Technologies for continuous glucose monitoring: current problems and future promises

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.     

动态血糖监测系统的准确性评估

良好的血糖控制能延缓和（或）阻止糖尿病慢性并发症的发生。但是,不管是对1型还是2型糖尿病患者,良好的血糖控制是以严重的低血糖发生增加为前提条件,低血糖成为血糖控制达标的最大障碍。在糖化血红蛋白（HbA1c）控制良好的患者,常出现血糖波动,即出现不可预料的低血糖和高血糖;而且,低血糖尤其是无症状性低血糖,     

The extended Kalman filter for continuous glucose monitoring

Glucose monitoring is a problem with evolving solutions using sensors and data processing techniques that are continually improving. This paper presents the development and application of the extended Kalman filter to the problem of real-time estimation of blood glucose levels and is consistent with sensors based on optical, electrical, or chemical processes. The structure of the extended Kalman filter provides the capability to systematically accommodate new information as it develops. This flexibility and the potential for performance improvement are demonstrated by processing patient data files generated using the Medtronic (Northridge, CA) MiniMed continuous glucose monitoring system (CGMS).     

Smart telemedicine support for continuous glucose monitoring: the embryo of a future global agent for diabetes care

Although current systems for continuous glucose monitoring (CGM) are the result of progressive technological improvement, and although a beneficial effect on glucose control has been demonstrated, few patients are using them. Something similar has happened to telemedicine (TM); in spite of the long-term experience, which began in the early 1980s, no TM system has been widely adopted, and presential visits are still almost the only way diabetologists and patients communicate. The hypothesis developed in this article is that neither CGM nor TM will ever be routinely implemented separately, and their consideration as essential elements for standard diabetes care will one day come from their integration as parts of a telemedical monitoring platform. This platform, which should include artificial intelligence for giving decision support to patients and physicians, will represent the core of a more complex global agent for diabetes care, which will provide control algorithms and risk analysis among other essential functions.     

Clinical use of real-time continuous glucose monitoring

Maintaining near-normal glycaemia in all patients with diabetes mellitus (DM) has become a standard and a well accepted recommendation. Unfortunately, most people with DM do not achieve this clinical goal because of marked glycaemic fluctuations and hypoglycaemia. Real-time continuous glucose monitoring (RT-CGM) has been introduced recently into clinical practice offering more knowledge about current glucose concentration and trend and enabling people with DM to intervene and prevent unwanted glucose excursions by acting upon real-time and predictive alarms. Several RT-CGM devices proved to be sufficiently accurate and feasible for routine use. Observational reports with The Guardian and Paradigm RT by Medtronic, the STS by DexCom, FreeStyle Navigator by Abbott and GlucoDay by Menarini established initial clinical benefit. Five randomised controlled trials (RCT) demonstrated significantly improved glucose variability or metabolic control, one of them showing a statistically significant and clinically meaningful decrease of HbA1c with a 3 months use of the Guardian RT (Medtronic, Northridge, CA). The great potential of RT-CGM devices to improve daily glucose control and quality of life in people with DM can only be developed further through RCTs, clarifying in more details the optimal clinical use and the most beneficial indications for this novel technique.     

The SCGM1 System: subcutaneous continuous glucose monitoring based on microdialysis technique

The SCGM1 System is designed to allow continuous glucose monitoring in the subcutaneous interstitial fluid for up to 120 h. The system is based on the microdialysis technique and is composed of three components: (1) a disposable Cassette, which contains the microdialysis catheter (with the necessary tubes), an electrochemical flow-through sensor for glucose measurement, and the fluid reservoirs for both the microdialysis perfusate and a reagent solution containing glucose oxidase; (2) the Sensor Unit, which houses the Cassette and is worn by the patient using a belt pack; and (3) the Data Manager, with an integrated blood glucose meter for the calibration of the glucose signal. The Data Manager also has the option of displaying the continuous glucose signal. The Sensor Unit and Data Manager exchange glucose data and calibration data by radio transmission. In vitro precision was assessed by measurements of two standard glucose solutions (90 mg/dL, 3.4%; 360 mg/dL, 2.4%) over a time course of 4 days. The mean difference (+/- SD) between SCGM1 System devices (n = 11) and 15 glucose standard solutions with different concentrations was 1.4 +/- 3.5 mg/dL. The mean relative difference and the mean absolute relative difference ranged from - 0.6% to 3.7% and from 0.2% to 3.8%, respectively. The inherent physical lag time was 31 +/- 2 min (n = 10). The interference on the glucose signal of ascorbic acid, acetaminophen, and uric acid at the highest physiological concentrations was below 4%. The SCGM1 System showed a reliable and precise performance under in vitro conditions.     

Evidence for continuous glucose monitoring: sufficient for reimbursement?

Evidence for continuous glucose monitoring is mounting. Meta‐analyses consistently show lowering of HbA_1c, and the first trial reporting a reduction in severe hypoglycaemic events in patients with hypoglycaemia unawareness has recently been presented. The more recent trials studied larger numbers of patients and may have shown better results because of improved technology. The various combinations of pump and sensor, with automated bolus calculators and low glucose suspend features, make evaluation more challenging from a reimbursement point of view, but evidence seems convincing enough to justify reimbursement for selected patient groups, including those who have shown a substantial improvement in HbA_1c during a trial period, and those with hypoglycaemia unawareness who encountered severe hypoglycaemia in the recent past. More data on cost–efficacy are needed.     

Real-life utilization of real-time continuous glucose monitoring: the complete picture

Background

Very few studies to date have analyzed the reasons why some people do not use real-time continuous glucose monitoring (RT-CGM) continuously, especially given its positive glycemic outcomes, or choose not to wear it at all, even after learning about its benefits.

Methods

A questionnaire was designed to assess real-life use of and issues surrounding RT-CGM. Hemoglobin A1c (HbA1c) and duration of sensor use were also obtained from the patients'' charts.

Results

Fifty-eight subjects with type 1 diabetes (T1DM), average age 15.0 ± 4.8 years, T1DM duration 5.7 ± 3.8 years, HbA1c 8.8 ± 2.1%, 50% with RT-CGM, were included in the analysis. Hemoglobin A1c was lower with increased RT-CGM use. Real-time continuous glucose monitoring was ordered to improve control. Users liked the continuous data. The most disliked part was pain and discomfort. Occasional users described RT-CGM as annoying, a hassle, and interfering with their lives. Reasons for discontinuing RT-CGM included problematic equipment and inaccuracy (64%), intrusion in life (36%), and insurance issues (29%). Twenty-one percent of nonusers reported RT-CGM to be inconvenient or a hassle or just did not want it. Fifty-two percent of subjects continue to use RT-CGM despite reported problems.

Conclusion

Real-time continuous glucose monitoring is a beneficial tool for improving glycemic control, and many use it despite reported problems and hassles with current devices. However, this technology has not been wholeheartedly embraced by many individuals with T1DM, especially in youngsters, because of issues mentioned here. Based on the findings of this study, it is hoped that improvements will be made to RT-CGM technology so that more people with diabetes will embrace this beneficial tool.     

Evaluating clinical accuracy of continuous glucose monitoring devices: other methods

With more and more continuous glucose monitoring devices entering the market, the importance of adequate accuracy assessment grows. This review discusses pros and cons of Regression Analysis and Correlation Coefficient, Relative Difference measures, Bland Altman plot, ISO criteria, combined curve fitting, and epidemiological analyses, the latter including sensitivity, specificity and positive predictive value for hypoglycaemia. Finally, recommendations for much needed head-to-head studies are given. This paper is a revised and adapted version of How to assess and compare the accuracy of continuous glucose monitors?, Diabetes Technology and Therapeutics 2007, in press, published with permission of the editor.