Continuous Glucose Profiles in Healthy People With Fixed Meal Times and Under Everyday Life Conditions.

BACKGROUND: The increased use of continuous glucose monitoring (CGM) and automated insulin delivery systems raises the question about therapeutic targets for glucose profiles in people with diabetes. This study aimed to assess averaged pre- and postprandial glucose profiles in people without diabetes to provide guidance for normal glucose patterns in clinical practice. For that, number and timing of meal intake were predefined. MATERIAL AND METHODS: To assess glucose traces in 36 participants without diabetes (mean age = 23.7 ± 5.7 years), CGM was performed for up to 14 days, starting with a run-in phase (first 3 days, excluded from analysis) followed by 4 days with fixed meal times at 8:00 am, 1:00 pm, and 6:00 pm and the remaining 7 days spent under everyday life conditions. Data from two simultaneously worn CGM sensors were averaged and adjusted to capillary plasma-equivalent glucose values. Glucose data were evaluated through descriptive statistics. RESULTS: Median glucose concentration on days with fixed meal times and under everyday life conditions was 95.0 mg/dL (91.6-99.1 mg/dL, interquartile range) and 98.1 mg/dL (93.7-100.8 mg/dL), respectively. On days with fixed meal times, mean premeal glucose was 92.8 ± 9.4 mg/dL, and mean peak postmeal glucose was 143.3 ± 23.5 mg/dL. CONCLUSIONS: By defining the time of meal intake, a clear pattern of distinct postprandial glucose excursions in participants without diabetes could be demonstrated and analyzed. The presented glucose profiles might be helpful as an estimate for adequate clinical targets in people with diabetes.

Time in Specific Glucose Ranges, Glucose Management Indicator, and Glycemic Variability: Impact of Continuous Glucose Monitoring (CGM) System Model and Sensor on CGM Metrics.

BACKGROUND: International consensus recommends a set of continuous glucose monitoring (CGM) metrics to assess quality of diabetes therapy. The impact of individual CGM sensors on these metrics has not been thoroughly studied yet. This post hoc analysis aimed at comparing time in specific glucose ranges, coefficient of variation (CV) of glucose concentrations, and glucose management indicator (GMI) between different CGM systems and different sensors of the same system. METHOD: A total of 20 subjects each wore two Dexcom G5 (G5) sensors and two FreeStyle Libre (FL) sensors for 14 days in parallel. Times in ranges, GMI, and CV were calculated for each 14-day sensor experiment, with up to four sensor experiments per subject. Pairwise differences between different sensors of the same CGM system as well as between sensors of different CGM system were calculated for these metrics. RESULTS: Pairwise differences between sensors of the same model showed larger differences and larger variability for FL than for G5, with some subjects showing considerable differences between the two sensors. When pairwise differences between sensors of different CGM models were calculated, substantial differences were found in some subjects (75th percentiles of differences of time spent <70 mg/dL: 5.0%, time spent >180 mg/dL: 9.2%, and GMI: 0.42%). CONCLUSION: Relevant differences in CGM metrics between different models of CGM systems, and between different sensors of the same model, worn by the same study subjects were found. Such differences should be taken into consideration when these metrics are used in the treatment of diabetes.

Proof of Concept for a New Raman-Based Prototype for Noninvasive Glucose Monitoring.

BACKGROUND: Noninvasive glucose monitoring (NIGM) in diabetes is a long-sought-for technology. Among the many attempts Raman spectroscopy was considered as the most promising because of its glucose specificity. In this study, a recently developed prototype (GlucoBeam, RSP Systems A/S, Denmark) was tested in patients with type 1 diabetes to establish calibration models and to demonstrate proof of concept for this device in real use. METHODS: The NIGM table-top prototype was used by 15 adult subjects with type 1 diabetes for up to 25 days at home and in an in-clinic setting. On each day, the subjects performed at least six measurement units throughout the day. Each measurement unit comprised two capillary blood glucose measurements, two scans with an intermittent scanning continuous glucose monitoring (CGM) system, and two NIGM measurements using the thenar of the subject's right hand. RESULTS: Calibration models were established using data from 19 to 24 days. The remaining 3-8 days were used for independent validation. The mean absolute relative difference of the NIGM prototype was 23.6% ± 13.1% for the outpatient days, 28.2% ± 9.9% for the in-clinic day, and 26.3% ± 10.8% for the complete study. Consensus error grid analysis of the NIGM prototype for the complete study showed 93.6% of values in clinically acceptable zones A and B. CONCLUSIONS: This proof of concept study demonstrated a practical realization of a Raman-based NIGM device, with performance on par with early-generation CGM systems. The findings will assist in further performance improvements of the device.

Skin Reaction Report Form: Development and Design of a Standardized Report Form for Skin Reactions Due to Medical Devices for Diabetes Management.

BACKGROUND: Skin reactions due to medical devices for diabetes management have become a common problem in diabetes technology. There is a varying degree in how detailed skin reactions are described in scientific literature and diabetes practice, and no uniform structured documentation is given. Whereas most articles only describe findings, some others already document final diagnoses, such as contact dermatitis. Furthermore, inconsistent wordings for comparable issues were used. METHODS: A more detailed and standardized documentation, possibly facilitated by a generally accepted guideline for structured descriptions, of skin reactions could be helpful to enable better differentiations between the described skin reactions. Therefore, a report form to assess skin reactions due to medical devices in diabetes therapy was developed and will be presented in this article. RESULTS: The one-page report form is divided into four categories and a separate instruction paper. Beside general information the form includes the location, size, severity and duration of skin appearances, the grading of itching, and suspected diagnoses. CONCLUSION: A consistent use of the form in daily practice and clinical trials could facilitate a fast and standardized documentation and help to evaluate the occurrence and severity of different skin reactions due to medical devices in diabetes management.

A Prospective Study of Insulin Infusion Set Use for up to 7 Days: Early Replacement Reasons and Impact on Glycemic Control.

Background: There is limited evidence supporting a replacement interval of infusion sets for continuous subcutaneous insulin infusion (CSII). The aim of this study was to investigate if steel and soft cannula infusion sets can be used in CSII therapy for up to 7 days without negative impact on infusion sites or glycemic control. Methods: The insulin infusion sets YpsoPump® Orbit®micro (steel needle) and YpsoPump® Orbit®soft (soft cannula) were each used for up to 7 days by 40 adult subjects with CSII. Each subject used both infusion set types twice. Early replacement reasons were documented and glycemic control was monitored. Results: Of 160 inserted insulin infusion sets, 66% were used for 7 days with no obvious difference between steel and soft infusion sets. The mean wearing time was 6.2 ± 1.5 days. Main reasons for early infusion set replacements were occlusions (19%), plaster issues (4%), and accidental pull-out (4%). Comparing glycemic control during day 1-3 and 1-7, mean glucose was 146 ± 21 mg/dL versus 148 ± 18 mg/dL, coefficient of variation was 34% ± 7% versus 33% ± 5%, and insulin dose was 40 ± 11 U versus 41 ± 11 U. Only mild and nonserious infusion site reactions occurred. Conclusions: In this study, 7 days indwelling time of insulin infusion sets did not show a clinically relevant impact on glycemic control or insulin requirements and the infectious risk appeared to be low. The replacement interval of infusion sets may be individualized beyond the currently labeled maximum use duration.

System accuracy evaluation of 18 CE-marked current-generation blood glucose monitoring systems based on EN ISO 15197:2015.

OBJECTIVE: Accuracy of 18 current-generation blood glucose monitoring systems (BGMS) available in Europe was evaluated applying criteria adapted from EN ISO 15197:2015 with one reagent system lot. BGMS were selected based on market research data. RESEARCH DESIGN AND METHODS: The BGMS ABRA, Accu-Chek Guide, AURUM, CareSens Dual, CERA-CHEK 1CODE, ContourNext One, eBsensor, FreeStyle Freedom Lite, GL50 evo, GlucoCheck GOLD, GlucoMen areo 2K, GluNEO, MyStar DoseCoach, OneTouch Verio Flex, Pic GlucoTest, Rightest GM700S, TRUEyou, and WaveSense JAZZ Wireless were tested using capillary blood from 100 different subjects and assessing the percentage of results within ±15 mg/dL (0.83 mmol/L) or 15% of comparison method results for BG concentrations below or above 100 mg/dL (5.55 mmol/L), respectively. In addition, the minimal deviation from comparison method results within which ≥95% of results of the respective BGMS were found was calculated. RESULTS: In total, 14 BGMS had ≥95% of results within ±15 mg/dL (0.83 mmol/L) or ±15% and 3 BGMS had ≥95% of results within ±10 mg/dL (0.55 mmol/L) or ±10% of the results obtained with the comparison method. The smallest deviation from comparison method results within which ≥95% of results were found was ±7.7 mg/dL (0.43 mmol/L) or ±7.7%; the highest deviation was ±19.7 mg/dL (1.09 mmol/L) or ±19.7%. CONCLUSIONS: This accuracy evaluation shows that not all CE-labeled BGMS fulfill accuracy requirements of ISO 15197 reliably and that there is considerable variation even among BGMS fulfilling these criteria. This safety-related information should be taken into account by patients and healthcare professionals when making therapy decisions. TRIAL REGISTRATION NUMBER: NCT03737188.

Documentation of Skin-Related Issues Associated with Continuous Glucose Monitoring Use in the Scientific Literature.

Background: The average wear time of continuous glucose monitoring (CGM) systems steadily increased over the last years. Increased wear times are likely achieved by using adhesives with a longer adherence time, which may have a more pronounced effect on the skin than adhesives with shorter adherence time. Methods: In this project, a structured literature search was performed to assess how potential skin-related issues with CGM usage have been reported in scientific literature in the last 5 years. The literature search was performed with four search terms in the PubMed database. Results: In sum, 279 articles were analyzed. Skin-related issues were mentioned in 19.0% of articles (53 out of 279). With respect to articles mentioning skin-related issues, CGM performance or efficacy was the study's main topic of most of these studies, whereas the minority used CGM as "add-on" to assess other objectives. There was a varying degree in how detailed skin-related issues were described and no uniform structured documentation was given. While some articles only described findings, other articles already documented final diagnoses, such as contact dermatitis. Furthermore, inconsistent wordings for comparable issues were used. The most frequent issues were pain, itching, erythema, bleeding, bruising, and allergic reactions. Conclusion: To draw possible conclusions about the occurrence of skin-related issues during CGM use, more reports about skin-related issues in scientific literature are needed. A more detailed and uniformly structured documentation, possibly facilitated by a generally accepted guideline for structured descriptions, of skin-related issues could be helpful to enable clear differentiations between the described skin reactions.

First User Experiences With a Novel Touchscreen-Based Insulin Pump System in Daily Life of Patients With Type 1 Diabetes Experienced in Insulin Pump Therapy.

INTRODUCTION: A new insulin pump system was tested under everyday conditions for user evaluation and safety assessment prior to its launch in Europe. This insulin pump is focused on easy handling and uses prefilled cartridges. METHODS: The pump system was used by 35 adult subjects with type 1 diabetes, experienced in insulin pump therapy, under everyday conditions for approximately one month each. All subjects rated various aspects of the system after home use; technical issues and safety parameters were assessed throughout the study. RESULTS: All 35 subjects completed the study as planned and used the system for a total of 1013 days. After home use, 74% of the subjects were very satisfied or quite satisfied with the new pump. The subjects confirmed that the system is easy to use, especially considering general handling, bolus delivery and basal rate settings, infusion set, and cartridge change. Potential for improvements was seen in the touchscreen, warnings and alarms, the blind bolus function, the availability of a bolus calculator (was not available at time of study), and the cartridge size as rated by the study participants. Safety analysis did not raise any concerns for the use of this system. CONCLUSION: The majority of the users testing the system were satisfied with the novel insulin pump system and the system was safe for use under everyday conditions by this study population.

Rate-of-Change Dependence of the Performance of Two CGM Systems During Induced Glucose Swings.

INTRODUCTION: The accuracy of continuous glucose monitoring (CGM) systems is often assessed with respect to blood glucose (BG) readings. CGM readings are affected by a physiological and a technical time delay when compared to BG readings. In this analysis, the dependence of CGM performance parameters on the BG rate of change was investigated for 2 CGM systems. METHODS: Data from a previously published study were retrospectively analyzed. An established CGM system (Dexcom G4, Dexcom, San Diego, CA; system A) and a prototype system (Roche Diagnostics GmbH, Mannheim, Germany; system B) with 2 sensors each were worn by 10 subjects in parallel. Glucose swings were induced to achieve rapidly changing BG concentrations. Mean absolute relative differences (MARD) were calculated in different BG rate-of-change categories. In addition, sensor-to-sensor precision was assessed. RESULTS: At BG rates of change of -1 mg/dl/min to 0 mg/dl/min and 0 mg/dl/min to +1 mg/dl/min, MARD results were 12.6% and 11.3% for system A and 8.2% and 10.0% for system B. At rapidly changing BG concentrations (<-3 mg/dl/min and ≥+3 mg/dl/min), higher MARD results were found for both systems, but system B was less affected (system A: 24.9% and 29.6%, system B: 10.6% and 16.3%). The impact of rate of change on sensor-to-sensor precision was less pronounced. CONCLUSIONS: Both systems were affected by rapidly changing BG concentrations to some degree, although system B was mostly unaffected by decreasing BG concentrations. It would seem that technological advancements in CGM systems might allow for a more precise tracking of BG concentrations even at rapidly changing BG concentrations.

Evaluation of the performance of a novel system for continuous glucose monitoring.

BACKGROUND: The performance of a continuous glucose monitoring (CGM) system in the early stage of development was assessed in an inpatient setting that simulates daily life conditions of people with diabetes. Performance was evaluated at low glycemic, euglycemic, and high glycemic ranges as well as during phases with rapid glucose excursions. METHODS: Each of the 30 participants with type 1 diabetes (15 female, age 47 ± 12 years, hemoglobin A1c 7.7% ± 1.3%) wore two sensors of the prototype system in parallel for 7 days. Capillary blood samples were measured at least 16 times per day (at least 15 times per daytime and at least once per night). On two subsequent study days, glucose excursions were induced. For performance evaluation, the mean absolute relative difference (MARD) between CGM readings and paired capillary blood glucose readings and precision absolute relative difference (PARD), i.e., differences between paired CGM readings were calculated. RESULTS: Overall aggregated MARD was 9.2% and overall aggregated PARD was 7.5%. During induced glucose excursions, MARD was 10.9% and PARD was 7.8%. Lowest MARD (8.5%) and lowest PARD (6.4%) were observed in the high glycemic range (euglycemic range, MARD 9.1% and PARD 7.4%; low glycemic range, MARD 12.3% and PARD 12.4%). CONCLUSIONS: The performance of this prototype CGM system was, particularly in the hypoglycemic range and during phases with rapid glucose fluctuations, better than performance data reported for other commercially available systems. In addition, performance of this prototype sensor was noticeably constant over the whole study period. This prototype system is not yet approved, and performance of this CGM system needs to be further assessed in clinical studies.

Performance evaluation of a continuous glucose monitoring system under conditions similar to daily life.

BACKGROUND: This study aimed at evaluating and comparing the performance of a new generation of continuous glucose monitoring (CGM) system versus other CGM systems, under daily lifelike conditions. METHODS: A total of 10 subjects (7 female) were enrolled in this study. Each subject wore two Dexcom G4™ CGM systems in parallel for the sensor lifetime specified by the manufacturer (7 days) to allow assessment of sensor-to-sensor precision. Capillary blood glucose (BG) measurements were performed at least once per hour during daytime and once at night. Glucose excursions were induced on two occasions. Performance was assessed by calculating the mean absolute relative difference (MARD) between CGM readings and paired capillary BG readings and precision absolute relative difference (PARD), i.e., differences between paired CGM readings. RESULTS: Overall aggregate MARD was 11.0% (n = 2392). Aggregate MARD for BG <70 mg/dl was 13.7%; for BG between 70 and 180 mg/dl, MARD was 11.4%; and for BG >180 mg/dl, MARD was 8.5%. Aggregate PARD was 7.3%, improving from 11.6% on day 1 to 5.2% on day 7. CONCLUSIONS: The Dexcom G4 CGM system showed good overall MARD compared with results reported for other commercially available CGM systems. In the hypoglycemic range, where CGM performance is often reported to be low, the Dexcom G4 CGM system achieved better MARD than that reported for other CGM systems in the hypoglycemic range. In the hyperglycemic range, the MARD was comparable to that reported for other CGM systems, whereas during induced glucose excursions, the MARD was similar or slightly worse than that reported for other CGM systems. Overall PARD was 7.3%, improving markedly with sensor life time.

Performance evaluation of three continuous glucose monitoring systems: comparison of six sensors per subject in parallel.

BACKGROUND: This study is aimed at comparing the performance of three continuous glucose monitoring (CGM) systems following the Clinical and Laboratory Standards Institute's POCT05-A guideline, which provides recommendations for performance evaluation of CGM systems. METHODS: A total of 12 subjects with type 1 diabetes were enrolled in this study. Each subject wore six CGM systems in parallel, two sensors of each CGM system [FreeStyle Navigator™ (Navigator), MiniMed Guardian® REAL-Time with Enlite sensor (Guardian), DexCom™ Seven® Plus 3rd generation (Seven Plus)]. Each sensor was used for the lifetime specified by the manufacturer. To follow POCT05-A recommendations, glucose excursions were induced on two separate occasions, and venous and capillary blood glucose (BG) concentrations were obtained every 15 min for five consecutive hours. Capillary BG concentrations were measured at least once per hour during the day and once at night. Parameters investigated were CGM-to-BG differences [mean absolute relative difference (MARD)] and sensor-to-sensor differences [precision absolute relative difference (PARD)]. RESULTS: Compared with capillary BG reference readings, the Navigator showed the lowest MARD, with 12.1% overall and 24.6% in the hypoglycemic range; for the Guardian and the Seven Plus, MARD was 16.2%/34.9% and 16.3%/32.7%, respectively. PARD also was lowest for the Navigator (9.6%/9.8%), followed by the Seven Plus (16.7%/25.5%) and the Guardian (18.1%/20.2%). During induced glucose excursions, MARD between CGM and BG was, again, lowest for the Navigator (14.3%), followed by the Seven Plus (15.8%) and the Guardian (19.2%). CONCLUSIONS: In this study, two sensors of each of the three CGM systems were compared in a setting following POCT05-A recommendations. The Navigator CGM system achieved more accurate results than the Guardian or the Seven Plus with respect to MARD and PARD. Performance in the hypoglycemic range was markedly worse for all CGM systems when compared with BG results.

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.