Supplementary appendix

Transcription

1 Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Haidar A, Legault L, Matteau-Pelletier L, et al. Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial. Lancet Diabetes Endocrinol 2015; published online June 9.

2 Algorithm Description The dosing algorithm was based on model predictive control and adopts the compartmental approach to describe insulin-glucagon-glucose dynamics. The algorithm was initialized using daily insulin requirements and insulin-to-carbohydrate ratios, and did not utilize body weight. The dosing algorithm utilized a physiologically-motivated compartmental parametric model that consists of six submodels: insulin absorption kinetics (2 compartments), glucagon absorption kinetics (2 compartments), meal absorption kinetics (2 compartments), plasma glucose kinetics (2 compartments) and interstitial glucose kinetics (1 compartment). Control and prediction horizons were set to 4.5 hours, and a quadratic objective function was used. The state of the model was continuously updated by Kalman filtering based on the mismatch between the model and the measurements. Glucagon delivery was based on heuristic logical rules that employed estimates of plasma glucose concentrations and their trends as provided by the Kalman filter. The algorithm gives glucagon boluses with sizes [0.01, 0.02, 0.03, or 0.04] mg x (subject weight) / 75, and previous glucagon delivery does not restrict future glucagon delivery (i.e., delivery of glucagon at any time point is not reduced due to recent large accumulated glucagon delivery). The aggressiveness of insulin delivery was identical in both the single-hormone and the dual-hormone artificial pancreas algorithms, but glucagon-on-board was taken into account in the predictions during dual-hormone visits. 1

3 Study Exclusion Criteria 1. Clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator. 2. Severe hypoglycemic episode within two weeks of inclusion in the study. 3. Current use of oral glucocorticoid medication (except low stable dose). Stable doses of inhaled steroids are acceptable. 4. Known or suspected allergy to the trial products. 5. Other serious medical illness likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator. 6. Failure to comply with team s recommendations (e.g. not willing to use trial pump, etc). 2

4 Pictures of Some Tents 3

5 Camp Nocturnal Hypoglycemia Protocol 250 ml of juice (20 g CHO) Test in 15 min If glucose 5.0 mmol/l, give a snack* and the camper goes back to tent. If glucose 4.9 mmol/l, give another 250 ml of juice and retest in 15 min: If glucose 5.0 mmol/l, give a snack* and the camper goes back to tent. If glucose 4.9 mmol/l, give another 250 ml of juice and retest in 15 min *The snack is composed on 1 cup of milk (12g CHO) and peanut butter sandwich made using 2 soda crackers (10g CHO). 4

6 Camp Nocturnal Hyperglycemia Protocol If glucose 15 mmol/l accompanied with ketones 1.0 mmol: Using a syringe, give 1.5 times the correction bolus recommended by the pump bolus wizard. Change the pump catheter and reservoir. Retest glucose and ketone levels in 2 hours. 5

7 Sensor Accuracy Outcomes Outcome Conventional pump therapy Single-hormone artificial pancreas Dual-hormone artificial pancreas Sensor bias (mmol/l) 0 1 (0 8) 0 0 (1 6) 0 0 (0 83) Relative absolute difference (%) 11 8 (8 7) 15 5 (10 8) 13 3 (8 6) Outcomes were calculated using the capillary finger-stick measurements that were used in the calibration prior to the evening snack (i.e., last calibration before the start of the interventions). None of the differences was statistically significant. Sensor minus plasma glucose. Data are mean (SD). 6