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      Spurious HbA1c results in patients with diabetes treated with dapsone

      research-article
      1 , 2 , 3 , 4 , 2 , 1 , 1 , 1 , 2 , 2
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd
      Adult, Female, Male, Other, Ireland, Pancreas, Diabetes, Insulin, Diabetes mellitus type 1, Diabetes mellitus type 2, Anaemia, Haemolysis*, Methemoglobinemia*, Dermatitis herpetiformis*, Coeliac disease*, Hyperglycaemia, Hypoglycaemia, Urticarial rash*, Granuloma, Diabetes mellitus type 1, Diabetes mellitus type 2, Haemolysis*, Methemoglobinemia*, Coeliac disease, Dermatitis herpetiformis*, Polydipsia, Polyuria, Weight loss, Hypoglycaemia, Hyperglycaemia, Rash, Anaemia, Haemoglobin A1c, Fructosamine*, Glucose (blood), GADA, Methaemoglobin*, Haptoglobin*, Mean corpuscular volume*, Haemoglobin , Bilirubin, Reticulocyte count*, Lactate dehydrogenase, Antibiotics, Dapsone*, Metformin, Gliclazide, Sulphonylureas, Dapagliflozin, SGLT2 inhibitors, Insulin, Unusual effects of medical treatment, September, 2019

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          Summary

          Measurement of glycated haemoglobin (HbA1c) has been utilised in assessing long-term control of blood glucose in patients with diabetes, as well as diagnosing diabetes and identifying patients at increased risk of developing diabetes in the future. HbA1c reflects the level of blood glucose to which the erythrocyte has been exposed during its lifespan, and there are a number of clinical situations affecting the erythrocyte life span in which HbA1c values may be spuriously high or low and therefore not reflective of the true level of glucose control. In the present case series, we describe the particulars of three patients with diabetes who had spuriously low HbA1c levels as a result of dapsone usage. Furthermore, we discuss the limitations of HbA1c testing and the mechanisms by which it may be affected by dapsone in particular.

          Learning points:
          • Various conditions and medications can result in falsely low HbA1c.

          • Dapsone can lead to falsely low HbA1c by inducing haemolysis and by forming methaemoglobin.

          • Capillary glucose measurement, urine glucose measurements and fructosamine levels should be used as alternatives to HbA1c for monitoring glycaemic control if it was falsely low or high.

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          Most cited references16

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          Pitfalls in hemoglobin A1c measurement: when results may be misleading.

          Since the beginning of clinical use in the 1970s, hemoglobin A1c (A1c) has become the standard tool for monitoring glycemic control in patients with diabetes. The role of the A1c test was broadened in 2010, when the American Diabetes Association added A1c as a diagnostic criterion for diabetes. Because of hemoglobin A1c's integral role in diagnosis and treatment, it is important to recognize clinical scenarios and interfering factors that yield false results. The purpose of this review is to describe the A1c measurement, outline clinical scenarios or factors that may yield false results, and describe alternative laboratory biomarkers.
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            The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.

            Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c.
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              The Effect of Iron and Erythropoietin Treatment on the A1C of Patients With Diabetes and Chronic Kidney Disease

              OBJECTIVE To examine the effect of intravenous iron and erythropoietin-stimulating agents (ESAs) on glycemic control and A1C of patients with diabetes and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS This was a prospective study of patients with type 2 diabetes and CKD stage IIIB or IV undergoing intravenous iron (group A) and/or ESA (group B). Full blood profiles were determined over the study period. Glycemic control was monitored using A1C, seven-point daily glucose three times weekly, and continuous glucose monitoring (CGM). RESULTS There were 15 patients in both group A and group B. Mean A1C (95% CI) values fell in both groups (7.40% [6.60–8.19] to 6.96% [6.27–7.25], P < 0.01, with intravenous iron and 7.31% [6.42–8.54] to 6.63% [6.03–7.36], P = 0.013, ESA). There was no change in mean blood glucose in group A (9.55 mmol/l [8.20–10.90] vs. 9.71 mmol/l [8.29–11.13], P = 0.07) and in group B (8.72 mmol/l [7.31–10.12] vs. 8.78 mmol/l [7.47–9.99], P = 0.61) over the study period. Hemoglobin and hematocrit values significantly increased following both treatments. There was no linear relationship found between the change in A1C values and the rise of hemoglobin following either treatment. CONCLUSIONS Both iron and ESA cause a significant fall in A1C values without a change to glycemic control in patients with diabetes and CKD. At the present time, regular capillary glucose measurements and the concurrent use of CGM remain the best alternative measurements of glycemic control in this patient group.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                30 August 2019
                2019
                : 2019
                : 19-0027
                Affiliations
                [1 ]Department of Endocrinology , St James Hospital, Dublin, Ireland
                [2 ]Department of Endocrinology , Royal College of Surgeons in Ireland, Connolly Hospital Blanchardstown, Dublin, Ireland
                [3 ]Department of Endocrinology , St Columcille’s Hospital, Dublin, Ireland
                [4 ]Department of Clinical Biochemistry , Connolly Hospital, Blanchardstown, Dublin, Ireland
                Author notes
                Correspondence should be addressed to K Aljenaee; Email: k.jenaee@ 123456gmail.com
                Article
                EDM190027
                10.1530/EDM-19-0027
                6765317
                31566188
                c03ff4ed-b08e-42c7-8ad2-cc5cfd326cf5
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 27 July 2019
                : 30 August 2019
                Categories
                Unusual Effects of Medical Treatment

                adult,female,male,other,ireland,pancreas,diabetes,insulin,diabetes mellitus type 1,diabetes mellitus type 2,anaemia,haemolysis*,methemoglobinemia*,dermatitis herpetiformis*,coeliac disease*,hyperglycaemia,hypoglycaemia,urticarial rash*,granuloma,coeliac disease,polydipsia,polyuria,weight loss,rash,haemoglobin a1c,fructosamine*,glucose (blood),gada,methaemoglobin*,haptoglobin*,mean corpuscular volume*,haemoglobin ,bilirubin,reticulocyte count*,lactate dehydrogenase,antibiotics,dapsone*,metformin,gliclazide,sulphonylureas,dapagliflozin,sglt2 inhibitors,unusual effects of medical treatment,september,2019

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