Diabetes Care, Vol 16, Issue 5 780-788, Copyright © 1993 by American Diabetes Association

ARTICLES

Immunogenetic and clinical characterization of slowly progressive IDDM

T Kobayashi, K Tamemoto, K Nakanishi, N Kato, M Okubo, H Kajio, T Sugimoto, T Murase and K Kosaka
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.

OBJECTIVE--To examine the clinical and immunogenetic heterogeneity of IDDM. RESEARCH DESIGN AND METHODS--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 (> or = 13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C. RESULTS--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 than 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 associated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQA1*0301-DQB1*0302, and DQA1*0301-DQB1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1*0301-DQB1*0401 were more common in this group than in control subjects. CONCLUSIONS--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 beta-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 beta-cell destruction in group A patients.
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