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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

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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) Ab−T+ group had a significantly lower FCP compared with Ab−T− 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 (Ab−T−).

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Acknowledgements

We are indebted to the individuals with phenotypic T2D participating in this study. We also extend our sincere thanks to Prof. Xiangbing Wang from Rutgers University-Robert Wood Johnson Medical School and Dr. Yufei Xiang for suggestions in manuscript writing.

Funding

This research was supported by the National Key R&D Program of China (2018YFC2001005), European Foundation for the Study of Diabetes (EFSD/CDS/Lilly Collaborative Grant Programme-2009) and the National Key R&D Program of China (2018YFC1315603).

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Authors and Affiliations

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

    Huiying Liang, Ying Cheng, Wei Tang, Qiuyan Cui, Jiao Yuan, Gan Huang, Lin Yang & Zhiguang Zhou

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

    Huiying Liang, Ying Cheng, Wei Tang, Qiuyan Cui, Jiao Yuan, Gan Huang, Lin Yang & Zhiguang Zhou

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  1. Huiying Liang
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Correspondence to Lin Yang or Zhiguang Zhou.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (the Second Xiangya Hospital, Central South University, China) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Liang, H., Cheng, Y., Tang, W. et al. 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. Acta Diabetol 56, 1225–1230 (2019). https://doi.org/10.1007/s00592-019-01391-w

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