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PubMed1991

Vibratory and thermal thresholds in diabetics with and without clinical neuropathy.

Vibration and thermal detection threshold and heat pain threshold were determined in 34 diabetics scrutinized for clinical neuropathy using a standardized questionnaire and examination form. On the basis of the clinical grading patients were classified as having either no neuropathy or a neuropathy of increasing severity. As expected thermal and vibratory detection threshold increased with increasing severity of neuropathy. Comparison between diabetics without symptoms and signs of neuropathy and a corresponding non-diabetic control group showed that a warm sensibility index (WSI = the range in which non-noxious heat is perceived) was significantly lower on feet in diabetics than in their matched non-diabetic controls. The findings show that quantitative assessment of thermal sensitivity may be of value to detect early small nerve fiber dysfunction even in patients without symptoms or signs of a clinical neuropathy.

Adult↗
PubMed2005

Comparison of different screening tests for detecting diabetic foot neuropathy.

INTRODUCTION: Regarding the major role of sensory neuropathy in diabetic foot ulcers, the use of an appropriate screening test for early detection of this neuropathy has a crucial role in the management of diabetic foot disorders. As there were no previous studies that performed all screening tests in the same group of patients, we performed all tests in a single group of diabetic patients and compared them to find out the possible differences between the results. METHODS: A total of 142 diabetic outpatients at Shariati Teaching Hospital were chosen by systematic randomized selection. Different screening tests for detecting neuropathy in diabetic foot such as symptom and sign scores, Michigan Neuropathy Disability Score (MNDS), and testing by a monofilament were performed for each patient. RESULTS: According to the neuropathy symptom score, 54.9% of the patients were neuropathic, their score was higher than 5, and by neuropathy sign score, 10.1% were neuropathic with a score higher than 6. Regarding MNDS, 42.7% of the subjects were neuropathic, with a score higher than 3. Finally, 23.9% were unable to sense at least one point in the monofilament examination. CONCLUSIONS: There were obvious differences between the results of different methods in our study. However, there were significant correlations between them, except between sign and symptom score methods. For determining the most reliable screening test, further studies are needed to compare these methods with a gold standard test and reveal the specificity and sensitivity of these tests.

Adult↗
PubMed2005

SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies.

BACKGROUND: The variable clinical features of hereditary sensory and autonomic neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory neuropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be recognised as familial. OBJECTIVE: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. PATIENTS: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients with idiopathic sensory neuropathy were also screened for known mutations of these genes. RESULTS: Of the 25 kindreds, only one had a mutation (SPTLC1 399T-->G). This kindred, and 10 without identified mutations, had prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity with injuries but no weakness, one had restless legs and burning feet, and one had dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neuropathy. CONCLUSIONS: Adult onset HSAN I is clinically and genetically heterogeneous and further work is required to identify additional genetic causes. Known SPTLC1or RAB7 mutations were not found in idiopathic sensory neuropathy.

Acyltransferases↗
PubMed1970

Electrophysiological studies in diabetic neuropathy.

In 30 patients with diabetic neuropathy sensory potentials in the median nerve, motor conduction in the lateral popliteal and median nerves, and electromyographic findings in distal and proximal muscles were compared with the severity of symptoms and signs. All patients had abnormalities in at least one of the electrophysiological parameters. The sensory potentials were the most sensitive indicator of subclinical involvement; abnormalities were found in 24 patients, 12 of whom had no sensory symptoms or signs and five of whom had no other clinical or electrophysiological evidence of neuropathy in the upper extremities. This indicates that sensory nerve fibres may be affected before motor. The next most sensitive parameter was the presence of fibrillation potentials, found in more than half the distal muscles examined. Slowing in motor conduction in the lateral popliteal nerve was the only electrophysiological change correlated to the severity of the neuropathy, and no other electrophysiological parameter was correlated to the duration or the severity of the neuropathy or the diabetes. An onset of neuropathy before or simultaneously with the manifestations of the diabetes, as well as the frequent occurrence of asymptomatic changes in sensory conduction, support the evidence at hand that the neuropathy develops concomitantly with and as an integral part of the metabolic disturbance rather than as a consequence of the vascular complications of diabetes. Of three patients with clinical signs or symptoms of a diabetic amyotrophy, two had asymptomatic electrophysiological abnormalities in distal nerves and muscles, consistent with widespread involvement of the peripheral nerves. The third patient had electromyographic changes in the medial vastus muscles suggestive of a myopathy. Motor and sensory conduction in distal and proximal nerves were normal.

Adult↗
PubMedDate not supplied

Capillary morphology and muscle blood flow in diabetic neuropathy.

21 diabetic patients were examined neurologically and neurophysiologically and were divided into two groups: one with neuropathy (10 patients) and the other without neuropathy (11 patients). Ultrastructural dimensions and density of capillaries in the gastrocnemius muscle were examined in 11 patients. Capillary basement membranes were significantly thicker in patients with neuropathy (p less than 0.05), whereas there was no difference in endothelial, luminal or pericytial fractions of the total capillary area. No difference was found in capillary densities of capillary/fiber (C/F) ratios. Muscle blood flow was estimated using the 133Xe clearance method in all the patients, and was found to be reduced in the 4 patients with the most severe neuropathy (p less than 0.01) even though there was no difference on the whole between the groups with or without neuropathy. The results suggest that the development of diabetic neuropathy is associated with basement membrane thickening. The causes of the basement membrane thickening are discussed.

Adult↗
PubMedDate not supplied

Diversity of the neuropathies in patients with non-insulin-dependent diabetes mellitus.

The relationships between cardiac autonomic neuropathies, diabetic somatic neuropathy, metabolic parameters, general parameters (such as age and duration of illness) and diabetic microangiopathy and macroangiopathy were investigated in 103 patients with non-insulin-dependent diabetes mellitus (NIDDM). Spearman's correlation coefficients were calculated for the comparisons of all the parameters of the neuropathies with all the other parameters. Variables were selected using a stepwise procedure and multiple regression analysis was carried out using these variables. The results of the regression analysis show that diabetic neuropathy is correlated with vascular parameters including blood pressure and pulse-wave velocity, as well as with parameters of sugar and lipid metabolism. The results confirm the diversity of the clinical characteristics of the neuropathies in patients with NIDDM and confirm that these neuropathies do not always occur in parallel.

Aged↗
PubMed2000

Development of a health-related quality of life measure for peripheral neuropathy.

STATEMENT OF PROBLEM: To develop and evaluate a self-administered health-related quality of life (HRQOL) measure for peripheral neuropathy. METHODS: A field test measure of 162 items was developed that included the RAND-36 Health Survey as a generic core and a neuropathy-targeted supplement whose content was driven by results from three focus groups with 22 adults having peripheral neuropathy. It was administered at baseline and at 3- and 6-month follow-ups to 80 adult clinical trial enrollees with diabetic neuropathy. Item reduction and placement into scales, reliability, construct validity, responsiveness, and HRQOL comparisons to a general U.S. population were conducted. RESULTS: The final 97-item instrument includes 16 multi-item scales and 6 single items. Internal consistency reliabilities ranged from 0.67 to 0.93 (median = 0.88); intraclass correlation coefficients for those reporting no change in health between baseline and 3 months ranged from 0.42 to 0.84 (median = 0.77). Factor analysis of scales revealed physical and mental health as the two underlying dimensions. Correlations between selected HRQOL scales and sociodemographic variables were modest; there were more noteworthy associations between HRQOL scales and employment, disability days, and neurologic symptom ratings. Associations of HRQOL with neurologic examination (strength and reflexes) and with electrophysiologic findings were nonsignificant (all p > 0.10). Responsiveness of a physical health summary score relative to a criterion of change in subject's ratings of neuropathy symptom severity yielded a moderate effect size (= 0.60) and a Guyatt statistic exceeding 1.0. CONCLUSIONS: Results provide preliminary support for the measure's reliability and validity among adults with diabetic peripheral neuropathy. HRQOL was more strongly associated with symptom ratings than with examination and electrophysiologic test results.

Adult↗
PubMed2001

Neuropathy is a major contributing factor to diabetic erectile dysfunction.

Erectile dysfunction (ED) in diabetes is multifactorial. So far, the impact of neuropathy has not been well determined. This study was performed to assess the frequency of abnormal neurophysiological tests in patients with ED due to diabetes compared to patients with ED due to nondiabetic neuropathies in order to estimate the contribution of neuropathy in diabetic ED. Forty-nine men with ED were studied. We classified ED as 'diabetic', 'neuropathic' or 'ED of other origin'. 26.6% of the men fulfilled the criteria of diabetic ED, 42.9% had neuropathic ED. In every patient history taking, a questionnaire focusing on autonomic symptoms other than ED, clinical examination, nerve conduction studies (NCS), sphincter ani electromyography (EMG), heart rate variability testing (HRV) and quantitative sensory testing (QST) was performed. Vascular function was assessed by the intracavernosal prostaglandin E1 (PGE1) injection test. The frequency of abnormal results in diabetic and neuropathic patients was compared. Vascular function was abnormal in only one patient with diabetic ED and three patients with neuropathic ED. Both groups had similar frequencies of autonomic symptoms other than ED (64% in diabetic vs. 64% in neuropathic patients), abnormal EMG (33% vs. 40%) and abnormal QST (vibratory perception 83% vs. 84%, cold perception 9% vs. 19%, warm perception 42% vs. 43%). Abnormal clinical findings (50% vs. 33%), NCS (75% vs. 50%) and HRV (39% vs. 25%) were slightly, but not significantly more frequent in men with diabetic ED than neuropathic ED. The tests indicating neuropathy showed abnormalities in men with diabetic ED as frequently as in men with neuropathic ED. Some tests even suggested neuropathy more often in diabetic than in neuropathic ED. The findings support the hypothesis that neuropathy contributes significantly to the pathophysiology of ED in diabetes mellitus.

Adult↗
PubMed2005

Potential risk factors for diabetic neuropathy: a case control study.

BACKGROUND: Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. METHODS: In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS) was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography). The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI), blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. RESULTS: Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, < 0.001 and 0.005). No correlation was found with any atherosclerosis risk factor (high BP, hyperlipidemia, cigarette smoking). CONCLUSION: In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.

Adult↗
PubMed2005

APOE epsilon4 is not a susceptibility gene in idiopathic or diabetic sensory neuropathy.

The presence of an APOE epsilon4 allele may be a risk factor for neuropathy severity in diabetes. The authors assessed the frequency of APOE epsilon4 in patients presenting with sensory predominant neuropathy. APOE epsilon4 frequency among patients with early diabetic neuropathy and impaired glucose tolerance-associated neuropathy was 16 to 17%, and not different from patients with idiopathic neuropathy (17%) or published normative values (16%). APOE epsilon4 may not function as a susceptibility gene in sensory predominant neuropathy.

Apolipoprotein E4↗
PubMed1992

The Rochester Diabetic Neuropathy Study: reassessment of tests and criteria for diagnosis and staged severity.

We evaluated the initial assessments of the 380 diabetic patients with and without polyneuropathy in the Rochester Diabetic Neuropathy Study for (1) associations among neuropathy test results, (2) usefulness of different tests for diagnosing and staging polyneuropathy, (3) appropriateness of different minimal criteria for the diagnosis of polyneuropathy, and (4) significant differences in test results with increasing stage of polyneuropathy. Nerve conduction ([NC]; abnormality in two or more nerves) and quantitative autonomic examination ([QAE]; decreased heart-beat response to deep breathing [DB] or the Valsalva maneuver [VAL]) were the most sensitive and objective and were especially suitable for detection of subclinical neuropathy. We propose the following minimal criteria for the diagnosis of diabetic polyneuropathy: greater than or equal to 2 abnormal evaluations (from among neuropathic symptoms, neuropathic deficits, NC, quantitative sensory examination [QSE], and QAE) with one of the two being abnormality of NC or QAE (DB or VAL). Neuropathy Symptom Score, Neuropathy Disability Score, QSE (vibratory or cooling detection threshold), and summated compound muscle action potential of ulnar, peroneal, and tibial nerves were best for judging severity. Inability to walk on heels provided a discrete separation of diabetic patients into those with mild and those with more severe neuropathy--a separation helpful in staging.

Diabetic Neuropathies↗
PubMed1995

Variables influencing neuropathic endpoints: the Rochester Diabetic Neuropathy Study of Healthy Subjects.

We determined the normal limits for various neuropathic tests in healthy subjects. The study, the Rochester Diabetic Neuropathy Study (RDNS), is noteworthy because of its size (more than 400 subjects), random selection of subjects, and selection of at least 15 men and 15 women without neuropathy, neurologic disease, or diseases predisposing to neuropathy from each hemidecade between 18 and 74 years of age from the population of a defined region (Rochester, MN). Subjects were classified into those with (nonhealthy subjects, RDNS-NS) and without (healthy subjects, RDNS-HS) neuropathy, neurologic or psychiatric disease, or diseases known to predispose to neuropathy. The study provides normal limits for tests used in the RDNS but it has broader uses as well. We found that (1) less than 10% of subjects in the third decade, approximately 20% in the fourth decade, and approximately 30% in the fifth or older decades were placed into the RDNS-NS category; (2) healthy subjects (RDNS-HS) retain their ability to walk on toes and heels regardless of age, excessive weight, or lack of physical fitness, but not their ability to arise from a kneeled position--lost in more than 5% of persons 60 years and older; (3) the frequency of decreased or absent ankle reflexes exceeds 5% in healthy subjects older than 50 years--limiting their value as a sign of diabetic polyneuropathy and necessitating a grading change with age in the neuropathy impairment score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1998

Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain. METHODS: This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics. RESULTS: Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.

Activities of Daily Living↗
PubMedDate not supplied

Evidence of nephropathy and peripheral neuropathy in US adults with undiagnosed diabetes.

PURPOSE: Nearly one third of diabetes cases in the United States is undiagnosed, with mounting evidence that complications accrue even before clinical diagnosis. We wanted to determine whether persons with undiagnosed diabetes have signs of nephropathy and peripheral neuropathy. METHODS: We examined the prevalence of positive screening tests for nephropathy and peripheral neuropathy in adults aged > or = 40 years with undiagnosed diabetes using secondary analysis of survey and examination data from the population-based United States National Health and Nutrition Examination Survey 1999-2002. We defined a positive screening test for nephropathy as a spot urine albumin-creatinine ratio > 30.0 mg/g, representing at least microalbuminuria. We defined > or = 1 insensate area on Semmes-Weinstein monofilament testing as a positive finding for neuropathy. Undiagnosed diabetes was defined as a combination of no history of diagnosed diabetes and a measured fasting glucose > or = 126 mg/dL. We used SUDAAN for chi2 and regression analyses. RESULTS: The prevalence of a positive test when screening for nephropathy among those with undiagnosed diabetes was 26.5% compared with 7.1% in those with no diabetes (chi2, P <.01). After adjusting for age and diagnosed or undiagnosed hypertension, the association of undiagnosed diabetes with nephropathy persisted (odds ratio = 2.35; 95% confidence interval, 1.38-4.01). For peripheral neuropathy, 21.5% with undiagnosed diabetes had positive screening tests compared with 10.1% with no diabetes (chi2, P <.01); however, this effect was not significant after adjustment for age. There was no significant difference in positive screening tests for nephropathy or neuropathy when comparing those with undiagnosed and diagnosed diabetes. CONCLUSIONS: A significant proportion of adults with undiagnosed diabetes have signs of nephropathy and peripheral neuropathy. These findings may influence policies about early screening for diabetes.

Adult↗
PubMed2006

Abnormal function of C-fibers in patients with diabetic neuropathy.

The mechanisms underlying the development of painful and nonpainful neuropathy associated with diabetes mellitus are unclear. We have obtained microneurographic recordings from unmyelinated fibers in eight patients with diabetes mellitus, five with painful neuropathy, and three with neuropathy without pain. All eight patients had large-fiber neuropathy, and seven patients had pathological thermal thresholds in their feet, indicating the involvement of small-caliber nerve fibers. A total of 163 C-fibers were recorded at knee level from the common peroneal nerve in the patients (36-67 years old), and these were compared with 77 C-fibers from healthy controls (41-64 years old). The ratio of mechano-responsive to mechano-insensitive nociceptors was approximately 2:1 in the healthy controls, whereas in the patients, it was 1:2. In patients, a fairly large percentage of characterized fibers (12.5% in nonpainful and 18.9% in painful neuropathy) resembled mechano-responsive nociceptors that had lost their mechanical and heat responsiveness. Such fibers were rarely encountered in age-matched controls (3.2%). Afferent fibers with spontaneous activity or mechanical sensitization were found in both patient groups. We conclude that small-fiber neuropathy in diabetes affects receptive properties of nociceptors that leads to an impairment of mechano-responsive nociceptors.

Adult↗
PubMed1998

Mexiletine. A review of its therapeutic use in painful diabetic neuropathy.

UNLABELLED: Mexiletine is an orally active local anaesthetic agent which is structurally related to lidocaine (lignocaine) and has been used for alleviating neuropathic pain of various origins. Mexiletine has been evaluated in several randomised, placebo-controlled trials in patients with painful diabetic neuropathy. The drug decreased mean visual analogue scale (VAS) pain ratings in all studies that used this measure, although in only 2 studies was this effect significantly greater than the often substantial responses seen with placebo. The clinical significance of these decreases is not clear. Statistically significant (vs placebo) reductions in VAS pain ratings were observed in 16 patients receiving mexiletine 10 mg/kg/day for 10 weeks in 1 study and in nocturnal (but not diurnal) pain in 31 patients receiving mexiletine 675 mg/day for 3 weeks in another. Retrospective analysis of another study revealed that mexiletine recipients (225 to 675 mg/day) who described their pain as stabbing, burning or formication on the pain-rating-index-total instrument of the McGill Pain Questionnaire, experienced statistically significant reductions in VAS pain scores after 5 weeks, compared with placebo recipients. Mexiletine generally did not have a significant influence on the quality of sleep in patients with diabetic neuropathy. In Japanese patients, statistically significant reductions in subjective pain ratings were achieved with mexiletine 300 mg/day in 1 study and with 450 mg/day in a further study. In controlled trials, the frequency of adverse events in patients receiving mexiletine for painful diabetic neuropathy ranged from 13.5 to 50%. Gastrointestinal complaints, of which nausea was the most frequent, were the most common adverse events in mexiletine recipients. Central nervous system complaints were uncommon, but included: sleep disturbance, headache, shakiness, dizziness and tiredness. Serious cardiac arrhythmias have not been reported in patients receiving mexiletine for painful diabetic neuropathy; however, transient tachycardia and palpitations have been reported. There are significant differences in the metabolism of mexiletine between people who have cytochrome P450 2D6 [CYP2D6; extensive metabolisers (EMs)] and those who lack this isoenzyme [poor metabolisers (PMs)]. EMs, but not PMs, are susceptible to drug interactions between mexiletine and drugs that inhibit CYP2D6 (e.g. quinidine). Moreover, mexiletine inhibits CYP2D6-mediated metabolism of metoprolol and cytochrome P450 1A2-mediated metabolism of theophylline. Phenytoin and rifampicin (rifampin) induce the metabolism of mexiletine. Clearance of mexiletine is impaired in patients with hepatic, but not renal, dysfunction. Hence, dosage adjustments may be necessary in patients with liver disease. CONCLUSIONS: Tricyclic antidepressants (TCAs) are the agents of choice for painful diabetic neuropathy; however, they are ineffective in approximately 50% of patients and are generally not well tolerated. Mexiletine is an alternative agent for the treatment of painful diabetic neuropathy in patients who have not had a satisfactory response to, or cannot tolerate, TCAs and/or other drugs.

Diabetic Neuropathies↗
PubMed1989

Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study.

The natural history of diabetic neuropathy and its risk factors are not well understood, apart from the recognition that prevalence increases with duration and, in many studies, degree of glycemia. The role of potential risk factors was therefore evaluated in a cross-sectional analysis from the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study. We present results from the first 400 subjects seen at baseline examination. Neuropathy was determined by a trained internist with a standardized examination and was defined as the presence of at least two of three criteria: abnormal sensory or motor signs, symptoms consistent with neuropathy, and decreased tendon reflexes. The prevalence of neuropathy in this cohort was 34% (18%, 18-29 yr old, 58% greater than or equal to 30 yr old) with no difference by sex. By focusing on subjects greater than or equal to 18 yr old, all significant univariate variables (e.g., duration, glycosylated hemoglobin [HbA1]) were analyzed in 3 multiple logistic regression models: all subjects greater than or equal to 18 yr old and separating the same subjects into two groups based on age (18-29 and greater than or equal to 30 yr). Duration, HbA1, smoking status, and high-density lipoprotein cholesterol were found to be associated with neuropathy in the models for the greater than or equal to 18-yr-old group and the greater than or equal to 30-yr-old group. In the 18- to 29-yr-old group, duration, HbA1, and hypertension status were found to be significantly associated with neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Abnormal myoinositol influx in human leucocytes in diabetes but not specifically in diabetic neuropathy.

Abnormal myoinositol metabolism has been implicated as a contributor to the development of diabetic neuropathy. Furthermore, in vitro glucose inhibits animal and human myoinositol transporters. To investigate whether myoinositol transport is abnormal in diabetic subjects with and without neuropathy, we used a triple-isotope technique to measure [14C]myoinositol uptake in leucocytes from 23 insulin-dependent diabetic subjects and 13 matched nondiabetic subjects. All subjects with diabetes underwent neurophysiological studies, and subjects without neuropathy were compared with those with various degrees of neuropathy. The relationship between glycemia and flux was also studied. Diabetic subjects had similar intracellular and plasma myoinositol concentrations but had higher rates of uptake of myoinositol over the extracellular concentrations of myoinositol studied. Although the derived Km, Vmax, and passive components were not significantly different, the Vmax:Km ratio was significantly higher in diabetic subjects compared with nondiabetic subjects (0.25 [0.17-0.32] vs. 0.16 [0.13-0.19], respectively (P = 0.006). In diabetic subjects, the rate of myoinositol uptake correlated with HbA1c, particularly at 3 microM extracellular myoinositol where active uptake was a high proportion of the total influx (P less than 0.005). No difference in myoinositol uptake was found among diabetic subjects with various degrees of neuropathy. We conclude that although myoinositol transport is abnormal in diabetes, it is not specifically abnormal in diabetic neuropathy. Prolonged hyperglycemia is associated with higher myoinositol flux.

Biological Transport↗