To examine the clinical and immunogenetic heterogeneity of IDDM.
We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (<3 mo, acute clinical-onset group, n = 134), group B (3–12 mo, intermediate group, n = 31), and group C (>13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C.
The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C uhan in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were assocciated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQAl*0301-DQBl*0302, and DQA1 *0301-DQB 1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1* 0301-DQB 1*0401 were more common in this group than in control subjects.
These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved β-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe β-cell destruction in group A patients.