Comparative performance assessment of point-of-care testing devices for measuring glucose and ketones at the patient bedside.

Point-of-care (POC) testing devices for monitoring glucose and ketones can play a key role in the management of dysglycemia in hospitalized diabetes patients. The accuracy of glucose devices can be influenced by biochemical changes that commonly occur in critically ill hospital patients and by the medication prescribed. Little is known about the influence of these factors on ketone POC measurements. The aim of this study was to assess the analytical performance of POC hospital whole-blood glucose and ketone meters and the extent of glucose interference factors on the design and accuracy of ketone results. StatStrip glucose/ketone, Optium FreeStyle glucose/ketone, and Accu-Chek Performa glucose were also assessed and results compared to a central laboratory reference method. The analytical evaluation was performed according to Clinical and Laboratory Standards Institute (CLSI) protocols for precision, linearity, method comparison, and interference. The interferences assessed included acetoacetate, acetaminophen, ascorbic acid, galactose, maltose, uric acid, and sodium. The accuracies of both Optium ketone and glucose measurements were significantly influenced by varying levels of hematocrit and ascorbic acid. StatStrip ketone and glucose measurements were unaffected by the interferences tested with exception of ascorbic acid, which reduced the higher level ketone value. The accuracy of Accu-Chek glucose measurements was affected by hematocrit, by ascorbic acid, and significantly by galactose. The method correlation assessment indicated differences between the meters in compliance to ISO 15197 and CLSI 12-A3 performance criteria. Combined POC glucose/ketone methods are now available. The use of these devices in a hospital setting requires careful consideration with regard to the selection of instruments not sensitive to hematocrit variation and presence of interfering substances.

GlucoMen Day continuous glucose monitoring system: a screening for enzymatic and electrochemical interferents.

BACKGROUND: While most of the common drugs with the potential to interfere with continuous glucose monitoring (CGM) systems are accessible over the counter and can be assumed by CGM patients without medical supervision, many other chemicals are frequently used to treat critically ill patients. Continuous glucose monitoring reading accuracy may also be compromised in patients characterized by abnormally high concentrations of physiological interferents. In this article, 22 species selected from endogenous and exogenous chemicals were screened as possible interferents of GlucoMen®Day (GMD), the new microdialysis-based CGM system from A. Menarini Diagnostics. METHOD: Interference testing was performed according to the EP7-A2 guideline (Clinical and Laboratory Standards Institute 2005). Interference was evaluated at two levels of glucose, with each interferent additionally tested at two concentrations. Furthermore, two configurations of the GMD disposable sensor kit--one designed for subcutaneous application, the other for direct intravascular CGM--were challenged with interferent-spiked serum and blood samples, respectively. RESULTS: With the exception of dopamine (however, at very high, nonphysiological concentrations), no interference was observed for all the tested substances. Interestingly, none of the common electrochemical interferents (including ascorbic acid, acetaminophen, and salicylic acid, which represent the major specificity issue for the competing CGM systems) significantly affected the system's output. CONCLUSIONS: These results provide clear insights into the advantages offered by the use of a microdialysis-based CGM system that additionally relies on the detection of hydrogen peroxide at low operating potential. GlucoMen Day may become the CGM system of choice for those patients who require either regular administration of drugs or their glycemia to be tightly controlled in the intensive care unit or similar environments.

Minimizing the impact of time lag variability on accuracy evaluation of continuous glucose monitoring systems.

BACKGROUND: Despite all commercially available continuous glucose monitoring (CGM) systems being designed to operate in the extracellular interstitial fluid, and even though there is a well-recognized time lag between the interstitial and the venous compartments, the accuracy of the CGM device readings is still evaluated against the glucose concentration in venous blood (VB) samples, thus resulting in a perceived decrease in accuracy. This article explains how different time lag compensation methods (no compensation, compensation with a fixed delay, compensation with a variable delay based on an intercompartmental diffusional model) have an impact on how CGM accuracy is evaluated. METHODS: The data set used consisted of 210 CGM/blood glucose data pairs from 18 diabetes subjects (15 type 1 and 3 type 2) selected from a data base collected during two independent clinical trials. All CGM measurements were performed using the GlucoMen ®Day CGM system (A. Menarini Diagnostics, Italy), and the reference VB glucose measurements by means of a standard laboratory instrument. For each applied time lag compensation method, the CGM accuracy evaluation was performed as recommended by the POCT05-A consensus guideline. RESULTS: The perceived accuracy of the CGM device significantly improved when applying both the fixed or the variable delay compensation method. However, it is worth noting how the variable delay method, which relies on a closer description of the intercompartmental diffusion processes, provided the best perception of the clinical accuracy of the device. CONCLUSIONS: When assessing the accuracy of a CGM system, a crucial step in data analysis is to account for time lag, which enables minimization of the apparent decline in system accuracy.

Glucose variability in diabetic pregnancy.

BACKGROUND: Fetal overgrowth is the most important complication of gestational (GDM) and pregestational diabetes mellitus. METHODS: We correlated maternal glucose profiles, as detected by continuous glucose monitoring (CGM), with fetal growth parameters for 80 pregnant women (32 with type 1 diabetes, 31 with GDM, and 17 healthy controls). Glucose profiles were monitored in the first, second, and third trimesters of pregnancy for type 1 diabetes women and in the second and third trimesters for GDM women and controls. To analyze glycemic variability, we considered the mean amplitude of glycemic excursion, mean glycemia, the continuous overlapping net glycemic action (CONGA), the SD, the High Blood Glucose Index (HBGI), the Low Blood Glucose Index, and the interquartile range (IQR). RESULTS: Mean age was the same for the three groups. Prepregnancy body mass index was higher for the women with diabetes (GDM and type 1) than for controls. The newborn's mean birth weight and ponderal index were higher, although not significantly so, for the women with diabetes than for controls. For the type 1 diabetes patients, ponderal index correlated with the HBGI in the first trimester, CONGA1 and IQR in the second, and mean glycemia and SD in the third. For GDM patients, ponderal index correlated with mean glycemia and the HBGI in the second trimester. CONCLUSIONS: Fetal exposure to glycemic variability and hyperglycemia seems to be important in determining fetal overgrowth in pregnant women with diabetes. Optimal glucose control and less glucose variability are needed as early as possible in both type 1 diabetes and GDM patients to ensure normal fetal growth.

Evaluating the clinical accuracy of GlucoMen®Day: a novel microdialysis-based continuous glucose monitor.

BACKGROUND: The objective of this work was to determine the clinical accuracy of GlucoMen®Day, a new microdialysis-based continuous glucose monitoring system (CGMS) from A. Menarini Diagnostics (Florence, Italy). Accuracy evaluation was performed using continuous glucose-error grid analysis (CG-EGA), as recommended by the Performance Metrics for Continuous Interstitial Glucose Monitoring; Approved Guideline (POCT05-A). METHODS: Two independent clinical trials were carried out on patients with types 1 and 2 diabetes mellitus, the glycemic levels of whom were monitored in an in-home setting for 100-hour periods. A new multiparametric algorithm was developed and used to compensate in real-time the GlucoMen®Day signal. The time lag between continuous glucose monitoring (CGM) and reference data was first estimated using the Poincaré plot method. The entire set of CGM/reference data pairs was then evaluated following the CG-EGA criteria, which allowed an estimation of the combined point and rate accuracy stratified by glycemic ranges. RESULTS: With an estimated time lag of 11 minutes, the linear regression analysis of the CGM/reference glucose values yielded r = 0.92. The mean absolute error (MAE) was 11.4 mg/dl. The calculated mean absolute rate deviation (MARD) was 0.63 mg/dl/min. The data points falling within the A+B zones of CG-EGA were 100% in hypoglycemia, 95.7% in euglycemia, and 95.2% in hyperglycemia. CONCLUSIONS: The GlucoMen®Day system provided reliable, real-time measurement of subcutaneous glucose levels in patients with diabetes for up to 100 hours. The device showed the ability to follow rapid glycemic excursions and detect severe hypoglycemic events accurately. Its accuracy parameters fitted the criteria of the state-of-the-art consensus guideline for CGMS, with highly consistent results from two independent studies.

Toward continuous glucose monitoring with planar modified biosensors and microdialysis. Study of temperature, oxygen dependence and in vivo experiment.

Glucose biosensors based on the use of planar screen-printed electrodes modified with an electrochemical mediator and with glucose oxidase have been optimised for their application in the continuous glucose monitoring in diabetic patients. A full study of their operative stability and temperature dependence has been accomplished, thus giving useful information for in vivo applications. The effect of dissolved oxygen concentration in the working solution was also studied in order to evaluate its effect on the linearity of the sensors. Glucose monitoring performed with serum samples was performed to evaluate the effect of matrix components on operative stability and demonstrated an efficient behaviour for 72 h of continuous monitoring. Finally, these studies led to a sensor capable of detecting glucose at concentrations as low as 0.04 mM and with a good linearity up to 2.0 mM (at 37 degrees C) with an operative stability of ca. 72 h, thus demonstrating the possible application of these sensors for continuous glucose monitoring in conjunction with a microdialysis probe. Moreover, preliminary in vivo experiments for ca. 20 h have demonstrated the feasibility of this system.