Elevated level of methylglyoxal during diabetic ketoacidosis and its recovery phase

Carbonyl stress is hypothesized to be an associated complication of diabetic ketoacidosis. The production of the glycolytic intermediate methylglyoxal (MG) was followed up in 7 diabetic patients treated for ketoacidosis during pretreatment and recovery phase. Blood samples for methylglyoxal analysis were collected upon patient arrival in emergency department (0 h), and during ketoacidosis treatment between 12-24 h and at 168 h. The study also included 10 normoglycaemic healthy volunteers and 31 type 1 diabetic patients (control diabetes group). The methylglyoxal assay, based on methylglyoxal derivation with 1,2-diamino-4,5-dimethoxybenzene (DDB), was performed by HPLC, only assessing the level of free methylglyoxal. The baseline level of methylglyoxal recorded in normoglycemic healthy controls was 338 +/- 62 nmol/l versus 374 +/- 89 nmol/l in control diabetes group (P = 0.0407). A consistent feature of diabetic ketoacidosis before and during treatment was striking elevation of methylglyoxal as compared with control diabetes group (median test chi(2) = 14.6, df = 3, P = 0.0021). Friedman's ANOVA indicated differences (P = 0.04) among the three sampling times with a peak value (601 +/- 95 nmol/l) at 12-24 h following therapy initiation. However, fasting treatment values at 168 h were still significantly higher than the mean fasting methylglyoxal level in control diabetes group (P = 0.008). The study indicated that diabetic ketoacidosis results in an increase in methylglyoxal level. Excessive production of toxic intermediates such are alpha-dicarbonyls may be a link connecting an acute metabolic event with accelerated tissue damage, a feature characteristic of long-term complications of diabetes.