Subjects and parents reported high overall satisfaction with the Navigator and did not demonstrate deterioration in quality of life during 3-month use CGM are tolerable and effective in children using MDI regimens Conclusions Use of the Navigator CGM was associated with an improvement in glycemic control without an accompanying rise in hypoglycemia Glycemic variability decreased with use of the Navigator Subjects and parents reported high overall satisfaction with the Navigator and did not demonstrate deterioration in quality of life during 3- month use CGM are tolerable and effective in children using MDI regimens