Mizoribine-induced severe hyperglycemia in a patient with microscopic polyangiitis.

A 77-year-old woman had been receiving prednisolone (PSL) for 5 months as induction therapy for microscopic polyangiitis. Because of repeated elevation of the antineutrophil cytoplasmic autoantibody titer, we added mizoribine (MZR), and, 2 months later, the patient developed severe hyperglycemia with low serum and urinary C-peptide reactivity (CPR). The MZR was, therefore, withdrawn and insulin therapy was started. One month later, the serum and urinary CPR had increased and postprandial hyperglycemia had improved. Previous in vitro studies have shown that MZR can induce hyperglycemia through at least two mechanisms. One is the alteration of insulin secretion from islet cells, and the other is action via the glucocorticoid receptor (GR). MZR reduces insulin secretion through the depletion of intracellular guanosine triphosphate (GTP), which leads to the inhibition of mitogenesis and induction of beta cell apoptosis. MZR affects insulin resistance by activating the GR through interaction with the 14-3-3 protein, leading to postprandial hyperglycemia. Although postprandial hyperglycemia generally appears between 3 and 7 weeks after PSL administration, that in our patient did not become apparent during 5 months of PSL monotherapy, but was manifested 2 months after the introduction of MZR, and improved after MZR had been withdrawn. We conclude from these findings that MZR had been responsible for the hyperglycemia in our patient.