S119 Axonal excitability studies in diabetic neuropathy

Abstract

Diabetic polyneuropathy (DPN) is a complication of diabetes involving complex mechanisms. The introduction of automated threshold-tracking has led to a number of abnormal axonal excitability findings associated with diabetes without neuropathy (DWN) and DPN. The first abnormality described was a striking resistance to ischaemia in DWN. Superexcitability measurements showed that this ischaemic resistance was not due to a depolarized resting potential, but was related to the mean blood glucose over 24 h, indicating a rapid effect of glucose on nerve metabolism. Glycaemic control by insulin treatment in patients with diabetic neuropathy restored sensitivity to ischaemia. In contrast to DWN, patients with established DPN exhibited ‘fanning-in’ of threshold electrotonus and reduced superexcitability, indicating membrane depolarization. Using the rate of recovery of excitability following maximum voluntary contraction as a measure of electrogenic sodium pump activity, excitability measurements indicated that sodium pump function was normal in DWN, but reduced in DPN, accounting for the membrane depolarization. Further excitability studies have attempted to determine changes, other than resistance to ischaemia, that precede the development of neuropathy. Evidence that depolarization precedes neuropathy has been found both in Type 1 and Type 2 diabetics. An ischaemic cause was suggested by the finding that excitability abnormalities correlated better with vascular-related factors than with HgbA1c. Recently excitability studies have moved on from assessing pathophysiology to treatment. In Type 1 DWN, glycaemic control by continuous insulin infusion preserved membrane potential much better than comparable control by multiple injections, perhaps because glucose variability can cause microvascular dysfunction.