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Glycolytic Intermediate Methylglyoxal during Diabetic Ketoacidosis and Its Recovery Phase

Carbonyl stress is hypothesized to be an associated complication of diabetic ketoacidosis. 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 MG 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 MG derivation with 1, 2-diamino-4, 5-dimethoxybenzene (DDB), was performed by HPLC. The baseline level of MG recorded in normoglycemic healthy controls was 338 62 nmol/l. There was a scatter of individual MG values measured in the blood of 31 type 1 diabetic patients (95% confidence interval for mean range: 335-411). A consistent feature of diabetic ketoacidosis before and during treatment was striking elevation of MG 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 MG level in control diabetes group (p=0.008). Metabolic detoxification of methylglyoxal via glyoxalase system followed by D-lactate measurement could not be demonstrated. The study indicated diabetic ketoacidosis to result in an increase in the methylglyoxal level apart from metabolic abnormalities. Excessive production of toxic intermediates such as  -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 ; carbonyl stress ; methylglyoxal

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