Diabetologisk disputation

ABSTRACT DIABETIC NEUROPATHY - CLINICAL AND EXPERIMENTAL STUDIES PER LUNDSTRÖM

October 3, 1997

EFFECTS OF TOTAL PARENTERAL NUTRITION ON THE EXOCRINE AND ENDOCRINE PANCREAS - an experimental study

The Dpt of Clinical Neurosciencie, Div of Neurology and Clin Neurophysiology, Karolinska Institute and Karolinska Hosp, Sthlm

ABSTRACT
A classification of impaired thermal sensibility is proposed, reflecting the severity of diabetic polyneuropathy in terms of its regional extension, The classification may be 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 neeeded for 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 inactivation of the Na-channels.

An increased resistance to ischemia 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/KATPase activity with oubain. As there is evidence of decreased Na/KATPase activity in diabetic rat nerve the common mechanism may be a decreased ATP-consumption.

A delayed recovery after anoxia was demonstrated in diabetic rat nerves in vitro. A delayed recovery was also found after ischemia in diabetic patients, studying median nerve conduction and vibratory thresholds in the same innervation territory. After the ischemic test the nerve action potential in the diabetic group recovered to the 50 per cent level after 5.13+-0.45 min, whereas it took less than one minute 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 oubain-treated normal nerve, results in an intra-axonal Na-accumulation, which in turn, through the axolemmal Na/Ca exchange, may cause an increase in the intracellular Ca-concentration and in impaired post-ischemic recovery. The impaired recovery after ischemic injuries may contribute to the higher incidence of entrapment neuropathies in diabetes mellitus.

Osteopenia can be a complication in type 1 diabetes mellitus. Overweight, common among patients with type 2 diabetes mellitus, 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 type 2 diabetes. 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 type 2 diabetes.

Keywords: diabetes mellitus, neuropathy, ischemia, sensibility, thermal sensibility, quantitative sensory testing, mammalian nerve, oubain, osteopenia, neurophysiology, peripheral nerve, anoxia.

Fakultetsopponent Göran Solders, Avd för neurofysiologi, Huddinge sjukhus, 141 86 Huddinge. Handledare Prof Tom Brismar och prof em Ulf Lindblom, KS.

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