Objectives: According to the nonenzymatic glycation hypothesis, excessive production of toxic alpha-oxoaldehydes is associated with diabetes tissue damage. The aim of this study was to examine the hypothesis that methylglyoxal overproduction is affected by glycemic fluctuation.
Design and methods: Methylglyoxal was measured by HPLC in 41 patients with diabetes, and correlated with 9-point daily glucose profiles, fasting glucose level, as well as early (HbA1c) and advanced glycation products. The 24-h glycemia variability was expressed as the M value, a quantitative index of diurnal glucose fluctuation.
Results: Methylglyoxal was, in parallel, analyzed in the whole blood and the plasma of the same individual. Significantly higher concentrations were measured in plasma samples of both, patients with diabetes (n=41) (742+/-141 vs. 409+/-131 nmol/L; P=0.000001) and normoglycemic controls (n=10) (520+/-42 vs. 338+/-62 nmol/L; P=0.0002). Difference between plasma and whole blood methylglyoxal (DeltaMG) in the same individual showed higher DeltaMG values in patients with diabetes (346+/-165 vs. 167+/-86 nmol/L; P=0.0027). Elevated methylglyoxal production was observed in patients with M values>20, yielding a significant correlation between M values and methylglyoxal levels. A significant negative correlation between methylglyoxal and creatinine clearance was observed (r=-0.38, P=0.019).
Conclusions: Methylglyoxal was demonstrated to be a parameter characterized by high sensitivity to glycemic fluctuation. The difference between plasma and whole blood concentrations, in the diabetic population versus control subjects might be associated with increased biogenesis, less efficient endogenous detoxification and/or decreased elimination.