Closed-loop insulin delivery using a subcutaneous glucose sensor and intraperitoneal insulin delivery: feasibility study testing a new model for the artificial pancreas

Abstract

Objective: Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm.

Research design and methods: Two-day closed-loop therapy (except for a 15-min pre-meal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4-6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean +/- SEM percentage of time spent with blood glucose in the 4.4-6.6 mmol/l range was significantly higher (39.1 +/- 4.5 vs. 27.7 +/- 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4-6.6 mmol/l range (46.3 +/- 5.3 vs. 28.6 +/- 7.4, P = 0.025) and lower mean blood glucose levels (6.9 +/- 0.3 vs. 7.9 +/- 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases.

Conclusions: Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial beta-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the pre-meal bolus in terms of timing and amount warrant further research.

Figure 1

Correlations between measured (lab) and algorithm-estimated (model) plasma insulin levels during the closed-loop phases in each of the eight type 1 diabetic patients investigated by the HyPID system.

Figure 2

Blood glucose levels (mean 95% CI) during closed-loop (continuous lines) and control (dashed lines) phases in the eight type 1 diabetic patients investigated by the HyPID system. A: from 2200 to 0800. B: From 1 h before to 5 h after meal start.

Figure 3

Cumulative distribution of blood glucose values during closed-loop and control (open-loop) phases in the eight type 1 diabetic patients investigated by the HyPID system. Individual data are presented as thin continuous lines during closed-loop phases and as thin dashed lines during control (open-loop) phases. Thick lines indicate the median cohort distributions of blood glucose values. Vertical red dotted lines denote the glucose range between 4.4 (80) and 6.6 (120) mmol/l (mg/dl).