In conclusion, the observation of impaired cerebral hemodynamics and systemic endothelial function in T2DM patients with well-controlled disease and preserved autonomic balance, but with clinical features of metabolic syndrome strongly suggests that factors other than chronic hyperglycemia (insulin-resistance, glucose variability) play a role in vascular dysfunction even in the absence of marked metabolic derangement. The gene discussed is INS; the disease is type 2 diabetes mellitus.