Diabetic neuropathy clinical and experimental studies

A classification of impaired thermal sensibility is proposed, reflecting the severity of diabetic polyneuropathy in terms of its regional extension. The classification may be a useful tool in cross-sectional and long-term studies of patients with diabetes mellitus.

Anoxic effects were studied on normal nerve in vitro, which showed that nerve conduction block follows, not as a consequence of inhibition of Na/K ATPase, but is caused by another ATP-dependent mechanism. This energy dependent mechanism may either be needed for the maintenance of the resting potential or it may be directly related to the function of the Na-channels. The likely effect in both cases, is a reversible in activation of Na-channels.

An increased resistance to ischaemia was demonstrated in diabetic nerve in vitro (nerve conduction studies), and in diabetic patients (studied with nerve conduction and vibratory thresholds). A delayed effect of anoxia was similarly discovered in normal nerve after blocking of Na/K-ATP-ase activity with ouabain. As there is evidence of a decreased Na/K-ATP-ase activity in diabetic rat nerve, the common mechanism maybe a decreased ATP-consumption.

A delayed recovery after anoxia was demonstrated in diabetic rat nerves in vitro. A delayed recovery was also found after ischaemia in diabetic patients studying median nerve conduction and vibratory thresholds in the same innervation territory. After the ischaemic test the nerve action potential in the diabetic group recovered to the 50% level after 5.13 +-0.45 min, whereas it took less than one min in the controls. The half time for recovery of vibration threshold was 8.8 +-1.0 min in the patients with diabetes mellitus and 2.6 +-0.3 min in controls.

A model is proposed where a decreased Na/K-ATPase activity in diabetic nerve, like in ouabain-treated normal nerve, results in an intra-axonal Na accumulation, which in turn, through the axolemmal Na/Ca exchange, may cause an increase in intracellular the Ca-concentration and an impaired post-ischaemic recovery. The impaired recovery after ischaemic injuries may contribute to the higher incidence of entrapment neuropathies in diabetes mellitus.

Osteopenia can be a complication in insulin-dependent diabetes mellitus. Overweight, common among patients with non-insulin-dependent diabetes mellitus (NIDDM), could be a confounding factor, counteracting the development of osteopenia. We found evidence of osteopenia and neuropathy in the non-obese GK rat model of NIDDM. The GK rat could thus be a suitable model for studies of reduced bone density and a possible causal relationship between neuropathy and osteopenia in NIDDM.