Late Onset Diabetes Mellitus in Patients with Hereditary Aceruloplasminemia

Abstract

Aceruloplasminemia is a systemic degenerative disorder characterized by mutations in the ceruloplasmin gene, the absence of serum ceruloplasmin, and iron accumulation in the brain, liver, and other tissues. Iron is an important catalyst of oxyradical-mediated cellular and tissue injury, and β-cells in the pancreatic islets are susceptible to the cytotoxic effects of oxidative stress. We report three patients with aceruloplasminemia who have late-onset diabetes mellitus (DM) and impaired glucose tolerance (IGT) as well as neurologic symptoms. Their basal lipid peroxide levels, measured as thiobarbituric acid-reactive products, in plasma samples were three times the values for the controls. This increased susceptibility to lipid peroxidation in patients with aceruloplasminemia suggests that free-radical-mediated tissue injury plays a role in the occurrence of DM and IGT.