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

<p><strong>AIMS: </strong>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).</p><p><strong>METHODS: </strong>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.</p><p><strong>RESULTS: </strong>(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].</p><p><strong>CONCLUSIONS: </strong>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^-).</p>