DECREASE OF NERVE NA-ATPASE ACTIVITY IN THE PATHOGENESIS OF HUMAN DIABETIC NEUROPATHY(,K+)

A decrease in Na+,K+-ATPase activity is claimed to play a central role in the pathogenesis of electrophysiological and morphological abnorma lities that characterize the neuropathic complications in different an imal models of diabetes mellitus. The peripheral nerves from 17 patien ts with either type I or type II diabetes mellitus were studied to ass ess the importance of changes in Na+,K+-ATPase activity in chronic hum an diabetic neuropathy. Sixteen nerves from age- and sex-matched norma l individuals, and 12 nerves from non-diabetic neuropathic subjects un dergoing vascular or orthopedic surgery served as negative and positiv e controls, respectively. All specimens were processed blind. Ouabain- sensitive ATPase activity was measured by a modified spectrophotometri c coupled-enzyme assay. Standard histology, fiber teasing and electron microscopy were used to establish the normal or neuropathological pat terns of surgical material. Morphometric analysis permitted calculatio n of fiber density in each nerve specimen and correlation of this figu re with the relevant enzymatic activity. Na+,K+-ATPase activity was ap proximately 59% lower in nerves from diabetic patients than in normal controls (P < 0.01) and approximately 38% lower in nerves from non-dia betic patients with neuropathy (P < 0.01). Although nerves from both n europathic conditions had significantly fewer fibers than those from n ormal individuals (diabetic -33%, and non-diabetic -22%), the decrease s in Na+,K+ATPase activity and fiber density were not correlated only in specimens from diabetic patients (r2 = 0.096; P = 0.22). Taken toge ther with data from experimental animal models, these results suggest that the reduction in Na+,K+-ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber loss; rather, it may be an import ant factor in the pathogenesis and self-maintenance of human diabetic neuropathy.