Technologies for continuous glucose monitoring: current problems and future promises

Abstract

Devices for continuous glucose monitoring (CGM) are currently a major focus of research in the area of diabetes management. It is envisioned that such devices will have the ability to alert a diabetes patient (or the parent or medical care giver of a diabetes patient) of impending hypoglycemic/hyperglycemic events and thereby enable the patient to avoid extreme hypoglycemic/hyperglycemic excursions as well as minimize deviations outside the normal glucose range, thus preventing both life-threatening events and the debilitating complications associated with diabetes. It is anticipated that CGM devices will utilize constant feedback of analytical information from a glucose sensor to activate an insulin delivery pump, thereby ultimately realizing the concept of an artificial pancreas. Depending on whether the CGM device penetrates/breaks the skin and/or the sample is measured extracorporeally, these devices can be categorized as totally invasive, minimally invasive, and noninvasive. In addition, CGM devices are further classified according to the transduction mechanisms used for glucose sensing (i.e., electrochemical, optical, and piezoelectric). However, at present, most of these technologies are plagued by a variety of issues that affect their accuracy and long-term performance. This article presents a critical comparison of existing CGM technologies, highlighting critical issues of device accuracy, foreign body response, calibration, and miniaturization. An outlook on future developments with an emphasis on long-term reliability and performance is also presented.

Figure 1

Classification of various CGM technologies according to their (a) invasiveness and (b) transduction mechanism of the sensor. Code definitions in Figure 1A correspond to the respective transduction mechanisms shown in Figure 1B. The asterisk in Figure 1a displays code definitions corresponding to the detection technologies shown in Figure 1B. For example, code E-1-a corresponds to electrochemical (E) detection based on enzymatic (1) reaction that is oxygen mediated (a).

Figure 2

Various modes of electrochemical detection of glucose: (A) first-generation biosensors based on the use of natural oxygen cofactor, (B) second-generation biosensors based on artificial redox mediators, (C) third-generation biosensors based on direct electron transfer between GO_x and the electrode, and (D) direct electro-oxidation of glucose.

Figure 3

Optical detection of glucose based on (A) fluorescence intensity decrease as a result of affinity binding and (B) decrease in FRET-induced fluorescence intensity.

Figure 4

Clarke error grid applicable for both T1DM and T2DM patients, (B) Parkes error grid applicable to T1DM patients, and (C) Parkes error grid applicable to T2DM patients.