Serum levels of leptin and changes during the course of recovery from diabetic ketoacidosis

Secretion of leptin, the obese gene product, is stimulated by insulin and g lucocorticoids and reduced by fasting. In subjects with diabetic ketoacidos is (DKA), severe insulinopenia and prolonged fasting might cause a decrease in serum leptin levels, and subsequent insulin therapy would reverse the d ecrease. Otherwise, some other confounding factors, neither insulin nor fas ting, might affect serum leptin levels in patients with DKA. The present st udy was undertaken to address these issues. Eleven patients with type 1 dia betes mellitus (seven males and four females, aged 44 +/- 6 years, mean +/- SEM), admitted to Jichi Medical School Hospital presenting DKA, were studi ed during the therapeutic period. Thirty-five sex-, age- and body mass inde x-matched healthy subjects served as controls. Serum leptin levels at the h ospitalization were significantly greater than those of the matched control subjects (5.5 +/- 1.0 vs. 3.2 +/- 0.3 mu g/l, P < 0.01). After the start o f therapy with a small dose of short-acting insulin and a large volume of f luid infusion, serum leptin concentrations further increased to 10.6 +/- 3. 6 mu g/l at 24 h, and thereafter the concentrations gradually decreased and normalized at the discharge (3.3 +/- 0.7 mu g/l, day 24 +/- 4). The peak l evels at 24 h were significantly higher than the levels at the discharge (P < 0.05), and also +77 +/- 34% higher than those at the hospitalization (P < 0.005). Serum cortisol levels (1830 +/- 200 nmol/l) were markedly elevate d at hospitalization. These results indicate that serum leptin levels are i ncreased even under insulinopenia and fasting in the patients with DKA. Suc h a finding may be associated with marked hyperglycemia or enhanced secreti on of glucocorticoid hormone, although the exact mechanisms remain to be el ucidated. We speculate that leptin may serve as a stress peptide in DKA, bu t further analysis is necessary to explore a physiological role of leptin i n DKA. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.