Enhanced T Cell Glucose Uptake Is Associated With Progression of Beta-Cell Function in Type 1 Diabetes

Abstract

BackgroundAbnormal intracellular glucose/fatty acid metabolism of T cells has tremendous effects on their immuno-modulatory function, which is related to the pathogenesis of autoimmune diseases. However, the association between the status of intracellular metabolism of T cells and type 1 diabetes is unclear. This study aimed to investigate the uptake of glucose and fatty acids in T cells and its relationship with disease progression in type 1 diabetes.MethodsA total of 86 individuals with type 1 diabetes were recruited to detect the uptake of glucose and fatty acids in T cells. 2-NBDG uptake and expression of glucose transporter 1 (GLUT1); or BODIPY uptake and expression of carnitine palmitoyltransferase 1A(CPT1A) were used to assess the status of glucose or fatty acid uptake in T cells. Patients with type 1 diabetes were followed up every 3-6 months for 36 months, the progression of beta-cell function was assessed using generalized estimating equations, and survival analysis was performed to determine the status of beta-cell function preservation (defined as 2-hour postprandial C-peptide >200 pmol/L).ResultsPatients with type 1 diabetes demonstrated enhanced intracellular glucose uptake of T cells as indicated by higher 2NBDG uptake and GLUT1 expression, while no significant differences in fatty acid uptake were observed. The increased T cells glucose uptake is associated with lower C-peptide and higher hemoglobin A1c levels. Notably, patients with low T cell glucose uptake at onset maintained high levels of C-peptide within 36 months of the disease course [fasting C-petite and 2-hour postprandial C-peptide are 60.6 (95%CI: 21.1-99.8) pmol/L and 146.3 (95%CI: 14.1-278.5) pmol/L higher respectively], And they also have a higher proportion of beta-cell function preservation during this follow-up period (P<0.001).ConclusionsIntracellular glucose uptake of T cells is abnormally enhanced in type 1 diabetes and is associated with beta-cell function and its progression.