INS and type 2 diabetes mellitus: However, since first being noticed in 1983,[3] clinical trials have demonstrated that insulin IT can cause a paradoxical early aggravation of DR called “ early worsening of diabetic retinopathy” (EWDR) in type 1[2,4,5] and type 2 diabetes.[6,7] Most patients at baseline in these studies were with minimal-to-moderate non-proliferative diabetic retinopathy (NPDR) or even without DR.