Comparing Multiple Measures of Glycemia: How to Transition from Biomarker to Diagnostic Test?

The underlying pathophysiology of diabetes varies, but all patients share a common a metabolic derangement of carbohydrate metabolism, which causes hyperglycemia. Many patients with diabetes develop debilitating complications, ranging from retinopathy and nephropathy, to myocardial infarction and stroke. The accumulated evidence reveals that reducing an increased glucose concentration, as documented by a lower hemoglobin A1c (Hb A1c)4 concentration, decreases complications (1, 2). Hb A1c is extensively used to monitor glycemic control and to adjust therapy, and it has recently been accepted as a criterion for the diagnosis of diabetes (3).Hb A1c reflects long-term glycemia, because glucose attaches irreversibly (the process is termed glycation) to hemoglobin in erythrocytes. Hb A1c can be modified independently of glycemia, however, by conditions (e.g., anemia or renal failure) that alter the mean age of erythrocytes by changing either their production or their rate of disappearance. Recent observations have revealed that the life span of erythrocytes in healthy individuals who have normal blood counts and indices can vary sufficiently from the commonly taught 120 days to cause clinically relevant differences in Hb A1c concentrations (4). These limitations have led to investigations of an expanding group of alternative markers of glycemia.The best studied of these analytes is fructosamine, which is the generic name for plasma protein ketoamines. Because albumin is the most abundant protein in serum, fructosamine is predominantly a measure of glycated albumin. The covalent attachment of glucose to albumin forms glycated albumin, which can also be assayed directly (5). The half-life of albumin in the blood is 14–20 days, so both fructosamine and glycated albumin indicate the mean blood glucose concentration over the preceding 2 weeks. The fructosamine assay was developed in 1983 (6), but it was modified—and improved—in 1990 by the addition …