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.     

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。     

Pregnancy is Not a Risk Factor for a Deterioration of Autonomic Nervous Function in Diabetic Women

Pregnancy may have an untoward effect on diabetic retinopathy and nephropathy and symptoms of autonomic neuropathy may also be exacerbated during pregnancy. To test the hypothesis that previous pregnancies during the diabetic state are associated with increased risk of development of autonomic dysfunction, autonomic nervous function and pregnancy history were assessed in 117 women with long-standing Type 1 diabetes mellitus. Thirty-eight women (32 %) had autonomic dysfunction, defined as at least one abnormal cardiovascular test. The presence of autonomic dysfunction was not related to the number of pregnancies during the disease state. Thus, this cross-sectional study suggests that pregnancies do not represent a risk factor for a deterioration of autonomic nervous function and development of autonomic neuropathy in diabetic women.     

Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat

Summary It has been shown that parameters of oxidative stress are increased in experimental diabetic neuropathy. The glutathione redox system is one of the intracellular scavenger systems for neutralizing free oxygen radicals. In this investigation we studied the effect of glutathione-treatment on the development of diabetic neuropathy in streptozotocin-induced diabetic rats by measuring sensory and motor nerve conduction velocities. The total study period was 10 weeks. Four groups of rats were studied: Group 1 consisted of non-diabetic, age-matched control rats; Group 2, of diabetic rats treated with placebo from week 0 to 10; Group 3, of diabetic rats treated with 200 mg glutathione/kg body weight i. v. two times per week from weeks 0 to 10; and Group 4, of diabetic rats treated with placebo from weeks 0 to 4 and as Group 3 from weeks 4 to 10. The sensory and motor nerve conduction velocity of rats treated prophylactically with glutathione (Group 3) were significantly different from those of rats treated with placebo (Group 2) or with glutathione administered at a later time point (Group 4). Complete restoration of sensory and motor nerve conduction velocity was not reached. There was a significant improvement in motor nerve conduction velocity from weeks 4 to 6 (p<0.005), but not in sensory nerve conduction velocity in the delayed treatment group (Group 4). In conclusion, treatment with glutathione, a free radical scavenger, is partially effective in the prevention of diabetic neuropathy in streptozotocin-induced diabetic rats, but is of limited value when the neuropathy is already present.     

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.     

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.     

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.     

The role of cyclic adenosine 3',5'-monophosphate and polyol metabolism in diabetic neuropathy.

The effects of a stable prostacyclin analog, Iloprost, and aldose reductase inhibitors (ONO-2235 and isoliquiritigenin) were studied to elucidate the role of cAMP in diabetic neuropathy in relation to polyol metabolism. In in vivo experiments, the cAMP and myoinositol contents in sciatic nerves and motor nerve conduction velocity were significantly reduced in diabetic rats. Iloprost significantly restored the reduced cAMP content in sciatic nerves and improved motor nerve conduction velocity in diabetic rats. However, the contents of sorbitol or myoinositol in sciatic nerves were not affected by Iloprost in diabetic rats. On the other hand, aldose reductase inhibitors significantly reduced the sorbitol content and increased the cAMP and myoinositol contents in the sciatic nerves of diabetic rats. The motor nerve conduction velocity was also slightly but significantly improved by treatment with aldose reductase inhibitors. There was a negative correlation between cAMP and sorbitol in the sciatic nerves of diabetic rats treated with aldose reductase inhibitors and a positive correlation between cAMP and motor nerve conduction velocity. In in vitro experiments, Iloprost significantly increased cAMP, but did not affect the sorbitol content in sciatic nerves. Aldose reductase inhibitors inhibited sorbitol accumulation and increased cAMP in sciatic nerves. Our data suggest that polyol pathway activation somehow results in cAMP reduction in sciatic nerves and that the reduction of cAMP in peripheral nerves may be closely related to the pathogenesis of diabetic neuropathy.     

Neurophysiological study of the effect of combined kidney and pancreas transplantation on diabetic neuropathy: a 2-year follow-up evaluation

Previous study have reported a significant improvement of peripheral neuropathy following combined pancreas and kidney transplantation attributed to improvement of blood glucose control by some authors and to elimination of uraemia by others. To asses the specific role of uraemia and hyperglycaemia in neuropathy, 16 diabetic uraemic patients with combined pancreas and kidney transplantation were compared to 9 diabetic patients with a renal graft only. Neurophysiological studies of peripheral neuropathy included ulnar and deep peroneal nerve motor conduction velocity, median and sural nerve sensory conduction velocity were performed at baseline and 1 and 2 years after transplantation. One year after transplantation mean nerve conduction velocity significantly improved in both groups. However, changes were statistically significant in the kidney-pancreas group only. At the 2 year follow-up nerve conduction velocity had increased further in the pancreas-kidney group only. These data suggest that improvement of nerve conduction velocity following pancreas and kidney transplantation is predominantly due to the long-term euglycaemic state.     

Motor pathway function in normoalbuminuric IDDM patients

Summary Central motor pathways were studied in 17 normoalbuminuric insulin-dependent diabetic (IDDM) patients who had been diabetic for more than 20 years, and compared with findings in 17 age-, sex-, and height-matched control subjects. The central motor conduction time was calculated from recordings of the compound muscle action potentials of the abductor pollicis brevis muscle after single transcranial and spinal root magnetic stimulation. The central motor conduction time from motor cortex to cervical spinal roots was 9.8±1.65 ms in diabetic patients and 10.1±1.48 ms in control subjects. In diabetic patients with neuropathy the central motor conduction time was 9.5±1.76 ms vs 10.1±1.56 ms in patients without neuropathy. The excitability of the motor pathways was studied by paired transcranial magnetic stimulation at interstimulation intervals of 30–1000 ms. In normal control subjects, an early facilitation of the amplitude of the compound muscle action potential at an interstimulation interval of 30 ms was found, while no facilitation was present in diabetic patients. In addition the compound muscle action potential latencies were prolonged at interstimulation intervals of 30–50 ms in diabetic patients. The changes of excitability did not correlate with the presence of peripheral neuropathy, metabolic control or diabetes duration. It is concluded that long-term normoalbuminuric IDDM patients have impaired excitability but normal central conduction time of the motor pathways.Abbreviations CMCT Central motor conduction time - CMAP compound muscle action potential - ISI interstimulation interval - MNCV motor nerve conduction velocity - SNCV sensory nerve conduction velocity - APB abductor pollicis brevis muscle - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus     

Vascular factors in diabetic neuropathy

Summary Despite considerable research we still do not have a comprehensive explanation for the pathogenesis of diabetic neuropathy. Although chronic hyperglycaemia is almost certainly involved, it is not known whether the primary pathology is metabolic, microvascular, or an interaction between the two. Hyperglycaemia-induced polyol pathway hyperactivity associated with nerve sorbitol accumulation and myo-inositol depletion may play a part in the genesis of diabetic neuropathy. The case for microvascular disease in diabetic neuropathy is now strong. Fibre loss in human sural nerve is multifocal, suggesting ischaemia. The degree of vessel disease has been related to the severity of neuropathy. People with chronic obstructive pulmonary disease develop the so called hypoxic neuropathy in which similar microvascular changes occur as in diabetic neuropathy. In rats with experimental diabetic neuropathy nerve blood flow is reduced and oxygen supplementation or vasodilator treatment improved the deterioration in conduction velocity and nerve blood flow. Similarly, in human diabetic neuropathy, there is impaired nerve blood flow, epineurial arterio-venous shunting and a reduction in sural nerve oxygen tension. At what stage during the development of nerve damage these changes occur is yet to be determined.Abbreviations RICF resistance to ischaemic conduction failure     

硫辛酸联合甲钴胺用于糖尿病周围神经病变的治疗效果研究

目的分析α-硫辛酸联合甲钴胺用于糖尿病周围神经病变的治疗效果。方法选取该院2017年1月—2019年4月糖尿病周围神经病变患者共102例,数字表随机分两组,每组51例,对照组的患者给予甲钴胺治疗,观察组给予甲钴胺联合硫辛酸治疗。比较两组治疗前后患者神经传导速度中腓总神经运动神经传导测定值、感觉神经传导测定值以及胫神经速度运动神经传导测定值、感觉神经传导测定值、总有效率。结果治疗前两组患者神经传导速度中腓总神经运动神经传导测定值、感觉神经传导测定值以及胫神经速度运动神经传导测定值、感觉神经传导测定值比较,差异无统计学意义(P>0.05)。治疗后两组测定值均加速,差异有统计学意义(t=4.480、3.914、4.194、6.233,P<0.05)。观察组总有效率100.00%高于对照组,差异有统计学意义(χ²=7.799,P<0.05)。结论甲钴胺联合α-硫辛酸对于糖尿病周围神经病变的治疗效果确切,可显著改善患者症状及周围神经功能,是一种有效的治疗方案。     

Long-term effects of tolrestat on symptomatic diabetic sensory polyneuropathy.

Tolrestat is an aldose reductase inhibitor that is undergoing extensive clinical investigation for the treatment of diabetic complications including polyneuropathy. As part of a larger European trial, we report here the results from a single clinical center on the efficacy of tolrestat in patients with confirmed diabetic neuropathy. The trial was conducted in two phases: a 6-month double-blind, placebo-controlled phase, and a 6-month open-label phase in which most patients were treated with tolrestat. Following the double-blind phase, motor and sensory nerve conduction velocity had significantly deteriorated in the placebo group, which did not occur during treatment with tolrestat. Deterioration of vibration threshold also occurred during placebo treatment and did not occur with tolrestat. During the open-label phase, motor nerve condition velocity and vibration threshold improved with tolrestat. Moreover, the deterioration of motor nerve conduction velocity and vibration threshold that had occurred in patients initially treated with placebo, was stopped during open-label treatment with tolrestat.     

Diabetic Peripheral Neuropathy: Nerve Conduction Studies Before, During and After Carbamazepine Therapy

Summary: Diabetic peripheral neuropathy: Nerve conduction studies before, during and after carbamazepine therapy. A. K. Chakrabarti and S. K. Samantaray, Aust. N.Z. J. Med., 1976, 6, pp. 565–568.
Fifty-four patients with diabetic peripheral neuropathy were treated with carbamazepine for a period of one year. Clinical assessment and nerve conduction velocity studies (NCV) were done periodically. Forty-nine patients had symptomatic relief of all sensory manifestations but NCV remained essentially unchanged. Untoward effects of the drug were frequent but transitory. It was concluded that carbamazepine is a dependable drug for the treatment of symptomatic diabetic sensory polyneuropathy.     

Pentoxifylline effects on nerve conduction velocity and blood flow in diabetic rats

Pentoxifylline has several actions that improve blood rheology and tissue perfusion and may therefore potentially be applicable to diabetic neuropathy. The aims of this study were to ascertain whether 2 weeks of treatment with pentoxifylline could correct nerve conduction velocity and blood flow deficits in 6-week streptozotocin-diabetic rats and to examine whether the effects were blocked by co-treatment with the cyclooxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, NG-nitro-L-arginine. Diabetic deficits in sciatic motor and saphenous sensory nerve conduction velocity were 56.5% and 69.8% corrected, respectively, with pentoxifylline treatment. Sciatic endoneurial blood flow was approximately halved by diabetes and this deficit was 50.4% corrected by pentoxifylline. Flurbiprofen co-treatment markedly attenuated these actions of pentoxifylline on nerve conduction and blood flow whereas NG-nitro-L-arginine was without effect. Thus, pentoxifylline treatment confers neurovascular benefits in experimental diabetic neuropathy, which are linked at least in part to cyclooxygenase-mediated metabolism.     

Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy

Summary Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x 3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80% age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p<0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p<0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcutaneous temperature rose significantly in normal subjects (p<0.01, mean increase 2.07°C) and non-neuropathic diabetic subjects (p<0.001, mean increase 2.52 °C) but not in neuropathic subjects (mean increase 0.15 °C). However, sural sensory conduction velocity increased by 1.2 m · s^–1. °C^–1 following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m · s^–1. °C^–1). The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.     

糖尿病周围神经病变神经传导速度、F波及皮肤交感反应的变化及临床意义

目的 探讨糖尿病周围神经病变（DPN）患者神经传导速度（NCV）、F波及交感神经皮肤反应（SSR）的变化特点及临床应用价值.方法 97例DPN患者进行神经电生理检查,包括运动神经传导速度（MCV）、感觉神经传导速度（SCV）、F波及SSR检测.结果 异常率分别为SSR 75.2％,NCV 48.8％,F波34.5％,下肢神经病变重于上肢（P＜0.05）.结论 NCV、F波及SSR联合应用可全面地评估糖尿病周围神经的损害,三者相辅相成,缺一不可.     

阿魏酸钠治疗糖尿病周围神经病变的作用机制

目的　观察阿魏酸钠治疗 2型糖尿病周围神经病变的临床疗效 ,探讨其作用机制。方法　将 32例 2型糖尿病并发周围神经病变患者随机分成治疗组 2 0例、对照组 12例 ,在常规治疗基础上 ,观察组加用阿魏酸钠30 0 mg/ d,对照组予以丹参注射液 2 0 ml/ d,总疗程均为 4周。治疗前后测定运动神经传导速度 (MNCV)、感觉神经传导速度 (SNCV)、血浆内皮素 - 1(ET- 1)、血清一氧化氮 (NO)水平及红细胞山梨醇含量。结果　治疗组神经传导速度明显改善 (P<0 .0 5 ) ,血浆 ET- 1及红细胞山梨醇含量明显下降 (P<0 .0 1) ,血清 NO明显升高 (P<0 .0 1) ;对照组则无明显变化。结论　阿魏酸钠治疗糖尿病性周围神经病变的作用与其拮抗 ET- 1、升高 NO和降低神经组织山梨醇水平有关。     

Acute effects of adrenergic-mediated ischemia on nerve conduction in subjects with type 2 diabetes

Several lines of evidence support peripheral nerve ischemia as a contributing factor in the etiology of human diabetic neuropathy. We questioned whether diabetic subjects with relatively normal nerve function in the baseline state would be more likely than healthy control subjects to show either improvement of ulnar nerve function with acute intraarterial infusion of nitroprusside (vasodilation) or be more sensitive than control subjects to worsening of nerve function with acute intraarterial infusion of norepinephrine (vasoconstriction). We measured forearm blood flow (FABF) using venous occlusion plethysmography and assessed ulnar nerve function at baseline and during two intrabrachial artery infusions. Six nondiabetic control subjects (mean age, 56 years) and 11 subjects with type 2 diabetes (mean age, 58 years) in good general health participated. Only three type 2 diabetic subjects had peripheral sensory neuropathy, which was mild. Among control subjects, there was no significant change in sensory distal latency, motor distal latency, motor proximal latency, or sensory or motor conduction velocity during norepinephrine infusion. In contrast, among type 2 diabetic subjects, there was a significant increase in sensory (baseline vnorepinephrine, 2.73+/-0.10 v 2.94+/-0.10 milliseconds [MS], P< or =.01) and motor distal latencies (baseline v norepinephrine, 2.90+/-0.06 v 3.18+/-0.1 ms, P< or =.001) and motor proximal latency (baseline v norepinephrine, 7.15+/-0.18 v 7.60+/-0.23 ms, P<.01) and a decrease in sensory conduction velocity (baseline v norepinephrine, 52.1+/-2.0 v 47.7+/-1.6 m/s, P<.01) during norepinephrine infusion. There were no consistent changes in nerve function during nitroprusside infusion in either group. In summary, we found that subjects with type 2 diabetes, but not control subjects, demonstrate a decrement in nerve function with vasoconstriction during intraarterial infusion of norepinephrine, but no consistent change during nitroprusside-induced vasodilation. These findings suggest there may be enhanced sensitivity of nerve function to ischemia in type 2 diabetic subjects with mild or absent clinical neuropathy.     

Oxidative stress and diabetic neuropathy: pathophysiological mechanisms and treatment perspectives

Increased oxidative stress is a mechanism that probably plays a major role in the development of diabetic complications, including peripheral neuropathy. This review summarises recent data from in vitro and in vivo studies that have been performed both to understand this aspect of the pathophysiology of diabetic neuropathy and to develop therapeutic modalities for its prevention or treatment. Extensive animal studies have demonstrated that oxidative stress may be a final common pathway in the development of diabetic neuropathy, and that antioxidants can prevent or reverse hyperglycaemia-induced nerve dysfunction. Most probably, the effects of antioxidants are mediated by correction of nutritive blood flow, although direct effects on endoneurial oxidative state are not excluded. In a limited number of clinical studies, antioxidant drugs including alpha-lipoic acid and vitamin E were found to reduce neuropathic symptoms or to correct nerve conduction velocity. These data are promising, and additional larger studies with alpha-lipoic acid are currently being performed.