Immunologically-related or incidental coexistence of diabetes mellitus andGraves' disease; Discrimination by anti-GAD antibody measurement

Coexistence of diabetes mellitus and Graves' disease may be classified into either an immunologically-related or an incidental phenomenon. It has been reported that anti-GAD antibody (GAD-Ab) persists at high levels for longe r duration in subjects with type 1 diabetes and Graves' disease, whereas th e prevalence of positive GAD-Ab (1.5%) in 131 non-diabetic subjects with Gr aves' disease was comparable to that in normal subjects (0.3%, P=0.2012). T hus, GAD-Ab might be a marker of the immunologically-related coexistence of the two diseases. To test this hypothesis, we investigated characteristics of Japanese subjects having both diseases according to the presence or abs ence of GAD-Ab. Sixty-one patients having diabetes mellitus and Graves' dis ease (24 men, 37 women, aged 53+/-2 years old, mean+/-SE) were consecutivel y registered between 1993-1997. The patients were divided into two groups o f 14 GAD-Ab positive and 47 negative subjects. In the GAD-Ab positive subje cts, earlier (32+/-3 years old) and abrupt onset (86%) of diabetes and insu lin dependency (64%) were documented, as would be expected from the feature s of type 1 diabetes. Graves' disease often preceded diabetes (57%), presen ting typical manifestations (79%). In contrast, older (45+/-2 years old, P= 0.0031) and gradual onset (87%, P<0.0001) of diabetes, non-insulin dependen cy (74%, P<0.0001), and masked manifestations of Graves' disease (57%, P=0. 0214) were common in the negative subjects. Precedence of diabetes dominate d in these subjects (43%, P=0.0109). Immunological studies showed less freq uent HLA-DR 2 locus (0%, P<0.02) in the GAD-Ab positive subjects. There was also a trend of higher frequency of HLA-DQA1*03 allele and of lower freque ncy of DQAI*01 allele in these subjects. Allelic frequency of cytotoxic T l ymphocyte antigen 4 (CTLA-4) differed between the positive and negative sub jects (P=0.0432). There were distinct clinical and immunological difference s between the GAD-AI, positive and negative subjects having both diabetes m ellitus and Graves' disease. The present results indicate that GAD-Ab measu rement could draw a distinction between the immunologically-related and inc idental coexistence of the two diseases.