Time Course of Islet Cell Antibodies and β-Cell Function in Non-Insulin-Dependent Stage of Type I Diabetes
Time Course of Islet Cell Antibodies and β-Cell Function in Non-Insulin-Dependent Stage of Type I Diabetes
复制标题
I 型糖尿病非胰岛素依赖性阶段胰岛细胞抗体和 β 细胞功能的时程
作者：
T. Kobayashi;T. Itoh;K. Kosáka;K. Sato;K. Tsuji
对32例ICA阳性者[28例非胰岛素依赖型糖尿病（NIDDM），4例糖耐量减低（IGT）;平均年龄45岁]，96名在研究开始时伊卡阴性的匹配受试者[56名NIDDM患者，8名IGT患者和32名胰岛素依赖型糖尿病（IDDM）患者的正常一级亲属;平均年龄45岁]。此外，人类白细胞抗原（HLA）对伊卡和β细胞功能的时间进程的影响进行了评估。在10例伊卡阳性受试者（8例NIDDM和2例IGT）中，在本研究开始后15 ± 2个月（平均值± SE），伊卡变得不可检测，即使通过灵敏的伊卡测定。在这些受试者中，响应OGTT的综合血清CPR值（σCPR）和2小时血糖值显著改善（P <0.05 - 0.01）。相反，其余22例伊卡阳性受试者的伊卡持续阳性。在这22名受试者中，CPR和血糖反应进行性恶化，该组中有7名受试者进展为胰岛素依赖状态。64例患者（56例NIDDM和8例IGT）和32例ICA阴性的IDDM患者的正常一级亲属的血清CPR和OGTT血糖反应无明显变化。随访期间10名伊卡阴性受试者的HLABW 54和HLA-DR 4频率低于整个研究期间22名伊卡受试者的HLABW 54和HLA-DR 4频率（未校正P < .02）。22名伊卡持续阳性受试者中这两种抗原的频率高于正常对照（未校正P < .02），而在研究期间伊卡阴性的10名受试者中没有观察到这些差异。我们的研究中观察到伊卡负转换后β细胞功能逆转，为I型糖尿病的自然史提供了新的见解，特别是在晚发型病例中。提示HLA相关的遗传易感性是胰腺自身免疫缓慢进行性β细胞破坏的先决条件。
The time course of islet cell antibodies (ICA) and serum C-peptides responses (CPRs) to oral glucose tolerance tests (OGTTs) were studied prospectively up to 60 (mean 35) mo in 32 ICA-positive subjects [28 with non-insulin-dependent diabetes (NIDDM) and 4 subjects with impaired glucose tolerance (IGT); mean age 45 yr], 96 matched subjects [56 with NIDDM, 8 with IGT, and 32 normal first-degree relatives of patients with insulin-dependent diabetes (IDDM); mean age 45 yr] who were negative for ICA at the beginning of the study. In addition, the effects of human leukocyte antigens(HLA) on the time course of ICA and (β-cell function were evaluated. In 10 subjects (8 with NIDDM and 2 with IGT) who were ICA positive, ICA became undetectable, even by sensitive ICA assay, 15 ± 2 mo (mean ± SE) after initiation of this study. In these subjects, integrated serum CPR values (σCPR) and 2-h blood glucose values in response to OGTTs improved significantly (P < .05-.01). In contrast, the remaining 22 subjects who were ICA positive were persistently positive for ICA. CPR and blood glucose responses deteriorated progressively in these 22 subjects, and 7 subjects in this group progressed to the insulin-dependent state. Serum CPR and blood glucose responses to OGTTs showed no remarkable changes in 64 patients (56 with NIDDM and 8 with IGT) and 32 normal first-degree relatives of patients with IDDM who remained negative for ICA throughout the study. The frequencies of HLABW54 and HLA-DR4 in 10 subjects who became ICA negative during the follow-up period were lower than those in 22 subjects with ICA throughout the study (uncorrected P < .02). The frequencies of these two antigens were higher in the 22 subjects with persistently positive ICA than in normal controls (uncorrected P < .02), whereas these differences were not observed in 10 subjects who became ICA negative during the study. The reversed β-cell function after negative conversion of ICA observed in our study yields a new insight into the natural history of type I diabetes, especially in late-onset cases. It suggests that HLA-related genetic predisposition is a prerequisite to the slowly progressive β-cell destruction through pancreatic autoimmunity.