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Emma English,1 Elise T Milosevich,1 W Garry John2 1School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom; 2Department of Clinical Biochemistry, Norfolk and Norwich University Hospital, Norwich, United Kingdom Abstract: 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. Keywords: glycated hemoglobin, HbA1c, IFCC

ObjectiveTo report trends in underweight, overweight and obesity in 12–15-year-old adolescents and examine changes in dieting behaviour, which have been less well documented.DesignComparison of two independent representative cross-sectional surveys.SettingNorthern Ireland.SubjectsWeight and height were objectively measured in 1324 boys and 1160 girls in 1996 and 1274 boys and 1374 girls in 2007. Participants reported whether they were following any particular diet including a self-proposed or prescribed weight-reduction diet.ResultsOverweight and obesity increased in girls from 15 % to 23 % and 2 % to 6 %, respectively. Increases were more modest in boys with overweight increasing from 13 % to 18 % and obesity from 3 % to 6 %. The proportion of underweight adolescents decreased from 9 % to 6 % in girls and 8 % to 5 % in boys. Evidence of social disparity was observed in girls from a manual socio-economic background, with overweight/obesity prevalence rates increasing from 21 % to 36 % compared with 15 % to 26 % in girls from a non-manual background. Despite these trends fewer adolescents, in particular girls, reported following weight-reduction diets (14 % of overweight/obese girls in 2007 v. 21 % in 1996; 8 % of boys in 2007 v. 13 % in 1996). Of these girls, the proportion from a manual background following weight-reduction diets decreased from 25 % to 11 %.ConclusionsOverweight and obesity are continuing to increase in adolescents despite government and media awareness strategies. There also appears to be reduced dieting behaviour, despite increasing body weight, particularly in girls from manual socio-economic backgrounds. [ABSTRACT FROM AUTHOR]

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 beta = 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. Copyright © 2005 American Society for Clinical Nutritionn [ABSTRACT FROM AUTHOR]

Abstract Background Coxiella burnetii causes the common worldwide zoonotic infection, Q fever. It has been previously suggested that patients who had recovered from acute Q fever (whether symptomatic or otherwise) may be at increased risk of ischaemic heart disease. We undertook this study to determine if past infection with Coxiella burnetii, the aetiological agent of Q fever, is a risk factor for the subsequent development of ischaemic heart disease. Methods A nested case-control study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME). The PRIME study is a cohort study of 10,593 middle-aged men undertaken in France and Northern Ireland in the 1990s. A total of 335 incident cases of ischaemic heart disease (IHD) were identified and each case was matched to 2 IHD free controls. Q fever seropositivity was determined using a commercial IgG ELISA method. Results Seroprevalence of Q fever in the controls from Northern Ireland and France were 7.8% and 9.0% respectively. No association was seen between seropositivity and age, smoking, lipid levels, or inflammatory markers. The unadjusted odds ratio (95% CI) for Q fever seropositivity in cases compared to controls was 0.95 (0.59, 1.57). The relationship was substantially unaltered following adjustment for cardiovascular risk factors and potential confounders. Conclusion Serological evidence of past infection with C. burnetii was not found to be associated with an increased risk of IHD.

Background: Most approved vaccines utilise a two-dose strategy. To enable larger groups of patients to receive the first dose, the UK government increased the gap between the two doses from three to twelve weeks. Here we report on the immunogenicity of the first dose, including effect of age and vitamin D status on these levels over an 8 week-period., Methods: Blood samples were collected from healthcare workers (HCW) receiving their first BNT162b2 vaccine dose between January and February 2021. Antibody (Ab) production was measured, prior to and weekly for 4 weeks post immunization, and a final measurement was performed at 8 weeks. Serum vitamin D concentrations were also measured at baseline., Findings: Immunization of 97 HCW induced an Ab response that peaked 3•2 weeks post immunization to decrease thereafter. Ab levels remained positive at 8 weeks. IgG peak concentration was negatively associated with age (β=-0•440, p<0.001). Response to immunization was also significantly affected by vitamin D status (p=0•022), on average 29•3% greater peak value in individuals with 25(OH)D>50nmol/L. No other variable showed significant effect., Interpretation: The first dose of BNT162b2 produced Ab levels that remained positive after 8 weeks. Peak was greater in younger subjects and 25(OH)D>50nmol/L was beneficial. Booster campaigns should take into consideration vitamin D status which is at its highest following a period of sunshine exposure or following oral supplementation (400-1000IU daily)., Funding: Abbott Diagnostics Ltd supplied the kits used to quantify the anti-SARS -CoV-2 Spike IgG and technical support as well as provided financial support for sample collections., Competing Interests: Declaration of Competing Interest Two of the authors (SR and MB) are employees of Abbott Diagnostics Ltd who supplied the kits used to quantify the anti-SARS -CoV-2 Spike IgG and technical support as well as provided financial support for sample collections. All other authors have no conflict of interest., (Copyright © 2022. Published by Elsevier Masson SAS.)

Introduction: The 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 Methods: Validation: 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., Results: There was a strong correlation between the first and the stored sample (R 2 =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., Conclusions: A 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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/m 2 , 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 < 65 years old (difference in mean HbA1c compared to CON -4.76 mmol/mol; 95% CI -7.75, -1.78 mmol/mol) than in older participants (-0.46 mmol/mol; 95% CI -2.67, 1.75; interaction 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 and -0.22 mmol/mol; 95% CI -2.7, 2.25; aged > 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., (© 2021. The Author(s).)

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 (<3.5%) and was linear throughout the positive range (tested to 38,365 AU/ml). The sensitivity (based on ≥14-day post-positive reverse transcription-PCR [RT-PCR] samples) and specificity were 98.3% (90.6% to 100.0%) and 99.5% (97.1% to 100%), respectively. The candidate reference materials showed poor correlation across methods, with mixed responses noted in methods that use the spike protein versus the nucleocapsid proteins as their binding antigen. The Abbott IgG II anti-SARS-CoV-2 measurement appears to be the first linear method potentially capable of monitoring the immune response to natural infection, including from new emerging variants. The candidate reference materials assessed did not generate uniform results across several methods, and further steps are needed to enable the harmonization process.

Aims: Diabetic microvascular complications of retinopathy, nephropathy and neuropathy may occur at hemoglobin A1c levels (HbA1c) below the 6.5% (48 mmol/mol) diagnostic threshold. Our objective was to assess the validity of the HbA1c diagnostic cutpoint of 6.5% based upon published evidence of the prevalence of retinopathy, nephropathy and neuropathy as markers of diabetes., Methods: Data Sources PubMed, Embase, Cochrane, Scopus and CINAHL from 1990-March 2019, grey literature sources. Study Selection All studies reported after 1990 (to ensure standardized HbA1c values) where HbA1c levels were presented in relation to prevalence of retinopathy, nephropathy or neuropathy in subjects not known to have diabetes. Data Extraction Studies were screened independently, data abstracted, and risk of bias appraised. Data Synthesis Data were synthesized using HbA1c categories of < 6.0% (< 42 mmol/mol), 6.0-6.4% (42-47 mmol/mol) and ≥ 6.5% (≥ 48 mmol/mol). Random-effects meta-analyses were conducted for retinopathy, nephropathy and neuropathy prevalence stratified by HbA1c categories. Random-effects multivariable meta-regression was conducted to identify predictors of retinopathy prevalence and sources of between-study heterogeneity., Results: Pooled mean prevalence was: 4.0%(95% CI: 3.2-5.0%) for retinopathy, 10.5% (95% CI: 4.0-19.5%) for nephropathy, 2.5% (95% CI: 1.1-4.3%) for neuropathy. Mean prevalence when stratified for HbA1c < 6.0%, 6.0-6.4% and ≥ 6.5% was: retinopathy: 3.4% (95% CI: 1.8-5.4%), 2.3% (95% CI: 1.6-3.2%) and 7.8%(95% CI: 5.7-10.3%); nephropathy: 7.1% (95% CI: 1.7-15.9%), 9.6% (95% CI: 0.8-26.4%) and 17.1% (95% CI: 1.0-46.9%); neuropathy: 2.1% (95% CI: 0.0-6.8%), 3.4% (95% CI: 0.0-11.6%) and 2.8% (95% CI: 0.0-12.8%). Multivariable meta-regression showed HbA1c ≥ 6.5% (OR: 4.05; 95% CI: 1.92-8.57%), age > 55 (OR: 3.23; 95% CI 1.81-5.77), and African-American race (OR: 10.73; 95% CI: 4.34-26.55), to be associated with higher retinopathy prevalence. Marked heterogeneity in prevalence estimates was found across all meta-analyses (Cochran's Q-statistic p < 0.0001)., Conclusions: The prevalence of nephropathy and moderate retinopathy was increased in subjects with HbA1c values ≥ 6.5% confirming the high specificity of this value for diagnosing T2DM; however, at HbA1c < 6.5% retinopathy increased at age > 55 years and, most strikingly, in African-Americans, suggesting there may be excess microvascular complication prevalence (particularly nephropathy) in individuals below the diabetes diagnostic threshold.

In 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. SARS-CoV-2 patient samples (n = 43) were analyzed 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. EDI 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 was 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%. Serological 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., Competing Interests: The authors acknowledge the Norfolk, Suffolk, Essex and Bedfordshire Freemasons for their material support in providing funding for some equipment used in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Nearly half of the older adult population has diabetes or a high-risk intermediate glycemic category, but we still lack trial evidence for effective type 2 diabetes prevention interventions in most of the current high-risk glycemic categories., Objective: To determine whether a group-based lifestyle intervention (with or without trained volunteers with type 2 diabetes) reduced the risk of progression to type 2 diabetes in populations with a high-risk glycemic category., Design, Setting, and Participants: The Norfolk Diabetes Prevention Study was a parallel, 3-arm, group-based, randomized clinical trial conducted with up to 46 months of follow-up from August 2011 to January 2019 at 135 primary care practices and 8 intervention sites in the East of England. We identified 141 973 people at increased risk of type 2 diabetes, screened 12 778 (9.0%), and randomized those with a high-risk glycemic category, which was either an elevated fasting plasma glucose level alone (≥110 and <126 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) or an elevated glycated hemoglobin level (≥6.0% to <6.5%; nondiabetic hyperglycemia) with an elevated fasting plasma glucose level (≥100 to <110 mg/dL)., Interventions: A control arm receiving usual care (CON), a theory-based lifestyle intervention arm of 6 core and up to 15 maintenance sessions (INT), or the same intervention with support from diabetes prevention mentors, trained volunteers with type 2 diabetes (INT-DPM)., Main Outcomes and Measures: Type 2 diabetes incidence between arms., Results: In this study, 1028 participants were randomized (INT, 424 [41.2%] [166 women (39.2%)]; INT-DPM, 426 [41.4%] [147 women (34.5%)]; CON, 178 [17.3%] [70 women (%39.3)]) between January 1, 2011, and February 24, 2017. The mean (SD) age was 65.3 (10.0) years, mean (SD) body mass index 31.2 (5) (calculated as weight in kilograms divided by height in meters squared), and mean (SD) follow-up 24.7 (13.4) months. A total of 156 participants progressed to type 2 diabetes, which comprised 39 of 171 receiving CON (22.8%), 55 of 403 receiving INT (13.7%), and 62 of 414 receiving INT-DPM (15.0%). There was no significant difference between the intervention arms in the primary outcome (odds ratio [OR], 1.14; 95% CI, 0.77-1.7; P = .51), but each intervention arm had significantly lower odds of type 2 diabetes (INT: OR, 0.54; 95% CI, 0.34-0.85; P = .01; INT-DPM: OR, 0.61; 95% CI, 0.39-0.96; P = .033; combined: OR, 0.57; 95% CI, 0.38-0.87; P = .01). The effect size was similar in all glycemic, age, and social deprivation groups, and intervention costs per participant were low at $153 (£122)., Conclusions and Relevance: The Norfolk Diabetes Prevention lifestyle intervention reduced the risk of type 2 diabetes in current high-risk glycemic categories. Enhancing the intervention with DPM did not further reduce diabetes risk. These translatable results are relevant for current diabetes prevention efforts., Trial Registration: ISRCTN Registry Identifier: ISRCTN34805606.

Introduction: To 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 Methods: A 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., Results: Data from 73 703 participants demonstrated a significant mean difference between the referral and POC HbA1c of -2.48 mmol/mol (-0.23%) (t=157, p<0.001) with significant differences in the mean difference between devices (F(2, 73 700)=738, p<0.001). The SD of POC HbA1c was 4.46 mmol/mol (0.41%) with significant differences in SDs between devices (F(2, 73 700)=1542, p<0.001). Participants who were older, from more deprived areas and from Asian, black and mixed ethnic groups were associated with smaller HbA1c differences. Normoglycemic POC HbA1c versus NDH POC HbA1c values were associated with lower subsequent attendance at behavioral interventions (58% vs 67%, p<0.001)., Conclusion: POC 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., Competing Interests: Competing interests: JV is the national clinical director for Diabetes and Obesity at NHS England and is the Clinical Lead for the Healthier You: NHS Diabetes Prevention Programme. EB is the Head of Health Intelligence (diabetes) for Public Health England and leads analysis of the Diabetes Prevention Programme. CB is the primary care advisor to the NHS Diabetes Programme. BY is clinical lead of the National Diabetes Audit for England and Wales and a Trustee of Diabetes UK. KK was chair of the Programme Development Group for the National Institute for Health and Care Excellence (NICE) public health guidance on type 2 diabetes: prevention in people at high risk (NICE PH38). KK is also codirector of the Leicester Diabetes Centre, and one of the programme providers, Ingeus UK Ltd, provide interventions based on the type 2 Diabetes Prevention Programme developed by LDC. NJW was Chair of the Programme Development Group for NICE public health guidance on Type 2 diabetes prevention: population and community-level interventions (NICE PH35). JS represents Public Health England on the NHS England Diabetes Programme Board. SON is the clinical director at Diabetes UK. MS is primary investigator for the NDPS programme. WGJ was chair of the IFCC-WG on Haemoglobin A1c Standardisation and of the IFCC-TF., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To investigate factors influencing diagnostic discordance for non-diabetic hyperglycaemia and Type 2 diabetes., Methods: Some 10 000 adults at increased risk of diabetes were screened with HbA 1c and fasting plasma glucose (FPG). The 2208 participants with initial HbA 1c ≥ 42 mmol/mol (≥ 6.0%) or FPG ≥ 6.1 mmol/l were retested after a median 40 days. We compared the first and second HbA 1c results, and consequent diagnoses of non-diabetic hyperglycaemia and Type 2 diabetes, and investigated predictors of discordant diagnoses., Results: Of 1463 participants with non-diabetic hyperglycaemia and 394 with Type 2 diabetes on first testing, 28.4% and 21.1% respectively had discordant diagnoses on repeated testing. Initial diagnosis of non-diabetic hyperglycaemia and/or impaired fasting glucose according to both HbA 1c and FPG criteria, or to FPG only, made reclassification as Type 2 diabetes more likely than initial classification according to HbA 1c alone. Initial diagnosis of Type 2 diabetes according to both HbA 1c and FPG criteria made reclassification much less likely than initial classification according to HbA 1c alone. Age, and anthropometric and biological measurements independently but inconsistently predicted discordant diagnoses and changes in HbA 1c ., Conclusions: Diagnosis of non-diabetic hyperglycaemia or Type 2 diabetes with a single measurement of HbA 1c in a screening programme for entry to diabetes prevention trials is unreliable. Diagnosis of non-diabetic hyperglycaemia and Type 2 diabetes should be confirmed by repeat testing. FPG results could help prioritise retesting. These findings do not apply to people classified as normal on a single test, who were not retested., (© 2019 Diabetes UK.)

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.