Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery

Abstract

OBJECTIVEAttempts 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 METHODSTwo-day closed-loop therapy (except for a 15-min premeal 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.RESULTSDuring 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.CONCLUSIONSOur results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial β-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the premeal bolus in terms of timing and amount warrant further research.

Impact of sensing and infusion site dependent dynamics on insulin bolus based meal compensation

“…Insulin formulations with faster absorption kinetics from the SC tissue are being developed (Heise et al, 2015). Alternatively, the peritoneal cavity could be chosen as a site for insulin infusion (Micossi et al, 1986;Oskarsson et al, 2000;Renard et al, 2010) to enhance the meal mitigation. Faster dynamics may even obviate the need for explicit meal detection.…”

Development and in silico validation of the PID-algorithm for the artificial pancreas with intraperitoneal insulin delivery

“…Различные варианты ИПЖ уже были испытаны в кли-нических исследованиях, а некоторые проходят испы-тания в амбулаторных условиях [3,4]. При этом одной из самых серьезных проблем на пути к успеху является слишком медленная фармакокинетика инсулина (и его генно-инженерных аналогов ультракороткого действия) при довольно высокой скорости изменения гликемии под действием внешних факторов, не позволяющая эф-фективно прогнозировать значения гликемии и верно дозировать инсулин.…”

The Artificial Pancreas: A Dynamic Challenge

“…Intraperitoneal insulin delivery; I IP Intraperitoneal insulin infusion (I IP ) has been applied with some success (Liebl et al 2009, Renard et al 2010. Physiologically, this option is quite appealing, and it has a fast dynamic effect.…”

“…Information about faults is mainly derived by comparing CGM data with the expected response to the given insulin infusion. I IP potentially involves less local tissue irritation, less clotting and more predictable insulin absorption compared to the I SC route (Liebl et al 2009, Renard et al 2010, Schaepelynck Bélicar et al 2003. Thus, one can expect faster detection of insulin infusion system failures, e.g.…”