Persons with spinal cord injury (SCI) are at an increased risk for metabolic disorders,
including that of insulin resistance. As a result of neurological injury, they often have
impaired mechanisms that regulate blood vessel function below the level of injury. Insulin,
which facilitates the transport of glucose into muscle cells, is also capable of regulating
skin blood flow, with insulin resistance reducing perfusion. Although beyond the scope of
this proposal, the possibility exists that impaired microvascular skin blood flow responses
due to insulin may further predispose to ischemia of the skin at pressure points of bony
prominence. This perturbed cutaneous vascular response may place persons with SCI at risk for
the development and poor healing of pressure ulcers due to microvascular dysfunction
secondary to neurologic and metabolic disorders.
Primary Aim: To determine the association between systemic insulin sensitivity and
insulin-mediated vasodilatation below the neurological level of injury.
We hypothesize that individuals with systemic insulin sensitivity compared to those with
insulin resistance will have greater insulin-mediated vasodilatation and an associated
proportional increase in cutaneous blood perfusion. Thus, intact and appropriate
endothelial-mediated regulation by insulin will be operative despite sub-lesional
neurological impairment in insulin sensitive individuals with SCI. However, because of the
absence of the SNS-mediated insulin action on the microvasculature (i.e., insulin-mediated
sympathetic withdrawal), it is being hypothesized that the vasodilatory response to
iontophoresis with insulin in insulin sensitive subjects with SCI will be less than that
observed in neurologically intact controls with insulin sensitivity.
Secondary Aim: To compare peak microvascular perfusion responses to endothelial-dependent
vasodilatation by iontophoresis with acetylcholine to insulin.
We hypothesize that the peak blood perfusion responses to iontophoresis with insulin will be
comparable in magnitude to that of acetylcholine in individuals with greater systemic insulin
sensitivity. This will be in contrast to individuals with systemic insulin resistance who
will demonstrate a diminished response to iontophoresis with insulin when compared to that of
acetylcholine. Because of SNS impairment, the peak vasodilatory response observed to these
interventions will be lower in the group with SCI.