Recently, the interplay between lymphocyte function and metabolic status has become increasingly appreciated. Specific metabolic programs and energy substrates have been shown to modulate T cell activation, differentiation, and function. The implication is that T cell activity may be manipulated to elicit specific immune environments for improved self-tolerance, allograft tolerance, anti-tumor responses, and vaccine responses. We are currently using extracellular flux analyses to define the metabolic profile of human T cells, and to discover biomarkers of T1D onset or progression. These studies are also aimed at confirming findings from murine studies and at the identification and modulation of metabolic pathways to favor regulatory T cell development.