Use Of HbA1c Research Articles

Glycated hemoglobin independently or in combination with fasting plasma glucose versus oral glucose tolerance test to detect abnormal glycometabolism in acute ischemic stroke: a Chinese cross-sectional study.

BackgroundThe investigation of glycated hemoglobin (HbA1c) as a diagnostic tool for abnormal glycometabolism is lack in acute ischemic stroke patients in China and worldwide. This paper was aimed to determine whether HbA1c, fasting plasma glucose (FPG), or HbA1c combined with FPG, could be used to screen for diabetes mellitus (DM) or prediabetes in acute ischemic stroke patients without previous DM.MethodsAcute ischemic stroke patients without previous DM (n = 1,316) were selected from the Abnormal gluCose Regulation in Patients with Acute StrOke acrosS China Study (ACROSS-China). Oral glucose tolerance test (OGTT), HbA1c, FPG, and HbA1c combined with FPG were used as the screening methods to categorize the glycometabolic status. OGTT was taken as the golden method. Venn diagrams and the overlap index were used to determine the associations among the three methods of identifying abnormal glycometabolism. The area under the receiver operating characteristic curve (AUROC) and Youden index were used to assess and compare the accuracy in detecting abnormal glycometabolism. Youden analyses were performed to determine the ideal cutoff values of HbA1c in diagnosing abnormal glycometabolism.ResultsIn acute ischemic stroke patients without previous DM, the overlaps of HbA1c versus OGTT, HbA1c versus FPG, and all the three methods independently, were low for detecting abnormal glycometabolism (all <50%). HbA1c can significantly detect more cases of prediabetes than OGTT (P < 0.001). The combination of HbA1c and FPG significantly raised the sensitivity to over 60.0%, specificity to over 80.0%, and the diagnostic accuracy (Youden index from under 40.0% to 42.4%)for DM. HbA1c of 5.7%-6.4% had a low to moderate concordance with OGTT for identifying prediabetes (AUROC = 0.557, P = 0.001). HbA1c values of 6.3% and 5.9% were found to be the ideal cutoff values for detecting DM and abnormal glycometabolism in our data, respectively.ConclusionsThe combination of HbA1c and FPG increased the diagnostic rate of DM when compared with OGTT, and increased the diagnostic accuracy for DM compared with HbA1c or FPG alone. Our results advocate the use of HbA1c as screening tool for the diagnosis of pre-diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-014-0177-0) contains supplementary material, which is available to authorized users.

In vitro determination of hemoglobin A1c for diabetes diagnosis and management: technology update

In vitro determination of hemoglobin A1c for diabetes diagnosis and management: technology update 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

Abstract 387: Utility of Glycated Hemoglobin for Assessment of Glucose Metabolism in Patients with ST segment elevation Myocardial Infarction

Background: The performance of glucose tolerance test (OGTT) in patients with STEMI results in the new recognition of diabetes mellitus (DM) in over 25% of subjects. However, due to presence of stress hyperglycemia and critical patient condition, diagnosis of DM using traditional tests (fasting glucose and OGTT) during initial hospital stay is challenging. The ADA definition now enables use of HbA1c for diagnosis of DM. We sought to evaluate the incidence and trends in newly diagnosed DM utilizing HbA1c in patients with STEMI. Methods: Consecutive patients (N=1,812) undergoing primary PCI for STEMI at the Cleveland Clinic between Jan 05-Dec 12 were included. Medical charts were queried to identify patients with an established history of DM. Admission HbA1c was used to identify patients with previously undiagnosed DM (HbA1c ≥ 6.5) and pre DM (HbA1c ≥ 5.7 and &lt; 6.5). Results: Mean age was 60 years with 68% males. Overall, 428 patients (23.6%) had an established history of DM. Of the remainder, only 118 (8.5%) were diagnosed with DM while 593 patients (42.9%) had pre-DM based on admission HbA1c (Figure 1). There was no significant increase in mean body mass index (BMI) and incidence of DM over time (p=0.5). Conclusions: Utilization of admission HBA1c in patients with STEMI enables cardiologists to establish a new diagnosis of DM in a significant minority of subjects. Although convenient, HbA1c appears to under diagnose DM when compared to historical data with OGTT. Despite the increasing prevalence of obesity and DM in overall US population, we did not observe differences in mean BMI and prevalence of DM over time. The manifest cardiovascular consequences of DM may yet represent the exposed tip of the iceberg.

Interpretation of HbA1c : association with mean cell volume and haemoglobin concentration.

The utility of HbA1c in diabetes diagnosis is reduced in settings associated with altered haemoglobin glycation. We have studied whether HbA1c varies with mean cell volume and mean cell haemoglobin concentration as measures of haemoglobin metabolism. Randomly selected adults from rural Victoria, Australia, were invited for biomedical assessment. After excluding patients with known diabetes and/or serum creatinine ≥ 0.12 mmol/l, 1315 adults were included. Demography, arthropometric measurements, oral glucose tolerance test, analyses of full blood count and HbA1c were undertaken. After adjusting for age, sex, ethnicity, BMI, town and socio-economic status, there were no significant differences in haemoglobin, mean cell volume or mean cell haemoglobin concentration by glycaemic status (defined by oral glucose tolerance test). HbA1c was significantly and independently associated with fasting glucose, town, mean cell haemoglobin concentration, ethnicity, age and BMI among men < 50 years (R² = 33.8%); fasting glucose, 2-h glucose, mean cell haemoglobin concentration and town among men ≥ 50 years (R² = 47.9%); fasting glucose, mean cell volume, mean cell haemoglobin concentration, town, 2-h glucose and age among women < 50 years (R² = 46.3%); fasting glucose, mean cell haemoglobin concentration, mean cell volume and 2-h glucose among women ≥ 50 years (R² = 51.6%). A generalized linear model showed a gradient from an adjusted mean HbA1c of 36 (95% CI 34-38) mmol/mol with a mean cell haemoglobin concentration of ≤ 320 g/l to 30 (95% CI 29-31) mmol/mol with a mean cell haemoglobin concentration of > 370 g/l. The gradient across mean cell volume was negative, but only by 1 mmol/mol (0.1%) HbA1c . A mean HbA1c difference of 5 mmol/mol (0.5%) across the mean cell haemoglobin concentration reference range suggests that an accompanying full blood count examination may be required for its use in the diagnosis of diabetes. Further studies are required to confirm this.

Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.

Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [P value = 1.3 × 10−23], HBS1L/MYB [8.5 × 10−15], MYO9B [9.0 × 10−12], and CYBA [1.1 × 10−8] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA1c. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (<7.0 mmol/L) but elevated HbA1c (≥6.5%), 36.1% had HbA1c <6.5% after adjustment for these six variants. Our East Asian GWAS meta-analysis has identified novel variants associated with HbA1c as well as demonstrated that the effects of known variants are largely transferable across ethnic groups. Variants affecting erythrocyte parameters rather than glucose metabolism may be relevant to the use of HbA1c for diagnosing diabetes in these populations.

Normoglisemik Bireylerde Demir Eksikliği Anemisinin Hemoglobin A1c Düzeylerine Etkisi

Objective Recently published ADA criteria recommends the use of hemoglobin A1c (HbA1c) levels in the diagnosis and treatment of diabetes. Iron deficiency anemia (IDA) is one of the most common anemias and restricts the use of HbA1c in diagnosis and treatment as it is known to be a cause of potential interference. This study was designed to investigate the effect of IDA on HbA1c levels in normoglisemic patients.Methods 80 patients without diabetes and 70 healthy controls who were admitted to Ankara Numune Training and Research Hospital between September 2012 and March 2013 with fasting glucose, iron, unsaturated iron binding capacity, HbA1c levels and complete blood count were involved in the study. HbA1C levels were measured by Premier Hb9210 HbA1c Analyzer using Boronat affinity HPLC method.Results HbA1c levels were 5,61 (±0,39) % and 5.56 (±0,36) % for patient and control group respectively. There was no significant difference between the patient and the control group in HbA1c levels (p> 0,05). Hemoglobin, iron, unsaturated iron binding capacity and ferritin levels were significantly different between the patient and the control group (p <0.001). There was no significant correlation between hemoglobin and HbA1c levels. There were significant correlations between HbA1c and age, fasting blood glucose levels (p:0.002, r :0.255; p: <0,001, r :0.309 respectively).Conclusion In our study, no significant difference was found between IDA and healthy group in HbA1c levels. In iron deficiency anemia, the HbA1c levels has not been affected according to the unchanged red blood cell survival rate.

Use of HbA1c for Diagnoses of Diabetes and Prediabetes: Comparison with Diagnoses Based on Fasting and 2-Hr Glucose Values and Effects of Gender, Race, and Age

Glycated hemoglobin (HbA1c) has been advocated for the diagnosis of diabetes and prediabetes. Its performance has been commonly assessed in corroboration with elevated fasting plasma glucose (FPG), but not the combination of FPG and 2-hr glucose values. This study assesses receiver operating characteristics (ROC) curves of HbA1c pertaining to the diagnoses of prediabetes and diabetes by FPG and/or 2-hr glucose, and the effects of age, gender, and race. We assessed the utility of HbA1c for diagnosing diabetes and prediabetes among 5395 adults without known diabetes from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Current cutoffs of HbA1c for diabetes (6.5%) or prediabetes (5.7%) exhibited low sensitivity (0.249 and 0.354, respectively) and high specificity in identifying patients diagnosed using both FPG and 2-hr glucose, resulting in large false-negative rates (75.1% and 64.9%). Misdiagnosis rates increased with age and in non-Hispanic whites and Mexican Americans. When HbA1c was combined with FPG for diagnoses, the false-negative rate remained high for diabetes (45.7%), but was reduced for prediabetes (9.2%). When assessed against diagnoses using both FPG and 2-hr glucose, HbA1c had low sensitivity and high specificity for identifying diabetes and prediabetes, which varied as a function of age and race. Regarding recently released American Diabetes Association (ADA) and joint European guidelines, it is important to consider that HbA1c values below 6.5% and 5.7% do not reliably exclude the presence of diabetes and prediabetes, respectively. Overall, the data argue for greater use of oral glucose tolerance tests (OGTTs) and both FPG and 2-hr glucose values for diagnosis of diabetes and prediabetes.

Screening for type 2 diabetes and pre-diabetes in general practice: A descriptive study of Maltese practices

ObjectiveThe aim of this research study was to ascertain the awareness of Maltese family doctors to the prevalence and significance of impaired glucose regulation and early diagnosis of type 2 diabetes and whether practices were influenced by employment status, post-graduate training in diabetes or years since graduation. MethodsA specially constructed questionnaire was distributed by mail to all the 298 family doctors listed as Specialists in Family Medicine in the Maltese Medical Council register. Participants had to be practising family medicine in Malta. Results were analysed using SPSS 20.0 aiming for a significance criterion of 0.05 and a power of 80%. ResultsValid replies were received from 154 GPs (51.7%). 93.2% claimed to offer their patients some form of screening. Screening levels reached up to 95.9% in the presence of specific risk factors (e.g. high previous HbA1c levels) but fell to between 46.2% and 58.7% in patients over 50, the physically inactive and those who suffer from polycystic ovarian syndrome. Screening using capillary glucose is widespread (70.8%) as opposed to the oral glucose tolerance test (23.4%). Results also show a high use of urinalysis in screening (53.2%) and a paradoxical lack of use of HbA1c in screening by young doctors and by those with recent extra training in diabetes. ConclusionsThe need for a structured screening programme in Malta and its viability need to be evaluated by further studies. Educational support to GPs together with logistic support for GPs needs to be improved.

Glycosylated Haemoglobin (HbA 1 c) - A Marker of Circulating Lipids in Type 2 Diabetic Patients

Diabetic patients with concomitant dyslipidemia are often soft targets for cardiovascular disease and deaths. An early intervention to normalize circulating lipids has been shown to reduce cardiovascular morbidity and mortality. Glycosylated hemoglobin (HbA1c) is routinely used as a marker to indicate long-term glycemic control. Our aim was to test whether HbA1c can serve as a marker of circulating lipids among Type 2 diabetic patients. The sera of 130 Type 2 diabetic patients was analyzed for fasting blood sugar (FBS), HbA1c and lipid profile consisting of total cholesterol (TC), triglycerides (TG), High-density Lipoprotein (HDL) cholesterol and LDL cholesterol. We divided the subjects based on their glycemic index into three groups; HbA1c< 6% as good, HbA1c>6% - <9% as poor and HbA1c>9% as worst glycemic control. One-way analysis of variance (ANOVA) and post-hoc Dunnett's multiple comparison tests was used to examine the significance levels for various biochemical parameters in age-categorized groups. The mean ± SD levels of HbA1c was significantly higher in females (8.598 ± 2.284 %) compared to males (7.323±2.18 %). Older patients had HbA1c, FBS and lipid profile levels similar to younger ones. HbA1c showed direct and significant correlations with cholesterol, TG and LDL. Univariate analysis showed that HbA1c was a good predictor of circulating lipid levels. The study indicates the usefulness of HbA1c as a marker for lipid profile for screening of diabetic patients at high risk of developing cardiovascular diseases.

Changing from glucose to HbA1c for diabetes diagnosis: predictive values of one test and importance of analytical bias and imprecision

In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted from March 2012. We evaluated the change in the number of diabetes cases diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG), and estimated the influence of analytical variation and bias on the HbA1c-based prevalence of diabetes. The study population constituted 4239 individuals not known to have diabetes randomly selected from all inhabitants aged 25-75 years in the former County of Vejle, Denmark. The number of undiagnosed patients with diabetes in the study population using FPG or HbA1c as the diagnostic criterion was estimated. Furthermore, changes in the analytical bias and coefficient of variation (CV) for HbA1c analysis were simulated and the effect on the number of diabetes cases was observed. Changing the diagnostic test from FPG to HbA1c reduced the number of patients with diabetes by approximately 46% based on one measurement. The predictive value of one test of HbA1c was 91% versus only 66% for one test of FPG. Analytical variation had a much greater impact on the number of patients with diabetes than bias. At a bias of 0%, an increase of CVanalytical from 2.7% to 3.7% increased the number of diabetes cases by 90%. In the study population, the percentage of undiagnosed patients with diabetes aged 25-75 years was reduced from 3.6% (95% CI 3.0%-4.2%) based on one FPG measurement (FPG ≥7.0 mmol/L) to only 1.9% (95% CI 1.5%-2.3%) if the diagnosis of diabetes was based on the criterion of HbA1c ≥48 mmol/mol (6.5% DCCT).

Diagnosing Diabetes Mellitus: Performance of Hemoglobin A1c Point-of-Care Instruments in General Practice Offices

Hemoglobin A1c (Hb A1c) measurement by hospital laboratory instruments, but not by point-of-care (POC) instruments, has been recommended for use to diagnose diabetes mellitus. We evaluated results from 13 Hb A1c external quality assurance (EQA) surveys over a 6-year period in Norway, from both POC instruments used in general practice (GP) offices and instruments in hospital laboratories, against the analytical quality specifications recommended for use of Hb A1c to diagnose diabetes mellitus. All GP offices (n = 1288) and hospital laboratories (n = 52) measuring Hb A1c in Norway participated in the EQA survey. The percentage of participants that performed measurements within the quality specifications was calculated. Pooled within-laboratory CVs were estimated for the Afinion, DCA 2000, DCA 2000+, DCA Vantage(TM), and Nycocard Hb A1c Reader instruments and for hospital laboratory instruments. Between 60% to 90% of Afinion and DCA users and hospital laboratories performed Hb A1c measurements within the quality specifications for both trueness (6.0%) and imprecision (CV ≤2.0%) at 2 levels in each EQA survey. The pooled within-laboratory CVs for the Afinion and DCA instruments and hospital laboratories were below the recommended limit of 2.0% for most of the surveys. A large proportion of GP offices using Afinion and DCA POC instruments to measure Hb A1c fulfill the analytical quality specifications for diagnosing diabetes mellitus, and these instruments demonstrate analytical quality comparable to that of hospital laboratory instruments. When GP offices participate in a stringent quality assurance program and generate Hb A1c measurements that meet analytical quality specifications, these measurements can be recommended for use to diagnose diabetes mellitus.

Impact of HbA1c criterion on the definition of glycemic component of the metabolic syndrome: the China health and nutrition survey 2009.

BackgroundIn 2009, a unified definition of metabolic syndrome (MetS) was proposed, of which, the glycemic component is defined on the basis of fasting plasma glucose (FPG) level. Recently, the American Diabetes Association (ADA) recommended the use of glycated hemoglobin (HbA1c) as an alternative to FPG to define prediabetes. Hence, we aim to compare the performance of HbA1c and FPG in the definition of glycemic component of the MetS among Chinese adults.MethodsWe conducted a cross-sectional analysis of 7641 Chinese participants aged ≥18 years using data from the China Health and Nutrition Survey 2009. MetS was defined according to the consensus criteria in 2009. We compared the use of HbA1c versus FPG in the definition of the glycemic component of MetS. Increased HbA1c value was defined following the criterion of HbA1c cut-off point of ≥5.7% recommended by the ADA.ResultsOverall, 1136 (14.9%) had MetS according to FPG ≥ 5.6 mmol/l, and 1640 (21.5%) had MetS according to HbA1c ≥ 5.7%. Compared with individuals with FPG-based diagnosis of MetS, individuals with HbA1c-based diagnosis of MetS were older, had higher levels of LDL-C, magnesium, and transferrin, and lower levels of uric acid. Of those found to have MetS according to either FPG or HbA1c (n = 2008), overlap between HbA1c- and FPG-based diagnosis of MetS was limited (n = 768, 38.2%). The overlap index regarding MetS diagnosed by FPG or HbA1c persisted low in each evaluated subgroup (≤ 50.0%).ConclusionsWe note limited overlap and poor agreement between FPG- and HbA1c-based diagnosis of MetS. Screening MetS through introduction of HbA1c in addition to FPG could contribute to identification of more people with MetS.

Diabetes Mellitus: Too Many Controversies Affecting Care

Diabetes care is in disarray mainly due to a lack of consensus among professionals in the diagnosis and management of diabetes. The most common trend is the use of HbA1c (glycosylated hemoglobin) above 6.5% in making the diagnosis of diabetes. Similarly, the most common prescription written for treatment of diabetes is metformin, 500 mg to 1000 mg twice daily. FBG (Fasting blood glucose) above 126 mg/dL is a common accompaniment of HbA1c, but 2hPPG (2-h postprandial glucose) or 4-h oral glucose tolerance tests are not included in the diagnosis of diabetes. In the early stage of diabetes or impaired glucose tolerance associated with obesity, FBG or HbA1c may be useful, but with rising FBG or HbA1c despite dual or triple oral antidiabetic therapy, 2hPPPG becomes the mainstay to determine the severity of diabetes and the need for initiation of insulin therapy. It is needless to underscore that 2hPPG relates to outcome measures such as cardiovascular disorders, nephropathy and death. Thus the cornerstone of therapy when 2hPPG is above 200 mg/dL (≥ 11.1 mmol/L) is insulin with a goal to reduce the risk of complications. There is no or only subtle evidence that oral antidiabetic agents will affect 2hPPG or reduce the risk of complications of diabetes. Therefore, the optimal goal of therapy in diabetes is not limited to merely glycemic control, but the intent of glycemic control which is prevention of diabetes complications.

The monitoring of diabetes mellitus

Changes in clinical practice are often preceded by the gathering of evidence which can take several years. Diabetes mellitus is a prime example of how its management has changed with a mix of advances in laboratory medicine and technology. I was first introduced to the world of the Maillard reaction, Amadori rearrangement and Schiff bases in the early 1980s while working with Professor Sir George Alberti when he handed me a paper on nonenzymatic glycosylation of proteins and their use in diabetes control. Fast forward to the late 1980s when the University of Manchester Department of Medicine at Manchester Royal Infirmary moved from World War II hutments to a new building. The departmental library moved too, and volumes lay haphazardly on shelves. Professor Peter Adams, turning to me, a research fellow, said ‘You look a bit spare, how about sorting out this library?’ Among the journal volumes, there was a historical treasure trove of publications from famous names, but it was here that I first saw a complete collection of the Annals of Clinical Biochemistry starting from volume one. It belonged to the late Jeff Lumb who produced seminal works on vitamin D and calcium metabolism. It was interesting to see the current Annals evolve from the Proceedings of the Association of Clinical Biochemist meetings around the country. The monitoring of diabetes was initially based on urine glucose testing. RD Lawrence, the well-known Chemical Pathologist and Physician, in his 1937 edition of his book gave details of the best times to test for urine glucose and suggested that the Benedict’s test was better than using Fehling’s reagent. For general practitioners, he recommended tests such as the fermentation test for sugars and an iodine test for starch to determine suitability of ‘diabetic’ foods. By 1941, tablets were available to test for urine sugar and over time these morphed into the present day urine dipsticks. In 1962, a semiquantitative method for blood glucose was available. By the 1970s, self-monitoring of blood glucose (SMBG) was being developed and demonstrated to improve glycaemic control. In parallel to these developments, a new way to monitor glycaemic control was being developed. It started very much with Samuel Rahbar’s chance discovery of an unidentified band on electrophoresis in blood from a 67-year-old diabetic woman when he was working on a project looking at haemoglobin variants in Iran. He published his findings in a sister clinical biochemistry journal and confirmed his results in a larger series in the USA. Glycosylated haemoglobin A1c (HbA1c) was first described in 1958 by Huisman et al. and was characterized later in 1966, but the diabetes connection was only confirmed by Rahbar in 1969. Further work by Koenig et al. established the clinical utility of HbA1c through a series of papers in the mid 1970s. In the early 1990s, the Diabetes Control and Complications Trial confirmed the utility of HbA1c in type 1 diabetes and in the late 1990s, the United Kingdom Prospective Diabetes Study demonstrated

Stress hyperglycaemia in hospitalized patients with coronary artery disease and type 2 diabetes risk

(i) To evaluate glucometabolic status of patients without known diabetes hospitalized due to coronary artery disease (CAD), (ii) to assess markers of systemic inflammation determined during admission and to evaluate their relationship with glucometabolic status and (iii) to analyse usefulness of HbA1c determined during admission in patients with CAD to detect abnormal glucose regulation (AGR). We studied 440 patients with CAD admitted to the cardiology ward. Patients were grouped in four groups during admission according to clinical data, fasting plasma glucose and HbA1c: diabetes, HbA1c > 5·9%, stress hyperglycaemia (SH) and normal. In 199 subjects without known diabetes, an oral glucose tolerance test (OGTT) was performed 3 months after discharge, and they were reclassified according to WHO 1998 criteria. Biochemical and inflammatory markers were measured. The OGTT showed that 27·4% of subjects without known diabetes at admission had diabetes, 11·2% had impaired fasting glucose + impaired glucose tolerance, 33·5% impaired glucose tolerance, 3·6% impaired fasting glucose, and 24·4% normal glucose metabolism. Odds ratio for having diabetes 3 months after discharge in HbA1c > 5·9% group was 5·91 (P < 0·0001) and in SH group was 1·82 (P = 0·38). The best HbA1c cut-off point to predict AGR was 5·85%. HbA1c levels during admission were highly predictive of having AGR (AUC ROC 0·76 [95% CI 0·67-0·84]). We reported a high prevalence of AGR in subjects with CAD. Stress hyperglycaemia in patients with CAD was not associated with an increased risk of diabetes 3 months later. HbA1c in patients hospitalized with CAD was a useful tool to detect AGR.

Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies.

AimsHaemoglobinA1c (HbA1c) is recommended for diabetes diagnosis but fasting plasma glucose (FPG) has been useful for identifying patients with glucokinase (GCK) mutations which cause lifelong persistent fasting hyperglycaemia. We aimed to derive age-related HbA1c reference ranges for these patients to determine how well HbA1c can discriminate patients with a GCK mutation from unaffected family members and young-onset type 1 (T1D) and type 2 diabetes (T2D) and to investigate the proportion of GCK mutation carriers diagnosed with diabetes using HbA1c and/or FPG diagnostic criteria.MethodsIndividuals with inactivating GCK mutations (n = 129), familial controls (n = 100), T1D (n = 278) and T2D (n = 319) aged ≥18years were recruited. Receiver Operating Characteristic (ROC) analysis determined effectiveness of HbA1c and FPG to discriminate between groups.ResultsHbA1c reference ranges in subjects with GCK mutations were: 38–56 mmol/mol (5.6–7.3%) if aged ≤40years; 41–60 mmol/mol (5.9–7.6%) if >40years. All patients (123/123) with a GCK mutation were above the lower limit of the HbA1c age-appropriate reference ranges. 69% (31/99) of controls were below these lower limits. HbA1c was also effective in discriminating those with a GCK mutation from those with T1D/T2D. Using the upper limit of the age-appropriate reference ranges to discriminate those with a mutation from those with T1D/T2D correctly identified 97% of subjects with a mutation. The majority (438/597 (73%)) with other types of young-onset diabetes had an HbA1c above the upper limit of the age-appropriate GCK reference range. HbA1c ≥48 mmol/mol classified more people with GCK mutations as having diabetes than FPG ≥7 mmol/l (68% vs. 48%, p = 0.0009).ConclusionsCurrent HbA1c diagnostic criteria increase diabetes diagnosis in patients with a GCK mutation. We have derived age-related HbA1c reference ranges that can be used for discriminating hyperglycaemia likely to be caused by a GCK mutation and aid identification of probands and family members for genetic testing.

Hemoglobin-A1c level to predict for clinical outcomes in patients with pancreatic cancer.

4039 Background: An association between diabetes mellitus (DM) and pancreatic ductal adenocarcinoma (PDA) has long been recognized. While long-standing DM may be a risk factor for developing PDA, new-onset DM may be a manifestation of the cancer. Here we assess the role of an objective and quantifiable measure of glucose intolerance, hemoglobin-A1c (HbA1c), in predicting clinical outcomes in PDA. Methods: HbA1c values were prospectively collected on 656 consecutive patients presenting to the Johns Hopkins Pancreas Multidisciplinary Cancer Clinic from 2009-2012. Patients were diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable (R), borderline/locally advanced (BL), or metastatic (M) PDA. Patients with prior treatment for PDA or a history of DM greater than a 1-year were excluded. Univariate Cox regression analyses and multivariable proportional hazards models were used to identify poor prognostic factors for overall survival. Results: Of 284 patients included, 44 had benign disease, 62 R-PDA, 115 BL-PDA, and 63 M-PDA. Patients with malignant disease (R-, BL-, and M-PDA) collectively had higher HbA1c values on average at presentation than patients with BPD (6.1% vs. 5.6%, p&lt;0.001). There was a trend towards higher HbA1c at presentation in patients with advanced PDA (BL and M) compared to patients with R-PDA (6.2% vs. 5.9%, p=0.100); moreover, the proportion of patients with HbA1c levels in the diabetic range (&gt;6.4%) increased with more advanced stage of disease. Among patients with PDA (n=240), univariate analyses showed HbA1c≥6.5, age≥65, ECOG≥1, CA19-9&gt;90, tumor size &gt;3cm, and advanced stage to be significantly associated with inferior survival (all HR&gt;1, p&lt;0.05). After multivariate analysis with backward elimination, all of the above factors except for tumor size &gt;3cm remained in the model for inferior survival. Conclusions: HbA1c level at presentation appears to correlate with disease stage and, moreover, to predict for survival among all stages of PDA. Patients with PDA have significantly higher HbA1c levels at presentation than patients with BPD. This study highlights the potential utility of HbA1c as a screening tool and prognostic factor.

Use of glycosylated hemoglobin increases diabetes screening for at-risk adolescents in primary care settings

To examine rates of diabetes screening in obese adolescents in an ethnically diverse primary care health care system before and after an internal recommendation to use HbA1c-based screening. Adolescents 12-18-years old with BMI > 95% were identified through electronic medical record review during two 18-month periods in 8 community health clinics and 13 school-based health centers: period 1 (P1, 19 April 2008 to 19 October 2009) and period 2 (P2, 3 May 2010 to 3 November 2011). Testing for diabetes in the 2 yr preceding the most recently elevated BMI was reviewed. A total of 2870 obese adolescents were identified in P1 and 3940 in P2. Ethnicity was primarily Hispanic, with smaller populations of Black and White youth. The percent of obese teens screened for diabetes increased from 40% in P1 to 47% in P2. Use of HbA1c increased 493% during P2. Older teens (>15 yr), those seen during P2, and those with BMI ≥ 30 kg/m2 were more likely to be screened. Record review confirmed equal rates of type 2 diabetes in the two periods: 8 incident (0.7%) cases in P1 and 13 (0.7%) in P2. The use of HbA1c, a non-fasting and logistically simpler test, was associated with increased diabetes screening in primary care. The percentage of screened patients with confirmed type 2 diabetes remained unchanged. Thus, despite potential pitfalls, the use of HbA1c for screening appears to be as successful as previous approaches in identifying adolescents with diabetes.

Diagnostic accuracy of HbA1c in diabetes between Eastern and Western

In 2010, the American Diabetes Association recommended the use of HbA1c as a diagnostic criterion for diabetes. However, HbA1c is not an accepted diagnostic tool for diabetes in Eastern Asia, because genetic differences compromise the standardization of the diagnostic cut-off point. This study evaluated differences in the use of HbA1c for diagnosing diabetes in Eastern and Western populations and investigated whether HbA1c cut-off point of ≥ 6.5% is diagnostic of diabetes in patients from Eastern Asia. Literature was obtained from MEDLINE, EMBASE and Cochrane databases. The pooled sensitivity and specificity of each HbA1c cut-off point were extracted and compared between Western and Eastern populations. Differences in the cut-off point for diagnosing diabetes in each region were compared by examining differences in the area under summary receiver operating characteristic (SROC) curves. Twelve publications from Eastern countries (n = 59,735) and 13 from Western countries (n = 22,954) were included in the analysis. Areas under SROC curves in the Eastern and Western groups were 0.9331 and 0.9120, respectively (P = 0.98). The cut-off point of the highest Youden index was 6.0%. At the HbA1c cut-off point of 6.5%, the pooled sensitivity and specificity were 58.7% and 98.4% for Eastern countries and 65.5% and 98.1% for Western countries, respectively. HbA1c exhibits the same diagnostic value for diabetes in Eastern and Western populations. In both populations, HbA1c levels > 6.0% identify the population at high risk of diabetes, and HbA1c > 6.5% is diagnostic of clinically established diabetes.

Utility of HbA1c in the Screening of Diabetes Mellitus in Pregnancy

Background and objectives: Diabetes mellitus is a major public health concern with adverse pregnancy outcome. The objective of this study was to assess the validity of HbA1c as a screening tool in pregnant ladies not known to have diabetes before pregnancy. Patients and methods: Three hundred pregnant women with gestational age between 24 - 28(25.3±2.1) weeks were evaluated for diabetes mellitus using HbA1c, fasting and postprandial plasma glucose for the period of October 2010 - October 2012, using McNamara's test which is expressed as percentages and 95% confidence intervals of the percentages. Results: Of pregnant ladies with non-diabetic fasting plasma glucose values: 79% had HbA1c level of <6.1%, 17% had an HbA1c level of > 6.1% and 5% showed diabetic 2-h plasma glucose values (17% CI 51–71 vs. 5% CI 35–55, respectively; P = 0.007). Of pregnant ladies with diabetic fasting plasma glucose:72% had an HbA1c level of ≥6.1%, 28% had HbA1c level of ≤ 6.0 % and 11% subjects in this group showed nondiabetic 2-h plasma glucose values (28% CI 66 – 86 vs. 11% CI 32–52, respectively; P = 0.003).Of pregnant ladies with postprandial blood glucose >200mg/dL; 42% had normal, 18% had impaired, 39% had high fasting plasma glucose while 71% had HbA1c ≥ 6.1% (71 % CI 51–71 vs. 39% CI 35–55, respectively; P = 0.003). Conclusion: HbA1c is an important alternative screening tool to identify pregnant ladies with undiagnosed diabetes.