Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11 %, p Ͻ 0.05) SF patients and 6 of 200 (3 %) NSF patients were anti-GAD positive. 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 patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure of sulphonylurea therapy. KEY WORDS Non-insulin-dependent diabetes mellitus Sulphonylurea agent Secondary failure Antibodies to glutamic acid decarboxylase Pathogenesis
autoantigen. 9 Antibodies to glutamic acid decarboxylase
Patients and Methods
Glutamic acid decarboxylase (GAD) is the biosynthesizing enzyme of the inhibitory neurotransmitter ␥-
We studied 200 Japanese SF patients, who had a history of good diabetes control with SU agents for at least 1 aminobutyric acid, which is a pancreatic islet beta cell year. The criteria for secondary failure of SU agents were a HbA 1c level more than 8 %, despite treatment with Abbreviations: GAD glutamic acid decarboxylase, SF NIDDM with secondary failure of oral hypoglycaemic therapy, NSF NIDDM well more than 7.5 mg glibenclamide and the clinical need controlled by diet and/or sulphonylurea agents, SU sulphonylurea for insulin. The interval before the development of