Evidence for Consistency of the Glycation Gap in Diabetes

OBJECTIVE Discordance between HbA(1c) and fructosamine estimations in the assessment of glycemia is often encountered. A number of mechanisms might explain such discordance, but whether it is consistent is uncertain. This study aims to coanalyze paired glycosylated hemoglobin (HbA(1c))-fructosamine estimations by using fructosamine to determine a predicted HbA(1c), to calculate a glycation gap (G-gap) and to determine whether the G-gap is consistent over time. RESEARCH DESIGN AND METHODS We included 2,263 individuals with diabetes who had at least two paired HbA(1c)-fructosamine estimations that were separated by 10 ± 8 months. Of these, 1,217 individuals had a third pair. The G-gap was calculated as G-gap = HbA(1c) minus the standardized fructosamine-derived HbA(1c) equivalent (FHbA(1c)). The hypothesis that the G-gap would remain consistent in individuals over time was tested. RESULTS The G-gaps were similar in the first, second, and third paired samples (0.0 ± 1.2, 0.0 ± 1.3, and 0.0 ± 1.3, respectively). Despite significant changes in the HbA(1c) and fructosamine, the G-gap did not differ in absolute or relative terms and showed no significant within-subject variability. The direction of the G-gap remained consistent. CONCLUSIONS The G-gap appears consistent over time; thus, by inference any key underlying mechanisms are likely to be consistent. G-gap calculation may be a method of exploring and evaluating any such underlying mechanisms.