ANTIBODIES TO GLUTAMIC-ACID DECARBOXYLASE IN JAPANESE DIABETIC-PATIENTS WITH SECONDARY FAILURE OF ORAL HYPOGLYCEMIC THERAPY

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (N IDDM) are positive for antibodies to glutamic acid decarboxylase (anti -GAD), which have been shown to be a useful marker for the diagnosis a nd prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. W e investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controll ed by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11%, p < 0.05) SF patients and 6 of 200 (3%) NSF patients were anti-GAD pos itive. The positive rate for anti-GAD was as high as 23.8% in the non- obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The interval before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11% of the SF patien ts, suggesting that autoimmune mechanisms may play an important role i n the pathogenesis of secondary failure of sulphonylurea therapy.