Hydroxyl radicals (.
OH) may contribute to beta cell death. Because
iron catalyzes .
OH production, we examined whether administration of a novel, long-acting
iron chelator, hydroxyethyl
starch-deferoxamine (
HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of
diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of
HES-DFO (a high molecular weight hydroxyethyl
starch-conjugated derivative of
deferoxamine) or equimolar hydroxyethyl
starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of
IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of
HES-DFO further significantly decreased the incidence of
IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%)
HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of
HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum
iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly
weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)