INS and diabetes mellitus: While the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study demonstrated that controlling the blood glucose, as measured by HbA1c and periodic blood glucose levels, reduced the development and progression of DR complications (190, 191), post-hoc analysis of the DCCT data has revealed that only 11% of the risk in retinopathy development could be attributed to HbA1c, with later studies showing significant, perhaps even greater impact of the glucose fluctuations (192), as well as the usage of insulin in type 2 DM with insulin resistance (193).