The Epidemiology of Diabetes Intervention and Complication (EDIC) study has demonstrated persistent beneficial effects of early strict glycemic control on microvascular complications and also on DAN: although CAN prevalence increased in both groups, the former intensive insulin treatment group continued to have a significantly lower decline in CAN through 13 or 14 years of EDIC follow-up. This evidence concerns the gene INS and Crouzon syndrome-acanthosis nigricans syndrome.