Review of hemoglobin A_1c in the management of diabetes

Abstract

Hemoglobin HbA1c (A1c) has been used clinically since the 1980s as a test of glycemic control in individuals with diabetes. The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glycemic control, quantified by lower blood glucose and A1c levels, reduced the risk of the development of complications from diabetes. Subsequently, standardization of A1c measurement was introduced in different countries to ensure accuracy in A1c results. Recently, the International Federation of Clinical Chemists (IFCC) introduced a more precise measurement of A1c, which has gained international acceptance. However, if the IFCC A1c result is expressed as a percentage, it is lower than the current DCCT‐aligned A1c result, which may lead to confusion and deterioration in diabetic control. Alternative methods of reporting have been proposed, including A1c‐derived average glucose (ADAG), which derives an average glucose from the A1c result. Herein, we review A1c, the components involved in A1c formation, and the interindividual and assay variations that can lead to differences in A1c results, despite comparable glycemic control. We discuss the proposed introduction of ADAG as a surrogate for A1c reporting, review imprecisions that may result, and suggest alternative clinical approaches.

Short-term impact of HbA1c on morbidity and all-cause mortality in people with type 2 diabetes: a Danish population-based observational study

“…Diagnoses were obtained from record linkage with the Danish National Patient Register (DNPR), which covers all hospitalisations in Denmark. As an association between low HbA 1c and mortality/morbidity might be due to reverse causality, we identified all individuals who, prior to inclusion, had been hospitalised with diseases known to decrease HbA 1c [16] Information on the outcome measures was obtained by record linkage with either the nationwide Danish Civil Registration System (mortality) or the DNPR (morbidity). We included the following as diabetes-related morbidities: arteriosclerosis, acute complications of diabetes, retinopathy, nephropathy, acute myocardial infarction (AMI), stroke and neuropathy (ICD-10 codes are shown in ESM Table 2).…”

New screening technologies for type 2 diabetes mellitus appropriate for use in tuberculosis patients [Review article]

“…12 In addition, race, ethnicity and hemoglobin variants may all impact on A1c readings, as is the case with conditions such as anemia (including that caused by malaria) and vitamin B12 defi ciency. 36,37 Taking these factors into consideration, there is a paucity of data regarding A1c performance from the high TB burden countries featured in Table 1. Despite the low sensitivity of urinary glucose testing, it may be useful in LMICs where no other procedure is possible.…”

Clinical applications of glycosylated haemoglobin

“…7 In the 1980s, HbA1c evolved as a better index of glycaemic control in clinical trials. 7,8 This, along with the other method that emerged by that time, namely, selfmonitoring of blood glucose (SMBG) greatly enhanced the achievement of glycaemic control. Regular SMBG had a positive effect on improving glycaemia especially in individuals treated with insulin.…”

“…Some of the well documented causes for elevated HbA1c include alcoholism, iron deficiency, renal failure, and hyperbilirubinaemia. 8 Any condition that shortens the life span of erythrocytes is likely to decrease HbA1c levels, since the average erythrocyte is younger, lasting for lesser time in circulation to be glycated. Falsely decreased HbA1c values are seen in conditions with a reduced erythrocyte life span (i.e., increased haemoglobin turnover) or where a large number of reticulocytes are produced.…”

“…Pregnancy may falsely increase or decrease HbA1c, suggesting that this investigation is not to be considered appropriate for the diagnosis of gestational diabetes mellitus. 8 In case of aplastic anaemias, cessation of erythropoiesis leads to an increase in the number of circulating aged red cells resulting in a progressive rise in HbA1c.…”