Development of non-insulin-dependent (autoimmune) diabetes mellitus has been suggested in patients treated with interferon- [1-3]. We describe a patient who developed this disease with no evidence of an immune process while receiving interferon- for hepatitis C.

A 50-year-old man was referred to us because of chronic active hepatitis C. His cousin had insulin-dependent diabetes, but no family member had a history of non-insulin-dependent diabetes. Recombinant interferon- was started at a dose of 32 million U three times a week. Before therapy, the patient had glucose intolerance. After 1 week of treatment, his fasting plasma blood glucose level was 5.5 mmol/L. After 7 weeks of therapy, the glucose level suddenly increased to 25.6 mmol/L. The patient's hemoglobin A_1c value was 9.5%. The thyroid-stimulating hormone value was in the normal range, and tests for thyroid peroxidase antibodies were negative. Interferon- therapy was discontinued, and diabetes was controlled after 0.55 U of insulin per kg of body weight per day was given for 1 week. The patient's insulin requirement then decreased quickly, and he stopped taking insulin 3 months after discontinuing interferon- therapy. His glucose levels were well controlled by diet alone. Results of tests for islet-cell antibodies by immunofluorescence and for insulin autoantibodies by immunoprecipitation were negative before interferon- therapy and 10 days and 1.5 months after interferon- therapy was discontinued. Results of tests for glutamic acid decarboxylase antibodies by immunoprecipitation were negative 10 days after cessation of interferon- therapy. The patient's basal and poststimulation C peptide values were not low before, while, or after insulin therapy was received.

Previous reports [1-3] have described patients with islet-cell antibodies and insulin autoantibodies during interferon- therapy or when diabetes was diagnosed. Pancreatic autoimmunity probably did not occur in our patient because he had no autoimmune markers. Interferon- could have led to reduced sensitivity of the patient's liver and peripheral tissues to insulin and to exacerbation of preexisting glucose intolerance [4]. The high doses of interferon- our patient received could explain the intensity of the metabolic disorder. We believe that interferon- can exacerbate glucose intolerance independently of an autoimmune process, especially if given in high doses.