SELF ASSESSMENT ANSWERS Low HbA1c levels in a poorly controlled diabetic

Q3: What is the pathophysiological basis of the discrepancies observed and how would you assess this man’s long term glycaemic control? Non-enzymatic binding of glucose to the valine residue of the beta chain of the haemoglobin molecule gives rise to glycated haemoglobin (HbA1a, HbA1b, and HbA1c). The level of HbA1c reflects ambient blood sugar concentrations during the life span of the patient’s red cells (half life about 6–8 weeks)—that is, uncontrolled hyperglycaemia results in high HbA1c levels. Current guidelines recommend HbA1c levels of less than 7% as a target for satisfactory control. HbA1c can be measured chemically, chromatographically, and electrophoretically. Most autoanalysers use the chromatographic method. Haemoglobin variants may affect chromatographically measured HbA1c levels either by inducing an abnormal peak and thereby making the estimation of the fraction of HbA1c unreliable, or by reducing time available for glycation as a result of reduced red cell survival. These two effects may coexist. Physicians should be aware of the potential pitfalls of HbA1c as a measure of long term diabetic control. Apparent discrepancies between glycaemic control reflected in day to day blood glucose concentrations, and HbA1c values should be noted. HbA1c levels are inappropriately affected by factors other than long term glycaemia as shown in boxes 1 and 2. Schnedl et al reported a prevalence of abnormal haemoglobin variants of 0.6% among 15 000 HbA1c estimations in a period of over six years. In such individuals a method unaffected by abnormal haemoglobin variants, such as a turbidimetric inhibition immunoassay or alternate methods of chromatography should be used. Final diagnosis Abnormal haemoglobin variant.