Diabetic neuropathy clinical and experimental studies

Sammanfattning: DIABETIC NEUROPATHY - clinical and experimental studies Per Lindström The Department of Clinical Neuroscience Divisions of Neurologyand Clinical Neurophysiology Karolinska Institute and Karolinska Hospital A classification of impaired thermal sensibility is proposed, reflecting the severityof diabetic polyneuropathy in terms of its regional extension, The classificationmay be a useful tool in cross-sectional and long-term studies of patients with diabetesmellitus. Anoxic effects were studied on normal nerve in vitro, which showed that nerve conductionblock follows, not as a consequence of inhibition of Na/K ATPase, but is caused byanother ATP-dependent mechanism. This energy dependent mechanism may either be neededfor the maintenance of the resting potential or it may be directly related to thefunction of the Na-channels. The likely effect in both cases, is a reversible inactivationof Na-channels. An increased resistance to ischaemia was demonstrated in diabetic nerve in vitro(nerve conduction studies), and in diabetic patients (studied with nerve conductionand vibratory thresholds). A delayed effect of anoxia was similarly discovered innormal nerve after blocking of Na/K-ATP-ase activity with ouabain. As there is evidenceof a decreased Na/KATP-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 mediannerve conduction and vibratory thresholds in the same innervation territory. Afterthe ischaemic test the nerve action potential in the diabetic group recovered tothe 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 patientswith diabetes mellitus and 2.6 +-0.3 min in controls. A model is proposed where a decreased Na/K-ATPase activity in diabetic nerve, likein ouabain-treated normal nerve, results in an intra-axonal Na accumulation, whichin turn, through the axolemmal Na/Ca exchange, may cause an increase in intracellularthe Ca-concentration and an impaired post-ischaemic recovery. The impaired recoveryafter ischaemic injuries may contribute to the higher incidence of entrapment neuropathiesin diabetes mellitus. Osteopenia can be a complication in insulin-dependent diabetes mellitus. Overweight,common among patients with non-insulin-dependent diabetes mellitus (NIDDM), couldbe a confounding factor, counteracting the development of osteopenia. We found evidenceof osteopenia and neuropathy in the non-obese GK rat model of NIDDM. The GK rat couldthus be a suitable model for studies of reduced bone density and a possible causalrelationship between neuropathy and osteopenia in NIDDM. KEYWORDS: diabetes mellitus, neuropathy, ischaemia, sensibility, thermal sensibility,quantitative sensory testing, mammalian nerve, ouabain, osteopenia, neurophysiology,peripheral nerve, anoxia.