Large electrodes improve nerve conduction repeatability in controls as well as in patients with diabetic neuropathy.

Recording site is an important cause of variability of compound muscle action potential (CMAP) and conduction parameters, which can be reduced by using large electrodes. Repeatability of CMAP and conduction parameters of conventional and large electrodes was compared in 16 controls and 17 diabetic neuropathic patients, using defined recording sites linked to anatomical landmarks. Right-sided median, peroneal, and tibial nerves were investigated twice with a 1-2 week interval by the same examiner. Compared to previous studies, conventional electrodes on strictly defined recording sites resulted in better repeatability: intraindividual coefficients of variation (CV) varied between 4% and 14.4% for all parameters. CV of conduction parameters, not published previously, was smaller than CV of CMAP parameters. The use of large electrodes improved repeatability further: large electrodes resulted in substantially smaller CV for duration, amplitude, area, and changes of amplitude and area over a length of nerve, which were reduced by 10%, 31%, 29%, 27%, and 16%, respectively. Patients had higher CV than controls; large electrodes reduced patient CV more than control CV, resulting in less contrast between groups. Strictly defined recording sites and large electrodes improve repeatability of motor conduction studies to relevant degrees: all CMAP and conduction parameters are suitable for longitudinal studies of neuropathic patients.

Treatment of diabetic polyneuropathy with the neurotrophic peptide ORG 2766.

The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDTwarmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDTcold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy.

Determinants of vibration perception thresholds in IDDM and NIDDM patients.

The relative influence of diabetes mellitus-related and physiological factors on vibration perception thresholds was assessed in 353 patients in a hospital-based setting (173 insulin-dependent and 180 non-insulin dependent patients, aged 51.1 +/- 15.9 years) and 80 healthy controls (aged 43.3 +/- 15.2 years) employing a Biothesiometer. Vibration perception thresholds were bilaterally measured at the thumbs, medial malleoli and halluces. Sixty (17.0%) older patients had off-scale thresholds (> 50 V). As no systematic side differences were found, values of contralateral sites were averaged. Considering the effects of age, height, gender and skin temperature in controls, age accounted for 46.7 and 52.2% threshold variance at the ankles and halluces, respectively, while height explained 5.1 and 5.1%, respectively. At the thumbs, only age was of relevance. Age relationships with vibration thresholds in health did not differ from published reports at any site. In the patient group, influences of age, height, gender, skin temperature, years from diagnosis, HbAlc, serum creatinine, drop in systolic blood pressure on standing, and ankle/arm blood pressure indices were assessed for each type of diabetes. For both types, age and height again had relevant effects at the lower extremities as did age and gender at the thumbs. Skin temperature was only marginally significant at the halluces of NIDDM patients. Of the disease-related factors, HbAlc had the strongest effect: for both IDDM and NIDDM higher levels were associated with lower vibration sensitivity. Increasing disease duration led to significantly higher thresholds in IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of aldose reductase inhibitors in the management of diabetic complications. Comparison with intensive insulin treatment and pancreatic transplantation.

Recently, aldose reductase inhibitors (ARIs) have been registered in several countries for the improvement of glycaemic control. However, their efficacy is still controversial. ARIs inhibit the enhanced flux of glucose through the polyol pathway. As such, they can never be more effective than normoglycaemia, and so their potential benefits and limitations should be considered relative to the effects of prolonged euglycaemia. The clinical effects of ARIs can be put into perspective by assessing the effects of improved glycaemic control attained in randomised trials of intensive insulin treatment [such as the Diabetes Control and Complications Trial (DCCT)] and after pancreatic transplantation. Although direct comparison of these 3 interventions is hampered by differences in patient populations, duration and methods of follow-up and in the potency of ARIs, the effects of these 3 metabolic interventions and their course in time appear remarkably similar. For neuropathy, all 3 interventions induce an increase in average motor nerve conduction velocity of approximately 1 m/sec during the first months of treatment. At the same time, improvement of painful symptoms may occur. These changes probably largely represent a metabolic amelioration of the condition of the nerves. Around the second year of treatment with all 3 forms of metabolic improvement, an acceleration of nerve conduction of a similar magnitude occurs, with signs of structural nerve regeneration and some sensory recuperation. Experience with ARIs in nephropathy is still limited, but similar improvements in glomerular filtration rate and, less consistently, in urinary albumin excretion were found during short term normoglycaemia produced by all 3 forms of treatment. Comparison of a small number of studies, however, shows differences between intensive insulin regimens, pancreatic transplantation and ARIs in effects on retinopathy. Retinopathy often temporarily deteriorates in the early phases of improved glycaemic control, but this is not noted with ARIs. New microaneurysm formation was slightly reduced in a single long term study with the ARI sorbinil, but the preventive effects on the overall levels of retinopathy seemed less strong than in normoglycaemia trials of similar duration. However, the pharmacodynamic effects on inhibiting the polyol pathway differ among ARIs, and the half-life of the inhibiting effect of sorbinil may have been too short for a complete reduction of polyol pathway activity. The trials of prolonged intensive insulin therapy and pancreatic transplantation have demonstrated that very strict metabolic control must be maintained continuously for many years before a significant reduction of complications can be demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of supine blood pressure on interpretation of standing up test in 500 patients with diabetes mellitus.

The relationship between fall in blood pressure (BP) on standing and supine BP before standing up was studied in 75 healthy controls and in 500 patients with diabetes mellitus (DM) using conventional BP measurements. The influences of physiological (sex, age, height) and DM-related factors (type, duration, HbA1c-level, use of insulin, oral antidiabetic and anti-hypertensive medication) on BP-fall were assessed. The effects of using a fixed abnormality threshold and a new supine BP-related abnormality definition on interpretation of the test were determined. Highly significant relationships of BP-fall with supine BP were found in control and DM subjects. Slopes did not differ between these groups. Slopes for systolic BP-fall were steeper in type 1 than in type 2 DM patients. A forward stepwise regression procedure revealed that supine BP (explaining 24% of variance) and HbA1c (explaining 1%) had significant influences on systolic BP-fall. Diastolic supine BP explained 14% of diastolic BP-fall, age 3%, and sex 2%. Only supine BP was thus of practical relevance in explaining BP-fall. Taking supine BP into consideration affected test results: of 74 subjects with an abnormal conventional systolic BP-fall, 10 (13.5%) had been misclassified according to the new method, and 4 additional patients had been misclassified as normal. Classification changes were much larger for diastolic BP-fall (63% of conventionally abnormal results were reclassified as normal), but the range of diastolic BP is smaller than for systolic BP, meaning that the measurement error interferes with its clinical utility.(ABSTRACT TRUNCATED AT 250 WORDS)