Effect of initiation of insulin therapy on T-lymphocyte activation in type 1 diabetes.

Levels of activated T-lymphocytes are characteristically increased in recently diagnosed patients with Type 1 diabetes and remain elevated up to 6 months after diagnosis. To determine whether insulin treatment has a role in initiating or maintaining this activation 12 patients were studied at diagnosis and again 1, 5, and 70 days after the start of insulin therapy. Levels of activated T-lymphocytes were found to be elevated at diagnosis (9.7 +/- 1.6% (+/- SD)) before insulin treatment compared with normal control subjects (4.2 +/- 1.1%; p less than 0.001). One day after starting insulin therapy, the level of activated T-lymphocytes had not changed but by day 5 it had fallen significantly (7.6 +/- 1.9%; p less than 0.05) compared with pre-treatment levels. By day 70, activated T-lymphocytes were returning towards the high levels found before treatment. Investigation of the phenotype of the activated T-lymphocytes showed that there was an increase in the percentage of activated cells expressing the CD8 (suppressor/cytotoxic) phenotype at 70 days compared with pre-treatment values (p less than 0.02). These results show that elevated levels of activated T-lymphocytes found in recently diagnosed Type 1 diabetes are not a result of insulin treatment. Treatment may, however, have a role in maintaining T-lymphocyte activation and modifying the distribution of functional subsets of the activated cells.