Glycated hemoglobin-the clinical and biochemical divide: A review

Diabetes mellitus is a chronic metabolic disorder characterized by rise in blood glucose level called "hyperglycaemia". The main long term vascular complications are coronary artery disease, stroke, renal failure etc. The measurement of glycosylated hemoglobin (GHb) is one of the well established means of monitoring glycemic control in patients with diabetes mellitus. Hemoglobin (Hb) is composed of four globin chains. Adult hemoglobin (HbA) is the most abundant form in most adults and consists of two α and two β chains. Fetal hemoglobin (HbF), which is predominantly present at birth, consists of two α and two γ chains. Glycosylation is a nonenzymatic reaction between free aldehyde group of glucose and free amino groups of proteins. The biosynthesis of glycosylated hemoglobins (HbA_1a, HbA_1b, and HbA_1c) occurs slowly, continuously and almost irreversibly throughout the four month life span of erythrocytes and the process is non-enzymatic. Recent reports have shown that the concentration of total glycosylated hemoglobin measured by commonly used methods may change significantly over a period of hours. This reflects the short term fluctuations in glucose concentration. It is now realized that these rapid changes depend on the synthesis or dissociation of the labile fraction of HbA_1c, which is not separable from the stable form of HbA_1c, by most routine methods. Physicians should be aware of the expected variation in HbA_1c measurements performed in associated diseases.