Nina Jendrike

System Accuracy Evaluation of 27 Blood Glucose Monitoring Systems According to DIN EN ISO 15197

BACKGROUND Blood glucose (BG) monitoring systems enable diabetes patients to effectively control and adjust their therapy. BG monitoring systems with a Conformité Européenne (CE) label should meet the standard DIN EN ISO 15197:2003: > or =95% of the BG results shall fall within +/-15 mg/dL of the reference method at BG concentrations <75 mg/dL and within +/-20% at BG concentrations > or =75 mg/dL. We intended to verify if BG monitoring systems with a CE label fulfill these minimum accuracy requirements. METHODS We evaluated 27 BG monitoring systems from 18 manufacturers for system accuracy according to DIN EN ISO 15197:2003. Twenty-four systems were compared with the glucose oxidase reaction (YSI 2300 glucose analyzer [YSI Life Sciences, Yellow Springs, OH]) and three systems with the hexokinase reaction (Hitachi 917 [Roche Diagnostics GmbH, Mannheim, Germany]). Duplicate measurements of 100 blood samples with a defined distribution of BG concentrations from 20 mg/dL to 600 mg/dL from > or =100 subjects were included in the evaluation. RESULTS Sixteen of the 27 BG monitoring systems fulfilled the minimum accuracy requirements of the standard, i.e., > or =95% of their results showed the minimum acceptable accuracy. Overall, the mean percentage of results showing the minimum acceptable accuracy was 95.2 +/- 5.2%, ranging from 80.0% to 100.0%. CONCLUSIONS More than 40% of the evaluated BG monitoring systems did not fulfill the minimum accuracy requirements of DIN EN ISO 15197:2003. As inaccurate BG monitoring systems bear the risk of false treatment decisions by the diabetes patient and subsequent possible severe health injury, manufacturers should regularly and effectively check the quality of BG meters and BG test strips.

Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals

Background: This study investigated continuous glucose profiles in nondiabetic subjects. Methods: Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) and after ingestion of four meals with standardized carbohydrate content (50 grams), but with different types of carbohydrates and variable protein and fat content. Twenty-four healthy volunteers (12 female, 12 male, age 27.1 ± 3.6 years) participated in the study. Each subject wore two microdialysis devices (SCGM1, Roche Diagnostics) simultaneously. Results: The mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 ± 6.2 mg/dl (mean ± SD, n = 21), and mean interstitial glucose concentrations at daytime and during the night were 93.0 ± 7.0 and 81.8 ± 6.3 mg/dl, respectively. The highest postprandial glucose concentrations were observed after breakfast: 132.3 ± 16.7 mg/dl (range 101–168 mg/dl); peak concentrations after lunch and dinner were 118.2 ± 13.4 and 123.0 ± 16.9 mg/dl, respectively. Mean time to peak glucose concentration was between 46 and 50 minutes. After ingestion of standardized meals with fast absorption characteristics, peak interstitial glucose concentrations were 133.2 ± 14.4 and 137.2 ± 21.1 mg/dl, respectively. Meals with a higher fiber, protein, and fat content induced a smaller increase and a slower decrease of postprandial glucose concentrations with peak values of 99.2 ± 10.5 and 122.1 ± 20.4 mg/dl, respectively. Conclusions: This study provided continuous glucose profiles in nondiabetic subjects and demonstrated that differences in meal composition are reflected in postprandial interstitial glucose concentrations. Regarding the increasing application of continuous glucose monitoring in diabetic patients, these data suggest that detailed information about the ingested meals is important for adequate interpretation of postprandial glucose profiles.

Clinical Performance of Three Bolus Calculators in Subjects with Type 1 Diabetes Mellitus: A Head-to-Head-to-Head Comparison

BACKGROUND Insulin pump systems now provide automated bolus calculators (ABCs) that electronically calculate insulin boluses to address carbohydrate intake and out-of-range blood glucose (bG) levels. We compared the efficacy of three ABCs (Accu-Chek(®) Combo [Roche Insulin Delivery Systems (IDS), Inc., Fishers, IN, a member of the Roche Group], Animas(®) 2020 [Animas Corp., West Chester, PA, a Johnson and Johnson company], and MiniMed Paradigm Bolus Wizard(®) [Medtronic MiniMed, Northridge, CA]) to safely reduce postprandial hyperglycemia in type 1 diabetes mellitus (T1DM). METHODS T1DM subjects (n = 24) were recruited at a single center for a prospective, triple crossover study. ABCs with the programmed target range (80-140 mg/dL) were used in random order. Postprandial hyperglycemia was induced by reducing the calculated bolus by 25%. Two hours after test meals, the ABCs were allowed to determine whether a correction bolus was needed. Differences between 6-h bG values after test meals that achieved 2-h postprandial hyperglycemia and the mean of the target range (110 mg/dL) were determined. RESULTS The mean difference between 6-h bG levels following test meals and the 110 mg/dL bG target with the MiniMed device (47.4 ± 31.8 mg/dL) was significantly higher than the Animas (17.3 ± 30.9 mg/dL) and Roche IDS (18.8 ± 33.8 mg/dL) devices (P = 0.0022 and P = 0.0049, respectively). The number of meals with 2-h postprandial hyperglycemia and bG levels at 2 h was similar. Roche IDS and Animas devices recommended correction boluses significantly (P = 0.0001 and P = 0.0002, respectively) more frequently than the MiniMed device. ABC use was not associated with severe hypoglycemia. There was no significant difference in the rate of mild hypoglycemia (bG <60 mg/dL not requiring assistance) among the three groups (Roche IDS and Animas, n = 2; MiniMed, n = 0). CONCLUSIONS In this study, the Roche IDS and Animas devices were more efficacious in controlling postprandial hyperglycemia than the MiniMed device. This may be due, in part, to differences in ABC setup protocols and algorithms. Use of ABCs can assist in controlling postprandial glycemia without significant hypoglycemia.

Clinical Performance of a Device That Applies Local Heat to the Insulin Infusion Site: A Crossover Study

Background: Fast-acting insulin analogs have been available since 1996. The absorption rate of these insulins is still too slow to mimic the physiological insulin action in healthy subjects. This study investigates the clinical performance of InsuPatch™, a local skin-heating device, on postprandial glucose excursion. Methods: Twenty-four type 1 diabetes mellitus subjects on continuous subcutaneous insulin infusion were included in this crossover study [10 male, 14 female, age: 43.5 ± 11.3 years, diabetes duration: 18.3 ± 10.5 years, glycosylated hemoglobin: 7.4 ± 0.8%, body mass index: 25.0 ± 3.0 kg/m2 (mean ± standard deviation)]. The impact of local skin heating was measured by dividing the two-hour area under the curve by integration time (AUC/t120) for blood glucose (BG) above baseline after two standardized breakfast and dinner meal pairs (with and without heating) per subject. For the first breakfast pair, venous insulin concentration was also measured. Results: A significant reduction was found for the AUC/t120 after breakfast and after dinner meals (42 breakfast meal pairs, AUC/t120 not heated 66.4 ± 32.8 mg/dl vs heated 56.8 ± 34.0 mg/dl, p = .017; 38 dinner meal pairs, AUC/t120 not heated 30.8 ± 31.0 mg/dl vs heated 18.4 ± 23.9 mg/dl, p = .0028). The maximum venous insulin concentration with heating was 27% higher than without heating (n = 23). The number of hypoglycemic events on days with heating (n = 9) was similar to the number of days without heating (n = 13). Conclusions: Local heating of the skin around the infusion site significantly reduced postprandial BG by enhancing insulin absorption. The heating device was well tolerated, and it could facilitate development of closed-loop systems.

Effect of Infusion Rate and Indwelling Time on Tissue Resistance Pressure in Small-Volume Subcutaneous Infusion like in Continuous Subcutaneous Insulin Infusion

BACKGROUND To deliver exact volumes of liquid subcutaneously (e.g., during continuous subcutaneous insulin infusion [CSII]), the insulin pump has to overcome not only frictional losses of the mechanical drive and pressure losses in the tubing and infusion set, but also the tissue resistance pressure (TRP). Up to now, detailed information about the dependence of TRP on volumes and delivery rates common for CSII is missing. However, knowledge of the typical range of TRP during CSII is important to optimize occlusion detection and the design of insulin pumps. MATERIALS AND METHODS TRP was examined in 24 subjects (12 patients with type 1 diabetes mellitus and long-term CSII therapy and 12 subjects without diabetes) while subcutaneously infusing a liquid test solution via infusion sets with 8-mm steel cannulas using four different infusion rates (infused volume, 0.3 mL of saline solution). The primary objectives were to estimate the TRP and its dependence on the infusion rate, as well as the impact of the cannula indwelling time of roughly 80 h. RESULTS Stepwise increases in the infusion rate were associated with significant rises in median TRP: 0.01 mL/min (= 1 U/min for U100 insulin), 8.09 mbar; 0.05 mL/min, 18.28 mbar; 0.1 mL/min, 25.18 mbar; and 0.5 mL/min, 62.59 mbar. No statistically significant changes in TRP could be attributed to the catheter indwelling time of roughly 80 h. CONCLUSIONS Median TRP increased significantly with higher infusion rates. Catheter indwelling time had no significant effect on the TRP. Occlusion detection may be improved by using rate-dependent detection thresholds.

Performance of two updated blood glucose monitoring systems: an evaluation following ISO 15197:2013

Abstract Objective For patients with diabetes, regular self-monitoring of blood glucose (SMBG) is essential to ensure adequate glycemic control. Therefore, accurate and reliable blood glucose measurements with SMBG systems are necessary. The international standard ISO 15197 describes requirements for SMBG systems, such as limits within which 95% of glucose results have to fall to reach acceptable system accuracy. The 2013 version of this standard sets higher demands, especially regarding system accuracy, than the currently still valid edition. ISO 15197 can be applied by manufacturers to receive a CE mark for their system. Research design and methods This study was an accuracy evaluation following ISO 15197:2013 section 6.3 of two recently updated SMBG systems (Contour* and Contour TS; Bayer Consumer Care AG, Basel, Switzerland) with an improved algorithm to investigate whether the systems fulfill the requirements of the new standard. For this purpose, capillary blood samples of approximately 100 participants were measured with three test strip lots of both systems and deviations from glucose values obtained with a hexokinase-based comparison method (Cobas Integra† 400 plus; Roche Instrument Center, Rotkreuz, Switzerland) were determined. Percentages of values within the acceptance criteria of ISO 15197:2013 were calculated. This study was registered at clinicaltrials.gov (NCT02358408). Main outcome Both updated systems fulfilled the system accuracy requirements of ISO 15197:2013 as 98.5% to 100% of the results were within the stipulated limits. Furthermore, all results were within the clinically non-critical zones A and B of the consensus error grid for type 1 diabetes. Conclusions The technical improvement of the systems ensured compliance with ISO 15197 in the hands of healthcare professionals even in its more stringent 2013 version. Alternative presentation of system accuracy results in radar plots provides additional information with certain advantages. In addition, the surveillance error grid offers a modern tool to assess a system’s clinical performance.

Use of Microdialysis-Based Continuous Glucose Monitoring to Drive Real-Time Semi-Closed-Loop Insulin Infusion

Background: Continuous glucose monitoring (CGM) and automated insulin delivery may make diabetes management substantially easier, if the quality of the resulting therapy remains adequate. In this study, a semi-closed-loop control algorithm was used to drive insulin therapy and its quality was compared to that of subject-directed therapy. Method: Twelve subjects stayed at the study site for approximately 70 hours and were provided with the investigational Automated Pancreas System Test Stand (APS-TS), which was used to calculate insulin dosage recommendations automatically. These recommendations were based on microdialysis CGM values and common diabetes therapy parameters. For the first half of their stay, the subjects directed their diabetes therapy themselves, whereas for the second half, the insulin recommendations were delivered by the APS-TS (so-called algorithm-driven therapy). Results: During subject-directed therapy, the mean glucose was 114 mg/dl compared to 125 mg/dl during algorithm-driven therapy. Time in target (90 to 150 mg/dl) was approximately 46% during subject-directed therapy and approximately 58% during algorithm-driven therapy. When subjects directed their therapy, approximately 2 times more hypoglycemia interventions (oral administration of carbohydrates) were required than during algorithm-driven therapy. No hyperglycemia interventions (delivery of addition insulin) were necessary during subject-directed therapy, while during algorithm-driven therapy, 2 hyperglycemia interventions were necessary. Conclusions: The APS-TS was able to adequately control glucose concentrations in the subjects. Time in target was at least comparable or moderately higher during closed-loop control and markedly fewer hypoglycemia interventions were required, thus increasing patient safety.

System Accuracy and User Performance Evaluation of an Improved System for Self-Monitoring of Blood Glucose:

An improved test cassette for the integrated Accu-Chek® Mobile system (Roche Diabetes Care GmbH, Mannheim, Germany) has been developed. System accuracy of this improved system was evaluated based on ISO 15197:2013, clause 6.3, for three reagent system lots. According to this standard, at least 95% of the system’s measurement results shall be within ±15 mg/dL and ±15% of the results of the comparison method at glucose concentrations <100 mg/dL and ≥100 mg/dL (accuracy criterion A), respectively, and at least 99% of results shall be within consensus error grid zones A and B (accuracy criterion B). In addition, accuracy was evaluated in the hands of users based on ISO 15197:2013, clause 8, with one reagent system lot.

Introduction of a Novel Smartphone-Coupled Blood Glucose Monitoring System

The novel system for self-monitoring of blood glucose (SMBG) PixoTest couples SMBG to a smartphone and does not require a separate glucose meter. The integrated system includes all components necessary for a glucose measurement, and owing to a colorimetric measurement principle, a smartphone camera can capture color changes and a software app calculates the corresponding glucose value. In the presented study, the system was evaluated in terms of system accuracy as described in ISO 15197:2013. It was shown to fulfill system accuracy requirements with 97-99% of results from three different reagent system lots within the accuracy limits and 100% of results within zone A of the consensus error grid.

ISO 15197: 2013 Evaluation of a Blood Glucose Monitoring System’s Measurement Accuracy:

Requirements for blood glucose monitoring systems (BGMS) for self-testing are regulated, for example, in the international standard ISO 15197:2013 (harmonized in the European Union as EN ISO 15197:2015). Regarding measuring accuracy of a BGMS, ISO 15197:2013 specifies the following criteria: (1) compared to a traceable laboratory method at least 95% of BGMS results have to be within ±15 mg/dl at glucose concentrations <100 mg/dl and within ±15% at ≥100 mg/dl; (2) in a consensus error grid analysis at least 99% of results have to be within zones A and B. This study was an ISO 15197:2013 accuracy evaluation at the Institut für Diabetes-Technologie Forschungsund Entwicklungsgesellschaft mbH an der Universität Ulm (accredited by the Deutsche Akkreditierungsstelle GmbH (DAkkS) as testing laboratory according to DIN EN ISO/ IEC 17025:2005 and 98/79/EC in terms of test procedures according to DIN EN ISO 15197) in compliance with all applicable regulatory requirements. The BGMS GlucoDr. autoTM AGM-4000 (All Medicus, Co, Ltd, Anyang-si, Republic of Korea) was tested. According to a statement of the manufacturer, this system is marketed in the UK as Glucozen.autoTM AGM-4000 (GlucoZen Ltd, Dudley, UK). Meters and three different lots of test strips were provided by the manufacturer. A YSI 2300 STAT Plus glucose analyzer (YSI Inc, Yellow Springs, OH, USA) that is traceable according to ISO 17511 was used for comparison measurements; trueness and precision were verified throughout the study. The BGMS was used according to its labeling and daily control measurements were performed. Each of the three test strip lots was tested in duplicate in 100 subjects; glucose concentrations of the capillary blood samples were distributed as specified in ISO 15197:2013. The accuracy criteria described above were applied to the BGMS and the relative bias was calculated. Over the whole glucose concentration range, the BGMS had 98.5% (Lot 1), 97% (Lot 2) and 96% (Lot 3) of results within the limits stipulated by ISO 15197:2013 (Figure 1). Percentages of results within the limits were 98.3%, 95%, and 98.3%, respectively, for glucose concentrations <100 mg/dl and 98.6%, 97.9%, and 95%, respectively, for glucose concentrations ≥100 mg/dl. All results of the three test strip lots were within zones A and B of the consensus error grid. The relative bias was 2.7% (Lot 1) and 2.6% (Lot 2 and Lot 3). In this study, the system showed more than the minimally required 95% of results within the ISO 15197 system accuracy limits and did not show obvious variations between the evaluated test strip lots. 727550 DSTXXX10.1177/1932296817727550Journal of Diabetes Science and TechnologyJendrike et al letter2017