The negative effect of hyperglycemia on Tregs phenotype and function was observed also in streptozotocin (STZ) induced hyperglycemic mice, where long-term hyperglycemia changed the phenotype of CD4+CD25+FoxP3+ Tregs into activated/memory phenotype with lower CD62L, CD45RB, GITR, and higher CTLA-4 expression and reduced their suppressive effect on effector T cells proliferation. This evidence concerns the gene TNFRSF18 and Hyperglycemia.