Kobayashi T, Tamemoto K, Nakanishi K, Kato N, Okubo M, Kajio H, Sugimoto T, Murase T, Kosaka K
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
Diabetes Care. 1993 May;16(5):780-8. doi: 10.2337/diacare.16.5.780.
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 (> or = 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 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 DQA10301-DQB10401, DQA10301-DQB10302, and DQA10301-DQB10303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA10301-DQB10401 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 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.
研究胰岛素依赖型糖尿病（IDDM）的临床及免疫遗传学异质性。
我们根据临床发病至开始胰岛素治疗的时间间隔，将207例IDDM患者分为几组：A组（<3个月，急性临床发病组，n=134），B组（3 - 12个月，中间组，n=31），C组（≥13个月，缓慢进展组，n=42）。比较A组和C组的免疫遗传学及临床指标。
C组的发病中位年龄（52岁）高于A组（10岁）。C组胰岛细胞抗体的患病率（42.9%，42例中有18例）高于A组（25.4%，134例中有34例，P=0.05）。通过放射免疫分析法检测，C组患者在口服100克葡萄糖耐量试验后血清C肽免疫反应性显著高于A组。C组患者一级亲属中患非胰岛素依赖型糖尿病（NIDDM）家族史的比例（26.1%，42例中有11例）高于A组患者（11.2%，134例中有15例，P=0.039）。C组和A组IDDM家族史及内分泌自身免疫性疾病的患病率无差异。A组（6.7%，134例中有9例）和C组（2.3%，42例中有1例）内分泌自身免疫性疾病并发症的发生率无差异。在A组中观察到与两种I类主要组织相容性复合体抗原（HLA - A24和 - Bw54）及一种II类抗原（HLA - DR4）有显著关联。A组患者与三种致糖尿病性HLA - DQ单倍型相关，包括DQA10301 - DQB10401、DQA10301 - DQB10302和DQA10301 - DQB10303。相比之下，C组缺乏与I类抗原的关联，尽管HLA - DR4和HLA - DQA10301 - DQB10401在该组中比在对照组中更常见。
这些结果表明，病程缓慢进展的临床亚型（缓慢进展型IDDM）有不同的表现，包括发病年龄晚、胰岛细胞抗体患病率高、β细胞功能保留以及NIDDM家族史高。I类和II类主要组织相容性复合体抗原的累加效应被认为是A组患者急性临床表现和更严重β细胞破坏的一种解释。
