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成人隐匿性自身免疫性糖尿病(LADA)的临床特征和胰岛β细胞功能:表型 2 型糖尿病中 T 细胞反应阳性。

Clinical manifestation and islet β-cell function of a subtype of latent autoimmune diabetes in adults (LADA): positive for T cell responses in phenotypic type 2 diabetes.

机构信息

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Central South University, Changsha, 410011, Hunan, China.

出版信息

Acta Diabetol. 2019 Nov;56(11):1225-1230. doi: 10.1007/s00592-019-01391-w. Epub 2019 Jul 31.

Abstract

AIMS

To investigate the possibility of identifying a subtype of latent autoimmune diabetes in adults (LADA), T-LADA (T cell responses-positive and autoantibody-negative) from patients with phenotypic type 2 diabetes (T2D) by enzyme-linked immunospot (ELISPOT).

METHODS

Eighty-two patients with phenotypic T2D were studied. Autoantibodies against glutamic acid decarboxylase (GAD), insulinoma-associated protein-2 and zinc transporter 8 were measured by radioligand assay. Thirty-nine Ab and 43 Ab patients with phenotypic T2D were enrolled for T cell assay of responses to GAD65 and C-peptide antigen by ELISPOT.

RESULTS

(1) Eleven of 43 Ab participants with phenotypic T2D were demonstrated interferon (IFN)-γ secreting T cells by ELISPOT, while 13 of 39 Ab patients with phenotypic T2D were positive for T cells responses to islet antigens. (2) The onset ages of T cell people with phenotypic T2D were younger than that of T cell individuals (42.7 ± 9.3 vs. 48.2 ± 10.2 years, P = 0.025). Moreover, T cell patients with T2D displayed a significantly lower fasting C-peptide (FCP) compared with T cell participants [0.28 (0.02-0.84) vs. 0.42 (0.05-1.26) nmol/L, P = 0.013]. (3) AbT group had a significantly lower FCP compared with AbT group [0.31 (0.13-0.84) vs. 0.51 (0.07-1.26) nmol/L, P = 0.023].

CONCLUSIONS

By measuring T cell responses to islet antigens in patients with phenotypic T2D, we identified a specific subtype of LADA who may be associated with worse basal β-cell function than classic T2D (AbT).

摘要

目的

通过酶联免疫斑点法(ELISPOT),从表型 2 型糖尿病(T2D)患者中寻找 T 细胞阳性和自身抗体阴性的潜伏自身免疫性糖尿病成人(LADA),即 T-LADA(T 细胞反应阳性和自身抗体阴性)的可能性。

方法

研究了 82 例表型 T2D 患者。采用放射性配体法检测谷氨酸脱羧酶(GAD)、胰岛素瘤相关蛋白-2 和锌转运体 8 的自身抗体。将 39 例 Ab 阳性和 43 例 Ab 阳性的 T2D 患者纳入 GAD65 和 C 肽抗原 T 细胞检测。

结果

(1)43 例 Ab 阳性的 T2D 患者中,11 例通过 ELISPOT 显示 IFN-γ分泌 T 细胞,而 39 例 Ab 阳性的 T2D 患者中有 13 例对胰岛抗原的 T 细胞反应阳性。(2)T 细胞阳性的 T2D 患者的发病年龄较 T 细胞阳性的 T2D 患者年轻[42.7±9.3 岁 vs. 48.2±10.2 岁,P=0.025]。此外,T 细胞阳性的 T2D 患者的空腹 C 肽(FCP)明显低于 T 细胞阳性的 T2D 患者[0.28(0.02-0.84)vs. 0.42(0.05-1.26)nmol/L,P=0.013]。(3)AbT 组的 FCP 明显低于 AbT 组[0.31(0.13-0.84)vs. 0.51(0.07-1.26)nmol/L,P=0.023]。

结论

通过测量表型 T2D 患者胰岛抗原的 T 细胞反应,我们发现了一种特定的 LADA 亚型,其基础β细胞功能可能比经典 T2D(AbT)更差。

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