IR and Microvascular Blood Flow in SCI

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: James J. Peters Veterans Affairs Medical Center
• Treatments: Acetylcholine; Insulin; Insulin, Globin Zinc

Criteria

Inclusion Criteria:

1. Male or female, age 20 to 69;

2. Chronic (e.g., duration of injury at least 6 months), stable SCI (regardless of level of neurological lesion);

3. American Spinal Injury Association Impairment Scale (AIS) designation of A or B (reflects the level of somato-sensory impairment below the neurological level of injury: AIS A being complete sensory and motor lesion; AIS B being incomplete sensory and complete motor lesion);

4. Neurologically intact, age-matched control subjects

5. insulin-sensitive group: Si ≥ 2.5 min-1 ∙ mU-1 ∙ L x 104; and

6. insulin resistant group: Si < 2.5 min-1 ∙ mU-1 ∙ L x 104

Exclusion Criteria:

1. Diminished mental capacity;

2. Inability or unwillingness of subject to provide informed consent;

3. Acute illness or infection;

4. Current pharmacological treatment for diabetes mellitus or insulin resistance with exogenous insulin (or its synthetic dialogues), insulin-sensitizing agents, or agents that alter pancreatic secretion of insulin;

5. Current pharmacological treatment with sympathomimetic agents demonstrating direct vascular actions or indirect implications (e.g., alpha-1 agonists, cholinesterase inhibitors, norepinephrine, calcium channel blockers, angiotensin converting enzymes);

6. Moderate to high dose glucocorticoid administrations (i.e., ≥ 40mg prednisone or equivalent steroid dose) within the past 3 months;

7. Atherosclerosis, congestive heart failure, or history of myocardial infarction;

8. Previous diagnosis of diabetes mellitus or insulin resistance; and

9. AIS designation of C, D or E (for SCI subjects only).