The standardization of methodology and the provision of age-related reference values have been addressed for the design of and interpretation of data from a multicentre neuropathy trial. Age-related reference values were generated from 120 healthy volunteers. Vibration perception thresholds (VPT) deteriorated significantly with age (p less than 0.001). Patients were selected on the basis of age-related abnormal VPT and peroneal motor nerve conduction velocity. They were assessed at the beginning and end of a placebo run-in period (baseline data). The coefficients of variation (CV%) for VPT at the medial malleolus (16.81 per cent, n = 316) and great toe (19.23 per cent, n = 313) were lower compared to results in healthy volunteers (29.7 per cent and 20.8 per cent, respectively, n = 49). The CV% for expiratory:inspiratory (E:I) ratio (4.82 per cent, n = 215), Valsalva manoeuvre (10.84 per cent, n = 249) and 30:15 ratio (7.73 per cent, n = 292) from patients corresponded to those recorded in volunteers (7.6 per cent, n = 45 11.0 per cent, n = 49 9.5 per cent, n = 48, respectively). Most patient values for VPT at the great toe fell beyond the 95 centile line for volunteers. E:I ratio for volunteers showed a more variable relationship with age, although patient values appeared to be located below the 5 centile line for volunteer data.
Aldose reductase has been shown to be present in both autonomic and somatic nerves. Activation of this enzyme and the polyol pathway has been demonstrated in diabetic animal models to cause a range of biochemical, functional, and structural consequences that include the accumulation of sorbitol and fructose; axoglial dysjunction; paranodal demyelination; abnormalities in axonal transport, blood flow, and vascular permeability; and resistance to ischemic transmission of action potentials. These data provide an insight into the range of processes that if activated may either singly or in combination result in altered patterns of nerve function and structural alterations in diabetic neuropathy. In animal models of diabetes, it has been shown that inhibition of aldose reductase can modify these diabetes-induced changes. It is hoped that the results of large-scale controlled trials will provide clinical evidence to support these data.
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