Specific glycation of albumin depends on its half-life

Some suggest that measurements of plasma fructosamine concentration should be corrected for the plasma protein (or albumin) concentration because the extent of glycation per volume depends on both protein and glucose concentrations. Several reports, however, demonstrate a poor correlation between plasma fructosamine and albumin concentrations in diabetic patients. In vitro kinetic and in vivo studies have shown that glycation is also dependent on the half-lives of plasma proteins. Because a decrease in plasma albumin diminishes its catabolism, we speculated that low albumin concentrations are associated with a greater extent of glycation on a molar basis (specific glycation) and vice versa. To test this hypothesis, we studied plasma albumin, total protein, and fructosamine in 63 nondiabetic subjects with normal plasma fasting glucose concentrations and hemoglobin A1c between 5.1% and 5.9%. Plasma fructosamine was poorly correlated with albumin concentration (r = 0.348) but a logarithmic plot of the specific glycation of albumin vs albumin concentration showed a better correlation (r = -0.842), suggesting that the kinetic considerations were operating in vivo. Therefore, because lower specific glycation of plasma albumin "compensates" for higher concentration, correction of fructosamine for albumin content in patients will overestimate mean blood glucose when albumin is low and underestimate it when albumin is high.