Metabolism and Sympathetic Function in Spinal Cord Injured Subjects

Abstract

Improved health care has increased the population of aged individualsaffected by spinal cord injury (SCI). Cardiovascular morbidity affects thisgroup earlier than able-bodied. SCI subjects exhibit decreased glucosetolerance and insulin resistance, together with increased fat mass, whichall may be risk factors for cardiovascular disease. These alterations maybe related to changes in sympathetic nervous system (SNS) function. Aspinal cord injury affecting motor and sensory nerves also decentralisesthe SNS. Centrally mediated stimulations do not activate SNS below lesionlevel, whereas stimuli in decentralised part of the body may induce anautonomic dysreflexia reaction. To evaluate metabolism and its relation tothe disturbed SNS function in spinal cord injured (SCI) subjects weinvestigated glucose tolerance, insulin sensitivity and adipose tissuemetabolism as well as SNS function in SCI (lesion level C7-T4) and controlsubjects. The hyperinsulinemic normoglycemic clamp and microdialysistechniques were used. Body composition was determined by DEXA-scanning. TheSNS function was evaluated in arm and leg by radiolabelled noradrenaline(NA) isotope dilution technique. A 24h continuous NA monitoring wasperformed in 7 SCI subjects.Following an oral glucose load the SCI group demonstrated normal glucosetolerance but impaired insulin sensitivity, while adipose tissue metabolismwas normal compared to siblings. Fat tissue mass was 66 % larger among SCIsubjects compared to weight-matched controls. Centrally mediatedsympathetic stimulation increased glycerol production in the umbilicalregion in controls but not in SCI subjects. Peripheral afferent activationresulted in increased blood pressure, decreased heart rate and reduction inmuscle and skin blood flow. Furthermore, lipolysis below lesion level wasactivated by peripheral stimulation. The 24h continuous monitoring revealedNA levels sufficient to induce lipolysis in 20 % of the registrations. LegNA spillover increased substantially following peripheral afferentstimulation, whereas central activation did not affect NA spillover in SCIsubjects. There was no difference in total body NA spillover between groupsduring baseline, in part due to lower NA spillover from legs than arms alsoamong able-bodied.In conclusion, normal regulation of lipolysis in the postabsorptive stateseems not critically dependent on SNS activation. Instead the relativeincrease in adipose tissue mass and thus the increased total body lipolyticrate should be emphasised. Peripheral activation of SNS was visualised inthe SCI group by increased transmitter spillover as well as increasedlipolysis and vasoconstriction. The diurnal registration of NA levelsindicated frequent episodes of peripheral sympathetic activation in thegroup. This may compensate for the inability of central activation of SNSand may contribute to maintain lipolysis activity and may contribute togenerate insulin resistance in the group.