Increased α₂-macroglobulin (α₂M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA₁. α₂M activity and α₂M concentration, and a direct correlation between both α₂M concentration with blood glucose and HbA₁ are found. Moreover, a direct correlation between α₂M activity and α₂M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases α₂M activity and α₂M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase α₂M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as α₂M.