Early Diabetic Neuropathy Research Articles

Construction of an Early Risk Prediction Model for Type 2 Diabetic Peripheral Neuropathy Based on Random Forest.

Diabetic peripheral neuropathy is a major cause of disability and death in the later stages of diabetes. A retrospective chart review was performed using a hospital-based electronic medical record database to identify 1020 patients who met the criteria. The objective of this study was to explore and analyze the early risk factors for peripheral neuropathy in patients with type 2 diabetes, even in the absence of specific clinical symptoms or signs. Finally, the random forest algorithm was used to rank the influencing factors and construct a predictive model, and then the model performance was evaluated. Logistic regression analysis revealed that vitamin D plays a crucial protective role in preventing diabetic peripheral neuropathy. The top three risk factors with significant contributions to the model in the random forest algorithm eigenvalue ranking were glycosylated hemoglobin, disease duration, and vitamin D. The areas under the receiver operating characteristic curve of the model ware 0.90. The accuracy, precision, specificity, and sensitivity were 0.85, 0.83, 0.92, and 0.71, respectively. The predictive model, which is based on the random forest algorithm, is intended to support clinical decision-making by healthcare professionals and help them target timely interventions to key factors in early diabetic peripheral neuropathy.

Pathological evaluation of the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy.

Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications leading to its cure is becoming increasingly urgent. Pathological examination of pancreatic tissues from patients with type 2 diabetes reveals a decrease in the volume of beta cells because of a combination of various stresses. In human type 2 diabetes, islet amyloid deposition is a unique pathological change characterized by proinflammatory macrophage (M1) infiltration into the islets. The pathological changes in the pancreas with islet amyloid were different according to clinical factors, which suggests that type 2 diabetes can be further subclassified based on islet pathology. On the other hand, diabetic peripheral neuropathy is the most frequent diabetic complication. In early diabetic peripheral neuropathy, M1 infiltration in the sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated by in vitro live imaging. Furthermore, islet parasympathetic nerve density and beta cell volume were inversely correlated in type 2 diabetic Goto-Kakizaki rats, suggesting that diabetic peripheral neuropathy itself may contribute to the decrease in beta cell volume. These findings suggest that the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy may be interrelated.

Circulating netrin-1 levels are reduced and related to corneal nerve fiber loss in patients with diabetic neuropathy.

Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin-1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin-1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy. A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN- n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy. Corneal nerve fiber density, branch density, fiber length and serum netrin-1 levels were significantly lower in the DN- and DN+ groups compared with controls (P < 0.001). Netrin-1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin-1 cut-off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76-0.94) for differentiating patients with and without corneal nerve loss. Serum netrin-1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin-1 could act as a biomarker for small nerve fiber damage in DN.

The vagus nerve cross-sectional area on ultrasound in patients with type 2 diabetes.

Diabetic neuropathy, including autonomic neuropathy is a serious complication related to type 2 diabetes mellitus (T2D). The vagus nerve (VN) is the longest nerve in the autonomic nervous system, and since diabetic neuropathy manifests first in longer nerves, the VN is commonly affected in early diabetic autonomic neuropathy. The use of high-resolution ultrasound for peripheral and cranial nerve imaging has significantly increased over the past 2 decades. The aim of the study is to compare the cross-sectional area of the VN in patients with T2D to that of a control cohort without T2D. A total of 52 VN cross-sectional areas were recorded from patients with T2D. A total of 56 VN cross-sectional areas were also recorded from asymptomatic subjects without T2D. In each subject, high-resolution ultrasound imaging of the bilateral VNs was performed in the short-axis between the common carotid artery and the internal jugular vein. The VN cross-sectional areas were recorded and compared. In the patients with T2D, HbA1c and fasting blood glucose levels were obtained as well as the duration of T2D in years and correlated with the cross-sectional areas. The bilateral VN cross-sectional areas were similar in both cohorts. Additionally, no correlation was seen between the VN cross-sectional areas, demographics, or clinical data of T2D. Our study demonstrated normal VN cross-sectional areas in patients with T2D without any significant relation with the patients' demographic or clinical data.

Skin microcirculatory responses: A potential marker for early diabetic neuropathy assessment using a low-cost portable diffuse optical spectrometry device.

Diffuse optical measurement is an evolving optical modality providing a fast and portable solution for microcirculation assessment. Diffuse optics in static and dynamic modalities are combined here in a system to assess hemodynamics in skin tissues of control and diabetic subjects. The in-house developed system consists of a laser source, fiber optic probe, a low-cost avalanche photodiode, a finite element model (FEM) derived static optical property estimator, and a software correlator for continuous flow monitoring through microvasculature. The studies demonstrated that the system quantifies the changes in blood flow rate in the immediate skin subsurface. The system is calibrated with in vitro flow models and a proof-of-concept was demonstrated on a limited number of subjects in a clinical environment. The flow changes in response to vasoconstrictive and vasodilative stimuli were analyzed and used to classify different stages of diabetes, including diabetic neuropathy.

Potential predictive biomarker for diabetic peripheral neuropathy: serum neuron-specific enolase

Abstract The early stages of diabetic peripheral neuropathy (DPN) are symptomless. A reliable dependable and sensitive biomarker is needed for the purpose of early identification of diabetic peripheral neuropathy. The main objective of the study was to evaluate the accuracy of serum neuron-specific enolase (NSE) as a biomarker for early identification of diabetic peripheral neuropathy. Patient samples were collected from the National Diabetes Center, Mustansiriyah University; a case control study was done from April 2022 to November 2022, in Baghdad, Iraq. One hundred sixty individuals between 30 to 60 years-old were included. Participants were divided into three groups: group one included 40 type 2 diabetic patients with peripheral neuropathy, group two consisted of 40 type 2 diabetic patients without peripheral neuropathy and group three included 80 apparently in good health as the control. Toronto Clinical Neuropathy Scoring System (TCSS) was used for clinical evaluation of peripheral neuropathy. Glycated hemoglobin (HbA1c) was measured by the CLOVER A1c system. In addition, serum NSE levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) technique. Age, sex, and other standard variables were used as a basis for comparisons between groups. Statistically, diabetic patients with peripheral neuropathy demonstrated higher level of NSE (28.42±6.93 ng/ml) than did either diabetic patients without peripheral neuropathy (21.07±2.0 ng/ml) or controls (12.54±2.34 ng/ml) with a high degree of significance (p &lt;0.001). In the context of Discrimination between DPN patients and diabetic patients without neuropathy, the area under curve for neuron-specific enolase was 0.812, 95% confidence interval [CI] = 0.716-0.909, p &lt;0.001. Cut-off value of serum neuron-specific enolase was 22.53 ng/ml, sensitivity and specificity were 70% and 77%, respectively. In the context of discrimination between DPN and controls, the area under curve for neuron-specific enolase was 1.00, 95% confidence interval was 1.0-1.0, p &lt;0.001. At a cut-off value of serum neuron-specific enolase = 18.3 ng/ml, both the sensitivity and specificity were 100%. Neuron-specific enolase could potentially be used as a biomarker to detect early diabetic peripheral neuropathy and prevent it from developing to an advanced state.

Early detection of diabetic peripheral neuropathy using EMLA-induced skin wrinkling

Background &amp; Objective: Screening for early diabetic peripheral neuropathy (DN) is essential for foot ulcer prevention. The Semmes–Weinstein monofilament (SWMF) is commonly used to detect DN in Thailand. However, SWMF interpretation requires patient participation, which is susceptible to risk of error in patients with impaired cognitive function or uncooperative patients. In contrast, stimulated skin wrinkling (SSW) can be interpreted by trained investigators, which is more appropriate. This study aimed to investigate the utility of SSW using a eutectic mixture of local anesthetic (SSW-EMLA) for early DN diagnosis. Methods: This cross-sectional study, recruited 102 patients with diabetes (DM group), 33 with diabetes with foot ulcer (DN control group), and 30 without diabetes (non-DN control group) from the Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Thailand, from February 3, 2021 to November 30, 2021. SSW was conducted by applying EMLA on the tips of the 2nd, 3rd, and 4th fingers of both hands. SWMF, sensory perception of pain (SPP), vibration perception threshold (VPT), joint position sense (JPS), and deep tendon reflexes (DTR) were also evaluated on the same day. Results: The Interrater agreement of two investigators for SSW-EMLA was high with intraclass correlation coefficients of 0.87 (0.824–0.904) for the right hand and 0.874 (0.830–0.907) for the left hand. The kappa coefficients of agreement of SSW-EMLA for SPP, SWMF, VPT, JPS, and DTR testing were 0.411, 0.478, 0.714, 0.444, and 0.681, respectively. The sensitivity and specificity of SSW-EMLA testing for DN detection were 83.3%, was 85.7%, respectively. Conclusion: The SSW-EMLA test can be considered as an alternative method for DN detection, due to its noninvasiveness, inexpensiveness (50THB), being a simple procedure, high sensitivity and specificity, and acceptable rater variation.

Development and validation of a risk prediction model for early diabetic peripheral neuropathy based on a systematic review and meta-analysis.

Early identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome. To establish a risk prediction model for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). The derivation cohort was from a meta-analysis. Risk factors and the corresponding risk ratio (RR) were extracted. Only risk factors with statistical significance were included in the model and were scored by their weightings. An external cohort were used to validate this model. The outcome was the occurrence of DPN. A total of 95,604 patients with T2DM from 18 cohorts were included. Age, smoking, body mass index, duration of diabetes, hemoglobin A1c, low HDL-c, high triglyceride, hypertension, diabetic retinopathy, diabetic kidney disease, and cardiovascular disease were enrolled in the final model. The highest score was 52.0. The median follow-up of validation cohort was 4.29 years. The optimal cut-off point was 17.0, with a sensitivity of 0.846 and a specificity of 0.668, respectively. According to the total scores, patients from the validation cohort were divided into low-, moderate-, high- and very high-risk groups. The risk of developing DPN was significantly increased in moderate- (RR 3.3, 95% CI 1.5-7.2, P = 0.020), high- (RR 15.5, 95% CI 7.6-31.6, P < 0.001), and very high-risk groups (RR 45.0, 95% CI 20.5-98.8, P < 0.001) compared with the low-risk group. A risk prediction model for DPN including 11 common clinical indicators were established. It is a simple and reliable tool for early prevention and intervention of DPN in patients with T2DM.

Diabetic peripheral neuropathy and their associations with overweight/obesity and impaired blood glucose among diabetic patients in Eastern Ethiopia: Institutional-based study.

This study aimed to determine the burden of diabetic peripheral neuropathy and its associations with overweight/obesity and impaired blood glucose among diabetic patients in Eastern Ethiopia. A total of 644 diabetic individuals were included in the study through systematic random sampling techniques. The Michigan neuropathy screening instrument was used to evaluate the presence of diabetic neuropathy. Data were presented using narrative, figures, and tables from the results of statistical analysis. The descriptive result was reported using frequency (percentage) for categorical variables and mean ± SD for continuous measures, respectively. Multivariable logistic regression was performed to identify factors associated with diabetic peripheral neuropathy. The overall prevalence of diabetic peripheral neuropathy was 47.8% (95% CI: 43.9%-51.7%). Low monthly income (AOR: 2.02, 95% CI: 1.09, 3.73), history of khat chewing (AOR: 2.32, 95% CI: 1.04, 4.907), impaired blood glucose (AOR: 1.52, 95% CI: 1.63, 1.94), physical inactivity (AOR: 2.76, 95% CI: 1.74, 4.36), and raised body mass index (AOR: 2.45, 95% CI: 1.01, 4.99) were factors significantly associated with diabetic peripheral neuropathy. The study emphasizes the value of early diabetic peripheral neuropathy detection and the widespread presence of diabetic peripheral neuropathy risk factors in diabetes patients. Any initiative intended to lessen the burden of diabetic peripheral neuropathy-related morbidity and high health care costs must be implemented as a strategy.

Taste dyfunction in obese type 2 diabetic individuals

Obesity is a well-known risk factor for many diseases. It is also known to enhance complications of many diseases eg. Type 2 Diabetes mellitus (T2DM). This study was done to assess the gustatory functions in obese T2DM individuals. This study was done to assess the gustatory functions in obese T2DM subjects and compare the same with lean T2DM individuals. A comparative study with a sample size of 40 was conducted. Patients aged 25 to 50 years with T2DM &amp;#60; 5 years duration and HBA1C ≤ 7 were divided into 2 groups, Group I- with normal weight (BMI of 18.5 to &amp;#60;25) and Group II with grade 1 obesity (BMI of 30 to &amp;#60; 35). Triple Drop Test was done to evaluate gustatory functions. Scoring from “5” to “1” was done on the identification of different concentrations of tastants. Taste scores for sweet, salty, sour, and bitter tastants were lesser in obese diabetics as compared to the lean T2DM subjects. This was statistically significant (p &amp;#60; 0.05) Conclusion: Taste impairment is observed in obese diabetic subjects. This could be an indication of early central diabetic neuropathy. Hypogeusia may cause an increased preference for sweet-tasting or salty foods thus imposing greater health risks, increasing obesity, and negatively affecting the quality of life.

Mosaic vs. Single Image Analysis with Confocal Microscopy of the Corneal Nerve Plexus for Diagnosis of Early Diabetic Peripheral Neuropathy.

The assessment of the corneal nerve fibre plexus with corneal confocal microscopy (CCM) is an upcoming but still experimental method in the diagnosis of early stage diabetic peripheral neuropathy (DPN). Using an innovative imaging technique-Heidelberg Retina Tomograph equipped with the Rostock Cornea Module (HRT-RCM) and EyeGuidance module (EG)-we were able to look at greater areas of subbasal nerve plexus (SNP) in order to increase the diagnostic accuracy. The aim of our study was to evaluate the usefulness of EG instead of single image analysis in diagnosis of early stage DPN. This prospective study was performed on 60 patients with type2 diabetes mellitus, classified equally into two subgroups based on neuropathy deficient score (NDS): patients without DPN (group1) or with mild DPN (group2). The following parameters were analysed in the two subgroups: corneal nerve fibre length (CNFL; mm/mm2), corneal nerve fibre density (CNFD;no./mm2), corneal nerve branch density (CNBD;no./mm2). Furthermore, we compared the data calculated with the novel mosaic, EG-based method with those received from single image analysis using different quantification tools. Using EG we did not find a significant difference between group1 and group2: CNFL (16.81 ± 5.87mm/mm2 vs. 17.19 ± 7.19mm/mm2, p = 0.895), CNFD (254.05 ± 115.36no./mm2 vs. 265.91 ± 161.63no./mm2, p = 0.732) and CNBD (102.68 ± 62.28no./mm2 vs. 115.38 ± 96.91no./mm2, p = 0.541). No significant difference between the EG method of analysing the SNP and the single image analysis of 10 images per patient was detected. On the basis of our results it was not possible to differentiate between early stages of large nerve fibre DPN in patients with type2 diabetes mellitus via SNP analysis. To improve sensitivity and specificity of this method newer technologies are under current evaluation. ClinicalTrials.gov Identifier NCT05326958.

Determination of median nerve conduction velocity and F-wave minimal latency to diagnose early onset of diabetic neuropathy

Diabetes mellitus is a metabolic disorder characterized by many abnormalities and leads to long term complications like diabetic neuropathy, nephropathy and retinopathy. Diabetic peripheral neuropathy causes symptoms of peripheral nerve dysfunction. Sensory nerve conduction velocity (SNCV), distal sensory latency and F-waves minimal latency of median nerve are important parameters of electro diagnosis for early detection of diabetic neuropathy. The objective of the study was to determine the specificity and sensitivity of the sensory nerve conduction velocity and F-wave minimal latency of median nerve in diabetic subjects in early detection of diabetic neuropathy. Thirty subjects recruited for the study were divided into group A comprising of healthy subjects (n=10, age: 62.70±10.49 years) and group B consisting of diabetic subjects (n=20, age: 68.05±6.44 years). NICOLET VIKING QUEST instrument was used for the nerve conduction velocity test. SNCV of the median nerve significantly decreased in diabetic subject when compared with control group. However, the F-wave minimal latency was not specific and sensitive over SNCV to diagnose early diabetic neuropathy in clinically asymptomatic patients. We concluded that sensory nerve conduction velocity was much more sensitive and specific than F-wave minimal latency to detect early diabetic neuropathy.

The Evaluation of Gait and Balance for Patients with Early Diabetic Peripheral Neuropathy: A Cross-Sectional Study.

ObjectiveFalls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.MethodsA total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.ResultsStride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p<0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p<0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p<0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p<0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p<0.05).ConclusionThe abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.Clinical Trial Registration NumberNo. ChiCTR1800019179, www.chictr.org.cn.

Lower / upper extremity F-wave ratio for detecting early diabetic neuropathy.

Results of conventional nerve conduction studies may be within normal limits in early diabetic neuropathy. Previous studies demonstrated that F-wave latency should be used to detect this early neuropathic process. The aim of this study is to evaluate the sensitivity of lower/upper extremity F latency ratios in detecting the early neuropathy in patients with diabetic neuropathic pain. 44 patients with diabetic neuropathic pain (DNP) and 44 control subjects whose both conventional nerve conduction studies and F-wave latencies were within normal limits were included to the study. We compared the nerve conduction parameters and lower/upper extremity (tibial/ulnar) F latency ratios of the groups. Tibial F latency was significantly prolonged and tibial/ulnar F latency ratio was significantly higher in DNP group. Our results support that F-waves are useful for detecting early diabetic neuropathy and suggest that comparison with a control group will demonstrate a difference even when the individuals' F-wave latencies are within the normal limits. The difference was significant for tibial but not for ulnar F latency values supporting the length dependent involvement. The tibial/ ulnar F-wave latency ratio was significantly higher in the DNP group, suggesting that it might also be useful to detect early neuropathy and to demonstrate that the underlying process was predominant in lower extremity. Further studies may provide additional information about the utility of this ratio for detecting early neuropathy even when F-wave latencies are within normal limits.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy.

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus, affecting nerves in all parts of the body including corneal nerves and peripheral nervous system, leading to diabetic corneal neuropathy and diabetic peripheral neuropathy, respectively. Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies, clinical scoring, and skin biopsies. However, these diagnostic methods have limited sensitivity in detecting small-fiber disease, hence they do not accurately reflect the status of diabetic neuropathy. More recently, analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy. In this review, we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy, elaborating on the foundational aspects of each: pathogenesis, clinical presentation, evaluation, and management. We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy, particularly early diabetic peripheral neuropathy; the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy; and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Optimization of the method for diagnostics of cardial autonomic neuropathy in diabetes mellitus 2 types

Introduction. Early diagnosis of cardiac autonomic neuropathy is the basis for the risk of heart disease and premature death in patients with type 2 diabetes mellitus (type 2 diabetes). All patients with type 2 diabetes and prediabetes should undergo annual screening, including history taking and neurophysiologic evaluation, for early diabetic autonomic neuropathy. This article describes a modern diagnostic technique based on changes in heart rate variability, which allows early detection of damage to the parasympathetic nervous system and timely prescribing disease-modifying treatment in patients with type 2 diabetes.Materials and methods. The study included 50 patients with type 2 diabetes (cf. Age 56.5 ± 13.5 years) and 30 healthy subjects (cf. Age 58 ± 10 years), matched by sex and age. according to the NSC questionnaire, the severity of neurological deficit - according to the NIS-LL scale, neuropathic pain syndrome - according to the TSS scale.Results. In the study group of patients with type 2 diabetes, severe CAN was detected in 13.3%, moderate CAN in 40% of patients, in 46.6% of patients, CAN was not detected. In the group of healthy volunteers, disorders of the autonomic nervous system of moderate were detected in 3.3%, in the remaining 96.7% of autonomic disorders were not accepted.Conclusion. The results of pulse oximetric tests with deep breathing are comparable to the results of the QAT device Case-4 (p &lt; 0.001). The method of pulse oximetric diagnostics is more practical to use in comparison with the hardware QAT.

Sensory and motor axonal excitability testing in early diabetic neuropathy

ObjectiveThe aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor axonal excitability testing. MethodsOne hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ± 0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48). ResultsMotor excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor excitability parameters and clinical scores. ConclusionsChanges in excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration. SignificanceLess pronounced excitability changes than NCS suggest that axonal excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.

Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy.

Background:Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications.Methods:Thirty-three type 1 diabetes patients, aged 20–35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques.Results:TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = −0.49 and r = −0.51, respectively), foot neuropathy impairment assessment score (NIA; r = −0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = −0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively).Conclusions:This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes.

Neuroprotective validation of pectin in T2DM-induced allodynia and hyperalgesia in diabetic peripheral neuropathic pain

Aim To validate neuroprotective effect of pectin against neuropathic pain in diabetic rodents. Material and method Pectin was isolated and characterised from different sources to validate its neuroprotective effect against T2DM associated neuropathic pain. The antioxidant activity of pectins was done by the DPPH method. Type-2 diabetes mellitus (T2DM) was induced in Wistar albino rats by high-fat diet and high-fat emulsion feeding for 2 weeks followed by a single i.p. of Sterptozotocin in 3rd week. The animals were grouped as positive control and Citrus sinensis (L.) Osbeck peel pectin (CSL-OP) as test group and treated for the next 4 weeks. Body weight and blood glucose were measured up to 8 weeks; however, behavioural assessment was done at the end of 5th to 8th week. Result CSL-OP restored the reduced body weight and elevated blood glucose with increased pain threshold and improved walking performance. Conclusion CSL-OP prevented progression of early diabetic neuropathy with anti-oxidant activity.

The Physiological Significance of A-Waves in Early Diabetic Neuropathy: Assessment of Motor Nerve Fibers by Neurophysiological Techniques.

Objective: This study aimed to investigate how early A-waves could occur in type II diabetes, and what it implied functionally.Methods: We performed conduction velocity distribution (CVD) test in peroneal nerves of 37 type II diabetic patients with normal nerve conduction study (NCS) and 22 age-matched controls. The electrophysiological data and clinical information were analyzed.Results: A-waves were observed in 45.9% of diabetic patients and only in 1 person in healthy controls, all detected in the tibial nerves. The diabetic patients with A-waves showed faster conduction velocity in all quartiles in the motor peroneal nerves compared to the patients without A-waves, and their CVD histograms were shifted to the right side, consisting of a significantly larger percentage of fast conducting fibers. There was no significant difference in the CVD values of the upper extremity nerves among the patients with and without A-waves and the healthy controls.Conclusion: A-waves could occur in type II diabetes as early as when NCS showed normal, and represented as a sign of neuropathy as well as a sign of rescued motor nerve function.