Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark.
Clin Exp Immunol. 2010 Sep;161(3):444-52. doi: 10.1111/j.1365-2249.2010.04193.x.
The progression of type 1 diabetes after diagnosis is poorly understood. Our aim was to assess the relation of disease progression of juvenile-onset type 1 diabetes, determined by preserved beta cell function the first year after diagnosis, with systemic cytokine concentrations and number of autoantibodies. Juvenile patients (n = 227) had a meal-stimulated C-peptide test 1 and 6 months after diagnosis. On the basis of the C-peptide course for the duration of 1-6 months, four progression groups were defined: patients with persistently low beta cell function ('stable-low'), rapid progressers, slow progressers and remitters. Serum concentrations of adiponectin, interleukin (IL)-1ra, inducible protein 10 (IP-10), IL-6 and glutamic acid decarboxylase (GAD), IA-2A and islet-cell antibodies (ICA) were measured at 1, 6 and 12 months. We found that adiponectin concentrations at 1 month predicted disease progression at 6 months (P = 0·04). Patients with low adiponectin had a higher probability of becoming remitters than rapid progressers, odds ratio 3·1 (1·3-7·6). At 6 and 12 months, adiponectin differed significantly between the groups, with highest concentrations among stable-low and rapid progressers patients (P = 0·03 and P = 0·006). IL-1ra, IP-10 and IL-6 did not differ between the groups at any time-point. The number of autoantibodies differed significantly between the groups at 1 month (P = 0·04), where rapid progressers had the largest number. There was no difference between the groups in human leucocyte antigen-associated risk. We define progression patterns distinguishing patients diagnosed with low beta cell function from those with rapid decline, slow decline or actual increase in beta cell function, pointing to different mechanisms of disease progression. We find that adiponectin concentration at 1 month predicts, and at 6 and 12 months associates with, distinct progression patterns.
1 型糖尿病确诊后的进展情况尚不清楚。我们的目的是评估青少年起病的 1 型糖尿病患者的疾病进展与细胞功能的关系,其通过诊断后第一年的β细胞功能得以确定,同时还评估了细胞因子浓度和自身抗体数量的关系。227 例青少年患者在确诊后 1 个月和 6 个月时进行了餐刺激 C 肽试验。根据 1-6 个月期间 C 肽的变化,将 4 个进展组定义为:β细胞功能持续低下(“稳定低下”)、快速进展、缓慢进展和缓解。在 1 个月、6 个月和 12 个月时测量血清脂联素、白细胞介素(IL)-1ra、诱导蛋白 10(IP-10)、IL-6、谷氨酸脱羧酶(GAD)、IA-2A 和胰岛细胞抗体(ICA)的浓度。我们发现,1 个月时的脂联素浓度可以预测 6 个月时的疾病进展(P = 0.04)。脂联素水平低的患者比快速进展患者更有可能成为缓解者,比值比为 3.1(1.3-7.6)。在 6 个月和 12 个月时,各组之间的脂联素差异有统计学意义,稳定低下和快速进展患者的脂联素浓度最高(P = 0.03 和 P = 0.006)。在任何时间点,各组之间的 IL-1ra、IP-10 和 IL-6 均无差异。1 个月时各组之间的自身抗体数量差异有统计学意义(P = 0.04),其中快速进展患者的数量最多。各组之间人类白细胞抗原相关风险无差异。我们确定了可以区分确诊时β细胞功能低下和β细胞功能快速下降、缓慢下降或实际增加的患者的进展模式,提示存在不同的疾病进展机制。我们发现,1 个月时的脂联素浓度可以预测,而在 6 个月和 12 个月时与不同的进展模式相关。