OBJECTIVE The aim of this study was to investigate whether insulin deficiency and increased catabolism may have a role in the regulation of plasma glucagon-like peptide (GLP)-1 and GLP-2 levels in children with diabetic ketoacidosis (DKA) and whether insulin treatment may affect the levels of these polypeptides. METHODS Plasma GLP-1 and -2 levels were measured in 24 patients with DKA aged 8 to 14 years before insulin infusion (time 0), when ketonemia and acidosis disappeared (time 1), and when weight gain started (time 2). Eighteen healthy children aged 8 to 14 years constituted the control group. RESULTS At time 0, mean plasma GLP-1 and GLP-2 levels were significantly elevated in the patients compared with the control group (p<0.05 and p<0.01, respectively). At time 1 when ketonemia and acidosis disappeared, GLP-1 and GLP-2 levels decreased significantly from the initial levels (p<0.05 and p<0.01, respectively). At this time, while GLP-1 level was not different from that of the controls, GLP-2 level was higher than that of the controls (p<0.05). GLP-1 and-2 levels did not show any significant differences between the patients and controls when weight gain started (time 2). CONCLUSION Our results show that DKA is associated with increased plasma GLP-1 and -2 concentrations. Effective fluid and insulin treatment resulted in a significant decrease in plasma GLP-1 and -2 levels. This may be due to the negative feedback effect of insulin on the production of these polypeptides.