Closing the loop, squaring the circle: Studies on insulin delivery, glucose monitoring and the artificial pancreas

This thesis focuses on the steps necessary to create a functional closed loop system. In part I of this thesis we investigate how the body reacts on a glucose load. We especially focus on ingestion of meals. In part II of this thesis we investigate the nuances and variability of insulin infusion, focussing on the differences in insulin infusion materials on insulin administration. In part III we investigate the accuracy of continuous glucose monitors (CGM), with a special focus on comparing CGM systems for use in a closed loop system. In part IV we investigate a closed loop prototype to provide glycaemic control using two different control algorithms

Accuracy of two continuous glucose monitoring systems: a head-to-head comparison under clinical research centre and daily life conditions

International audienceAIMS:To assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems.METHODS:We studied the Dexcom®G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6-h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points ≥15 min apart.RESULTS:The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Δ) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Δ = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [≤3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Δ 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%.CONCLUSIONS:During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL.TRIAL REGISTRATION:ClinicalTrials.gov NCT01751932