Ranirestat for the management of diabetic sensorimotor polyneuropathy.
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ABSTRACT:
SUBMITTER: Bril V
PROVIDER: S-EPMC2699746 | biostudies-literature | 2009 Jul
REPOSITORIES: biostudies-literature
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Ranirestat for the management of diabetic sensorimotor polyneuropathy.
Bril Vera V Hirose Toshiyuki T Tomioka Sasagu S Buchanan Robert R
Diabetes care 20090414 7
<h4>Objective</h4>Aldose reductase inhibitors (ARIs) are potential disease modifiers for diabetes complications. We aimed to determine whether ranirestat, an ARI, could slow or reverse the course of diabetic sensorimotor polyneuropathy (DSP).<h4>Research design and methods</h4>A total of 549 patients with DSP were randomly assigned to treatment with placebo or 10, 20, or 40 mg/day ranirestat for 52 weeks in this multicenter, double-blind study. Efficacy was evaluated by nerve conduction studies, ...[more]
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Project description:BackgroundDiabetic sensorimotor polyneuropathy (DSPN) is the commonest form of neuropathy. Loss of sensations in sole leads to diabetic foot ulcers (DFU) and its complications. Surgical decompression has been used in the treatment of diabetic peripheral neuropathy, however; its effectiveness has been questioned.Purpose of this study was to evaluate the sensory recovery in sole after tarsal tunnel decompression (TTD) in patients having DSPN.MethodsThirteen patients (Age28-70 years, average 35.57 years; 7 Males, 6 Females; 20 feet) with DSPN and positive Tinel's sign over the tarsal tunnel were included in the study. Pre and post-operative sensory tests performed on the sole included tests for touch, pain, temperature, pressure, vibration perception threshold (VPT) and two-point discrimination (2-PD). Results were classified as per British Medical Research Council (MRC) scoring system.Results-Sixteen feet were followed-up for 6 months. In all feet perception of touch, pain and pressure recovered. Temperature perception recovered in 75% feet. VPT came to normal range (16.81V) from 40.37 V and 2-PD came down to average of 6.0 mm from preoperative average of11.2 mm.MRC scale improved from S0 in 5 feet and S2 in 15 feet to S3+ in all 16 feet.There were no ulcers or amputation in operated limbs during follow up period of 6 months.ConclusionsTTD improves plantar sensations in diabetic neuropathy and prevents ulcers and its related complications.
| S-EPMC7211905 | biostudies-literature
Project description:Aims/hypothesisNo established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.MethodsThis cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.ResultsDSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.Conclusions/interpretationOur findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.
| S-EPMC9892145 | biostudies-literature
Project description:Diabetic peripheral neuropathy (DSPN), a major form of diabetic neuropathy, is a complication that arises in long-term diabetic patients. Even though the application of machine learning (ML) in disease diagnosis is a very common and well-established field of research, its application in diabetic peripheral neuropathy (DSPN) diagnosis using composite scoring techniques like Michigan Neuropathy Screening Instrumentation (MNSI), is very limited in the existing literature. In this study, the MNSI data were collected from the Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials. Two different datasets with different MNSI variable combinations based on the results from the eXtreme Gradient Boosting feature ranking technique were used to analyze the performance of eight different conventional ML algorithms. The random forest (RF) classifier outperformed other ML models for both datasets. However, all ML models showed almost perfect reliability based on Kappa statistics and a high correlation between the predicted output and actual class of the EDIC patients when all six MNSI variables were considered as inputs. This study suggests that the RF algorithm-based classifier using all MNSI variables can help to predict the DSPN severity which will help to enhance the medical facilities for diabetic patients.
| S-EPMC8146253 | biostudies-literature
Project description:Aims/hypothesisSmall cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP.MethodsNine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard.ResultsType 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm2 in type 1 diabetes and 12.3 mm/mm2 in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm2 to rule in DSP and an upper value of 15.3 mm/mm2 to rule out DSP were associated with 88% specificity and 88% sensitivity.Conclusions/interpretationWe established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.
| S-EPMC6061173 | biostudies-literature
Project description:Distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, has a complex pathophysiology and can be a major source of physical and psychologic disability. The management of DSPN can be frustrating for both patient and physician. This article provides a general overview of typical patient pathways in DSPN, and highlights variations in diagnosis, management, and referral patterns among different providers. DSPN is managed in several settings by primary care physicians (PCPs), specialists, and nurse practitioners. The initial clinical management of the patient is often dependent on the presenting complaint, the referral pattern of the provider, level of comfort of the PCP in managing diabetic complications, and geographic access to specialists. The primary treatment of DSPN focuses mainly on glycemic control and adjustment of modifiable risk factors, but other causes of neuropathy should also be investigated. Several pharmacologic agents are recommended by treatment guidelines, and as DSPN typically exists with comorbid conditions, a multimodal therapeutic approach should be considered. Barriers to effective management include failure to recognize DSPN, and misdiagnosis. Patient education also remains important. Referral patterns vary widely according to geographic location, access to services, provider preferences, and comfort in managing complex aspects of the disease. The variability in patient pathways affects patient education, satisfaction, and outcomes. Standardized screening tools, a multidisciplinary team approach, and treatment algorithms for diabetic neuropathy should improve future care. To improve patient outcomes, DSPN needs to be diagnosed sooner and interventions made before significant nerve damage occurs.
| S-EPMC4440893 | biostudies-literature
Project description:Aims/hypothesisDistal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes.MethodsA total of 249 participants, from the Pain in Neuropathy Study (UK) and the International Diabetic Neuropathy Consortium (Denmark), underwent a structured neurological examination, nerve conduction studies, quantitative sensory testing and skin biopsy. The study included four groups: healthy control study participants without diabetes (n = 45); participants with type 2 diabetes without DSP (DSP-; n = 31); and participants with evidence of DSP (DSP+; n = 173); the last were further separated into painless DSP+ (n = 74) and painful DSP+ (n = 99). Axonal swellings were defined as enlargements on epidermal-penetrating fibres exceeding 1.5 μm in diameter. Axonal swelling ratio is calculated by dividing the number of axonal swellings by the number of intraepidermal nerve fibres.ResultsMedian (IQR) IENFD (fibres/mm) was: 6.7 (5.2-9.2) for healthy control participants; 6.2 (4.4-7.3) for DSP-; 1.3 (0.5-2.2) for painless DSP+; and 0.84 (0.4-1.6) for painful DSP+. Swelling ratios were calculated for all participants and those with IENFD > 1.0 fibre/mm. When only those participants with IENFD > 1.0 fibre/mm were included, the axonal swelling ratio was higher in participants with type 2 diabetes when compared with healthy control participants (p < 0.001); however, there was no difference between DSP- and painless DSP+ participants, or between painless DSP+ and painful DSP+ participants. The axonal swelling ratio correlated weakly with HbA1c (r = 0.16, p = 0.04), but did not correlate with the Toronto Clinical Scoring System (surrogate measure of DSP severity), BMI or type 2 diabetes duration.Conclusions/interpretationIn individuals with type 2 diabetes where IENFD is >1.0 fibre/mm, axonal swelling ratio is related to type 2 diabetes but is not related to DSP or painful DSP. Axonal swellings may be an early marker of sensory nerve injury in type 2 diabetes.
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Project description:ObjectiveTo investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP.MethodsWe performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline.ResultsWe included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP.ConclusionMeasures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation.SignificanceThere are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients.
| S-EPMC9087194 | biostudies-literature
Project description:The purpose was to test whether physicians can validly and reproducibly diagnose diabetic sensorimotor polyneuropathy (DSPN). Twelve physicians assessed 24 patients with diabetes mellitus (DM) on consecutive days (576 examinations) with physical features and voice disguised. Results were compared to gold standard 75% group diagnosis (dx) and a nerve conduction score (Sigma5 NC nds). Masking of patients was achieved. Reproducibility measured by the kappa coefficient and compared to Sigma5 NC nd varied considerably among physicians: median and ranges: signs 0.8 (0.32-1.0); symptoms 0.79 (0.36-1.0), and diagnoses 0.47 (0.33-0.84), both low and high scores indicating poor performance. There was substantial agreement between 75% group dx and confirmed NC abnormality (abn). As compared to Sigma5 NC, individual physicians' clinical dx was excessively variable and frequently inaccurate. Study physician dx from signs and symptoms were excessively variable, often overestimating DSPN. Specific approaches to improving clinical proficiency should be tested.
| S-EPMC2956592 | biostudies-literature
Project description:ObjectiveIn vivo Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis.MethodsIn a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4±17.3y, HbA1c 5.5±0.4%) and 26 participants with type 1 diabetes (42.8±16.9y, 8.0±1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY-AUTOMATED). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols.ResultsMean CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-Automated was 12.5±2.8, 10.9 ± 2.9 mm/mm2. Inter-observer ICC and 95% confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p<0.05 for CNFLFully-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automated and CNFLFully-Automated underestimated CNFLManual by mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively.ConclusionsDespite an apparent measurement (underestimation) bias in comparison to the manual strategy of image analysis, fully-automated analysis preserves CNFL reproducibility. Future work must determine the diagnostic thresholds specific to the fully-automated measure of CNFL.
| S-EPMC4634969 | biostudies-literature
Project description:AbstractEndogenous pain modulation, as tested by the conditioned pain modulation (CPM) protocol, is typically less efficient in patients with chronic pain compared with healthy controls. We aimed to assess whether CPM is less efficient in patients with painful diabetic polyneuropathy (DPN) compared with those with nonpainful DPN. Characterization of the differences in central pain processing between these 2 groups might provide a central nervous system explanation to the presence or absence of pain in diabetic neuropathy in addition to the peripheral one. Two hundred seventy-one patients with DPN underwent CPM testing and clinical assessment, including quantitative sensory testing. Two modalities of the test stimuli (heat and pressure) conditioned to cold noxious water were assessed and compared between patients with painful and nonpainful DPN. No significant difference was found between the groups for pressure pain CPM; however, patients with painful DPN demonstrated unexpectedly more efficient CPMHEAT (-7.4 ± 1.0 vs -2.3 ± 1.6; P = 0.008). Efficient CPMHEAT was associated with higher clinical pain experienced in the 24 hours before testing (r = -0.15; P = 0.029) and greater loss of mechanical sensation (r = -0.135; P = 0.042). Moreover, patients who had mechanical hypoesthesia demonstrated more efficient CPMHEAT (P = 0.005). More efficient CPM among patients with painful DPN might result from not only central changes in pain modulation but also from altered sensory messages coming from tested affected body sites. This calls for the use of intact sites for proper assessment of pain modulation in patients with neuropathy.
| S-EPMC9009321 | biostudies-literature