Continuous Glucose Monitoring in Normal Mice and Mice with Prediabetes and Diabetes

Abstract

It is well established that the key to minimizing diabetes-associated complications, in both type 1 and type 2 diabetes, is tight regulation of blood glucose levels. Currently the major approach to regulating blood glucose levels in patients with diabetes relies on external blood glucose monitors. However, poor patient compliance usually results in limited insights into the dynamic range of blood glucose levels (i.e., hyperglycemia vs. hypoglycemia), and inadequate prediction and control of blood glucose levels in these patients. Implantable glucose sensors hold promise for controlling blood glucose levels, but currently these sensors have only limited in vivo life span. Recently we have developed an extremely robust murine model for implantable glucose sensors. In the present study, we have extended this model by developing a complete system for real-time continuous glucose monitoring in normal mice and mice with prediabetes and diabetes (type 1). These studies demonstrated that (1) glucose sensors can be implanted and maintained subcutaneously in the mice; (2) continuous glucose sensor data can be obtained for at least 5 days; and (3) subcutaneous blood glucose sensing paralleled blood glucose levels in normal mice and mice with prediabetes and diabetes. Subcutaneous blood glucose sensing also successfully tracked changes in blood glucose levels induced in the mice with diabetes by administration of oral glucose or insulin. These results mirror the results for subcutaneous blood glucose sensing seen in both normal subjects and patients with diabetes, and therefore validate both our continuous glucose monitoring system in the mouse, and the use of the mouse as a model for implantable glucose sensing in vivo.

Markers of glycemic control in the mouse: comparisons of 6-h- and overnight-fasted blood glucoses to Hb A1c

“…This system determines glucose level in interstitial fluid. A correlation between interstitial fluid and blood glucose levels has been demonstrated in humans and several other species (19,21,28). The present studies further demonstrate that this correlation also exists in inbred mice.…”

“…The data stored in the monitor were periodically downloaded into a computer for analysis. A correlation between interstitial glucose and blood glucose levels has previously been demonstrated in several species, including mice and humans (19,27,28). In the present studies, we adapted this system to mice.…”

Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo

“…Glucose sensors were implanted into IL-1Ra~KO, IL-1Ra~OE, or C57BL/6j mice, and CGM was undertaken for a period up to 28 days as described previously. [12][13][14] Blood glucose reference measurements were obtained periodically over the 28-day implantation period, using blood obtained from the tail vein and a FreeStyle blood glucose monitor. The Institutional Animal Care and Use Committee of the University of Connecticut Health Center (Farmington, CT) approved all mice studies.…”

Electrochemical biochip for applications to wireless and batteryless monitoring of free-moving mice

“…For molecular metabolites the story is quite different because it is typically needed to involve enzymes-based biosensors that require more complex integration of bio-membranes and electronics. In the area of metabolism monitoring in small animals, the most successful development is the monitoring of glucose in mice [9], even with implants remaining in-vivo up to 56 days [10]. More recent devices have shown detection of other endogenous metabolites (e.g., lactate, glutamate, and ATP) [11] though not within the same sensing platform.…”

“…More recent devices have shown detection of other endogenous metabolites (e.g., lactate, glutamate, and ATP) [11] though not within the same sensing platform. However, all these more recent developments still present electrical cables through the animals' skin [9]- [12], which allow only limited movement in the animal cage. In 2012, a novel system to transmit power and receive data on completely free-moving animals has been proposed [13], and at the end of last year the possibility of the integration with a fully implantable and biocompatible multi-panel array sensor has been proposed [14].…”