Femoral versus peroneal neuropathy in diabetic children and adolescents--relationships to clinical status, metabolic control and retinopathy

In order to estimate the prevalence of diabetic neuropathy in proximal and distal peripheral nerves, femoral and peroneal motor conduction was evaluated in 61 diabetic children, adolescents and young adults whose type 1 diabetes had become clinically apparent before the age of 14 years. Femoral motor nerve conduction velocity (FMNCV) in diabetic patients (63.8 +/- 10.4 m/sec) was not significantly different from FMNCV in control subjects (65.6 +/- 7.1 m/sec). By contrast, peroneal motor nerve conduction velocity (PMNCV) in diabetic patients (50.2 +/- 6.9 m/sec) was significantly lower than in controls (54.1 +/- 3.5 m/sec). Distal motor weakness, sensory deficit and absent Achilles reflexes were strongly correlated to impaired motor conduction in peroneal and also in femoral nerve. Peroneal nerve abnormality was negatively correlated with HbA1 levels, while femoral nerve abnormality was positively correlated with the presence of retinopathy. This discrepancy is not fully understood. Age and duration of diabetes were unrelated to femoral or peroneal motor nerve conduction velocity. Our data emphasize the frequent occurrence of subclinical proximal neuropathy in diabetic children and adolescents.     

Exercise training can modify the natural history of diabetic peripheral neuropathy

BACKGROUND: Diabetes is the most important cause of peripheral neuropathy (DPN). No definitive treatment for DPN has been established, and very few data on the role of exercise training on DPN have been reported. AIM OF THE STUDY: We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients. PARTICIPANTS AND METHODS: Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled, randomized, and subdivided in two groups: 31 diabetic participants [15 f, 16 m; 49+/-15.5 years old; body mass index (BMI)=27.9+/-4.7], who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50% to 85% of the heart rate reserve (exercise group: EXE), and a control group of 47 diabetic participants (CON; 24 f, 23 m; 52.9+/-13.4 years old; BMI=30.9+/-8.4). Vibration perception threshold (VPT), nerve distal latency (DL), nerve conduction velocity (NCV), and nerve action potential amplitude (NAPA) in the lower limbs were measured. RESULTS: We found significant differences on Delta (delta) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period (P<.001, for both). The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group (17% vs. 0.0%, P<.05, and 29.8% vs. 6.45%, P<.05, respectively). In addition, the percentage of diabetic patients who developed increased VPT (25 V) during the study was significantly higher in the CON than the EXE group (21.3% vs. 12.9%, P<.05). Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups (P<.05); no significant change in Malleolus VPT between the two groups occurred. CONCLUSIONS: This study suggests, for the first time, that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN.     

Phrenic nerve function in type 1 diabetic patients with diaphragm weakness and peripheral neuropathy.

Phrenic nerve latency was studied in 14 male type 1 diabetic patients with impaired diaphragm function and in 14 healthy control subjects. The diabetics showed significantly decreased values regarding inspiratory vital capacity and forced volume in 1 s compared with the control subjects. All other lung function parameters were similar in both groups. Although motor and sensory nerve conduction studies provided evidence for peripheral neuropathy in all patients, phrenic nerve latencies turned out to be normal. These results rule out a neuropathic disorder of the phrenic nerve. Thus, impaired diaphragm function in type 1 diabetic patients is not caused by phrenic neuropathy.     

糖尿病周围神经病700例临床与神经电生理分析

目的探讨糖尿病周围神经病的临床和电生理特点,明确电生理检查的诊断价值。方法对700患者进行感觉和运动神经传导测定,240例患者进行针极肌电图测定。结果507例(724%)患者电生理检查异常,其中307例(606%)为多发性周围神经病,74例(146%)为腕管综合征;感觉神经传导异常程度重于运动神经,波幅的下降程度较传导速度减慢明显,下肢重于上肢(P<005)。仅有46%的患者针极肌电图异常而神经传导正常。结论糖尿病周围神经病的临床和电生理表现均以感觉神经受损为主;电生理检查有助于发现临床病变,但并非所有患者均能发现电生理异常;建议不将针极肌电图进行糖尿病周围神经病的筛查作为常规使用。     

Heightened norepinephrine-mediated vasoconstriction in type 2 diabetes

Adrenergic responsiveness (AR) appears to be increased in subjects with diabetes, but measurement of arterial AR in normotensive people with type 2 diabetes mellitus has not been previously reported. We sought to determine whether, compared with control subjects, there is increased arterial AR in type 2 diabetes mellitus and its relationship to the level of systemic sympathetic nervous system activity (SNSa). We studied 15 type 2 diabetic subjects aged 57 +/- 3 years without hypertension or clinical signs of autonomic neuropathy and 13 age-matched control subjects aged 55 +/- 2 years. We assessed vascular alpha-AR by measuring forearm blood flow (FABF) by venous occlusion plethysmography during intrabrachial artery norepinephrine (NE) and phentolamine infusions, as well as arterial plasma NE levels and the extravascular NE release rate (NE2) derived from 3H-NE kinetics, as estimates of systemic SNSa. The vasoconstricting effect of NE during intrabrachial artery NE infusion was greater in type 2 diabetes compared with control subjects (P = .02). The vasodilating effect of phentolamine was greater in type 2 diabetics compared with control subjects (P = .05), suggesting increased endogenous arterial alpha-adrenergic tone. Arterial plasma NE levels (control v type 2, 1.8 +/- 0.10 v 1.84 +/- 0.14 nmol/L, P = .86) and NE2 (control vtype 2, 11.8 +/- 1.54 v 13.3 +/- 0.89 nmol/min/m2, P = .39) were similar in the two groups. In summary, in type 2 diabetes compared with control subjects, (1) the vasoconstriction response to intraarterial NE is greater, (2) plasma NE and NE2 are similar, suggesting similar levels of systemic SNSa, and (3) arterial alpha-adrenergic tone is greater. We conclude that subjects with type 2 diabetes demonstrate inappropriately increased alpha-AR for their level of systemic SNSa.     

Influence of glucoregulation with continuous subcutaneous insulin infusion on nerve conduction velocity and beat to beat variation in diabetics

Limited and contrasting data are available on the relationship between metabolic control and diabetic neuropathy. In eight type I diabetics peripheral and autonomic neuropathy were studied, first in conditions of poor metabolic control and then after one and three months during which an improved control of glycemic levels had been obtained by continuous subcutaneous insulin infusion. Autonomic neuropathy was investigated by evaluating beat to beat variation during deep breathing; peripheral neuropathy by measuring maximum motor conduction velocity of peroneal and median nerves and sensory conduction velocity of median nerve. Our data showed significant improvement of motor conduction velocity in both nerves studied, whilst sensory conduction velocity did not show any significant variation. The changes observed in beat to beat variation in five subjects with initially abnormal scores might reflect an improvement in autonomic nervous function, even if long-term studies are needed.     

The electrophysiological findings of subclinical neuropathy in patients with recently diagnosed type 1 diabetes mellitus

To assess the prevalence of subclinical neuropathy within the first year of type 1 diabetes mellitus, 30 patients and 14 healthy subjects have been studied prospectively. The patients whose diabetes duration was longer than 1 year have been excluded from the study. Control group consisted of healthy volunteers. Subjective neuropathy symptoms, neurological examination, and electrophysiological findings were evaluated. All patients were clinically asymptomatic. At least two abnormal independent neurophysiological nerve parameters, which were required as the criterion of the peripheral nervous system subclinical involvement, were found as in 96.6% of diabetic patients in the first years. The percentages of abnormal electrophysiological parameters in different motor and sensory nerves were 86.7% in sural nerve, 83.3% in peroneal motor nerve, 73.3% in posterior tibial motor nerve, 66.7% in median motor nerve, 63.3% in ulnar motor nerve, 60% in median sensory nerve, and 46.7% in ulnar sensory nerve. While distal motor latency, F conduction time, and minimum F latency were the most frequent abnormal parameters in the upper extremity electrophysiological study; conduction velocity, minimum and mean F latencies, F conduction time were the most frequent abnormal parameters in the lower extremity. In all sensory nerve conduction studies, the most frequent abnormal parameter was the onset latency. In the autonomic sympathetic nerve electrophysiological study, plantar SSR latency was found significantly longer than the control group. In the lower extremity generally somatic motor fibres, sensory large fibres and sympathetic autonomic nerve fibres were found to be more affected. There is a correlation between HbA1c levels and nerve conduction velocity in posterior tibial and peroneal nerves. However, upper extremity nerve conduction dysfunction was not correlated with HbA1c value. Neither the duration of disease nor the age of the subject correlated with the nerve dysfunction.     

C-peptide improves autonomic nerve function in IDDM patients

Summary In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during a 3-h i. v. infusion of either C-peptide (6 pmol · kg^–1 · min^–1) or physiological saline solution in a double-blind study. Plasma C-peptide concentrations increased from 0.11±0.02 to 1.73±0.04 nmol/l during C-peptide infusion. Clinical neurological examination quantitative sensory threshold evaluations and nerve conduction measurements failed to detect significant changes between C-peptide and saline study periods. Respiratory heart rate variability increased significantly from 13±1 to 20±2% during C-peptide infusion (p<0.001), reaching normal values in five of the subjects; control studies with saline infusion did not alter the heart rate variability (basal, 14±2; saline, 15±2%). A reduced brake index value was found in seven patients and increased significantly during the C-peptide infusion period (4.6±1.0 to 10.3±2.2%, p<0.05) but not during saline infusion (5.9±2 to 4.1±1.1%, NS). It is concluded that short-term (3-h) infusion of C-peptide in physiological amounts may improve autonomic nerve function in patients with IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - VT vibration perception threshold - CV conduction velocity - DL distal latency - CMAP compound action potential - S sensory amplitude - E/I ratio expiration/inspiration ratio     

Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin.

The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease.     

The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cochlear dysfunction in type 2 diabetes: a complication independent of neuropathy and acute hyperglycemia

The effects of type 2 diabetes on evoked otoacoustic emissions (e-OAEs) elicited by clicks in subjects with normal hearing and the involvement of the central (CNS) and peripheral nervous system and acute hyperglycemia were investigated. In study 1, 110 type 2 diabetic patients and 106 control subjects matched for age and gender were investigated by e-OAEs. Central and peripheral neuropathy were evaluated respectively by auditory brainstem responses (ABRs) and according to San Antonio Consensus Conference criteria. In study 2, 10 healthy and 10 type 2 diabetic men matched for age, all with normal e-OAEs, underwent a 5-hour hyperglycemic clamp study. e-OAE tests were performed before and during the hyperglycemic clamp. In study 1, e-OAEs were impaired in 51.8% (57 of 110) of the diabetic subjects, in comparison to 4.7% (five of 106) of the control group (P < .0001). Diabetics with impaired e-OAEs (e-OAEs-), in comparison to those with normal e-OAEs (e-OAEs+), were older (51.0+/-5.8 v 45.1+/-6.0 years, P < .001), had diabetes longer (11.5+/-4.4 v 7.0+/-3.9 years, P < .001), achieved poorer metabolic control as judged by hemoglobin A1c ([HbA1c] 6.9%+/-0.4% v 6.5%+/-0.3%, P < .001), and had more peripheral neuropathy (46% v 23%, P < .02). No difference was observed between e-OAEs- and e-OAEs+ subjects for retinopathy or nephropathy. Nevertheless, when the duration of diabetes was corrected by multiple regression analysis, the correlation between sensorineural damage and peripheral neuropathy lost significance (P = .12). Diabetic groups (e-OAEs+ and e-OAEs-) showed greater latency in waves I, III, and V and greater interwave latency for waves I to V than the control group, but there was no significant difference in ABRs between e-OAEs+ and e-OAEs- subjects. In study 2, there were no significant changes in e-OAE intensities compared with basal values during the entire hyperglycemic clamp in either type 2 diabetic or control subjects. No difference was observed between the two groups at each time of the clamp. Thus, type 2 diabetic subjects show a higher rate of compromised e-OAEs than healthy individuals. The e-OAE dysfunction does not associate with either an injury to the auditory nervous pathway or diabetic microvasculopathy. The apparent interference of peripheral neuropathy in e-OAEs loses significance when corrected for the duration of diabetes.     

Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function

Summary We have studied the temporal relationship of plasma von Willebrand Factor (vWF), a marker of endothelial damage, with the development of complications in 63 young diabetic patients (56 of whom were insulin-dependent) who took part in a prospective study. Results are presented from baseline to follow-up. In the group as a whole, no significant changes were found in any autonomic function tests, temperature discrimination threshold or nerve conduction velocities. Median motor and peroneal latency were significantly increased, while median motor, peroneal motor and sural sensory potentials were significantly decreased at follow-up compared with baseline (p<0.001). There was a significant fall in mean plasma vWF antigen and ristocetin co-factor activity in the entire group. Within the group, we identified eight patients whose peroneal motor and sural sensory conduction velocities had decreased by over 2 ms^–1. In these patients (Group A), baseline vWF antigen and activity were significantly higher than in the rest of the patients (Group B), (p=0.04) and vWF antigen was still significantly higher after 3 years (p=0.02). There were no differences between the groups in incidence of retinopathy, urinary albumin excretion rate or macrovascular disease. To assess the influence of glycaemic control on vWF, we first compared a matched group (C) of diabetic patients with similar HbA₁ to that of group A, but with normal nerve conduction velocities: vWF was still significantly higher in group A compared with group C (p=0.02). Furthermore, hierarchical regression showed that vWF predicted deteriorating nerve function independently of glycaemic control or the type of diabetes. Endothelial dysfunction may be associated with development of peripheral neuropathy in young diabetic patients.Abbreviations Standardized regression coefficient - B unstandardized regression coefficient - IQR inter-quartile ranges - MMCV median motor nerve conduction velocity - MSCV median sensory nerve conduction velocity - PMCV peroneal motor nerve conduction velocity - SSCV sural sensory nerve conduction velocity - UAER urinary albumin excretion rate - vWF von Willebrand factor - vWFact von Willebrand factor activity - vWFag von Willebrand factor antigen - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus     

Presence of carpal tunnel syndrome in diabetics: Effect of age,sex, diabetes duration and polyneuropathy

Summary Common thought is that diabetic neuropathy is a predisposing factor to entrapment syndromes. Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy; females and old people are most frequently affected (Comi et al., 1978). Prevalence of CTS in diabetics and associated risk factors were studied in 401 patients (208 males and 193 females) with insulin-dependent and non-insulin-dependent diabetes using electrophysiological techniques. Median nerve sensory and motor conduction velocity, ulnar and peroneal nerve motor conduction velocity and sural nerve sensory conduction velocity were investigated in all patients. Diagnostic criteria for CTS were the presence of delayed median nerve sensory conduction velocity in the palm-wrist tract and of increased distal motor latency. Polyneuropathy was defined by slowing-down of conduction velocity in two or more nerves. Forty-five patients (11.2%), 36 females and 9 males, showed CTS. One-hundred-sixty-eight patients (41.8%), 74 females and 94 males, were suffering from peripheral neuropathy. The strongest risk factors for CTS, in order of importance, were: female sex, older age and presence of neuropathy. Polyneuropathy but not CTS was related to duration of diabetes.     

Possible contribution of adipocytokines on diabetic neuropathy

Neuropathy is one of the typical features of chronic complications of diabetes mellitus. Recent analyses indicate that subjects with impaired glucose tolerance (IGT) already have disturbance of peripheral nerve function. To test the role of adipocytokines, that tend to be abnormal in IGT subjects, on diabetic neuropathy, we analyzed the relationship between plasma adipocytokine levels (TNFalpha, adiponectin, and leptin) and nerve conduction velocity in 105 type 2 diabetic subjects (M/F = 66/39, age = 60.8 +/- 11.8 years, BMI = 24.7 +/- 5.0kg/m2). Adipocytokines were measured by ELISA, and motor conduction velocity (MCV) and sensory conduction velocity (SCV) in median, ulnar, and tibial nerve were measured by electrical stimulation. Motor conduction velocity and SCV were corrected by age to be 1.0 as the normal value, and the average of three nerves were used to be the representative value. Relationship between corrected MCV or corrected SCV as a dependent variable and the duration of diabetes, HbA1C, BMI, TNFalpha, adiponectin, and leptin concentrations as independent variables were analyzed by multiple regression. Duration of diabetes and HbA1C were highly related with both corrected MCV (P < 0.02 and P < 0.001) and SCV (P < 0.02 and P < 0.05) by this analysis. Only corrected SCV was related significantly with TNFalpha (P < 0.05), and close to significantly with leptin (P = 0.059) concentrations. These results indicate that increased plasma glucose levels and duration of diabetes are the major factors that modulate diabetic neuropathy. However, nerve function may be affected by plasma cytokine levels like TNFalpha, and this effect was more significant on sensory nerves than motor nerves. The present results suggest that adipocytokines may play a role not only on angiopathy but also on neuropathy in diabetics.     

The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial

Twenty-two patients with distal diabetic polyneuropathy confirmed both clinically and by objective nerve function studies, completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid on their neuropathy. Patients received either 360 mg gamma-linolenic acid (12 patients) or indistinguishable placebo capsules (10 patients) for 6 months. All patients were assessed at the beginning and end of the study period by neuropathy symptom and sign scoring, motor and sensory nerve conduction studies, and thermal threshold measurements. When compared with the placebo group, patients on gamma-linolenic acid showed statistically significant improvement in neuropathy symptom scores (p less than 0.001), median nerve motor conduction velocity (p less than 0.01) and compound muscle action potential amplitude (p less than 0.01), peroneal nerve motor conduction velocity (p less than 0.05) and compound muscle action potential amplitude (p less than 0.05), median (p less than 0.01) and sural (p less than 0.001) sensory nerve action potential amplitude and ankle heat threshold (p less than 0.001) and cold threshold (p less than 0.01) values. gamma-Linolenic acid therapy might have a useful role in the prevention and treatment of distal diabetic polyneuropathy.     

The relationship between sural nerve morphometric findings and measures of peripheral nerve function in mild diabetic neuropathy.

The morphological findings in sural nerve biopsy specimens from 15 diabetic patients with mild neuropathy were compared with control biopsies from eight non-neuropathic, non-diabetic subjects, and correlations were sought with electrophysiological studies and quantitative sensory tests for vibration, thermal, and current perception thresholds. Myelinated fibre density was reduced compared with control biopsies (4042 +/- 2090 (+/- SD) vs 6800 +/- 1100 mm-2; p less than 0.01). A strong correlation existed between myelinated fibre density and sural sensory conduction velocity (r = 0.84, p less than 0.001), sural action potential amplitude (r = 0.74, p less than 0.001), peroneal motor conduction velocity (r = 0.58, p less than 0.02), and median sensory amplitude (r = 0.64, p less than 0.01) but there was no correlation between myelinated fibre density and any quantitative sensory test. We conclude that conventional electrophysiological tests in the lower limb are reliable surrogate measures for structural abnormalities in early diabetic neuropathy.     

Morphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy

Summary Nerve biopsies were obtained from 27 patients with diabetic neuropathy. All had a symmetric distal sensory and autonomic neuropathy or a purely sensory neuropathy. Mean age was 39.8 years (range 23–57 years). Two patients had Type 2 (non-insulin-dependent) diabetes mellitus and the remainder Type 1 (insulin-dependent) diabetes. Morphometric observations on endoneurial capillaries were compared with results from organ donor control cases and from patients with type 1 hereditary motor and sensory neuropathy. The area of the lumen of the capillaries did not differ between the three groups. The area occupied by the capillary endothelial cells in transverse section and the number of endothelial cell nuclei were increased both in the patients with diabetic neuropathy and hereditary motor and sensory neuropathy, as was the thickness of the surrounding basal laminal zone. Closure of endoneurial capillaries in diabetic neuropathy, reported in another study, was not confirmed. Capillary density and nearest-neighbour distances were similar in the diabetic and organ donor control cases. Capillary density was reduced in the patients with hereditary motor and sensory neuropathy, this being related to increased fascicular area consequent upon the presence of hypertrophic changes. The presence of thickening of the pericapillary basal laminal zone and endothelial cell hyperplasia both in diabetic and hereditary motor and sensory neuropathy, the latter being a neuropathy in which a vascular basis can be discounted, makes it difficult to use such changes as an argument favouring a vascular cause for diabetic neuropathy. There were differences in the basal laminal zone between the diabetic and hereditary motor and sensory neuropathy cases suggesting that the reduplicated basal lamina was more persistent in the diabetic patients.     

Effects of epalrestat,an aldose reductase inhibitor,on diabetic peripheral neuropathy in patients with type 2 diabetes,in relation to suppression of Nɛ-carboxymethyl lysine

ObjectiveWe investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes.MethodsA total of 38 type 2 diabetic patients (22 men and 16 women; mean±S.E.M. age 63.3±1.0 years; duration of diabetes 9.6±0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum N^?-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean±S.E.M. duration of diabetes 8.2±0.7 years) as control (C group).ResultsThe EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (?0.18±0.13 mU/ml in the EP group vs. +0.22±0.09 mU/ml in the C group, P<.05) after 1 year.ConclusionsEpalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs.     

Subclinical nerve dysfunction in children and adolescents with IDDM

Summary The purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of diabetes of more than 3 years, and 128 age-matched healthy control subjects underwent bilateral studies of median, peroneal, and sural nerves. Presence of diabetes lowered motor conduction velocity (p<0.0001), sensory conduction velocity (p<0.0001) and sensory nerve action potential (p<0.05) in all examined nerves. The mean change in conduction velocity induced by diabetes was –4.8 m/s in the peroneal nerve, –3.3 m/s in the median motor nerve, –2.6 m/s in the sural nerve and –2.4 m/s in the median sensory nerve. Fifty-seven percent of the patients had abnormal conduction (values outside 95% predictive interval) which was seen most often in the motor nerves, especially in the peroneal nerve (41%) followed by the median nerve (24%). In multiple regression analysis, long-term poor metabolic control and increased body length correlated with nerve dysfunction identified in most examined parameters. Three patients had signs or symptoms suggestive of neuropathy. It is concluded that despite modern multiple insulin injection therapy, with reasonably good metabolic control, nerve dysfunction is still common in children and adolescents with insulin-dependent diabetes mellitus. Risk factors are increased height and long-term poor metabolic control.Abbreviations IDDM Insulin-dependent diabetes mellitus - MIT multiple insulin injection therapy - MCV motor nerve conduction velocity - CMAP compound muscle action potential - DML distal motor latency - SCV sensory nerve conduction velocity - SNAP sensory nerve action potential     

Sympathetic mediated vasomotion and skin capillary permeability in diabetic patients with peripheral neuropathy

AIMS/HYPOTHESIS: A loss of sympathetic function could lead to changes in capillary fluid filtration in diabetic patients. We investigated whether a decreased sympathetically mediated vasomotion in the skin in diabetic patients with peripheral neuropathy is associated with an abnormal capillary leakage. METHODS: Three matched groups were studied: 18 diabetic patients with documented peripheral neuropathy (DN), 18 diabetic patients without peripheral neuropathy (D), and 18 healthy control subjects (C). Sensory and motor nerve function of the distal extremities were assessed by standard neurography, and expressed in a sensory-motor nerve function score. Sympathetic vasomotion of the skin microcirculation was assessed by determining the power of blood flow variability in the low-frequency (0.02-0.14 Hz) band by spectral analysis of laser Doppler flowmetry at the median ankle. Skin capillary leakage was evaluated by sodium fluorescein videodensitometry at the same site of the foot. RESULTS: Sympathetically mediated vasomotion of the foot skin microcirculation was lower in diabetic patients with documented peripheral neuropathy compared with diabetic patients without peripheral neuropathy and control subjects (p<0.001). Capillary sodium fluorescein leakage was larger in 18 diabetic patients with documented peripheral neuropathy than in diabetic patients without peripheral neuropathy (p<0.02) and C (p<0.005). Multiple regression analysis disclosed that a reduced sympathetically mediated vasomotion, together with a lower sensory-motor nerve function score, independently contributed to the variance in sodium fluorescein leakage, for 30% (p<0.001) and 17% (p<0.01), respectively. CONCLUSIONS: A loss of sympathetic tone, apart from sensory-motor nerve dysfunction, seems to be a major determinant of an increased capillary permeability in diabetic patients with neuropathy.