Small fiber neuropathy and neurovascular disturbances in diabetes mellitus

Functional and organic abnormalities in small unmyelinated C fibers are the hallmark of type 2 diabetes. These may be silent clinically or present wit h burning feet, neurovascular abnormalities, where-in warm, cold, and heat pain thresholds are disturbed in association with impairment in skin blood flow and loss of PGP 9.5 immunostaining nerves in the skin. There is a dysf unctional phase preceding organic structural damage to the neurovascular un it. It coexists with elements of the metabolic syndrome, particularly insul in resistance (IR), elevated systolic blood pressure, and diabetic dyslipid emia i.e. dysfunction of the neurovascular unit may contribute to IR due to compromised blood flow with decreased delivery of fuels to their target ti ssues. If this proves to be the case, it will become important to re-focus energies on the defective neuropeptidergic regulation of blood flow as an a pproach to ameliorating diabetes. Because there is a functional phase that precedes structural damage, reversibility of the defect is achievable.