Markedly Low Hemoglobin A1c in a Patient with an Unusual Presentation of ß-Thalassemia Minor

Danescu, Liviu G.; Levy, Shiri; Levy, Joseph

doi:10.4158/ep09160.cr

Cited by 9 publications

(5 citation statements)

References 16 publications

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“…Similarly, a recent study identified a significant hemolytic risk in women heterozygous for the G6PD Mahidol variant when treated with primaquine who were not detected by current screening methods [ 42 ]. Rarer hematologic conditions that reduce erythrocyte lifespan, e.g., hereditary hemolytic anemias, hereditary spherocytosis, and hemoglobinopathies have also been shown to lower HbA1c [ 9 , 43 ], and should also be considered before using HbA1c in these patients. We recommend additional testing using direct glucose measurements (e.g., FG or oral glucose tolerance testing) or other erythrocyte-independent methods to diagnose T2D.…”

Section: Discussionmentioning

confidence: 99%

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Wheeler¹,

Leong²,

Liu³

et al. 2017

PLoS Med

365

352

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BackgroundGlycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findingsUsing genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04–1.06, per HbA1c-raising allele, p = 3 × 10−29); whereas GS-E was not (OR = 1.00, 95% CI 0.99–1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66–0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38–0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55–0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.ConclusionsAs G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, ...

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Section: Discussionmentioning

confidence: 99%

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Wheeler¹,

Leong²,

Liu³

et al. 2017

PLoS Med

365

352

View full text Add to dashboard Cite

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“…This study was conducted to determine the effect of anemia on HbA1c, since anemia is highly prevalent among the diseases that can affect HbA1c levels and only a few studies have been performed to investigate the relationship between anemia and HbA1c in Korea. Moreover, although there have been many previous studies conducted in the United States and Europe on the influence of anemia on HbA1c, there is a vacuum in the literature concerning the sensitivity and specificity of using HbA1c in anemic subjects for the diagnosis of DM [8,17-19]. We limited our survey to common forms of anemia and other rare causes of anemia such as aplastic, hemolytic anemia, and other inherited disorders, and acute anemia due to hemorrhage or surgery was excluded.…”

Section: Discussionmentioning

confidence: 99%

“…Danescu et al [17] reported a case of a β-thalassemia minor patient with an HbA1c level of 1.6% despite an elevated blood glucose concentration and explained that the cause was decreased hemoglobin life span. In a Turkish study, the mean HbA1c level was 7.4% among nondiabetic patients with iron deficiency anemia (IDA) and 5.2% among the controls, with mean HbA1c level decreasing in patients with IDA from 7.4% to 6.2% after iron supplementation [8].…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

et al. 2013

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BackgroundRecently, a hemoglobin A1c (HbA1c) level of 6.5% has been determined to be a criterion for diabetes mellitus (DM), and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels.MethodsAnemic subjects (n=112) and age- and sex-matched controls (n=217) who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup.ResultsClinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580). However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05).ConclusionThese results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.

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“…Haemolytic anaemia [81] Thalassaemia [82] Haemoglobinopathies [83] Splenomegaly [11] Chronic liver disease [84,85] Drugs (e.g. ribavirin, dapsone) [86][87][88] b…”

Section: Reduced Erythropoiesismentioning

confidence: 99%

Current controversies in the use of haemoglobin A_1c

Hare

Shaw

Zimmet

2012

Journal of Internal Medicine

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Abstract. Hare MJL, Shaw JE, Zimmet PZ (Baker IDI Heart and Diabetes Institute, Melbourne, Vic.; and Monash University, Melbourne, Vic.; Australia). Current controversies in the use of haemoglobin A 1c (Review). J Intern Med 2012;271: 227-236.Haemoglobin A 1c (HbA 1c ) has recently been adopted by the World Health Organization into its recommended criteria for diabetes diagnosis. Much debate continues regarding the relative benefits and potential disadvantages surrounding the use of HbA 1c for this purpose. There is a lack of consensus as to whether this alteration to the definition of diabetes is a step forward or whether it could add further confusion and ambiguity to the debate on the method and criteria for the diagnosis of this globally important disease. This review provides a comprehensive overview of the current issues surrounding how HbA 1c is measured and reported; and of the evidence for and against its use in diagnosis.

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Markedly Low Hemoglobin A1c in a Patient with an Unusual Presentation of ß-Thalassemia Minor

Cited by 9 publications

References 16 publications

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

Current controversies in the use of haemoglobin A_1c

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Markedly Low Hemoglobin A1c in a Patient with an Unusual Presentation of ß-Thalassemia Minor

Cited by 9 publications

References 16 publications

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

Current controversies in the use of haemoglobin A1c

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Current controversies in the use of haemoglobin A_1c