Hypothesis: low Na/K-ATPase activity in the red cell membrane, a potential marker of the predisposition to diabetic neuropathy

Abstract

Objectives: The development of diabetic complications does not depend entirely on diabetes duration and control. Predisposing and aggravating factors, either constitutional or environmental, seem to play a role. We have previously observed that polyneuropathy is more frequent, of earlier onset, and more severe among North African insulin-dependent diabetic patients than among Europeans matched for sex, duration and control of diabetes. The Na/K-ATPase activity displays sex and ethnic differences and a dysfunction of this enzyme is probably involved in the pathogenesis of diabetic neuropathy. We have therefore postulated that the predisposition of some diabetic patients to develop a polyneuropathy could be related to a low Na/K-ATPase activity.

Design: Red cell membrane Na/K-ATPase activity was studied in European men presenting with insulin-dependent diabetes mellitus for more than 15 years. 10 patients with neuropathy were matched to 10 patients void of neuropathy on duration of diabetes and HbA1c values. Thirteen healthy European men and 13 North African men born and living in France were also studied.

Results: Na/K-ATPase activity was lower in patients with neuropathy (200 +/- 31 vs 289 +/- 42 nmol Pi.mg protein-1.h-1 mean +/- SD; p less than 0.05). When compared to that of 13 European healthy men, Na/K-ATPase activity was lower in the whole group of diabetic patients but appeared to be in the normal range for patients without neuropathy and decreased in those with neuropathy. The 13 North African healthy men had lower values than the European healthy men (227 +/- 46 vs 298 +/- 60 nmol Pi.mg protein -1.h-1, p less than 0.05).

Conclusion: Red cell membrane Na/K-ATPase activity is low in insulin dependent patients with neuropathy compared to those without neuropathy. This finding probably reflects a constitutional difference. This association could be explained if red cell and nerve membrane Na/K-ATPase abnormalities behave similarly according to glycaemic control in diabetic subjects. It is suggested that the predisposition to neuropathy of North African insulin-dependent diabetic patients may be related to lower Na/K-ATPase activity. A high level of activity of this enzyme may protect from diabetic neuropathy. This enzyme activity could be a marker of predisposition towards diabetic polyneuropathy.