Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
School of Medicine, Barbara Davis Center, University of Colorado Denver, Aurora, CO, USA.
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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