Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

Abstract

Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC) glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP) sensor sites, as an alternative to the SC location.Intraarterial (IA) and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70-360 mg/dL (approximately 3.8-20 mmol/L). Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing.The time delay in glucose excursions from central circulation (IA) to IP sensor location was found to be in the range 0-26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s), and the time constant was found to be 0.5-10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min).IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies.This study may provide a benchmark for future, rapid IP glucose sensors.

Effect of sensor location on continuous intraperitoneal glucose sensing in an animal model

“…Glucose sensing in the peritoneal space has been studied in rabbits [ 30 ], rats [ 31 , 32 ] and pigs [ 22 , 33 ]. Burnett et al reported the mean time delay and mean time constant to be 40.8 (SD 34.8) seconds and 5.6 (SD 2.9) minutes, respectively [ 22 ].…”

“…Burnett et al reported the mean time delay and mean time constant to be 40.8 (SD 34.8) seconds and 5.6 (SD 2.9) minutes, respectively [ 22 ]. Fougner et al have previously found a mean time delay of 9.7 (SD 9.5) seconds and mean time constant of 4.7 (SD 2.9) minutes in pigs [ 33 ]. The IP glucose dynamics (time delays and time constants) in the present investigation are slower compared to these previous studies.…”

“…First of all, different glucose sensors were used in the three studies: Burnett et al used modified Dexcom sensors in their trials, which is an amperometric sensor like the FreeStyle Libre sensor, but from a different manufacturer (Dexcom, San Diego, USA). Fougner et al used optical interferometric sensors to measure glucose [ 33 ]. Secondly, the studies handle the measured glucose dynamics in different ways.…”

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

“…The IP route is currently being investigated (Burnett et al, 2014;Fougner et al, 2016). A quick onset of the glucoselowering effect of administered insulin significantly contributes to the performance of meal compensation.…”

“…Reported mean values for SC glucose appearance including the sensor dynamics in pigs are τ G = 13 min and θ G = 2 min (Burnett et al, 2014), while faster dynamics of τ G = 6 min and θ G = 1 min have been observed for peritoneal glucose sensing in pigs (Burnett et al, 2014;Fougner et al, 2016). However, the SC route excluding sensor dynamics can be as fast as τ G = 5 min and θ G = 1 min for single subjects under well controlled clinical conditions (Basu et al, 2015).…”