Point-of-care testing: state-of-the art and perspectives.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e., presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

Performance of intermittently scanned continuous glucose monitoring systems in people with type 1 diabetes: A pooled analysis.

AIMS: To conduct a pooled analysis to assess the performance of intermittently scanned continuous glucose monitoring (isCGM) in association with the rate of change in sensor glucose in a cohort of children, adolescents, and adults with type 1 diabetes. MATERIAL AND METHODS: In this pooled analysis, isCGM system accuracy was assessed depending on the rate of change in sensor glucose. Clinical studies that have been investigating isCGM accuracy against blood glucose, accompanied with collection time points were included in this analysis. isCGM performance was assessed by means of median absolute relative difference (MedARD), Parkes error grid (PEG) and Bland-Altman plot analyses. RESULTS: Twelve studies comprising 311 participants were included, with a total of 15 837 paired measurements. The overall MedARD (interquartile range) was 12.7% (5.9-23.5) and MedARD differed significantly based on the rate of change in glucose (P < 0.001). An absolute difference of -22 mg/dL (-1.2 mmol/L) (95% limits of agreement [LoA] 60 mg/dL (3.3 mmol/L), -103 mg/dL (-5.7 mmol/L)) was found when glucose was rapidly increasing (isCGM glucose minus reference blood glucose), while a -32 mg/dL (1.8 mmol/L) (95% LoA 116 mg/dL (6.4 mmol/L), -51 mg/dL (-2.8 mmol/L)) absolute difference was observed in periods of rapidly decreasing glucose. CONCLUSIONS: The performance of isCGM was good when compared to reference blood glucose measurements. The rate of change in glucose for both increasing and decreasing glucose levels diminished isCGM performance, showing lower accuracy during high rates of glucose change.

Evaluation of the SPECTRUM training programme for real-time continuous glucose monitoring: A real-world multicentre prospective study in 120 adults with type 1 diabetes.

AIMS: Comprehensive knowledge, specific skills and data-analysis competences are prerequisites for the successful use of continuous glucose monitoring (CGM) systems. SPECTRUM is a structured training programme for real-time CGM (rtCGM) consisting of a web-based introduction and six group sessions of 90 min each. The 'CGM-TRAIN study' evaluated the efficacy and acceptance of SPECTRUM and rtCGM systems among adults with insulin therapy. METHODS: Participants (n = 120) were recruited from 10 German diabetes centres in which they were treated under usual care conditions. Outcome measures were rtCGM knowledge, practical skills, satisfaction with the training programme, satisfaction and acceptance of rtCGM system and glycaemic control. Data were collected at study entry, after training completion and at 6-month follow-up. RESULTS: All participants were diagnosed with type 1 diabetes (56% women, mean age 42.4 ± 13.4 years, diabetes duration 21.6 ± 11.6 years), 110 participants completed the course. After training completion, rtCGM-specific knowledge had improved by 43% (scale: 0-40 points) from 21.2 ± 7.6 to 30.4 ± 4.5 points; p < 0.001. The knowledge-level persisted until follow-up (29.4 ± 4.5). Participants were able to master nearly all the practical requirements of the technology. In addition, rtCGM was highly accepted, and participants were motivated to use their systems continuously. HbA1c improved slightly from 61 ± 14 mmol/mol (7.7 ± 1.3%) before training to 60 ± 14 mmol/mol (7.6 ± 1.3%) at follow-up (p = 0.04). The training programme itself was favourably rated by participants. CONCLUSIONS: Under usual out-patient daily care conditions, the training programme SPECTRUM improved knowledge and skills about rtCGM in adults with type 1 diabetes. This was associated with a reduced HbA1c , high satisfaction and acceptance of rtCGM (Clinical Trials Registry no.: DRKS00014380).

Accuracy assessment of bolus and basal rate delivery of different insulin pump systems used in insulin pump therapy of children and adolescents.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is commonly used in patients with diabetes. Accurate and reliable delivery by insulin pumps is essential for a safe and effective therapy, particularly when using small doses. In this study, accuracy of bolus and basal rate delivery of various available insulin pumps was evaluated. METHODS: In total, 13 insulin pump systems were tested: eight durable pumps with different infusion sets and one patch pump. Based on IEC 60601-2-24, insulin delivery was measured by recording weight gain of a beaker into which insulin was infused by the pumps. Bolus accuracy was determined by individually weighing 25 consecutive 0.1 or 1.0 U boluses and basal rate accuracy was determined during basal rate delivery of 0.1 or 1.0 U/h for 72 hours. For analyses, basal rate delivery was divided into 1-hour windows and deviation from target was calculated. RESULTS: Regarding different systems, average 0.1 U bolus delivery was -2% to +9% of the intended volume with 53% to 96% of boluses within ±15% of target. During 0.1 U/h basal rate delivery, most pumps showed an initial over-delivery for the first few hours. Three systems reached a total basal rate error <5%; others showed up to +24%. In general, delivery was more accurate when using larger doses. CONCLUSIONS: Considerable differences in insulin delivery accuracy were observed between the tested pumps. In general, when using very low doses, accuracy of insulin delivery is limited in most insulin pumps. This should be considered for CSII therapy in children.

Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose.

Background The professional-use systems HemoCue® Glucose 201+ (HC201+) and HemoCue® Glucose 201 RT (HC201RT) are widely used for point-of-care testing (POCT) of blood glucose (BG). HC201RT utilizes unit-use microcuvettes which can be stored at room temperature, whereas HC201+ microcuvettes have to be stored at <8 °C. In this study, system accuracy of HC201+ and HC201RT was evaluated using capillary and venous blood samples. Methods For each system, two reagent system lots were evaluated within a period of 2 years based on testing procedures of ISO 15197:2013, a standard applicable for self-monitoring of blood glucose (SMBG) systems. For each reagent system lot, the investigation was performed by using 100 capillary and 95 to 99 venous blood samples. Comparison measurements were performed with a hexokinase laboratory method. Accuracy criteria of ISO 15197:2013 and POCT12-A3 were applied. In addition, bias was analyzed according to Bland and Altman, and error grid analysis was performed. Results When measuring capillary samples, both systems fulfilled accuracy requirements of ISO 15197:2013 and POCT12-A3 with the investigated reagent system lots. When measuring venous samples, only HC201+ fulfilled these requirements. Bias between HC201+ and reference measurements was more consistent over venous and capillary samples and microcuvette lots than for HC201RT. Error grid analysis showed that clinical actions might have been different depending on which system was used. Conclusions In this study, HC201+ showed a high level of accuracy irrespective of the sample type (capillary or venous). In contrast, HC201RT measurement results were markedly affected by the type of sample.

Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial.

BACKGROUND: The effectiveness of real-time continuous glucose monitoring (rtCGM) in avoidance of hypoglycaemia among high-risk individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) is unknown. We aimed to ascertain whether the incidence and severity of hypoglycaemia can be reduced through use of rtCGM in these individuals. METHODS: The HypoDE study was a 6-month, multicentre, open-label, parallel, randomised controlled trial done at 12 diabetes practices in Germany. Eligible participants had type 1 diabetes and a history of impaired hypoglycaemia awareness or severe hypoglycaemia during the previous year. All participants wore a masked rtCGM system for 28 days and were then randomly assigned to 26 weeks of unmasked rtCGM (Dexcom G5 Mobile system) or to the control group (continuing with self-monitoring of blood glucose). Block randomisation with 1:1 allocation was done centrally, with the study site as the stratifying variable. Masking of participants and study sites was not possible. Control participants wore a masked rtCGM system during the follow-up phase (weeks 22-26). The primary outcome was the baseline-adjusted number of hypoglycaemic events (defined as glucose ≤3·0 mmol/L for ≥20 min) during the follow-up phase. The full dataset analysis comprised participants who wore the rtCGM system during the baseline and follow-up phases. The intention-to-treat analysis comprised all randomised participants. This trial is registered with ClinicalTrials.gov, number NCT02671968. FINDINGS: Between March 4, 2016, and Jan 12, 2017, 149 participants were randomly assigned (n=74 to the control group; n=75 to the rtCGM group) and 141 completed the follow-up phase (n=66 in the control group, n=75 in the rtCGM group). The mean number of hypoglycaemic events per 28 days among participants in the rtCGM group was reduced from 10·8 (SD 10·0) to 3·5 (4·7); reductions among control participants were negligible (from 14·4 [12·4] to 13·7 [11·6]). Incidence of hypoglycaemic events decreased by 72% for participants in the rtCGM group (incidence rate ratio 0·28 [95% CI 0·20-0·39], p<0·0001). 18 serious adverse events were reported: seven in the control group, ten in the rtCGM group, and one before randomisation. No event was considered to be related to the investigational device. INTERPRETATION: Usage of rtCGM reduced the number of hypoglycaemic events in individuals with type 1 diabetes treated by MDI and with impaired hypoglycaemia awareness or severe hypoglycaemia. FUNDING: Dexcom Inc.

Higher HbA1c Measurement Quality Standards are Needed for Follow-Up and Diagnosis: Experience and Analyses from Germany.

Measurement of HbA1c is an essential laboratory measure for the follow-up and therapy decision-making in patients with diabetes. HbA1c is one of the measurands in laboratory medicine that have to be successfully checked according to the criteria of the guidelines of the German Medical Association (Rili-BAEK) in external quality assurance using the reference method value concept, when applied in patient care. The allowed deviation of ±18% in external quality assessment (EQA) and ± 10% in internal quality control has been ultimately met by virtually all the different manufacturers and methods. However, such broad limits for permissible deviations are not suitable in view of medical requirements in patient care. The low-level acceptance criteria also depends on the previously used EQA materials used in Germany. In fact, HbA1c measurement results that are imprecisely measured or come from incorrectly calibrated devices are difficult to identify. With implementation of unprocessed fresh EDTA blood, the situation has changed. Until now systems with unit use reagents for point-of-care testing (POCT) of HbA1c are not mandatory to participate in EQA schemes in Germany. This paper outlines why there was a need to narrow the acceptance limits listed within the Rili-BAEK for HbA1c's internal (to ± 3%) and external (to ± 8%) quality controls in EQA schemes for Germany, which will take place after a transition period in the next years. Higher quality in HbA1c measurements will help to avoid misdiagnosis of diabetes as well as potential over- or undertreatment of patients at risk for diabetes.

System accuracy evaluation of systems for point-of-care testing of blood glucose: a comparison of a patient-use system with six professional-use systems.

BACKGROUND: Point-of-care testing (POCT) of blood glucose (BG) is performed by medical personnel in clinical settings as well as by patients themselves for self-monitoring of blood glucose (SMBG) at home. We investigated if a system mainly intended for SMBG by people with diabetes, but also suitable for BG measurements by medical personnel, can achieve measurement accuracy on capillary blood samples comparable with professional-use POCT systems. METHODS: System accuracy was evaluated under standardised conditions, following the ISO standard 15197:2003. For each system (one SMBG system with three test strip lots and six professional-use systems), measurement results from capillary blood samples of 100 subjects were compared with a standardised laboratory glucose oxidase method (YSI 2300 glucose analyser). RESULTS: The seven evaluated systems showed 99.5% or 100% of the measurement results within the required system accuracy limits of ISO 15197:2003 (±0.83 mmol/L at BG concentrations <4.2 mmol/L and ±20% at BG concentrations ≥4.2 mmol/L). Applying the more stringent requirements of the revision ISO 15197:2013, the systems showed between 99% and 100% of the measurement results within the accuracy limits (±0.83 mmol/L at BG concentrations <5.55 mmol/L and ±15% at BG concentrations ≥5.55 mmol/L) and between 82% and 98% when even more restrictive limits were applied (±0.56 mmol/L and ±10%, respectively). CONCLUSIONS: Data from this study, which focused on system accuracy, suggest that SMBG systems can achieve system accuracy that is comparable with professional-use systems when measurements are performed on capillary blood samples by trained personnel in a standardised and controlled setting.

A Proposal for the Clinical Characterization of Continuous Glucose Monitoring Trend Arrow Accuracy.

The assessment and characterization of trend accuracy, that is, the ability of a continuous glucose monitoring (CGM) system to correctly indicate the direction and rate of change (RoC) of glucose levels, has received comparatively little attention in the overall evaluation of CGM performance. As such, only few approaches that examine the trend accuracy have been put forward. In this article, we review existing approaches and propose the clinical trend concurrence analysis (CTCA) which is an adaptation of the conventional trend concurrence analysis. The CTCA is intended to directly evaluate the trend arrows displayed by the CGM systems by characterizing their agreement to suitably categorized comparator RoCs. Here, we call on manufactures of CGM systems to provide the displayed trend arrows for retrospective analysis. The CTCA classifies any deviations between the CGM trend and comparator RoC according to their risk for an adverse clinical event arising from a possibly erroneous treatment decision. For that, the existing rate error grid analysis and a specific set of trend arrow-based insulin dosing recommendations were used. The results of the CTCA are presented in an accessible graphical display and exemplified on data from three CGM systems. With this article, we hope to increase the awareness for the importance and challenges of assessing the accuracy of trend information displayed by CGM systems.

A Critical Discussion of Alert Evaluations in the Context of Continuous Glucose Monitoring System Performance.

Many continuous glucose monitoring (CGM) systems provide functionality which alerts users of potentially unwanted glycemic conditions. These alerts can include glucose threshold alerts to call the user's attention to hypoglycemia or hyperglycemia, predictive alerts warning about impeding hypoglycemia or hyperglycemia, and rate-of-change alerts. A recent review identified 129 articles about CGM performance studies, of which approximately 25% contained alert evaluations. In some studies, real alerts were assessed; however, most of these studies retrospectively determined the timing of CGM alerts because not all CGM systems record alerts which necessitates manual documentation. In contrast to assessment of real alerts, retrospective determination allows assessment of a variety of alert settings for all three types of glycemic condition alerts. Based on the literature and the Clinical and Laboratory Standards Institute's POCT05 guideline, two common approaches to threshold alert evaluation were identified, one value-based and one episode-based approach. In this review, a critical discussion of the two approaches, including a post hoc analysis of clinical study data, indicates that the episode-based approach should be preferred over the value-based approach. For predictive alerts, fewer results were found in the literature, and retrospective determination of CGM alert timing is complicated by the prediction algorithms being proprietary information. Rate-of-change alert evaluations were not reported in the identified literature, and POCT05 does not contain recommendations for assessment. A possible approach is discussed including post hoc analysis of clinical study data. To conclude, CGM systems should record alerts, and the episode-based approach to alert evaluation should be preferred.

Plasma Glucose Concentrations in Different Sampling Tubes Measured on Different Glucose Analysers.

INTRODUCTION: The German Diabetes Association recommends using sampling tubes with citrate and fluoride additives to diagnose diabetes by oral glucose tolerance test to inhibit glycolysis. The effect of different tubes on measurement results was assessed. MATERIALS AND METHODS: In a first study, an oral glucose tolerance test was performed on 41 participants without anamnestically known diabetes. Venous blood was sampled in two different tubes with citrate/fluoride additives from different manufacturers and one with only lithium-heparin additive. A second study with 42 participants was performed to verify the initial results with an adapted design, in which a third tube with citrate buffer was used, and glucose measurements were performed on two additional devices of another analyser model. Samples were centrifuged either immediately (<5 min incubation time) or after 20 min or 4 h. All glucose measurements were performed in plasma. Glucose concentrations in lithium-heparin tubes with<5 min incubation time served as baseline concentrations. RESULTS: In the first study, glucose concentrations in one of the citrate/fluoride tubes were similar to the baseline. In the other citrate/fluoride tube, markedly lower concentrations (approximately - 5 mg/dL (- 0.28 mmol/L)) were measured. This was reproduced in the verification study for the same analyser, but not with the other analyser model. Lithium-heparin tubes centrifuged after 20 and 240 min showed systematically lower glucose concentrations. CONCLUSIONS: The results confirm that glycolysis can be effectively inhibited in citrate/fluoride-containing sampling tubes. However, glucose measurement results of one analyser showed a relevant negative bias in tubes containing liquid citrate buffer.

An SMS-Guided Basal Insulin Titration in People with Type 2 Diabetes New on Insulin.

INTRODUCTION: The shortage of general practitioners (GPs) and the increasing prevalence of type 2 diabetes create significant pressure on primary healthcare services. To enable that medical services are available to all that need it, innovative solutions are needed. One of those, a Short Message Service (SMS)-supported basal insulin titration service is investigated in this study. The primary objective was to determine the percentage of subjects who achieved stable fasting blood glucose (FBG) within their individual target range with this service after week 16. METHODS: This single-arm, 16-week study aimed to enroll 111 adults diagnosed with type 2 diabetes that needed insulin. The study subjects measured their FBG 4 consecutive days to establish a baseline, then received SMS prompts for daily FBG measurements and evening insulin injections until their FBG stabilized within the target range. Adjusting the insulin based on the FBG. Once stabilization was achieved, subjects continued with their optimal insulin dose for the remainder of the study. Sixteen weeks after the baseline, subjects measured FBG for 4 days before visit 4, where these values were read by the healthcare provider. RESULTS: Out of the planned 111 subjects, only 30 were enrolled, with one withdrawal prior to service activation. Challenges in subject recruitment were attributed to the COVID-19 outbreak, limited eligibility, competing studies, and new medications delaying insulin initiation. Subjects were on average 59.97 years old, had an HbA1c of 9.29% a FBG of 205.64 mg/dl, and had diabetes for 10 years. Among the 29 subjects who started the service, 72% achieved successful titration at visit 4, with a median time of 49 days. Notable improvements were observed in HbA1c levels (decreased by 1.58%) and FBG levels (decreased by 64 mg/dl) over the 16-week study period. No adverse events or device-related issues were reported. CONCLUSIONS: Despite recruitment challenges, guided basal insulin titration holds promise for insulin therapy initiation in individuals. The findings emphasize the potential of tele-medical approaches, specifically through remote messaging, in managing diabetes and improving therapy adherence.

Nocturnal Hypoglycemia in the Era of Continuous Glucose Monitoring.

Nocturnal hypoglycemia is a common acute complication of people with diabetes on insulin therapy. In particular, the inability to control glucose levels during sleep, the impact of external factors such as exercise, or alcohol and the influence of hormones are the main causes. Nocturnal hypoglycemia has several negative somatic, psychological, and social effects for people with diabetes, which are summarized in this article. With the advent of continuous glucose monitoring (CGM), it has been shown that the number of nocturnal hypoglycemic events was significantly underestimated when traditional blood glucose monitoring was used. The CGM can reduce the number of nocturnal hypoglycemia episodes with the help of alarms, trend arrows, and evaluation routines. In combination with CGM with an insulin pump and an algorithm, automatic glucose adjustment (AID) systems have their particular strength in nocturnal glucose regulation and the prevention of nocturnal hypoglycemia. Nevertheless, the problem of nocturnal hypoglycemia has not yet been solved completely with the technologies currently available. The CGM systems that use predictive models to warn of hypoglycemia, improved AID systems that recognize hypoglycemia patterns even better, and the increasing integration of artificial intelligence methods are promising approaches in the future to significantly minimize the risk of a side effect of insulin therapy that is burdensome for people with diabetes.

Evaluation of System Accuracy, Precision, Hematocrit Influence, and User Performance of Two Blood Glucose Monitoring Systems Based on ISO 15197:2013/EN ISO 15197:2015.

INTRODUCTION: Sufficiently high analytical quality of blood glucose monitoring systems (BGMS) is a prerequisite for efficient diabetes therapy. In this study we assessed system accuracy, measurement repeatability, intermediate measurement precision, user performance, and the influence of hematocrit on two CE-marked blood glucose monitoring systems. For one BGMS, measurement accuracy using venous samples was additionally investigated. METHODS: Study procedures were based on the International Organization of Standardization (ISO) 15197:2013/EN ISO 15197:2015 ("ISO 15197"). User performance included data from 100 subjects who used one test strip lot, whereas for all other analyses three different reagent system lots were used. For system accuracy assessment, 100 capillary samples were measured in duplicate with each of three reagent system lots per system, resulting in 600 results per system. RESULTS: CareSens S Fit and CareSens H Beat both fulfilled the ISO 15197 accuracy criteria with 97.5-100% of each test strip lot's results falling within ± 15 mg/dL or ± 15% of the results of the comparison method and 100% of results in consensus error grid (CEG) zone A for all three lots. User performance evaluation revealed sufficient accuracy in the hands of lay users although some handling errors were documented by study staff. Assessment of measurement repeatability and intermediate measurement precision is given by standard deviation (SD) (glucose levels < 100 mg/dL) and by coefficient of variation (CV) (glucose concentrations ≥ 100 mg/dL). SD was ≤ 4.1 mg/dL and CV ≤ 4.2% for measurement repeatability and SD was ≤ 2.2 mg/dL and CV ≤ 2.6% for intermediate measurement precision. In case of hematocrit influence, both BGMS complied with all three tested lots with the defined criteria. CONCLUSION: Both BGMS analyzed in this study fulfilled the required accuracy criteria of ISO 15197. They showed high precision, good performance in the hands of lay users, and the influence of hematocrit was acceptable in the labeled range.

Effect of Arterialization on Venous Blood Glucose Concentrations and Implications for Observed Continuous Glucose Monitoring Accuracy.

Background: Heating of the arm and/or hand ("arterialization") is sometimes used in continuous glucose monitoring (CGM) performance studies with the reported aim of reducing differences between venous and capillary glucose concentrations. In this study, the effect of heating on venous glucose concentrations and CGM accuracy was investigated. Methods: A heating pad set to 50°C (122°F) was used with 20 participants to heat either the dominant or nondominant arm and hand. Venous and capillary samples were obtained every 15 min on both arms throughout each of three 6-h glucose challenges. CGM sensors were worn on each upper arm for each of the three visits. Results: Heating of the arm led to a median increase in venous glucose concentrations of +1.4%. No similar effect on capillary concentrations was observed. As a result, the median capillary to venous difference decreased from +5.9% in the nonheated arm to +4.2% in the heated arm. CGM accuracy observed in this study was affected by the selection of heated venous, nonheated venous, or capillary glucose concentrations as comparator data. The heating effect was more pronounced with rapidly decreasing glucose concentrations. Temperatures on the skin did not exceed 40°C (104°F). No adverse events or protocol deviations were associated with the use of the heating pad. Conclusions: Heating of the arm led to a small increase in venous glucose concentrations, but venous concentrations did not reach the level of capillary glucose concentrations. CGM accuracy observed in this study varied depending on the selected comparator data. This study was registered at the German Clinical Trials Register (DRKS00031197).

Quality assessment of glucose measurement with regard to epidemiology and clinical management of diabetes mellitus in Germany.

Background: During the last decade, Germany has seen an increased prevalence and a redistribution from undetected to diagnosed diabetes mellitus. Due to this substantial epidemiological development, the number of people with documented type 2 diabetes was 8.7 million in 2022. An estimated two million undiagnosed subjects are to be added. Beyond that, the life expectancy of diabetic subjects is increasing due to more responsive health systems in terms of care. Possible reasons include improved screening of at-risk individuals, the introduction of HbA1c for diagnosis in 2010, and the higher use of risk scores. Additionally, quality aspects of the laboratory methodology should be taken into consideration. Methods: Epidemiology and clinical management of diabetes in Germany are presented in the light of publications retrieved by a selective search of the PubMed database. Additionally, the data from German external quality assessment (EQA) surveys for the measurands glucose in plasma and HbA1c in whole blood, reviewed from 2010 until 2022, were evaluated. Above this, data concerning the analytical performance of near-patient glucometer devices, according to the ISO norm 15197:2013, were analyzed. Results: Two laboratory aspects are in good accordance with the observation of an increase in the diabetes mellitus prevalence when retrospectively reviewing the period 2010 to 2022: First, the analytical performance according to the ISO norm 15197:2013 of the glucometer devices widely used by patients with diabetes for the glucose self-testing, has improved during this period. Secondly, concerning the EQA program of INSTAND, the number of participating laboratories raised significantly in Germany. The spreads of variations of the specified results for plasma glucose remained unchanged between 2010 and 2022, whereas for HbA1c a significant decrease of the result scattering could be observed. Conclusion: These retrospectively established findings testify to an excellent analytical quality of laboratory diagnostics for glucose and HbA1c throughout Germany which may be involved in a better diagnosis and therapy of previously undetected diabetes mellitus.

Investigation of the Effect of 70 Potential Interferents on Measurement Results of Two Blood Glucose Monitoring Systems.

BACKGROUND: Reliable blood glucose (BG) measurements are important for people with diabetes to manage their therapy as well as in point-of-care testing (POCT) performed by health care professionals to monitor BG of patients or even to diagnose diabetes. Among other factors, endogenous and exogenous substances present in blood samples can impact the measurement results. To ensure and prove that blood glucose monitoring systems (BGMSs) are robust in terms of potential interferents, manufacturers have to perform extensive evaluations. METHOD: An interference screening test was performed for three reagent system lots of a POCT system and of a BGMS for self-monitoring of BG. A paired-difference approach based on ISO 15197:2013 and CLSI guideline EP07 was used with venous whole blood samples at two different glucose concentrations. Seventy potential interferents expected to be common in people with diabetes were evaluated. RESULTS: The interference effects were determined as normalized biases between test samples and corresponding control samples. For 69 of the 70 investigated potential interferents, both systems met the predefined acceptance criteria, with the normalized biases falling within ±10 mg/dL or ±10% at glucose concentrations ≤100 mg/dL or >100 mg/dL, respectively, for each of the three evaluated reagent system lots. CONCLUSIONS: The BGMS investigated in this study were found to be robust with respect to the 70 evaluated potential interferents. Interference effects were observed only for N-Acetyl-L-cysteine. Extensive evaluations of potential interfering factors can make an important contribution to ensure reliability of BGMS.

Characteristics of Nocturnal Hypoglycaemic Events and Their Impact on Glycaemia.

BACKGROUND: Nocturnal hypoglycaemia is a burden for people with diabetes, particularly when treated with multiple daily injections (MDI) therapy. However, the characteristics of nocturnal hypoglycaemic events in this patient group are only poorly described in the literature. METHOD: Continuous glucose monitoring (CGM) data from 185 study participants with type 1 diabetes using MDI therapy were collected under everyday conditions for up to 13 weeks. Hypoglycaemic events were identified as episodes of consecutive CGM readings <70 mg/dl or <54 mg/dl for at least 15 minutes. Subsequently, the time <54 mg/dl (TB54), time below range (TBR), time in range (TIR), time above range (TAR), glucose coefficient of variation (CV), and incidence of hypoglycaemic events were calculated for diurnal and nocturnal periods. Furthermore, the effect of nocturnal hypoglycaemic events on glucose levels the following day was assessed. RESULTS: The incidence of hypoglycaemic events <70 mg/dl was significantly lower during the night compared to the day, with 0.8 and 3.8 events per week, respectively, while the TBR, TB54, and incidence of events with CGM readings <54 mg/dl was not significantly different. Nocturnal hypoglycaemic events <70 mg/dl were significantly longer (60 vs 35 minutes) and enveloped by less rapidly changing glucose levels. On days following nights containing hypoglycaemic events, there was a decrease in TAR, mean CGM glucose level and morning glucose levels and an increase in TB54, TBR, and CV. CONCLUSIONS: The results showed that nocturnal hypoglycaemic events are a common occurrence in persons with type 1 diabetes using MDI with significant differences between the characteristics of nocturnal and diurnal events.

Performance of a Novel Continuous Glucose Monitoring Device in People With Diabetes.

BACKGROUND: In this multicenter study, performance of a novel continuous glucose monitoring (CGM) system was evaluated. METHODS: Adult participants with diabetes were included in the study. They each wore three sensors of the CGM system on the upper arms for up to 14 days. During four in-clinic visits, frequent comparison measurements with capillary blood glucose (BG) samples were performed. The primary endpoint was the 20/20 agreement rate (AR): the percentage of CGM readings within ±20 mg/dL (at BG values <100 mg/dL) or ±20% (at BG values ≥100 mg/dL) of the comparator. Further evaluations included mean absolute relative difference (MARD) and 20/20 AR in different BG ranges and across the wear time. RESULTS: Data from 48 participants and 139 sensors were analyzed. During in-clinic sessions the 20/20 AR was 90.5% and the MARD was 9.2%. For BG ranges <70, 70-180, and >180 mg/dL, 20/20 AR was 94.3%, 89.0%, and 92.5%, respectively. At the beginning, middle, and end of sensor wear time, 20/20 AR was 92.8%, 91.5%, and 85.9%, respectively. The 14-day survival probability was 82.4%. Pain and bleeding after sensor insertion were within the expected range. Based on the study outcome, the use of the device is regarded as safe. CONCLUSIONS: The system showed a good performance compared to capillary BG measurements. This level of accuracy could be shown over the entire measurement range, especially in the low glycemic range, and the whole wear time of the sensors. The results of this study are supporting a non-adjunctive use of the device.

Benefits of Usability Evaluation in the Development Process of Diabetes Technologies Using the Example of a Continuous Glucose Monitoring System Prototype.

BACKGROUND: Usability engineering analyzes the interaction between the intended users and a device. Its implementation is mandatory for manufacturers to obtain regulatory approval for the European market. The aim of this evaluation was assessing the role of usability testing in the development process. For this purpose, a continuous glucose monitoring (CGM) device under development was investigated to determine whether it could be used safely and effectively by the intended users. METHODS: Conduct of the usability testing was based on the international standard IEC 62366-1. Medical device use of CGM-experienced and non-experienced users (n = 15 each) was observed without initial training in use scenarios containing 18 tasks. The success rate of task completion was determined and the System Usability Scale (SUS) score was calculated from a questionnaire. A prototype of the FiberSense CGM System (EyeSense GmbH, Großostheim, Germany), comprising of a single-use sensor and a reusable detector, was investigated. RESULTS: Most use errors made by both user groups were related to ease of handling of the reusable detectors. The SUS scores achieved in this study were below the pre-defined SUS score acceptance criterion of ≥68. The most frequently mentioned reason for use errors was an incomprehensible and non-chronological instructions for use (IFU). CONCLUSIONS: The evaluation provides valuable insights on how to improve usability of the prototype device and demonstrates the value of conducting structured usability testing prior to product finalization. The results reflected areas for improvement of the user interface, mainly by restructuring the IFU, provision of an additional leaflet, and device training prior to use.