The number of unexpected HbA<sub>1c</sub> variants may be a greater problem in routine practice than is generally realized

Reynolds, Tim; Twomey, Patrick J; Harvey, Tim; Green, B N

doi:10.1111/j.1464-5491.2004.01278.x

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…The lack information provided on the detection and exclusion of variant haemoglobins in the majority of studies is a limitation of this review, however, haemoglobinopathies are unlikely to be present in numbers that will impact on the overall findings, given the ethnicity of the source populations and the sample sizes (1.7% prevalence found in the UK screening programme [8]). Clinically silent variants have now also been raised as a potential influence on HbA 1c analysis [32]. However, this observation was based on four cases drawn from a Caucasian population of about 500 000, so the overall chances of inclusion of undetected variant haemoglobin cases in the studies under review remain extremely small.…”

Section: Discussionmentioning

confidence: 99%

HbA_1c as a screening tool for detection of Type 2 diabetes: a systematic review

2007

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Aim To assess the validity of glycated haemoglobin A 1c (HbA 1c ) as a screening tool for early detection of Type 2 diabetes.Methods Systematic review of primary cross-sectional studies of the accuracy of HbA 1c for the detection of Type 2 diabetes using the oral glucose tolerance test as the reference standard and fasting plasma glucose as a comparison.Results Nine studies met the inclusion criteria. At certain cut-off points, HbA 1c has slightly lower sensitivity than fasting plasma glucose (FPG) in detecting diabetes, but slightly higher specificity. For HbA 1c at a Diabetes Control and Complications Trial and UK Prospective Diabetes Study comparable cut-off point of ≥ 6.1%, the sensitivity ranged from 78 to 81% and specificity 79 to 84%. For FPG at a cut-off point of ≥ 6.1 mmol/l, the sensitivity ranged from 48 to 64% and specificity from 94 to 98%. Both HbA 1c and FPG have low sensitivity for the detection of impaired glucose tolerance (around 50%).Conclusions HbA 1c and FPG are equally effective screening tools for the detection of Type 2 diabetes. The HbA 1c cut-off point of > 6.1% was the recommended optimum cut-off point for HbA 1c in most reviewed studies; however, there is an argument for population-specific cut-off points as optimum cut-offs vary by ethnic group, age, gender and population prevalence of diabetes. Previous studies have demonstrated that HbA 1c has less intra-individual variation and better predicts both micro-and macrovascular complications. Although the current cost of HbA 1c is higher than FPG, the additional benefits in predicting costly preventable clinical complications may make this a cost-effective choice.Diabet. Med. 24, 333-343 (2007) There is no consensus on the most accurate screening test for detection of diabetes. The most widely used screening tests include the fasting plasma glucose (FPG) test and the oral glucose tolerance test (OGTT). Both these tests involve measurement of blood glucose. However, the measurement of both OGTT and FPG require patients to fast overnight for at least 8 h and confirmation of diagnosis using FPG requires the test to be repeated at least twice. Furthermore, studies have shown that the sensitivity of FPG for diabetes diagnosis is not as high as expected, with nearly one-third of individuals with diabetes remaining undetected [6]. OGTT is also costly, time-consuming and labour intensive and has low reproducibility that can add confusion and uncertainty to the confirmation of diabetes diagnoses [7]. The accuracy of FPG and OGTT may be reduced by patient non-adherence to fasting, laboratory error and/or use of certain medications [6].The glycated haemoglobin (HbA 1c ) test has been suggested as an alternative screening test for Type 2 diabetes. HbA 1c levels represent a 2 -3-month average of blood glucose concentrations. The accuracy of HbA 1c analysis may be influenced by the presence of haemoglobinopathy or renal failure, as well as laboratory error and/or use of certain medications [6], but, compared with the OGTT, HbA 1c measur...

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Section: Discussionmentioning

confidence: 99%

HbA_1c as a screening tool for detection of Type 2 diabetes: a systematic review

2007

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“…An additional argument against the indiscriminate use of HbA1c is that the variation of the glycated hemoglobin also depends on HbA1c variants and ethnicity [25-28]. Other factors associated with plasma glucose levels have been reviewed recently by Herman [29] and Gomez-Perez et al [23] and include anemia and iron deficiency as well as abnormal hemoglobins.…”

Section: Discussionmentioning

confidence: 99%

Use of glucometer and fasting blood glucose as screening tools for diabetes mellitus type 2 and glycated haemoglobin as clinical reference in rural community primary care settings of a middle income country

et al. 2012

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BackgroundThailand is considered to be a middle income country, and to control and prevent type 2 diabetes mellitus (T2DM) is one of the main concerns of the Thai Ministry of Public Health (MoPH). Screening for T2DM and care for T2DM patients has been integrated into the primary health care system, especially in rural areas. The intention of this investigation is to link public health research at the academic level with the local health authorities of a district of a north-eastern province of the country.MethodsEpidemiological methods were applied to validate the screening tools fasting capillary blood glucose (CBG), measured by glucometer and venous blood for the determination of plasma glucose (VPG), used for screening for T2DM among asymptomatic villagers. For assessing the validity of these two methods glycated haemoglobin (HbA1c) values were determined and used as the ‘clinical reference’.ResultsAll together 669 villagers were investigated. Determinations of CBG and VPG resulted in suspected T2DM cases, with 7.3% when assessed by CBG and 6.4% by VPG using a cutoff point of 7 mmol/L (126 mg/dl). Taking HbA1c determinations with a cutoff point of 7% into account, the proportion of T2DM suspected participants increased to 10.4%. By estimating sensitivity, specificity and the positive predictive value of CBG and VPG against the ‘clinical reference’ of HbA1c, sensitivity below 50% for both screening methods has been observed. The positive predictive value was determined to be 58.5% for CBG and 56.8% for VPG. The specificity of the two screening tests was over 96%.ConclusionsThe low sensitivity indicates that using fasting CBG or VPG as a screening tool in the field results in a high proportion of diseased individuals remaining undetected. The equally low positive predictive values (below 60%) indicate a high working load for the curative sector in investigating suspected T2DM cases to determine whether they are truly diseased or false positive cases according to the screening method. Further implications of the results and the controversial discussion related to the use of HbA1c as clinical evidence for suffering from T2DM are also discussed.

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“…It should be noted however that rare Hb variants which interfere with HbA1c measurement have been identified in populations where a low prevalence would be expected. 6 Accordingly, laboratories should ensure that they review sufficient data before making a decision to abandon confirmation by an alternative method.…”

Section: Discussionmentioning

confidence: 99%

Appropriateness of the National Academy of Clinical Biochemistry recommendation of repeating HbA1c analysis for extreme results in clinical practice

2009

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Background: The National Academy of Clinical Biochemistry (NACB) recommends that the presence of a variant or modified haemoglobin be considered when any HbA1c result is below the lower limit of the reference interval or 15%. In those instances where a variant haemoglobin is suspected, repeat measurement using an alternative method is the usual course of action. In the present study, we undertook to determine the impact of this guideline on our identification of variant and modified haemoglobins. Methods: All requests for HbA1c estimation received over a 32-month period, and which gave a result of ,4% or .15% were re-analysed by a different method and the results compared. Results: Over the 32-month period, 94 samples with a HbA1c result of ,4% or 15% were identified. Of these, 80 were re-analysed using a different method. No chromatographic abnormalities were seen and there were no significant differences between the results obtained using the two methods. Conclusions: No variant or modified haemoglobins were identified in this study and this observation is likely to be representative of the ethnic makeup of our patient population. On the basis of this finding, we recommend that laboratories consider local factors when deciding whether to comply with the NACB guidelines.

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The number of unexpected HbA_1c variants may be a greater problem in routine practice than is generally realized

Abstract: Consequently, we propose greater interaction between diabetologists and the laboratory in an attempt to identify these clinically but not biochemically silent variants to achieve a true estimation of the glycaemic control in affected patients.

Cited by 10 publications

References 27 publications

HbA_1c as a screening tool for detection of Type 2 diabetes: a systematic review

HbA_1c as a screening tool for detection of Type 2 diabetes: a systematic review

Use of glucometer and fasting blood glucose as screening tools for diabetes mellitus type 2 and glycated haemoglobin as clinical reference in rural community primary care settings of a middle income country

Appropriateness of the National Academy of Clinical Biochemistry recommendation of repeating HbA1c analysis for extreme results in clinical practice

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The number of unexpected HbA1c variants may be a greater problem in routine practice than is generally realized

Abstract: Consequently, we propose greater interaction between diabetologists and the laboratory in an attempt to identify these clinically but not biochemically silent variants to achieve a true estimation of the glycaemic control in affected patients.

Cited by 10 publications

References 27 publications

HbA1c as a screening tool for detection of Type 2 diabetes: a systematic review

HbA1c as a screening tool for detection of Type 2 diabetes: a systematic review

Use of glucometer and fasting blood glucose as screening tools for diabetes mellitus type 2 and glycated haemoglobin as clinical reference in rural community primary care settings of a middle income country

Appropriateness of the National Academy of Clinical Biochemistry recommendation of repeating HbA1c analysis for extreme results in clinical practice

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The number of unexpected HbA_1c variants may be a greater problem in routine practice than is generally realized

HbA_1c as a screening tool for detection of Type 2 diabetes: a systematic review

HbA_1c as a screening tool for detection of Type 2 diabetes: a systematic review