老年起病的儿童 1 型糖尿病与 30 多年后胰岛自身抗体阳性相关：匹兹堡糖尿病并发症流行病学研究。
Older age of childhood type 1 diabetes onset is associated with islet autoantibody positivity >30 years later: the Pittsburgh Epidemiology of Diabetes Complications Study.
机构信息
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
School of Medicine, Barbara Davis Center, University of Colorado Denver, Aurora, CO, USA.
出版信息
Diabet Med. 2020 Aug;37(8):1386-1394. doi: 10.1111/dme.14261. Epub 2020 Feb 11.
AIMS
To examine the association between islet autoantibody positivity and clinical characteristics, residual β-cell function (C-peptide) and prevalence of complications in a childhood-onset (age <17 years), long-duration (≥32 years) type 1 diabetes cohort.
METHODS
Islet autoantibodies (glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter-8 antibodies) were measured in the serum of participants who attended the 2011-2013 Pittsburgh Epidemiology of Diabetes Complications study follow-up examination (n=177, mean age 51 years, diabetes duration 43 years).
RESULTS
Prevalences of islet autoantibodies were: glutamic acid decarboxylase, 32%; insulinoma-associated protein 2, 22%; and zinc transporter-8, 4%. Positivity for each islet autoantibody was associated with older age at diabetes onset (glutamic acid decarboxylase antibodies, P=0.03; insulinoma-associated protein 2 antibodies, P=0.001; zinc transporter-8 antibodies, P<0.0001). Older age at onset was also associated with an increasing number of autoantibodies (P = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA (P = 0.02), insulinoma-associated protein 2 antibody positivity was associated with lower prevalence of severe hypoglycaemic episodes (P=0.02) and both distal and autonomic neuropathy (P=0.04 for both), and zinc transporter-8 antibody positivity was associated with higher total and LDL cholesterol (P=0.01). No association between autoantibody positivity and C-peptide was observed.
CONCLUSIONS
The strong association between islet autoantibody positivity and older age at type 1 diabetes onset supports the hypothesis of a less aggressive, and thus more persistent, immune process in those with older age at onset. This observation suggests that there may be long-term persistence of heterogeneity in the underlying autoimmune process.
目的
在一个儿童发病（年龄<17 岁）、病程较长（≥32 年）的 1 型糖尿病队列中，研究胰岛自身抗体阳性与临床特征、残余β细胞功能（C 肽）和并发症患病率之间的关系。
方法
在参加 2011-2013 年匹兹堡糖尿病并发症流行病学研究随访检查的参与者（n=177，平均年龄 51 岁，糖尿病病程 43 年）血清中测量了胰岛自身抗体（谷氨酸脱羧酶、胰岛瘤相关蛋白 2 和锌转运体-8 抗体）。
结果
胰岛自身抗体的患病率分别为：谷氨酸脱羧酶，32%；胰岛瘤相关蛋白 2，22%；锌转运体-8，4%。每种胰岛自身抗体的阳性与糖尿病发病时年龄较大有关（谷氨酸脱羧酶抗体，P=0.03；胰岛瘤相关蛋白 2 抗体，P=0.001；锌转运体-8 抗体，P<0.0001）。发病年龄较大也与自身抗体数量的增加有关（P=0.001）。谷氨酸脱羧酶抗体阳性与较低的 HbA 相关（P=0.02），胰岛瘤相关蛋白 2 抗体阳性与严重低血糖发作的患病率较低相关（P=0.02），远端和自主神经病变的患病率也较低（P=0.04 两项），锌转运体-8 抗体阳性与总胆固醇和 LDL 胆固醇较高相关（P=0.01）。自身抗体阳性与 C 肽无相关性。
结论
胰岛自身抗体阳性与 1 型糖尿病发病时年龄较大之间的强关联支持了这样一种假说，即在发病年龄较大的患者中，免疫过程更具侵袭性，因此更为持久。这一观察结果表明，在潜在的自身免疫过程中，可能存在长期持续的异质性。
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