We report a 42 year-old woman with a hypothyroidism and a mixed connective tissue disease treated with prednisone and methotrexate. The patient had normal blood glucose levels but when the methotrexate dose was tapered, she presented a diabetic ketoacidosis that required tip to 520 units of insulin per day. Due to the intensification of the mixed connective tissue disease symptoms, the doses of methotrexate and prednisone were increased again with a simultaneous normalization of serum glucose levels and glucose tolerance. In the following six months, when the dose of methotrexate was tapered again, the hyperglycemia reappeared and was again controlled increasing the dose. Thirty months after the episode of keotacidosis, the patient was with a weekly dose of methotrexate, asymptomatic and with a normal glucose tolerance. Anti insulin antibodies were not detected and anti islet antibodies were indeterminate, due to interference with antinuclear antibodies. It is possible that the episode of ketoacidosis was unveiled by an autoimmune phenomenon.