One in Five Laboratories Using Various Hemoglobin A(1c) Methods Do Not Meet the Criteria for Optimal Diabetes Care Management

Background: We assessed the reference change value (RCV) of currently available hemoglobin A(1c) (HbA(1c)) laboratory assays, which is defined as the critical difference between two consecutive HbA(1c) measurements representing a significant change in health status. Methods: We examined the individual laboratory coefficients of variation (CVs) in the Dutch/Belgian quality scheme based on 24 lyophilized samples and calculated the RCV per laboratory (n-220) and per assay method. In addition, two pooled whole blood samples were sent to the participating laboratories. The individual laboratory results were compared to the assigned value +/- an allowable total error (TEa) of 6%. Results: At HbA(1c) values of 41.0 mmol/mol (5.9%-Diabetes Control and Complications Trial [DCCT]) and 61.8 mmol/mol (7.8%-DCCT), 99% and 98%, respectively, of the laboratories reported a value within a TEa limit of 6%. The analytical CV of the HbA(1c) method used in 78% of the laboratories is Conclusions: The analytical performance of the majority of laboratory HbA(1c) methods is within the clinical requirements. However, based on the calculated RCV, 21.8% of the laboratories using different HbA(1c) methods are not able to distinguish an HbA(1c) result of 59 mmol/mol (7.5%-DCCT) from a previous HbA(1c) result of 53 mmol/mol (7.0%-DCCT). It can be presumed that differences in HbA(1c) results of 5 mmol/mol (0.5%-DCCT) do influence treatment decisions

Improved well-being and decreased disease burden after 1-year use of flash glucose monitoring (FLARE-NL4)

Introduction: The FreeStyle Libre is a flash glucose monitoring (FSL-FGM) system. Compared with finger-prick based self-monitoring of blood glucose, FSL-FGM may provide benefits in terms of improved glycemic control and decreased disease burden. Methods: Prospective nationwide registry. Participants with diabetes mellitus (DM) used the FSL-FGM system for a period of 12 months. End points included changes in HbA1c, hypoglycemia, health-related quality of life (12-Item Short Form Health Surveyv2 (SF-12v2) and 3-level version of EuroQol 5D (EQ-5D-3L)), a specifically developed patient-reported outcome measures (PROMs) questionnaire, diabetes-related hospital admission rate and work absenteeism. Measurements were performed at baseline, and after 6 months and 12 months. Results: 1365 persons (55% male) were included. Mean age was 46 (16) years, 77% of participants had type 1 DM, 16% type 2 DM and 7% other forms. HbA1c decreased from 64 (95%CI 63 to 65) mmol/mol to 60 (95%CI 60 to 61) mmol/mol with a difference of -4 (95% CI -6 to 3) mmol/mol. Persons with a baseline HbA1c >70 mmol/mol had the most profound HbA1c decrease: -9 (95% CI -12 to to 5) mmol/mol. EQ-5D tariff (0.03 (95%CI 0.01 to 0.05)), EQ-VAS (4.4 (95%CI 2.1 to 6.7)) and SF-12v2 mental component score (3.3 (95%CI 2.1 to 4.4)) improved. For most, PROMs improved. Work absenteeism rate (/6 months) and diabetes-related hospital admission rate (/year) decreased significantly, from 18.5% to 7.7% and 13.7% to 2.3%, respectively. Conclusions: Real world data demonstrate that use of FSL-FGM results in improved well-being and decreased disease burden, as well as improvement of glycemic control

Performance of the Eversense versus the Free Style Libre Flash glucose monitor during exercise and normal daily activities in subjects with type 1 diabetes mellitus

Introduction Accurate blood glucose measurements are important in persons with diabetes during normal daily activities (NDA), even more so during exercise. We aimed to investigate the performance of fluorescence sensor-based and glucose oxidase-based interstitial glucose measurement during (intensive) exercise and NDA. Research design and methods Prospective, observational study in 23 persons with type 1 diabetes when mountain biking for 6 days, followed by 6 days of NDA. Readings of the Eversense (fluorescence-based continuous glucose monitoring (CGM); subcutaneously implanted) and of the Free Style Libre (FSL; glucose oxidase-based flash glucose monitoring (FGM); transcutaneously placed) were compared with capillary glucose levels (Free Style Libre Precision NeoPro strip (FSLCstrip)). Results Mean average differences (MAD) and mean average relative differences (MARD) were significantly different when comparing exercise with NDA (reference FSLCstrip); Eversense MAD 25±19 vs 17±6 mg/dL (p<0.001); MARD 17±6 vs 13%±6% (p<0.01) and FSL MAD 32±17 vs 18±8 mg/dL (p<0.01); MARD 20±7 vs 12%±5% (p<0.001). When analyzing the data according to the Integrated Continuous Glucose Monitoring Approvals (class II-510(K) guidelines), the overall performance of interstitial glucose readings within 20% of the FSLCstrip during exercise compared with NDA was 69% vs 81% for the Eversense and 59% vs 83% for the FSL, respectively. Within 15% of the FSLCstrip was 59% vs 70% for the Eversense and 46% vs 71% for the FSL. Conclusions During exercise, both fluorescence and glucose oxidase-based interstitial glucose measurements (using Eversense and FSL sensors) were less accurate compared with measurements during NDA. Even when acknowledging the beneficial effects of CGM or FGM, users should be aware of the risk of diminished accuracy of interstitial glucose readings during (intensive) exercise

The risk of clinical misinterpretation of HbA1c: Modelling the impact of biological variation and analytical performance on HbA1c used for diagnosis and monitoring of diabetes

Background: The validity of clinical interpretation of HbA1c depends on the analytical performance of the method and the biological variation of HbA1c in patients. The contribution of non-glucose related factors to the biological variation of HbA1c (NGBVA1c) is not known. This paper explores the cumulative impact of analytical errors and NGBVA1c on the risk of misinterpretation. Methods: A model has been developed to predict the risk of misinterpretation of HbA1c for diagnosis and monitoring with variables for analytical performance and levels of NGBVA1c. Results: The model results in probabilities of misinterpretation for a given HbA1c. Example: for an HbA1c 43 mmol/mol (6.1%), bias 1 mmol/mol (0.09%), CV 3% (2%) used for diagnosis, the probabilities of misinterpretation range from 1 to 19% depending on the contribution of NGBVA1c to the biological variation of HbA1c. Conclusions: In addition to analytical bias and imprecision, NGBVA1c contributes to the risk of misinterpretation, but the relative impact is different per clinical application of HbA1c. For monitoring, imprecision is the predominating factor, for diagnosis both biological variation and analytical bias. Given the increasing use of HbA1c for diagnosis, increase of knowledge on NGBVA1c, decrease of analytical bias, and awareness of the risk of misinterpretation are required

Haemoglobin A1c:Historical overview and current concepts

<p>Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a "gold standard" for glucose management in patients with diabetes mellitus. Recently, HbA1c has been advocated as a diagnostic marker for diabetes mellitus, which further underlines the importance of HbA1c. There are currently more than 30 methods available on the market with an analytical performance ranging from poor to state of the art. This review describes the biochemistry of HbA1c and the concepts of analytical and biological variation with respect to the measurement of HbA1c. Subsequently, aspects regarding the discovery of HbA1c are described. In addition, an overview is given on the assays methods that are currently available for the measurement of HbA1c. Finally, recommendations for the minimally required analytical performance characteristics of the current HbA1c assays are presented. (C) 2012 Elsevier Ireland Ltd. All rights reserved.</p>

Haemoglobin A1c: Historical overview and current concepts

Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a "gold standard" for glucose management in patients with diabetes mellitus. Recently, HbA1c has been advocated as a diagnostic marker for diabetes mellitus, which further underlines the importance of HbA1c. There are currently more than 30 methods available on the market with an analytical performance ranging from poor to state of the art. This review describes the biochemistry of HbA1c and the concepts of analytical and biological variation with respect to the measurement of HbA1c. Subsequently, aspects regarding the discovery of HbA1c are described. In addition, an overview is given on the assays methods that are currently available for the measurement of HbA1c. Finally, recommendations for the minimally required analytical performance characteristics of the current HbA1c assays are presented. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Repeat whole blood donors with a ferritin level of 30 mu g/L or less show functional iron depletion

BACKGROUND: Whole blood donors are screened for iron depletion through hemoglobin measurement alone or in combination with ferritin. Ferritin measurement gives the advantage of earlier detection of iron depletion. In a previous study we identified a ferritin level of 30 mu g/L or less as a possible indicator of suboptimal erythropoiesis. In this study, erythropoietic parameters were measured to determine if a ferritin level of 30 mu g/L or less is indicative of iron-deficient erythropoiesis in repeat whole blood donors. STUDY DESIGN AND METHODS: Twenty-one healthy male repeat whole blood donors were divided into two groups according to their predonation ferritin values: 30 mu g/L or less (low-ferritin group) and greater than 30 mu g/L (normal-ferritin group). Ferritin and erythropoietic parameters were measured before whole blood donation and weekly in the 8 weeks after donation. RESULTS: A significantly lower value was found for hemoglobin, mean corpuscular volume (MCV), reticulocytes, and reticulocyte hemoglobin content on at least three of the nine time points in the low-ferritin group compared to the normal-ferritin group (p <0.05). Of these parameters, MCV and reticulocyte hemoglobin content were significantly lower before donation as well as during all 8 weeks following donation (p <0.05). CONCLUSION: Based on the lower values of the erythropoietic parameters in the low-ferritin group, it can be concluded that repeat whole blood donors with a ferritin value of 30 mu g/L or less have iron-deficient erythropoiesis and therefore require a longer donation interval than the current 56 days