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IntroductionThe COVID-19 pandemic has reduced the accessibility to hemoglobin A1c (HbA1c) tests required for virtual diabetes clinics. The aim was to develop and validate a user-friendly postal system for remote HbA1c monitoring.Research design and methodsValidation: A total of 123 capillary blood samples from people with diabetes (PWD) needing face-to-face consultations along with healthy volunteers were measured on a point-of-care (POC) Siemens DCA Vantage Analyzer. Another sample of 5–10 drops was simultaneously collected in a K2EDTA tube (BD Microtainer) and stored for up to 12 days at room temperature for subsequent retesting. Feasibility: During October to December 2020, a total of 286 postal HbA1c kits were sent to PWD prior to their virtual consultation. These contained sample collection guidance, the necessary equipment and a feedback form. As per Packing Instruction 650 regulations, these were posted back to the diabetes center for HbA1c testing on the POC analyzer.ResultsThere was a strong correlation between the first and the stored sample (R2=0.978). There was a small clinically insignificant negative bias −1.53 mmol/mol (2 SD = 3.10 mmol/mol). Bland-Altman plots showed 93% of results within 2 SD. Of the 87% of returned kits, only one sample failed to be analyzed. 94% of PWD who provided feedback were happy to use the postal HbA1c system again.ConclusionsA robust user-friendly postal HbA1c system has been created and successfully integrated into clinical practice using the existing POC equipment at the diabetes center. It provides accurate HbA1c results and is an invaluable tool for remote monitoring of HbA1c in PWD—both during and after the pandemic.

In the initial stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, a plethora of new serology tests were developed and introduced to the global market. Many were not evaluated rigorously, and there is a significant lack of concordance in results across methods. To enable meaningful clinical decisions to be made, robustly evaluated, quantitative serology methods are needed. These should be harmonized to a primary reference material, allowing for the comparison of trial data and improved clinical decision making. A comprehensive evaluation of the new Abbott IgG II anti-SARS-CoV-2 IgG method was undertaken using CLSI-based protocols. Two different candidate primary reference materials and verification panels were assessed with a goal to move toward harmonization. The Abbott IgG II method performed well across a wide range of parameters with excellent imprecision (

Background The purpose of this trial was to test if the Norfolk Diabetes Prevention Study (NDPS) lifestyle intervention, recently shown to reduce the incidence of type 2 diabetes in high-risk groups, also improved glycaemic control in people with newly diagnosed screen-detected type 2 diabetes. Methods We screened 12,778 participants at high risk of type 2 diabetes using a fasting plasma glucose and glycosylated haemoglobin (HbA1c). People with screen-detected type 2 diabetes were randomised in a parallel, three-arm, controlled trial with up to 46 months of follow-up, with a control arm (CON), a group-based lifestyle intervention of 6 core and up to 15 maintenance sessions (INT), or the same intervention with additional support from volunteers with type 2 diabetes trained to co-deliver the lifestyle intervention (INT-DPM). The pre-specified primary end point was mean HbA1c compared between groups at 12 months. Results We randomised 432 participants (CON 149; INT 142; INT-DPM 141) with a mean (SD) age of 63.5 (10.0) years, body mass index (BMI) of 32.4 (6.4) kg/m2, and HbA1c of 52.5 (10.2) mmol/mol. The primary outcome of mean HbA1c at 12 months (CON 48.5 (9.1) mmol/mol, INT 46.5 (8.1) mmol/mol, and INT-DPM 45.6 (6.0) mmol/mol) was significantly lower in the INT-DPM arm compared to CON (adjusted difference −2.57 mmol/mol; 95% CI −4.5, −0.6; p = 0.007) but not significantly different between the INT-DPM and INT arms (−0.55 mmol/mol; 95% CI −2.46, 1.35; p = 0.57), or INT vs CON arms (−2.14 mmol/mol; 95% CI −4.33, 0.05; p = 0.07). Subgroup analyses showed the intervention had greater effect in participants p = 0.02). This effect was most significant in the INT-DPM arm (−6.01 mmol/mol; 95% CI −9.56, −2.46 age 65 years old; p = 0.007). The use of oral hypoglycaemic medication was associated with a significantly lower mean HbA1c but only within the INT-DPM arm compared to CON (−7.0 mmol/mol; 95% CI −11.5, −2.5; p = 0.003). Conclusion The NDPS lifestyle intervention significantly improved glycaemic control after 12 months in people with screen-detected type 2 diabetes when supported by trained peer mentors with type 2 diabetes, particularly those receiving oral hypoglycaemics and those under 65 years old. The effect size was modest, however, and not sustained at 24 months. Trial registration ISRCTN34805606. Retrospectively registered 14.4.16

BackgroundIn the emergency of the SARS-CoV-2 pandemic, great efforts were made to quickly provide serology testing to the medical community however, these methods have been introduced into clinical practice without the complete validation usually required by the regulatory organizations.MethodsSARS-CoV-2 patient samples (n=43) were analysed alongside pre-pandemic control specimen (n=50), confirmed respiratory infections (n=50), inflammatory polyarthritis (n=22) and positive for thyroid stimulating immunoglobulin (n=30). Imprecision, diagnostic sensitivity and specificity and concordance were evaluated on IgG serologic assays from EuroImmun, Epitope Diagnostics (EDI), Abbott Diagnostics and DiaSorin and a rapid IgG/IgM test from Healgen.ResultsEDI and EuroImmun imprecision was 0.02-14.0% CV. Abbott and DiaSorin imprecision (CV) ranged from 5.2% - 8.1% and 8.2% - 9.6% respectively. Diagnostic sensitivity of the assays were 100% (CI: 80-100%) for Abbott, EDI and EuroImmun and 95% (CI: 73-100%) for DiaSorin at ≥14 days post PCR. Only the Abbott assay had a diagnostic specificity of 100% (CI: 91-100%). EuroImmun cross-reacted in 3 non-SARS-CoV-2 respiratory infections and 2 controls. The DiaSorin displayed more false negative results and cross-reacted in six cases across all conditions tested. EDI had one cross-reactive sample. The Healgen rapid test showed excellent sensitivity and specificity. Overall, concordance of the assays ranged from 76.1% to 97.9%.ConclusionsSerological tests for SARS-CoV-2 showed good analytical performance. The head-to-head analysis of samples revealed differences in results that may be linked to the use of nucleocapsid or spike proteins. The point of care device tested demonstrated adequate performance for antibody detection.

IntroductionTo report the observations of point-of-care (POC) glycated hemoglobin (HbA1c) testing in people with non-diabetic hyperglycemia (NDH; HbA1c 42–47 mmol/mol (6.0%–6.4%)), applied in community settings, within the English National Health Service Diabetes Prevention Programme (NHS DPP).Research design and methodsA service evaluation assessing prospectively collected national service-level data from the NHS DPP, using data from the first referral received in June 2016–October 2018. Individuals were referred to the NHS DPP with a laboratory-measured HbA1c in the NDH range and had a repeat HbA1c measured at first attendance of the program using one of three POC devices: DCA Vantage, Afinion or A1C Now+. Differences between the referral and POC HbA1c and the SD of the POC HbA1c were calculated. The factors associated with the difference in HbA1c and the association between POC HbA1c result and subsequent attendance of the NHS DPP were also evaluated.ResultsData from 73 703 participants demonstrated a significant mean difference between the referral and POC HbA1c of −2.48 mmol/mol (−0.23%) (t=157, pConclusionPOC HbA1c testing in community settings was associated with significantly lower HbA1c values when compared with laboratory-measured referrals. Acknowledging effects of regression to the mean, we found that these differences were also associated with POC method, location, individual patient factors and time between measurements. Compared with POC HbA1c values in the NDH range, normoglycemic POC HbA1c values were associated with lower subsequent intervention attendance.

Background Diabetes mellitus is a major global issue and high quality testing is essential for the diagnosis and treatment of the disease. The IFCC Committee for the Education in the Utility of Biomarkers in Diabetes (C-EUBD) plays a global role in improving knowledge and understanding around diabetes testing. This paper describes a multi-stakeholder approach, to improving diagnostic and therapeutic testing for diabetes, using a multicentre study in China as an example of the global impact of the group. Methods Educational workshops were developed to support the scientific aims of the study in which 30 centres around China received identical, fresh frozen whole blood samples with values assigned using IFCC secondary reference methods and undertook precision (EP-5) and trueness studies. Performance was assessed using sigma metrics. Results A successful multi-stakeholder group was developed and sustained throughout the study through several educational workshops, which enabled the formation of a long-term collaboration with key opinion leaders and policy makers in China. All 30 centres showed good performance with within and between laboratory coefficient of variations (CVs) below 3% in SI units at both low and high haemoglobin A1c (HbA1c) levels. All individual laboratories met the criteria of a sigma of two or more at a total allowable error (TAE) of 5 mmol/mol (0.46% NGSP). Conclusions The study led to a successful multi-partner approach to improving diabetes testing in China. All centres involved in the study meeting the published IFCC quality criteria, paving the way for future clinical trials and an expanded role for HbA1c testing across the country.

BACKGROUND A major objective of the IFCC Committee on Education and Use of Biomarkers in Diabetes is to generate awareness and improvement of HbA1c assays through evaluation of the performance by countries and manufacturers. METHODS Fresh whole blood and lyophilized hemolysate specimens manufactured from the same pool were used by 17 external quality assessment organizers to evaluate analytical performance of 2166 laboratories. Results were evaluated per country, per manufacturer, and per manufacturer and country combined according to criteria of the IFCC model for quality targets. RESULTS At the country level with fresh whole blood specimens, 6 countries met the IFCC criterion, 2 did not, and 2 were borderline. With lyophilized hemolysates, 5 countries met the criterion, 2 did not, and 3 were borderline. At the manufacturer level using fresh whole blood specimens, 13 manufacturers met the criterion, 8 did not, and 3 were borderline. Using lyophilized hemolysates, 7 manufacturers met the criterion, 6 did not, and 3 were borderline. In both country and manufacturer groups, the major contribution to total error derived from between-laboratory variation. There were no substantial differences in performance between groups using fresh whole blood or lyophilized hemolysate samples. CONCLUSIONS The state of the art is that 1 of 20 laboratories does not meet the IFCC criterion, but there are substantial differences between country and between manufacturer groups. Efforts to further improve quality should focus on reducing between-laboratory variation. With some limitations, fresh whole blood and well-defined lyophilized specimens are suitable for purpose.

The world diabetes population quadrupled between 1980 and 2014 to 422 million and the enormous impact of Type 2 diabetes is recognised by the recent creation of national Type 2 diabetes prevention programmes. There is uncertainty about how to correctly risk stratify people for entry into prevention programmes, how combinations of multiple ‘at high risk’ glycemic categories predict outcome, and how the large recently defined ‘at risk’ population based on an elevated glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973 people at highest risk of diabetes in our population, and screened 10,000 of these with paired fasting plasma glucose and HbA1c for randomisation into a very large Type 2 diabetes prevention trial. Baseline discordance rate between highest risk categories was 45.6%, and 21.3–37.0% of highest risk glycaemic categories regressed to normality between paired baseline measurements (median 40 days apart). Accurate risk stratification using both fasting plasma glucose and HbA1c data, the use of paired baseline data, and awareness of diagnostic imprecision at diagnostic thresholds would avoid substantial overestimation of the true risk of Type 2 diabetes and the potential benefits (or otherwise) of intervention, in high risk subjects entering prevention trials and programmes.

The attraction of the simple biochemical concept combined with a clinical requirement for a long-term marker of glycolic control in diabetes has made hemoglobin A1c (HbA1c) one of the most important assays undertaken in the medical laboratory. The diversity in the biochemistry of glycation, clinical requirements, and management demands has resulted in a broad range of methods being developed since HbA1c was described in the late 1960s. A range of analytic principles are used for the measurement of HbA1c. The charge difference between hemoglobin A0 and HbA1c has been widely utilized to separate these two fractions, most notably found these days in ion-exchange high-performance liquid chromatography systems; the difference in molecular structure (affinity chromatography and immunochemical methods) are becoming widely available. Different results found in different laboratories using a variety of HbA1c analyses resulted in the need for standardization, most notably in the United States, Japan, and Sweden. Designated comparison methods are now located in these three countries, but as they are arbitrarily chosen and have differences in specificity, results of these methods and the reference values and action limits of the methods differ and only harmonized HbA1c in specific geographic areas. A reference measurement system within the concept of metrological traceability is now globally accepted as the only valid analytic anchor. However, there is still discussion over the units to be reported. The consensus statement of the International Federation of Clinical Chemistry (IFCC), the American Diabetes Association, the International Diabetes Federation, and the European Association for the Study of Diabetes suggests reporting HbA1c in IFCC units (mmol/mol), National Glycohemoglobin Standardization Program units (%), and estimated average glucose (either in mg/dl or mmol/liter). The implementation of this consensus statement raised new questions, to be answered in a concerted action of clinicians, biochemists, external quality assessment organizers, patient groups, and manufacturers.

Background: The IFCC Reference Measurement System for hemoglobin (Hb)A1c (IFCC-RM) has been developed within the framework of metrologic traceability and is embedded in a network of 14 reference laboratories. This paper describes the outcome of 12 intercomparison studies (periodic evaluations to control essential elements of the IFCC-RM).Methods: Each study included: unknown samples (to test individual network laboratories); known samples (controls); recently manufactured calibrators (to check calculated assigned value); stored calibrators (to test stability) and a calibration-set (to calibrate the IFCC-RM). The unknown samples are measured by use of the IFCC-RM and the designated comparison methods [DCMs; the National Glycohemoglobin Standardization Program (NGSP) in the US, Japanese Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC) in Japan, and Mono-S in Sweden] are used to investigate the stability of the Master Equation (ME), the relationship between IFCC-RM and DCMs.Results: A total of 105 IFCC-RM data sets were evaluated: 95 were approved, 5 were not, and for 5 no data were submitted. Trend analysis of the MEs, expressed as change in percentage HbA1c per year, revealed 0.000% (NGSP, not significant), −0.030%, (JDS/JSCC; significant) and −0.016% (Mono-S; not significant). Evaluation of long-term performance revealed no systematic change over time; 2 laboratories showed significant bias, 1 poor reproducibility. The mean HbA1c determined by laboratories performing mass spectrometry (MS) was the same as the mean determined by laboratories using capillary electrophoresis (CE), but the reproducibility at laboratories using CE was better. One batch of new calibrators was not approved. All stored calibrators were stable.Conclusion: A sound reference system is in place to ensure continuity and stability of the analytical anchor for HbA1c.

Aims/hypothesis: The use of HbA1c for the diagnosis of diabetes is now widely advocated despite caveats to its use. Anaemia is cited as a major confounder to this use; however, the effect of erythrocyte indices and to what degree anaemia influences HbA1c levels is not known. Methods: A systematic electronic database search of MEDLINE, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL) and the Cochrane Library was conducted for relevant articles published between January 1990 and May 2014. Included studies had at least one measurement of HbA1c and glucose, and a least one index of haematinic deficiency, involving non-pregnant adults, not known to have diabetes. Results: A total of 12 articles from 544 were included. The majority of studies focused on iron deficiency anaemia (IDA) and, in general, demonstrated that the presence of iron deficiency with or without anaemia led to an increase in HbA1c values compared with controls, with no concomitant rise in glucose indices. Data on the effects of other indices of erythrocyte abnormalities on HbA1c are limited but show a possible decrease in HbA1c values with non-iron deficiency forms of anaemia. Conclusions/interpretation: HbA1c is likely to be affected by iron deficiency and IDA with a spurious increase in HbA1c values; conversely, non-IDA may lead to a decreased HbA1c value. This may lead to confusion when diagnosing diabetes using HbA1c. This review clearly identifies the need for more evidence, especially in identifying the types and degrees of anaemia likely to have significant impact on the reliability of HbA1c.

BACKGROUND: Although hypovitaminosis D has been suggested to increase the risk of heart disease, its relation to components of the fasting lipid profile has not been clarified for specific ethnic groups. OBJECTIVE: The objective was to determine the relation of circulating 25-hydroxyvitamin D [25(OH)D] concentrations to fasting lipid concentrations in South Asian subjects at risk of hypovitaminosis D. DESIGN: The present study was conducted in 170 British Bangladeshi adults, 69 men and 101 women, from east London who were free of known diabetes or chronic disorders. Vitamin D repletion was assessed by measuring fasting serum 25(OH)D concentrations. Fasting lipid profiles were measured as part of a study of the risk factors for type 2 diabetes and ischemic heart disease, which included hypovitaminosis D. RESULTS: A univariate analysis showed that total cholesterol, LDL cholesterol, and both apolipoprotein (apo) A-I and apo B concentrations correlated directly with serum 25(OH)D concentrations. However, a multiple regression analysis, which included all the documented risk factors for diabetes and ischemic heart disease, showed that the 25(OH)D concentration (vitamin D status) was an independent predictor of increasing apo A-I concentrations (standardized coefficient {szligbeta} = 0.3; P < 0.001) but not of fasting lipid concentrations. CONCLUSIONS: In this study of British South Asians, the data showed a positive relation of fasting apo A-I concentrations to serum 25(OH)D concentrations, independent of glycemia and other dietary, anthropometric, and lifestyle risk factors for type 2 diabetes and ischemic heart disease after multiple regression analyses. Subjects with hypovitaminosis D are likely to have an increased risk of ischemic heart disease independent of their increased risk of type 2 diabetes.

Since better glucose control reduces microvascular complications in patients with diabetes, reliable evaluation of diabetes control is essential. Hemoglobin A1c (HbA1c) values reflect average glucose over approximately 120 days (the average erythrocyte lifespan) and are a better assessment of glucose control than blood glucose measurement, which provides information at only one point of time. Although HbA1c is universally accepted as a means for monitoring diabetes control, its measurement is challenging. Concerns have been expressed about deficiencies of HbA1c analysis—most notably, lack of accuracy and inability to use HbA1c in subsets of individuals (eg, patients with hemolytic anemia or acute blood loss). This Viewpoint addresses some important considerations relevant to laboratory determination of HbA1c.

Glycohemoglobin (gHb) is a marker of long-term glycemic control that has been shown to correlate with complications of diabetes mellitus (1). The National Glycohemoglobin Standardization Program (NGSP) was established to standardize gHb results so that clinical laboratory results are comparable to those reported by the Diabetes Control and Complications Trial (2)(3). Previous studies have shown that some gHb methods yield inaccurate results with samples heterozygous for hemoglobin (Hb) C or Hb S (4)(5)(6). At least 10% of black Americans have either Hb C or S trait, and there were 19 million black Americans over age 19 in 1990 (7)(8)(9)(10). The prevalence of diabetes is estimated to be 5.1% of the adult population, with the rate for non-Hispanic blacks being 1.6-fold higher than that of non-Hispanic whites (11). It is therefore probable that at least 150 000 Americans with diabetes have Hb C or S trait. Here, we investigate the measurement of gHb in specimens containing Hb C or S trait using eight gHb methods currently in clinical use. Whole blood samples from individuals homozygous for Hb A (n = 43) and heterozygous for Hb C or S (n = 43 and 61, respectively) were collected in EDTA tubes. Hb variants were identified by their characteristic Variant A1c HPLC chromatograms (Bio-Rad Laboratories). Aliquots of these samples containing between 4% and 14% Hb A1c (NGSP Hb A1c evaluation range) were stored refrigerated (2–8 °C) and analyzed within 10 days of collection. This study was approved by the Institutional Review Board of the University of Utah. The CLC 330 gHb analyzer (Primus Corporation) was operated at the University of Missouri. This method was chosen as the comparison method for this study because results from boronate affinity chromatography should not …

W. Garry John, Gunnar Nordin and Mauro Panteghini* 1 Clinical Biochemistry, Norfolk and Norwich University Hospital, and School of Medicine, Health Policy and Practice, UEA, Norwich, NR4 7UY, UK 2 External Quality Assurance in Laboratory Medicine in Sweden, Uppsala, Sweden 3 Centre for Metrological Traceability in Laboratory Medicine (CIRME) and Department of Clinical Sciences ‘‘Luigi Sacco’’, University of Milan, Milan, Italy

Mauro Panteghini* and W. Garry John on behalf of the IFCC Scientific Division 1 Centre for Metrological Traceability in Laboratory Medicine (CIRME), University of Milan, Milan, Italy 2 Department of Clinical Sciences ‘‘Luigi Sacco’’, University of Milan, Milan, Italy 3 Clinical Biochemistry, Norfolk and Norwich University Hospital, and School of Medicine Health Policy and Practice, UEA, Norwich, UK

The measurement of glycated hemoglobin is central in the monitoring of glycemic control in patients with diabetes. There are at least 30 different laboratory assays commercially available to measure the proportion of HbA1c in blood. In 1995 the IFCC established a Working Group (IFCC WG-HbA1c) to achieve international standardization of HbA1c measurement. The main achievements can be summarized as follows: a) a reference measurement procedure has been established with purified primary calibrators; b) a network of reference laboratories has been developed worldwide; and c) work has begun on implementation of traceability to the IFCC reference system. The IFCC WG-HbA1c recognizes the recommendation of the IFCC-IUPAC Committee on Nomenclature, Properties and Units that the analyte measured by the IFCC reference measurement procedure has been defined as betaN1-deoxyfructosyl-hemoglobin and that the recommended measurement units are mmol/mol. The IFCC WG-HbA1c recommends maintaining the use of the name HbA1c in clinical practice.

Objectives To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people. Design Diagnostic accuracy study. Participants Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjostrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis). Reference standard for hydration status Directly measured serum/plasma osmolality: current dehydration (serum osmolality >300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg). Index tests 39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality. Results Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality >300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve >0.8). The best equation was osmolarity=1.86×(Na + + K + )+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status. Conclusions Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults. Trial registration numbers: DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012.

The measurement of glycated haemoglobin has become centrally important in the monitoring of glycaemic control in the patient with diabetes. A number of analytical techniques have been described to measure this important haemoglobin fraction, and the fraction measured depends on the technique used; this has resulted in laboratories reporting different fractions i.e., HbA1, HbA1c and total glycated haemoglobin. This paper outlines methods currently used in clinical laboratories for the measurement of this glycated fraction. It describes the principles behind these methods and goes on to describe the new IFCC reference method, which will be used in the future to standardise methods used in the clinical laboratory. Analytical goals and factors that interfere with methods are also discussed.

It is fascinating to consider the analytical improvements that have occurred since glycated hemoglobin was first used in routine clinical laboratories for diabetes monitoring around 1977; at that time methods displayed poor precision, there were no calibrators or material with assayed values for quality control purposes. This review outlines the major improvements in hemoglobin A1c (HbA1c) measurement that have occurred since its introduction, and reflects on the increased importance of this hemoglobin fraction in the monitoring of glycemic control. The use of HbA1c as a diagnostic tool is discussed in addition to its use in monitoring the patient with diabetes; the biochemistry of HbA1c formation is described, and how these changes to the hemoglobin molecule have been used to develop methods to measure this fraction. Standardization of HbA1c is described in detail; the development of the IFCC Reference Measurement Procedure for HbA1c has enabled global standardization to be achieved which has allowed global targets to be set for glycemic control and diagnosis. The importance of factors that may interfere in the measurement of HbA1c are highlighted.

We have examined and compared the proteins present in guinea-pig bile as collected either from the common hepatic duct or from the gall bladder. Guinea-pig bile, collected from the common bile duct, has a rather low concentration of protein. Detailed examination shows that the concentrations of actively transported proteins such as immunoglobulin A and haptoglobin haemoglobin complexes are markedly lower than in rats although the concentrations of proteins which, like albumin, leak non-specifically into bile are similar in the two species. We also find that the protein composition of guinea-pig bile is extensively and selectively modified by resorp-tion of protein in the gall bladder.