Variable frequencies of peripheral T-lymphocyte subsets in the diabetes spectrum from type 1 diabetes through latent autoimmune diabetes in adults (LADA) to type 2 diabetes

Abstract

T lymphocytes are key players in the pathogenesis of autoimmune diabetes. We recruited subjects with T1D (n=81), LADA (n=82), T2D (n=95) and NGT (n=218) and analyzed the percentages of T-lymphocyte subsets, including T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), T cytotoxic 1 (Tc1), regulatory T cells (Tregs), effector T (Teff), naïve T, central memory T (Tcm), and effector memory T (Tem) cells by flow cytometry. LADA patients possessed similar frequencies of IFN-γ+CD4+ T (Th1), IFN-γ+CD8+ T and CD4+ Teff cells compared with T1D patients, but much lower than those of NGT subjects. Like T2D patients, LADA patients had increased frequencies of CD4+ Tem and CD8+ Tem cells with respect to T1D and NGT subjects. In LADA patients, Th2 cells were decreased while CD4+ Tcm cells were increased compared with NGT subjects. Notably, we observed significant negative correlations between the CD4+ Tcm cell frequency and C-peptide in LADA subjects. These data demonstrates that LADA patients possess T-cell subset changes resembling both T1D and T2D and represent the middle of the diabetes spectrum between T1D and T2D. Based on these T-cell subset alterations, we speculate that autoimmunity-induced β-cell destruction and inflammation-induced insulin resistance might both be involved in the pathogenesis of LADA.

The crucial role and mechanism of insulin resistance in metabolic disease

“…In the past, more attention has been paid to the regulation of insulin sensitivity by innate immune cells, particularly macrophage mediated, which have been mentioned before. Cells of the adaptive immune system, B lymphocytes and T lymphocytes, and their respective subsets, are also thought to be important regulators of glucose homeostasis and play an important role in the immunopathogenesis of autoimmune diabetes ( 168 , 173 , 174 ). Studies have shown that CD4(+) T lymphocytes in visceral adipose tissue (VAT) control the progression of metabolic abnormalities associated with obesity, including expansion of adiposity and pathogenic VAT T cells, which can be successfully reversed by immunotherapy ( 175 , 176 ).…”

Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals

“…This suggests that RPS26 might play a role in the development and progression of type 1 diabetes mellitus through its involvement in ER stress. However, autoimmunity is correlated with the pathogenesis of both type 1 diabetes mellitus and LADA, and T lymphocytes are crucial for this process 41 . Previous studies have shown that RPS26 is highly expressed in T lymphocytes, and that the ablation of RPS26 in T lymphocytes disrupts peripheral T lymphocyte homeostasis and impairs T lymphocyte development in the thymus 15 .…”

Association between a high triglyceride–glucose index and chronic kidney disease in adult patients with latent autoimmune diabetes

“…Latent autoimmune diabetes in adults is an autoimmune-mediated type of diabetes, and T lymphocytes are a key factor in its pathogenesis [ 14 ]. Data demonstrates that, based on these T-cell subset alterations, IR may be involved in the pathogenesis of LADA [ 15 ]. Positive correlations between the serum levels of autoantibodies and pancreatic islet dysfunction in the autoimmune disease model of mice may partially reflect the relationship between autoimmunity and LADA [ 16 ].…”