Insulin resistance and sympathetic function in high spinal cord injury

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.1(-1) in SCI compared to 50 in siblings, while adipose tissue metabolism was normal compared tb 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 mu mol.l(-1)), The 24 h continuous monitoring revealed p-NA levels > 1.40 nmol.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.min.(-1).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.