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Diabetologia. 2019 Mar;62(3):399-407. doi: 10.1007/s00125-018-4799-4. Epub 2018 Dec 29.

Tetraspanin 7 autoantibodies predict progressive decline of beta cell function in individuals with LADA.

Shi X1,2, Huang G1,2, Wang Y1,2, Liu Z3, Deng C1,2, Li X1,2, Zheng P4,5, Zhou Z6,7.

Author information

1
Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
2
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China.
3
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
4
Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China. peilinz@csu.edu.cn.
5
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China. peilinz@csu.edu.cn.
6
Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China. zhouzhiguang@csu.edu.cn.
7
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China. zhouzhiguang@csu.edu.cn.

Abstract

AIMS/HYPOTHESIS:

The aim of this work was to investigate whether tetraspanin 7 autoantibodies (TSPAN7A) are valuable in predicting poor beta cell function in individuals with latent autoimmune diabetes in adults (LADA).

METHODS:

The cross-sectional study involved participants with LADA (n = 173), type 1 diabetes (n = 158), type 2 diabetes (n = 204) and healthy control participants (n = 170). The longitudinal study involved 53 participants with LADA, with a 3-year follow-up. In both cohorts, TSPAN7A in the sera were measured by a luciferase immunoprecipitation system assay, and physical and clinical characteristics were recorded.

RESULTS:

The prevalence of TSPAN7A in LADA, type 1 diabetes, type 2 diabetes and healthy control participants was 21.4% (37/173), 26% (41/158), 0.5% (1/204) and 1.2% (2/170), respectively. Importantly, measurement of TSPAN7A significantly increased the number of individuals with LADA found to be positive for multiple antibodies (32.4% vs 22%; p < 0.001). Further logistic regression analysis demonstrated that positivity for TSPAN7A (OR 2.87, p = 0.034), disease duration (OR 1.83, p = 0.019) and GAD antibody titre (OR 2.67, p = 0.009) were risk factors for beta cell function in LADA, while BMI (OR 0.34, p = 0.001) was a protective factor. In the prospective study in individuals with LADA, the median annual decrease in rates of fasting C-peptide and 2 h postprandial C-peptide in individuals who were positive for TSPAN7A was significantly higher when compared with the decrease in those who were negative for TSPAN7A (34.6% vs 7.9%, p = 0.043 and 33.2% vs 11%, p = 0.041, respectively).

CONCLUSIONS/INTERPRETATION:

TSPAN7A are valid islet autoantibodies for use in East Asian populations with autoimmune diabetes and can discriminate individuals with LADA who have lower beta cell function after disease progression.

KEYWORDS:

Beta cell function; Islet autoantibodies; Latent autoimmune diabetes in adults; Tetraspanin 7; Type 1 diabetes

PMID:
30594957
DOI:
10.1007/s00125-018-4799-4

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