title: Immunologically-related or incidental coexistence of diabetes mellitus and Graves' disease; discrimination by anti-GAD antibody measurement.
abstract: 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 longer duration in subjects with type 1 diabetes and Graves' disease, whereas the prevalence of positive GAD-Ab (1.5%) in 131 non-diabetic subjects with Graves' disease was comparable to that in normal subjects (0.3%, P=0.2012). Thus, 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 absence of GAD-Ab. Sixty-one patients having diabetes mellitus and Graves' disease (24 men, 37 women, aged 53+/-2 years old, mean +/- SE) were consecutively registered between 1993-1997. The patients were divided into two groups of 14 GAD-Ab positive and 47 negative subjects. In the GAD-Ab positive subjects, earlier (32+/-3 years old) and abrupt onset (86%) of diabetes and insulin dependency (64%) were documented, as would be expected from the features of type 1 diabetes. Graves' disease often preceded diabetes (57%), presenting typical manifestations (79%). In contrast, older (45+/-2 years old, P=0.0031) and gradual onset (87%, P<0.0001) of diabetes, non-insulin dependency (74%, P<0.0001), and masked manifestations of Graves' disease (57%, P=0.0214) were common in the negative subjects. Precedence of diabetes dominated in these subjects (43%, P=0.0109). Immunological studies showed less frequent 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 frequency of DQA1*01 allele in these subjects. Allelic frequency of cytotoxic T lymphocyte antigen 4 (CTLA-4) differed between the positive and negative subjects (P=0.0432). There were distinct clinical and immunological differences between the GAD-Ab positive and negative subjects having both diabetes mellitus and Graves' disease. The present results indicate that GAD-Ab measurement could draw a distinction between the immunologically-related and incidental coexistence of the two diseases.
authors.affiliation: Department of Medicine, Jichi Medical School, Tochigi, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Kusaka
authors.forename: S
authors.initials: S
authors.lastname: Nagasaka
authors.forename: K
authors.initials: K
authors.lastname: Fujibayashi
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Rokkaku
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Higashiyama
authors.forename: K
authors.initials: K
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.forename: T
authors.initials: T
authors.lastname: Saito
mesh_terms: D000069594:Abatacept; D000328:Adult; D000906:Antibodies / Q000032:analysis; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006111:Graves Disease / Q000150:complications* / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006680:HLA Antigens; D018796:Immunoconjugates; D000069594:Abatacept; D005968:Glutamate Decarboxylase