Evidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetes

The phenomenon of a discrepancy between glycated haemoglobin levels and other indicators of average glycaemia may be due to many factors but can be measured as the glycation gap (GGap). This GGap is associated with differences in complications in patients with diabetes and may possibly be explained by dissimilarities in deglycation in turn leading to altered production of Advanced Glycation End (AGE) products. We hypothesised that variations in the level of the deglycating enzyme Fructosamine-3-kinase (FN3K) might be associated with the GGap. We measured erythrocyte FN3K concentrations and enzyme activity in a population dichotomised for a large positive or negative GGap. FN3K protein was higher and we found a striking 3-fold greater activity (323%) at any given FN3K protein level in the erythrocytes of the negative compared with positive GGap groups. This was associated with lower AGE levels in the negative GGap group (79%), lower pro-inflammatory adipokines (Leptin/Adiponectin ratio) (73%) and much lower pro-thrombotic PAI-1 levels (19%). We conclude that FN3K may play a key role in the GGap and thus diabetes complications such that FN3K may be potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide a novel approach to their prevention.