engleski

Enhanced generation of methylglyoxal, an AGE precursor, during ketoacidosis

Glycation of proteins is enhanced during hyperglycemia, both because of increased glucose per se and alterations in cellular metabolism leading to elevated production of reactive  -dicarbonyls. These compounds are implicated in the development of a number of pathologies via a condition known as "carbonyl stress". Carbonyl stress is hypothesized to be an associated complication of diabetic ketoacidosis. Study design. The production of 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 normoglycemic 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  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 diabetic ketoacidosis to result in an increase in the methylglyoxal level. Excessive production of toxic intermediates such are  -dicarbonyls may be a link connecting an acute metabolic event with accelerated tissue damage, a feature characteristic of long-term complications of diabetes.

diabetes ; ketoacidosis ; advanced glycation ; methylglyoxal

doi: 10.1111/j.1464-5491.2006.02039_11.x