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Insulin resistance and sympathetic function in high spinal cord injury
1Institute of Clinical Neuroscience, University of Göteborg, Sweden.
Insights
Spinal cord injury (SCI) is linked to cardiovascular disease risk factors like insulin resistance and increased fat mass. Peripheral sympathetic nervous system (SNS) activation in SCI may contribute to these metabolic disturbances.
Area of Science:
- Physiology
- Metabolism
- Cardiovascular Health
Background:
- Cardiovascular disease (CVD) is a leading cause of death, affecting individuals with spinal cord injury (SCI) earlier than the general population.
- Risk factors for CVD, including impaired glucose tolerance, insulin resistance, and increased fat mass, are prevalent in SCI subjects.
- These metabolic disturbances may be associated with alterations in sympathetic nervous system (SNS) function following SCI.
Purpose of the Study:
- To investigate the relationship between metabolic disturbances and altered SNS function in individuals with SCI.
- To assess glucose and adipose tissue metabolism, body composition, and SNS activity in SCI subjects.
Main Methods:
- Utilized hyperinsulinemic normoglycemic clamp and microdialysis to examine glucose and adipose tissue metabolism.
- Determined body composition using DEXA scanning.
- Evaluated SNS function via radiolabeled norepinephrine (NA) isotope dilution and 24-hour plasma NA monitoring.
Main Results:
- SCI subjects exhibited impaired insulin sensitivity and increased fat tissue mass (34% vs. 21% in controls).
- Peripheral SNS activation led to increased blood pressure, decreased heart rate, reduced blood flow, and enhanced lipolysis below the lesion level.
- 24-hour monitoring revealed frequent episodes of elevated plasma NA levels, sufficient to induce lipolysis.
Conclusions:
- Individuals with SCI show decreased insulin sensitivity and increased fat mass.
- Peripheral SNS activation, characterized by increased NA spillover, lipolysis, and vasoconstriction, is evident in SCI.
- These findings suggest that peripheral SNS activation may compensate for impaired central SNS function, contributing to lipolysis and insulin resistance in SCI.
Objective:
Cardiovascular disease (CVD) is today one of the main causes of death and affects spinal cord injured (SCI) earlier than able-bodied. Risk factors for CVD, such as decreased glucose tolerance, insulin resistance and increased fat mass, are all reported among SCI subjects and may be related to changes in sympathetic nervous system (SNS) function.
Methods:
In order to test our hypothesis of a relationship between metabolic disturbances and alterations in SNS function, glucose and adipose tissue metabolism was investigated by the hyperinsulinaemic normoglycaemic clamp and microdialysis. Body composition was determined by DEXA-scanning. The SNS function was evaluated in total body as well as above and below lesion level by radiolabelled noradrenaline (NA) isotope dilution technique. A 24 h continuous plasma-NA monitoring was performed in seven SCI subjects.
Results:
Following an oral glucose load the SCI group demonstrated normal glucose tolerance but impaired insulin sensitivity with a maximum insulin value of 83 mU x l(-1) in SCI compared to 50 in siblings, while adipose tissue metabolism was normal compared to siblings. Fat tissue mass constituted 34% of body mass in SCI group compared to 21% in weight-matched controls. Peripheral afferent activation resulted in increased blood pressure, decreased heart rate and reduction in muscle and skin blood flow. Furthermore, lipolysis below lesion level was activated by peripheral stimulation (89-135 micromol x l(-1)). The 24 h continuous monitoring revealed p-NA levels > 1.40 nmol x l(-1) sufficient to induce lipolysis in 20% of the registrations. NA spillover below lesion level increased substantially following peripheral afferent stimulation (0.06-0.90 pmol x min x (-1) x 100 g(-1)), whereas spillover above lesion level increased during central activation.
Conclusions:
We found signs of decreased insulin sensitivity and increased fat tissue mass. Peripheral activation of SNS was visualised in the SCI group by increased transmitter spillover as well as increased lipolysis and vasoconstriction. The diurnal registration of NA levels indicated frequent episodes of peripheral sympathetic activation in the group. This may compensate for the inability of central activation of SNS and may contribute to maintain lipolysis activity as well as to generate insulin resistance in the group.