Kinetics of HbA_1c, Glycated Albumin, and Fructosamine and Analysis of Their Weight Functions Against Preceding Plasma Glucose Level

OBJECTIVE To examine the kinetics of HbA_1c, glycated albumin (GA), and fructosamine (FA) levels in response to plasma glucose change and their relationship with the preceding plasma glucose level.

RESEARCH DESIGN AND METHODS The time courses of HbA_1c, GA, and FA after acute glycemic normalization were observed in nine patients with newly diagnosed non-insulin-dependent diabetes mellitus and compared with theoretical ones. Their weight functions against preceding plasma glucose level were analyzed assuming a stepwise plasma glucose change and compared with the theoretical prediction.

RESULTS The fasting plasma glucose level was acutely normalized after admission with a half-time of 6.3 ± 2.4 days (mean ± SD). The HbA_1c level decreased linearly during the initial 2 months with a half-time of 34.6 ± 10.1 days, followed by a gradual decrease thereafter. GA and FA levels decreased very rapidly during the initial 2–3 weeks with half-times of 17.1 ± 2.8 and 12.2 ± 4.8 days, respectively, followed by a gradual decrease thereafter. The time courses of HbA_1c, GA, and FA agreed well with theoretically estimated decay curves. Experimental values of weight functions against the preceding plasma glucose level agreed well with the theoretical prediction. The weight functions for glycated proteins had maximum values on the days just before the measurement of glycated proteins and gradually decreased with an increasing time interval. The lengths of the periods over which the weight functions for HbA_1c, GA, and FA extend back were estimated to be roughly 100, 40, and 30 days, respectively.

CONCLUSIONS The levels of HbA_1c, GA, and FA do not reflect the simple mean but reflect the weighted mean of the preceding plasma glucose level over a considerably longer period than was previously speculated.