All models were adjusted for duration of diabetes, total cholesterol level, use of insulin, use of anti-hypertensive drugs as significant risk factors in univariate analysis and for age [21], sex [21], fasting C-peptide level [22, 23] and smoking status [24] as known associated factors of CAN (Model 1–3, Table 3). The gene discussed is INS; the disease is Crouzon syndrome-acanthosis nigricans syndrome.