Clinical evaluation of non-insulin-dependent diabetes mellitus patients with autoantibodies to glutamic acid decarboxylase

We evaluated the frequency of antibodies to glutamic acid decarboxylase (GAD-Ab) in Japanese patients diagnosed initially as having non-insulin-dependent diabetes mellitus (NIDDM) and investigated a possible link between the presence of GAD-Ab and development of the insulin-dependent (ID) state. The population sample consisted of 583 Japanese NIDDM patients (age at onset >30 years) who were initially non-ketotic and did not require insulin treatment during at least 6 months of observation. GAD-Ab were measured using radioimmunoassay. The clinical characteristics of GAD-Ab(+) patients were carefully examined at four-year intervals from the onset of diabetes. We also examined the ID state by measuring the level of postprandial serum C-peptide and i.v. glucagon-stimulated serum C-peptide. The overall prevalence of GAD-Ab in Japanese NIDDM patients was 3.8%. The frequency of GAD-Ab(+) did not significantly decrease with a long history of diabetes. GAD-Ab(+) patients had a lower body mass index, compared with GAD-Ab(-) (20.8+/-2.9 vs 23.0+/-3.7, P<0.005), lower postprandial C-peptide levels (0.7+/-0.6 vs 1.4+/-1.2, P<0.01), and an early commencement of insulin therapy (3.6+/-4.7 vs 8.3+/-6.6, P<0.01). GAD-Ab(+) patients who had already developed the ID state had characteristically higher titers of GAD-Ab (421.4+/-359.1) and a higher frequency of islet cell antibodies (ICAs) (77.8%), compared with GAD-Ab(+) NID patients (titer: 60.2+/-86.9, P<0.005, 23.1%, P<0.05, respectively). GAD-Ab(+) ICAs+ patients showed higher frequencies of ID state at any diabetic duration compared with GAD(-) ICAs-, while GAD-Ab(+) ICAs- patients did not differ in the frequency of the ID state from GAD(-) ICAs-. Our results suggest that the presence of both GAD-Ab and ICAs represents a high risk for IDDM in GAD-Ab(+) NIDDM patients. (C) 1996 Academic Press Limited