1. Impact of Exercise on Overnight Glycemic Control in Children with Type 1 Diabetes (T1DM) Eva Tsalikian 1 ; Roy Beck 2 ; Peter Chase 3 ; Tim Wysocki 4 ; Bruce Buckingham 5 ; Stuart Weinzimer 6 ; Nelly Mauras 4 ; Craig Kollman 2 ; Dongyuan Xing 2 ; Katrina Ruedy 2 ; William Tamborlane 6 and the Diabetes Research in Children Network (DirecNet) Study Group. 1 Iowa City, IA; 2 Tampa, FL; 3 Denver, CO; 4 Jacksonville, FL; 5 Stanford, CA; 6 New Haven, CT

2. Hypoglycemia in children with T1DM Studies in children and adults have demonstrated that the majority of severe hypoglycemic events occur at night and suggest that such events are more frequent following days of increased physical activity

3. Nocturnal hypoglycemia in children with T1DM Limited data are available regarding the role of afternoon exercise on overnight severe hypoglycemic events in children with T1DM And No studies to date have examined the impact of exercise on asymptomatic, biochemical hypoglycemia during the overnight period using rigorously controlled research protocols.

4. The Diabetes Research in Children Network (DirecNet) is a multi-center study group whose objectives include the examination of factors that contribute to the risk of hypoglycemia and the development of strategies to prevent this complication of treatment of children with T1DM.

5. Aim of present study To examine the effect of late afternoon exercise that simulates common after- school sports activities on the frequency of overnight hypoglycemia. We hypothesized that such exercise would significantly increase the risk of nocturnal hypoglycemia compared to a sedentary day without afternoon exercise.

6. Study subjects (n=50) Female 44% Caucasian 90% Age (yrs: mean + SD) 15 ± 2 Duration T1DM (yrs: mean + SD) 7 ± 4 Pump 54% MDI 46% HbA1c (mean + SD) 7.8 ± 0.8%

7. Study procedures 2 CRC admissions 1-4 weeks apart Conditions: –Same meals and basal and bolus insulin doses based on home regimen for sedentary day –Exercise or rest between 4-6PM Glucose measurements –Q 15 min during exercise –Q 60 min from 6 PM to 10 PM –Q 30 min from 10 PM to 6 AM Primary outcome: –Glucose level < 60 mg/dL

8. Exercise protocol 0 15 20 35 40 55 60 75 TIME (minutes) Exercise Exercise Five minute rest periods Exercise at 60% maximum effort (VO2max): Heart rate 140 beats/minute All subjects achieved target heart rate for all cycles except for one subject that missed target for one cycle only Treadmill

9. Glucose lowering effect of exercise

10. Sedentary Exercise Mean glucose levels on the two study days Exercise Period 4:00 – 5:15 PM

11. Percentage of patients experiencing nocturnal hypoglycemia (<60mg/dL) on exercise and sedentary nights 46% 26% 6% 22% Exercise night only Neither night Both nights Sedentary night only

12. Nocturnal hypoglycemia by glucose level at bedtime 2/28=7% 8/22=36% 16/28=57% 12/22=55% Bedtime Glucose

13. Summary 63% of subjects with pre-exercise glucose of < 130 mg/dL became hypoglycemic during exercise Lower mean blood glucose levels were observed throughout the night following a 60-minute period of moderate aerobic exercise, in the afternoon, in children with T1DM. Afternoon exercise increased the risk of nocturnal hypoglycemia from 28% to 48% when food intake and insulin regimens were not altered. On sedentary but not exercise days, nocturnal hypoglycemia was rarely observed when the 9 PM glucose was >130 mg/dL.

14. Conclusion Our findings support the importance of modifying the child ’ s diabetes treatment regimen following afternoon exercise in order to reduce the risk of hypoglycemia.

15. Barbara Davis Center –H. Peter Chase –Rosanna Fiallo-Scharer –Jennifer Fisher –Barbara Tallant University of Iowa –Eva Tsalikian –Michael Tansey –Linda Larson –Julie Coffey Nemours Children’s Clinic –Tim Wysocki –Nelly Mauras –Larry Fox –Keisha Bird –Kelly Lofton Stanford University –Bruce Buckingham –Darrell Wilson –Jennifer Block –Paula Clinton Yale University –William Tamborlane –Stuart Weinzimer –Elizabeth Doyle –Kristen Sikes –Amy Steffen Jaeb Center for Health Research –Roy Beck –Katrina Ruedy –Craig Kollman –Dongyuan Xing –Cynthia Stockdale