Transmembrane electron transfer in diabetic nephropathy.
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OBJECTIVE: Erythrocytes (red blood cells [RBCs]) reduce extracellular ferricyanide by transmembrane transfer of reducing equivalents involving ascorbate recycling. RESEARCH DESIGN AND METHODS: Because ascorbate regeneration is glutathione (GSH) dependent and cells may be depleted of GSH in diabetes, we measured RBC GSH, plasma sulfhydryl (SH) groups, and RBC-mediated ferricyanide reduction in 30 type 1 diabetic patients (age 34 +/- 10 years, disease duration 20 +/- 8 years; no complications, n = 10; retinopathy, n = 10; nephropathy, n = 10), their 36 siblings (age 39 +/- 13 years), and matched healthy volunteers. RESULTS: Fasting plasma glucose was 15 +/- 7 mmol/l (vs. 5 +/- 1 in control subjects, P < 0.001), HbA1c 8.4 +/- 1.5% (vs. 5.4 +/- 0.3, P < 0.001), GSH 0.76 +/- 0.12 mg/ml packed RBCs (vs. 0.88 +/- 0.18, P < 0.01), SH groups 401 +/- 72 micromol/l (vs. 444 +/- 56, P < 0.05), and ferrocyanide generation 15 +/- 5 micromol/ml RBC per h (vs. 13 +/- 5, NS). In comparison with 10 normoalbuminuric diabetic subjects with retinopathy, 10 patients with diabetic nephropathy had similar fasting plasma glucose, HbA1c, and SH groups; lower RBC GSH (0.73 +/- 0.08 vs. 0.85 +/- 0.11, P < 0.05); and higher ferrocyanide generation (18 +/- 4 vs. 14 +/- 5, P < 0.05). The 10 patients without complications differed from the 10 healthy volunteers in glycemic control and RBC GSH. RBC electron transfer correlated with plasma lactate (r = 0.8, P = 0.01) only in the uncomplicated group. No difference was detected between siblings and healthy control subjects or between siblings of subjects in the nephropathy and retinopathy groups. Among diabetic patients, the rate of ferrocyanide generation was associated with urinary albumin excretion, plasma creatinine, and SH groups (multiple r = 0.6, P < 0.01). CONCLUSIONS: Transmembrane electron transfer is selectively increased in diabetic nephropathy, where RBC GSH is also depleted. The abnormality is peculiar to the nephropathy group and not contributed by familial or hereditary components because the electron flow was normal in siblings. The close relationship between cytosolic NADH and RBC electron transfer observed in diabetic patients without complications seems to be lost in the microangiopathic patients. Whereas patients with retinopathy alone still had normal activity of the RBC-reducing system, patients with nephropathy showed significantly increased activity, unrelated to metabolic parameters or plasma lactate concentration and correlated with renal function parameters and plasma thiols. (+info)
Assessment of autonomic function in patients with acute myocardial infarction or diabetes mellitus by heart rate variability, ventricular late potential and QT dispersion.
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To compare the efficacy and sensitivity of heart rate variability (HRV), QT dispersion (QTd) and ventricular late potential (VLP) examination in judging autonomic function. Thirty three patients with acute myocardial infarction (AMI) and 33 patients with diabetes mellitus (DM), all of whom were diagnosed with autonomic neuropathy determined by a standard test of cardiovascular autonomic function, were examined by HRV (timing domain methods), QTd and VLP. Thirty three normal individuals served as controls. The mean SD of the normal R-R interval (SDNN) in both the AMI and DM groups was significantly less than that in the control group (p< 0.01); and of course, the QTd of these groups was significantly greater than that of the controls (p< 0.01). The VLP positive rate of the AMI and DM groups were much higher than that of the control group (p< 0.001). SDNN was shown to be significantly negatively correlated to QTd (r= -0.45); and significantly negatively correlated to VLP (r= -0.47); QTd was shown to be positively, though not significantly, correlated to VLP (r=0.48). QTd could be looked as sieving index; HRV could be looked as routine examination of cardiovascular autonomic function, especially SDNN; the combination of HRV and VLP could improve the accuracy of diagnosis. (+info)
Evaluation of postural stability in elderly with diabetic neuropathy.
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OBJECTIVE: The objective of this study was to compare clinical and biomechanical characteristics of balance in diabetic polyneuropathic elderly patients and normal age-matched subjects. RESEARCH DESIGN AND METHODS: Fifteen elderly with distal neuropathy (DNP) and 15 healthy age-matched subjects were evaluated with the biomechanical variable COP-COM, which represents the distance between the center of pressure (COP) and the center of mass (COM). Measurements were taken in the quiet position with a double-leg stance, in eyes-open (EO) and eyes-closed (EC) conditions. Subjects were also assessed with clinical balance evaluations. RESULTS: The COP-COM variable was statistically significantly larger in the DNP group than in the healthy group in anterior-posterior (A/P) and medial-lateral (M/L) directions. Furthermore, the DNP group showed statistically significantly larger amplitudes of the COP-COM variable without vision. The severity of the neuropathy, as quantified using the Valk scoring system, was correlated with COP-COM amplitude in both directions. CONCLUSIONS: Evaluation of the postural stability of an elderly diabetic population using the COP-COM variable can detect a very small change in postural stability and could be helpful in identifying elderly with DNP at risk of falling. (+info)
Gabapentin inhibits excitatory synaptic transmission in the hyperalgesic spinal cord.
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In the present study we tested the effects of the antihyperalgesic compound gabapentin on dorsal horn neurones in adult spinal cord. Slices were taken from control and hyperalgesic animals suffering from streptozocin-induced diabetic neuropathy. At concentrations up to 100 microM, bath application failed to affect the resting membrane properties of dorsal horn neurones taken from both groups of animal. In contrast, bath application of gabapentin dramatically reduced the magnitude of the excitatory postsynaptic current (EPSC) in neurones taken from hyperalgesic animals without altering the magnitude of the EPSC in control animals. Using a paired pulse stimulation protocol, together with analysis of miniature EPSC's, it was possible to demonstrate that gabapentin mediated these effects via a pre-synaptic site of action. (+info)
The usefulness of minimal F-wave latency and sural/radial amplitude ratio in diabetic polyneuropathy.
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The possibility of whether minimal F-wave latency and a simple ratio between the sural and superficial radial sensory response amplitudes may provide a useful electrodiagnostic test in diabetic patients was investigated in this report. To evaluate the diagnostic sensitivity of minimal F-wave latency, the Z-scores of the minimal F-wave latency, motor nerve conduction velocity (MCV), amplitude of compound muscle action potentials (CMAP), and distal latency (DL) of the median, ulnar, tibial, and peroneal nerve were compared in 37 diabetic patients. For the median, ulnar, and tibial nerves, the Z scores of the minimal F-wave latency were significantly larger than those of the MCV. In addition for all four motor nerves, the Z scores of the minimal F-wave latency were significantly larger than those for the CMAP amplitude. Furthermore, 19 subjects showing abnormal results in the standard sensory nerve conduction study had a significantly lower sural/radial amplitude ratio (SRAR), and 84% of them had an SRAR of less than 0.5. In conclusion, minimal F-wave latency and the ratio between the amplitudes of the sural and superficial radial sensory nerve action potential are sensitive measures for the detection of nerve pathology and should be considered in electrophysiologic studies of diabetic polyneuropathy. (+info)
Corneal structure and sensitivity in type 1 diabetes mellitus.
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PURPOSE: Corneal wound healing is impaired in diabetic cornea. The purpose of this study was to examine patients with type 1 diabetes mellitus for changes in corneal morphology and to correlate corneal sensitivity, subbasal nerve morphology, and degree of polyneuropathy with each other. METHODS: Forty-four eyes of 23 patients with diabetes and nine control eyes were included. Corneal sensitivity was tested with a Cochet-Bonnet esthesiometer (Luneau, Paris, France), and corneal morphology and epithelial and corneal thickness were determined by in vivo confocal microscopy. The density of subbasal nerves was evaluated by calculating the number of long subbasal nerve fiber bundles per confocal microscopic field. The degree of polyneuropathy was evaluated using the clinical part of the Michigan Neuropathy Screening Instrument (MNSI) classification, and retinopathy was evaluated using fundus photographs. RESULTS: A reduction of long nerve fiber bundles per image was noted to have occurred already in patients with mild to moderate neuropathy, but corneal mechanical sensitivity was reduced only in patients with severe neuropathy. Compared with control subjects the corneal thickness was increased in patients with diabetes without neuropathy. The epithelium of patients with diabetes with severe neuropathy was significantly thinner than that of patients with diabetes without neuropathy. CONCLUSIONS: Confocal microscopy appears to allow early detection of beginning neuropathy, because decreases in nerve fiber bundle counts precede impairment of corneal sensitivity. Apparently, the cornea becomes thicker in a relatively early stage of diabetes but does not further change with the degree of neuropathy. A reduction in neurotrophic stimuli in severe neuropathy may induce a thin epithelium that may lead to recurrent erosions. (+info)
QT interval prolongation and mortality in type 1 diabetic patients: a 5-year cohort prospective study. Neuropathy Study Group of the Italian Society of the Study of Diabetes, Piemonte Affiliate.
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OBJECTIVE: The aim of the study was to assess the relationship between QT interval prolongation and mortality in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Data on survival after 5 years were obtained from 316 of 379 patients (83.3%) who took part in a study on the prevalence of diabetic neuropathy and QT interval prolongation. RESULTS: Mortality at 5 years was 6.32%. Patients who survived were significantly younger (P = 0.04), had a shorter duration of diabetes (P = 0.01), had lower systolic (P = 0.004) and diastolic (P = 0.03) blood pressure levels, and had a shorter QT interval corrected for the previous cardiac cycle length (QTc) (P = 0.000005) than subjects who died. In univariate analysis, patients had a higher risk of dying if they had a prolonged QTc (odds ratio [OR] 20.14 [95% CI 5.7-70.81) or if they were affected by autonomic neuropathy (3.55 [1.4-8.9]). QTc prolongation was the only variable that showed a significant mortality OR in multivariate analysis (24.6 [6.51-92.85]; P = 0.0000004). CONCLUSIONS: This is the first cohort-based prospective study indicating that QTc prolongation is predictive of increased mortality in type 1 diabetic patients. (+info)
Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin.
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BACKGROUND: High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function. METHODS: Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined. RESULTS: We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation. CONCLUSION: This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients. (+info)