In vivo and in vitro effects of theophylline administration in recent onset, Type I, diabetic patients

The metabolic and immunologic effects of short and long-term theophylline administration in recent onset Type I diabetic patients were studied in association with 'theophylline sensitivity' of lymphocytes in vitro as a marker of suppressive functions. Eighteen recent onset Type I diabetic patients entered the trial. Five were treated with theophylline (800 mg/d) for 1 mo (group A), 5 were treated with the theophylline (800 mg/d) for 8 mo (group B) and 8 were treated with placebo tablets (group C) in double blind. All patients were followed-up for 16-32 mo. A relationship between sensitivity to theophylline evaluated as inhibition of lymphocyte blastogenic response to Con A and the achievement of remission was observed. At the beginning of the study 8 patients were theophylline sensitive (Th+) (5 of group A, 2 of group B and 1 of group C) and 7 patients were theophylline resistant (Th-) (2 of group B and 5 of group C). Among the 9 Th+ patients, 6 reached the remission phase, while of the 7 Th- patients only 2 reached the remission phase. A high percentage (7/10) of the theophylline-treated patients achieved remission (4 of group A and 3 of group B), while only 3 of the 8 placebo treated patients achieved remission. In vivo theophylline effects were not improved by the longer (8 mo) treatment period. These results show that Th sensitivity in vitro can be considered a precocious marker of the clinical response to immunomodulating drugs in Type I diabetic patients. The favourable effects of theophylline treatment might provide the possibility of an immunomodulating drug free of side effects for recent onset Type I diabetes.