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 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.     

Diabetic neuropathy and plasma glucose control

Diabetic neuropathy is defined, and theories of its pathogenesis are reviewed. Recent studies designed to investigate the influence of plasma glucose on nerve function in noninsulin-dependent diabetic patients are summarized. Motor nerve conduction velocities in the median and peroneal nerves were measured using a double-stimulus technique, and sensory conduction velocity was measured by conventional methods before and after therapy with oral agents or insulin. The degree of hyperglycemia was assessed by measurement of fasting plasma glucose and glycosylated hemoglobin concentrations. The degree of slowing in motor nerve conduction velocity in untreated patients was found to correlate with the fasting plasma glucose and glycosylated hemoglobin concentrations, but sensory nerve function, although abnormal, did not show such correlation. Reduction of hyperglycemia was associated with improvement in motor nerve conduction velocity in the peroneal and median motor nerves of these patients, but sensory nerve conduction velocity showed no such improvement. Improvement in median motor nerve conduction velocity was directly related to the degree of reduction in fasting plasma glucose concentration. These findings suggest that metabolic factors related to hyperglycemia are important in the impaired motor nerve function seen in noninsulin-dependent patients with maturity-onset diabetes.     

Reproducibility of Parameters for Assessment of Diabetic Neuropathy

This study evaluated the reproducibility of nerve function assessment in a group of 132 diabetic patients with moderate peripheral polyneuropathy. Patients were investigated at the beginning and the end of the run-in period (a 1-month placebo period) of a multicentre trial of an aldose-reductase inhibitor (Ponalrestat). Reproducibility was evaluated by performing four types of tests: quantitative visual scales of symptoms, quantitative sensory assessment (vibration perception thresholds in medial malleolus and great toe, foot thermal perception threshold to hot and cold), electrophysiological investigations on the dominant side (conduction velocities and potential amplitudes of sensory and median motor nerve, sural and peroneal nerves, amplitudes of F waves of median motor and peroneal nerves) and cardiac autonomic tests (Valsalva, deep-breathing, lying-to-standing). Reproducibility was poor for symptoms, thermal sensitivity, and potential amplitudes. It was satisfactory (total coefficient of variation < 50%) for all the other parameters and even very good (total variation coefficient < 26%, intra-subject variation factors corresponding to < 56% of total variance) for velocities of sensory and median motor and peroneal nerves, the amplitudes of F waves and the three autonomic tests. For most of the parameters total variance was mainly related to inter-subject variability. However, inter-subject variability for the three cardiac autonomic tests was very low and at least one cardiac autonomic test was altered in all the patients. Inter-centre variability was low for all the parameters, except for action potential amplitudes and for F wave velocity of the median motor nerve. This study suggests those parameters that are appropriate for the assessment of diabetic neuropathy and for therapeutic trials. It also shows evidence of cardiac autonomic neuropathy in all these patients with moderate peripheral neuropathy.     

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     

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.     

Influence of continuous subcutaneous insulin infusion (CSII) treatment on diabetic somatic and autonomic neuropathy

Near-normal plasma daily glucose profile was induced by Continuous Subcutaneous Insulin Infusion (CSII) treatment in order to evaluate its influence on diabetic somatic and autonomic neuropathy. Twelve insulin-dependent diabetic subjects with somatic neuropathy were studied before and after a short term CSII treatment of 10 days. Four out of these subjects, all affected by autonomic neuropathy, were followed for 1 yr with controls every four months. Metabolic equilibrium was monitored by mean daily plasma glucose (MPDG) profile and by Glycosylated Hemoglobin (GHb) evaluation. Somatic neuropathy was studied assessing conduction velocity at peroneal motor (PMCV) nerve, ulnar motor (UMCV), ulnar sensory (USCV) and sural sensory (SSCV) nerves. Autonomic neuropathy was assessed by means of a battery of five cardiovascular autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (LS), Sustained HandGrip (SHG) and Postural Hypotension (PH). Short-term CSII treatment induced a near normalization of metabolic parameters, a significant improvement in VR (p less than 0.05) and DB (p less than 0.01) values, but no changes in NCV. The prolongation of CSII treatment in 4 subjects induced a significant (p less than 0.05) improvement in VR, DB and LS values and in PMCV and UMCV after 4 months. This improvement did not increase with the longer CSII treatment (1 yr).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

糖尿病周围神经病变的神经传导检查特点

目的 分析神经传导检查在糖尿病周围神经病变（DPN）中的特点,提高此方法诊断DPN的敏感性. 方法 对符合标准的213例患者的2283条神经行传统的神经传导、F波、H反射检查,并分析各条神经总的神经电生理检查情况. 结果 2283条神经进行常规神经传导检查结果显示,感觉神经传导速度（SCV）中,正中神经的异常率最高;运动神经传导速度（MCV）中,胫神经、正中神经异常率高;最长的胫神经运动神经神经传导异常率为47.45％,容易合并卡压的正中神经感觉神经传导异常率为46.83％,而腓肠神经感觉神经传导异常率最低（22.60％）.对有临床明确症状的21条神经进行神经传导检查,异常率可达76.19％.对感觉神经传导异常的尺神经进行运动神经传导检查,尺神经异常率为57.14％.常规神经传导检查,正中神经感觉神经传导异常率（46.83％）高于正中神经运动神经传导异常率（41.13％）.正中神经感觉神经传导异常者运动神经传导异常率为76.56％,正中神经运动神经传导异常者感觉神经传导异常率为89.63％.尺神经F波、胫神经H反射的异常率分别为25.83％、52.24％.结论 DPN具有长度依赖性、与临床表现一致、感觉重于运动、全长弥漫受累等特点,根据这些特点选择神经进行神经传导检查,可提高神经传导检查诊断DPN的敏感性.     

依帕司他联合甲钴胺治疗糖尿病周围神经病变的疗效分析

目的探讨依帕司他联合甲钴胺治疗糖尿病周围神经病变的临床疗效。方法选择该科2018年9月—2020年9月收治的87例2型糖尿病周围神经病变患者,随机分为对照组(43例)和依帕司他组(44例)。对照组采用甲钴胺治疗,依帕司他组增加依帕司他治疗,对比两组治疗前后神经病变改善情况,并监测氧化应激指标变化及用药安全性。结果依帕司他组治疗后TSS评分(3.83±1.02)分显著低于对照组(5.98±1.69)分,差异有统计学意义(P<0.05)。依帕司他组治疗后正中神经感觉与运动传导速度、腓总神经感觉与运动传导速度显著快于对照组,差异有统计学意义(P<0.05)。结论甲钴胺联合依帕司他治疗,可进一步提升糖尿病周围神经病变治疗效果,改善患者神经传导,有助于改善患者预后,临床应用价值较高。     

Nerve conduction in diabetic pregnancy. A prospective study

Repeated neurographic examinations were performed during and after the pregnancies of 32 diabetic women who had no signs of neuropathy before pregnancy or at the initial examination during the first trimester. The motor conduction velocity, the sensory conduction velocity and the peak amplitude of the compound action potential of the investigated peripheral nerves were not affected by pregnancy. It is concluded that pregnancy does not impair nerve conduction or induce neuropathy in most diabetic women.     

Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. United Kingdom/Scandinavian Ponalrestat Trial.

The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo-controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30:15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy.     

Clinical and neurophysiological studies with the aldose reductase inhibitor,sorbinil, in symptomatic diabetic neuropathy

Summary The effect of sorbinil (200 mg daily for 4 weeks) was examined in 13 patients, mean age 59.7 years (range 42–72 years), with symptomatic diabetic neuropathy of mean duration 6 years (range 1–18 years). In this double-blind, placebo-controlled crossover trial, studies were made of motor, sensory and autonomic nerve function, severity of painful symptoms and duration of sleep. One patient was withdrawn because of an adverse reaction to sorbinil. In the other 12, constant mean values for glycosylated haemoglobin A₁ between 11% and 12% indicated stable though not ideal diabetic control throughout the study. Example values for nerve conduction velocity on placebo and active treatment were: 44.3 ± 5.9 and 44.8 ± 5.1 metres/s (mean±SD) for median motor nerve, 38.4 ±8.2 and 37.2 ± 7.7 metres/s for median sensory nerve. Thus there was no significant effect of sorbinil on conduction velocity in these or any other of the motor and sensory nerves tested. Abnormal autonomic function was not improved by sorbinil. Subjective pain scores on a 10 cm visual analogue scale were 4.2 ± 2.4 on placebo and 4.3 ± 2.4 after sorbinil. Duration of sleep on placebo and active treatment was 6.1 ±1.6 and 6.2 ±1.7 h/night, respectively. We were not able to detect any beneficial effect of sorbinil on painful diabetic neuropathy in our patients.     

Peripheral nerve abnormalities in newly-diagnosed diabetic children

Summary The prevalence of clinical and subclinical peripheral neuropathy was evaluated in 51 unselected children at the time of onset of type I diabetes. Twenty-eight patients were followed for one year in order to establish the influence of metabolic control on peripheral nerve function. Twenty-two % of the diabetic children showed nerve conduction abnormalities at the onset and 11.7% had clinical features of peripheral neuropathy. After one year of disease, these figures had changed to 14.3% and 7.1%. Five of 7 children with altered electrophysiological tests in the baseline assessment had had normalization of all parameters one year later. No correlations between insulin requirement and nerve conduction were found. The M value was significantly correlated only with median sensory conduction velocity (p<0.005). Significant correlations were demonstrated between HbA₁ concentration and both peroneal motor conduction velocity (p<0.025) and median sensory conduction velocity (p<0.005); these correlations were still present after one year of disease. In the first period of diabetic disease there is functional rather than structural damage of the nerves. The pathogenetic role of hyperglycemia is confirmed; however individual susceptibility to nerve dysfunction may play an important role in the nerve impairment in diabetes. This study was supported by the C.N.R. Project ‘Preventive and Rehabilitative Medicine’, Subproject ‘Degenerative Diseases of the Nervous System’; Project N. 84.02472.56.115.10324.     

2型糖尿病患者高血压与糖尿病性神经病变的关系

目的 探讨2型糖尿病患者高血压与糖尿病性神经病变的关系。方法 利用心自主神经功能检测系统和神经电生理检测仪对107例（高血压组52例,非高血压组55例）2型糖尿病患者的心自主神经功能和肢体的末梢神经传导速度、皮肤痛温觉、振动沉进行测定,以判断心自主神经病变和末梢神经病变。结果 两组间末梢神经功能和心自主神经功能各指标除心的是距频谱分析的高频值外差异均无显著性（P＜0.05）。Logistic回归分析显示高血压与心自主神经病变显著相关（P＜0.01）,而与末梢神经病变无显著相关。结论 2型糖尿病患者高血压是心自主神经病变发病的危险因素,而与末梢神经病变无明显关系。     

A multicentre trial of the aldose-reductase inhibitor tolrestat, in patients with symptomatic diabetic peripheral neuropathy. North European Tolrestat Study Group.

One hundred and ninety patients with symptomatic diabetic peripheral neuropathy took part in a double blind multicentre trial of either placebo or tolrestat 200 mg once daily for 6 months. Painful and paraesthetic symptoms, vibration sensory threshold, and nerve conduction velocity (NCV) were assessed as efficacy end-points during the trial. There was an equally marked improvement of painful symptoms during the trial in the tolrestat and placebo groups. A difference in the improvement of paraesthetic symptoms was found however in favour of the placebo group at 24 weeks (p less than 0.02). The deterioration in mean vibration threshold of the tolrestat group was less than placebo at 24 weeks at all 3 sites measured, and reached significance at the carpal site (p less than 0.05). Significant improvements in median motor NCV and in the mean NCV of the four motor nerves were also seen in tolrestat treated patients at 24 weeks compared to placebo (p less than 0.05). In addition, significant changes in favour of tolrestat were seen when the number of motor nerves per patient with NCV increased during the trial was analysed (p less than 0.001). Concordance analysis of patients with increased mean motor NCV and improvement in painful symptoms demonstrated a positive effect for tolrestat compared to placebo (p less than 0.02). Mild reversible elevations of hepatic transaminases were seen in a few patients treated with tolrestat, with no other significant adverse effects. Tolrestat may therefore be helpful in diabetic peripheral neuropathy, where there is little opportunity for therapeutic intervention apart from effort to achieve normoglycaemic control.     

A Meta-analysis of Trials on Aldose Reductase Inhibitors in Diabetic Peripheral Neuropathy

Peripheral neuropathy is one of the most common and disabling long-term seque lae of diabetes mellitus. Aldose reductase inhibitors (ARIs) have been proposed and are increasingly used in many countries for the prevention and treatment of diabetic neuropathy. The aim of this study was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular reference to the type and clinical relevance of the end point used and to the consistency of results across studies. Thirteen randomized clinical trials (RTCs) comparing ARIs with placebo, published between 1981 and 1993 were included in the meta-analysis. Nerve conduction velocity (NCV) was the only end point reported in all trials. Treatment effect was thus evaluated in terms of NCV mean difference in four different nerves: median motor, median sensory, peroneal motor, and sural sensory. A statistically significant reduction in decline of median motor NCV was present in the treated group as compared to the control group (mean 0.91 ms⁻¹; 95 % CI 0.41–1.42 ms⁻¹). For peroneal motor, median sensory, and sural sensory nerves results did not show any clear benefit for patients treated with ARIs. When the analysis was limited to trials with at least 1-year treatment duration, a significant effect was present for peroneal motor NCV (mean 1.24 ms⁻¹; 95 % CI 0.32–2.15 ms⁻¹) and a benefit of borderline statistical significance was also present for median motor NCV (mean 0.69 ms⁻¹; 95% CI −0.07−1.45 ms⁻¹). A heterogeneous picture emerged when looking at the results of different studies and serious inconsistencies were also present in the direction of treatment effects among nerves in the same studies. Although the results of 1-year treatment on motor NCV seem encouraging, the uncertainty about the reliability of the end-point employed and the short treatment duration do not allow any clear conclusion about the efficacy of ARIs in the treatment of peripheral diabetic neuropathy.     

Cross sectional study to evaluate the effect of duration of type 2 diabetes mellitus on the nerve conduction velocity in diabetic peripheral neuropathy

ObjectiveTo study the nerve conduction velocity in clinically undetectable and detectable peripheral neuropathy in type 2 diabetes mellitus with variable duration.Material and methodsThis cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups: Group I (n = 37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n = 27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with T2DM patients (n = 22) without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Nerve conduction velocity was measured in both upper and lower limbs. Median, ulnar, common peroneal and posterior tibial nerves were selected for motor nerve conduction study and median and sural nerves were selected for sensory nerve conduction study.ResultsThe comparisons were done between nerve conduction velocities of motor and sensory nerves in patients of clinically detectable neuropathy and patients without neuropathy in type 2 diabetes mellitus population. This study showed significant electrophysiological changes with duration of disease. Nerve conduction velocities in lower limbs were significantly reduced even in patients of shorter duration with normal upper limb nerve conduction velocities.ConclusionDiabetic neuropathy symptom score (NSS) and neuropathy disability score (NDS) can help in evaluation of diabetic sensorimotor polyneuropathy though nerve conduction study is more powerful test and can help in diagnosing cases of 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。     

Sensory, motor, and autonomic neuropathy in patients with multiple symmetric lipomatosis

Clinical evaluation of 33 male patients affected by multiple symmetric lipomatosis has revealed a previously unreported high prevalence of somatic and autonomic neuropathies. In 84% of the patients, clinical examination revealed signs or symptoms of neural disturbances, ranging from a vibratory sensory loss to severely incapacitating trophic ulcers or Charcot's arthropathy. Electrodiagnostic investigations demonstrated a significant reduction of motor and sensory conduction velocity in the peroneal and sural nerves. Morphometric studies of nerve and muscle biopsies from five patients with multiple symmetric lipomatosis revealed a significant reduction in myelinated fiber density (4435 +/- 593 fibers/mm2 in MSL vs 7660 +/- 800 in controls; p less than 0.05), a selective reduction in the large fibers of 7 to 10 micron in diameter, and signs of chronic denervation-reinnervation processes. Bedside tests for autonomic neuropathy were abnormal in 15 of 20 patients studied. Metabolic studies in these patients confirmed a significant increase in plasma high-density lipoprotein fractions consistent with the diagnosis of hyperalphalipoproteinemia, and a significant reduction in plasma low-density lipoprotein fractions (hypobetalipoproteinemia) associated with a marked enhancement of lipoprotein lipase activity in adipose tissue. Thus, a metabolic factor has to be considered in the pathogenesis of MSL neuropathy.