Diabetic Neuropathy

OBJECTIVE To determine the accuracy of clinical methods for detection of sensory neuropathy as compared to biothesiometry. STUDY DESIGN Cross-sectional analytical study. PLACE AND DURATION OF STUDY 1 Mountain Medical Battalion, Azad Kashmir, from October 2013 to September 2014. METHODOLOGY Patients with type 2 diabetes were enrolled by convenience sampling. Exclusion criteria included other identifiable causes of neuropathy, extensive ulceration of feet, amputated feet, those on treatment for neuropathy and unwilling patients. Average of 3 vibration perception threshold values measured with a biothesiometer on distal hallux was calculated. Ten gm monofilament was used to examine touch sensation over dorsal surfaces of great toes. Vibration sensation was checked over the tips of great toes using 128Hz tuning fork. Ankle jerks were checked bilaterally. RESULTS Neuropathy (vibration perception threshold > 25 volts) was present in 34 (21.12%) out of 161 patients and 93 (57.76%) were ...

Painful diabetic peripheral neuropathy (DPN) is a common complication of diabetes and the few approved therapies for the management of pain have limited efficacy and side effects. With the aim to explore and develop new pharmacological treatments, we investigated the antihyperalgesic properties of St. John's Wort (SJW) and feverfew in streptozotocin (STZ)-diabetic rats. Acute administration of a SJW seed extract reversed mechanical hyperalgesia with a prolonged effect. A SJW extract obtained from the aerial portion of the plant and a feverfew flower extract partially relieved neuropathic pain whereas a feverfew leaf extract was ineffective. The antihyperalgesic efficacy of these herbal drugs was comparable to that of clinically used antihyperalgesic drugs (carbamazepine, lamotrigine, L-acetyl-levocarnitine). Further examinations of SJW and feverfew composition revealed that hyperforin and hypericin might be responsible for the antihyperalgesic properties of SJW whereas the efficacy of feverfew seems to be related to the presence of parthenolide. Rats undergoing treatment with SJW and feverfew did not show any behavioral side effect or sign of altered locomotor activity. Our results suggest that SJW and feverfew extracts may become new therapeutic perspectives for painful DPN.

Diabetes is a common chronic disease with a prevalence of 8.3%. Diabetic neuropathy is a common neurological complication of the disease which interferes with the quality of life (QoL) of patients due to painful symptoms leading to disability. This study aims to evaluate the effects of diabetic neuropathy on disability and QoL. Sixty-two patients with clinical diabetic neuropathy were enrolled in the study. All underwent electrophysiological evaluations. Brief disability scale (BDS) and Short form-36 (SF-36) were used to evaluate disability and QoL of patients. Results revealed a negative correlation among increased pain quality assessment scale (PQAS), BDQ scores and QoL, emphasizing the interfering effect of pain on QoL of patients with diabetic neuropathy.

Diabetic neuropathy (DN) is a neurodegenerative disorder that is primarily characterized by distal sensory loss, reduced mobility, and foot ulcers that may potentially lead to amputation. The multifaceted etiology of DN is linked to a range of inflammatory, vascular, metabolic, and other neurodegenerative factors. Chronic inflammation, endothelial dysfunction, and oxidative stress are the three basic biological changes that contribute to the development of DN. Although our understanding of the intricacies of DN has advanced significantly over the past decade, the distinctive mechanisms underlying the condition are still poorly understood, which may be the reason behind the lack of an effective treatment and cure for DN. The present study delivers a comprehensive understanding and highlights the potential role of the several pathways and molecular mechanisms underlying the etiopathogenesis of DN. Moreover, Schwann cells and satellite glial cells, as integral factors in the pathogenesis of DN, have been enlightened. This work will motivate allied research disciplines to gain a better understanding and analysis of the current state of the biomolecular mechanisms behind the pathogenesis of DN, which will be essential to effectively address every facet of DN, from prevention to treatment.

Neuropathic pain is believed to arise from damage to nociceptive C fibres in diabetic neuropathy (DN). We have utilised corneal confocal microscopy (CCM) to quantify the severity of small nerve fibre damage in relation to the severity of neuropathic pain and quality of life (QoL) in patients with and without painful DN. 30 controls and patients with painful (n = 78) and painless (n = 62) DN underwent assessment of large and small nerve fibre function, CCM, neuropathic symptoms (small fibre neuropathy symptom inventory questionnaire, neuropathic pain scale) and QoL (SF-36, pre-R-ODS and hospital anxiety and depression scale). Patients with painful compared to painless DN, had comparable neurophysiology and vibration perception, but lower corneal nerve fibre density (20.1 ± 0.87 vs. 24.13 ± 0.91, P = 0.005), branch density (44.4 ± 3.31 vs. 57.74 ± 3.98, P = 0.03), length (19.61 ± 0.81 vs. 22.77 ± 0.83, P = 0.01), inferior whorl length (18.03 ± 1.46 vs. 25.1 ± 1.95, P = 0.005) and cold sensation threshold (21.35 ± 0.99 vs. 26.08 ± 0.5, P < 0.0001) and higher warm sensation threshold (43.7 ± 0.49 vs. 41.37 ± 0.51, P = 0.004) indicative of small fibre damage. There was a significant association between all CCM parameters and the severity of painful neuropathic symptoms, depression score and QoL. CCM identifies small nerve fibre loss, which correlates with the severity of neuropathic symptoms and reduced QoL in patients with painful diabetic neuropathy.

Aims/hypothesisCorneal confocal microscopy is a rapid non-invasive ophthalmic imaging technique that identifies peripheral and central neurodegenerative disease. Quantification of corneal sub-basal nerve plexus morphology, however, requires either time-consuming manual annotation or a less-sensitive automated image analysis approach. We aimed to develop and validate an artificial intelligence-based, deep learning algorithm for the quantification of nerve fibre properties relevant to the diagnosis of diabetic neuropathy and to compare it with a validated automated analysis program, ACCMetrics.MethodsOur deep learning algorithm, which employs a convolutional neural network with data augmentation, was developed for the automated quantification of the corneal sub-basal nerve plexus for the diagnosis of diabetic neuropathy. The algorithm was trained using a high-end graphics processor unit on 1698 corneal confocal microscopy images; for external validation, it was further tested on 2137 ...

Diabetic polyneuropathy (DPN) is a complex and multifactorial entity in which various factors besides hyperglycemia play an important role. Symptoms of DPN are sensory, motor or autonomic. Intensive research proved that oxidative stress is the common denominator for the four major destructive pathways of hyperglycemia including increased hexosamine pathway flux, activation of Protein kinase-C (PKC) pathway, increased Advanced Glycated End-products (AGEs) formation, and increased Polyol Pathway flux. National data in Egypt confirms that more than 60% of Egyptian diabetic patients suffer from neuropathy. The most common complications of DPN are Cardiac Autonomic Neuropathy (CAN), diabetic foot and ulcers, neuromuscular disability, and anxiety. In addition, DPN affects the Quality of Life (QoL). According to common clinical practice, the common diagnostic tools are bed-side diagnosis and electrophysiological tests. Early diagnosis is critical to improve the prognosis of DPN and therape...

OBJECTIVE: This study aimed to investigate the therapeutic effect of ozone in combination with insulin on cranial and spinal neuropathy in rats with diabetes mellitus (DM). MATERIALS AND METHODS: Sixty adult male Sprague Dawley rats were randomly divided into the following six groups (n = 10): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone, insulin-treated diabetic (DOI). DM was induced by a single intraperitoneal (ip) streptozotocin injection (60 mg/kg), followed by 3 IU (ip) insulin administration for 60 days. Next, 1.1 mg/kg (50 μg/ml) ozone was administered to the O, DO, and DOI groups for 60 days. After inducing diabetes, the total oxidant status (TOS) and total antioxidant status (TAS) were measured; the oxidative stress index (OSI) was calculated. The brain and spinal cord tissues were obtained for histopathological evaluation. T his cross sectional study was conducted in Dumlupinar University Laboratory Animals Research Center e.g 11.03.2015 -15.05.2015. RESULTS: TAS was higher in the DO, DI, and DOI groups than in the D group. TOS and OSI were lower in the DO, DI, and DOI groups than in the D group. Little pathological alterations with degenerated axons and vascular congestion were observed in the DO, DI, and DOI groups compared with the D group. CONCLUSION: Ozone with insulin can stimulate the endogenous antioxidant defense mechanism in diabetic neuropathy, thereby preventing reactive oxygen species-induced da mage and protecting against cranial and spinal neuropathies (Fig. 6, Ref. 29).

Objective: To identify motor sensory deficits in the feet of neuropathic diabetic patients and compare their deficits with a group of healthy subjects. Method: 49 neuropathic diabetics (group NG) and 22 controls (group CG) underwent a three-stage protocol: (1) an interview using a questionnaire to characterize the neuropathy and symptoms; (2) assessment of muscle function and range of motion, and functional tests on the feet and ankles; (3) assessment of tactile and thermal sensitivity. The groups were compared using the chi-squared, Mann-Whitney and Student t tests (p< 0.05). Results: NG presented significant losses of tactile and thermal sensitivity in comparison with CG, especially in the heels (49.0% of NG and 97.3% of CG). Muscle function was decreased in NG, with predominance of loss of grade 5. The muscles most affected were the interossei (23.4%), extensor hallucis (42.5%) and triceps surae (43.2%), while all muscle function was preserved in CG. All ranges of motion in NG were reduced in comparison with CG. The functional tests on the ankles in NG presented a decrease of around 50%. Conclusion: There were significant differences between the groups with regard to sensitivity, muscle function, range of motion and functional losses. These differences can be attributed to the diabetic neuropathy.

Aim: Microangiopathy and neuropathy are late and severe complications of diabetes mellitus. Our aim was to examine the connection between neuropathy and microcirculatory disorder in type 2 diebetic patients in the mirror of metabolic state. Methods: In our study 50 patients with type 2 DM and symptoms of neuropathy were enrolled. The microcirculatary impairment was examined by Laser-Doppler flowmetry. Provocation probe, the venoarterial refex (VA) was implicated. The venoarterial reflex is is the decline in limb blood flow in the dependent position due to an increase in pre-capillary vascular resistance. To reify neuropathy, electroneurography (ENG) has been performed. Laboratory tests included lipid parameters and Hg A1C level. Examinations were done in age and sex matched control group. Results: During VA, decline in blood flow was sifgnificantly higher in the control group (78% vs. 31,8%; p<0,001). The results proved micrirculatory impairment. ENG confirmed peripherial neuropathy in every patient. Significant correlation could be detected between VA and triglyceride (R=0,35, p=0,015) and Hg A1C (R=0,322, p=0,024). There was no significant correlation between the VA and avarage disease course or severity of neuropathy. Conclusions: Our results show that VA is an excellent method to detect both neuropathy and microangiopathy in DM. Because of the relationship between the VA and glycemic control, the VA could be suitable for monitoring the effects of new therapies in DM.

The present study was conducted to assess the interrelationship and the influence of the coexistence of diabetes and hypothyroidism on thyroid hormone levels, insulin levels and biochemical variables related to carbohydrate, lipid and protein metabolism in addition to thyroid gland and Islets of Langerhans histological changes and antioxidant defense system. Methods: Diabetes mellitus was induced by intraperitoneal injection of streptozotocin to fasting albino rats at dose level of 45 mg/kg b. w. Hypothyroidism in diabetic and normal rats was induced by adding methimazole in drinking water (0.02% w/v) for 4 weeks. Results: The obtained results revealed that hypothyroidism interacts with diabetes in a way that prevents the progress of the hyperglycemic state. This may be due to the increase in the insulin secretory response in diabetic hypothyroid than diabetic rats. The serum leptin level and body weight gain were decreased in diabetic and diabetic hypothyroid rats; the leptin level was more deteriorated in diabetic hypothyroid rats while body weight gain was more affected in diabetic rats. Hepatic total thiols and glutathione contents and catalase and peroxidase activity were profoundly decreased in diabetic rats while they (except glutathione) were increased in hypothyroid and diabetic hypothyroid rats. Conclusions: In conclusion, the hypothyroidism may have a counteracting effect on the hyperglycemic state and the elevated serum T4 level as well as the deteriorated antioxidant defense system found in diabetes mellitus, but both experimentally-induced diseases may synergize in inducing more elevation of serum total lipids, total cholesterol and LDL-cholesterol and more decrease in leptin levels.

Introduction: Microvascular abnormalities have an important role in the most frequent neurological complications of diabetes mellitus: neuropathy and cerebrovascular disorders. Severity of neuropathy as well as of cerebral microvascular damage can be quantitatively evaluated by instrumental methods like nerve conduction studies and transcranial Doppler. In the present study, we investigated whether a correlation exists between the severity of peripheral neuropathy and the impairment of cerebrovascular reserve capacity (CRC) in 20 patients with Type 2 diabetes mellitus. Methods: CRC was measured by transcranial Doppler and defined as the maximal percentage increase in blood flow velocity in the middle cerebral artery within 20 min after an intravenous dose of 1000 mg of acetazolamide. Nerve conduction studies of the median, ulnar, peroneal, and sural nerves were performed. Severity of neuropathy was scored based on conduction velocities, amplitudes, and distal latencies. Results: There was no correlation between the neuropathic score and CRC (R = .003, P = .99). Neither CRC nor the neuropathic score correlated significantly with age, duration of diabetes, and serum values of HbA 1c , glucose, insulin, von Willebrand factor, and a 2 -macroglobulin. Severity of neuropathy but not CRC correlated with microalbuminuria (R = .47, P = .038 and R = .14, P = .54). Improper treatment reflected by HbA 1c > 10% was associated with significantly more severe albuminuria, higher actual blood glucose level, higher von Willebrand factor activity, and marginally higher neuropathic score (21 vs. 13, P = .096), but was not associated with CRC (44% vs. 42%, P = .81). When duration of diabetes was dichotomized to 15 years and less or over 15 years, CRC was significantly smaller (35% vs. 50%, P = .036) and neuropathy was more severe in the subgroup with longer diabetes duration (19 vs. 11.5 points, P = .07). Conclusions: Although both CRC and peripheral nerve function are affected more severely in patients with long-lasting Type 2 diabetes mellitus, damage in the cerebrovascular system and in the long peripheral nerves occur independently. As in diabetes mellitus pathological changes in autonomic and large peripheral nerves develop simultaneously, decreased CRC in diabetic patients might be predominantly due to structural changes of resistance arteries or to metabolic than to neurogenic factors.

Objective: To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN). Design: Randomized, placebo-control, parallel study. Setting: Forty-eight centers in 27 states. Participants: Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device. Intervention: Nerve conduction and/or quantified sensory testing were performed serially. Main Outcome Measures: Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (AN-COVA), and chi-square analysis were performed. Results: There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, Ϫ12%; for sham, Ϫ3%; PϽ.05, ANCOVA), numbness and tingling (magnet, Ϫ10%; sham, ϩ1%; PϽ.05, ANCOVA), and exercise-induced foot pain (magnet, Ϫ12%; sham, Ϫ4%; PϽ.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, Ϫ32%; sham, Ϫ14%; PϽ.01, ANOVA) and foot pain (magnet, Ϫ41%; sham, Ϫ21%; PϽ.01, ANOVA). Conclusions: Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.

Over the past 5 years there have been significant advances in the pathogenesis and management of diabetic peripheral neuropathic pain (DPNP) and this review attempts to summarize these. Recent research has shown that in addition to poor glucose control, traditional cardiovascular risk factors for macrovascular disease, are independent-risk factors for incident diabetic peripheral neuropathy (DPN). In contrast, the risk factors for DPNP are not known although data from the EURODIAB cohort suggest that female sex may be an independent-risk factor. The pathogensis of pain in DPNP is also not clear although differences in sural nerve epineurial blood flow, foot skin microcirculation and intraepidermal nerve fibre density (IENF), and thalamic magnetic resonance spectroscopy have been demonstrated between individuals with DPNP and painless neuropathy. Pharmacological treatment of DPNP includes tricyclic compounds (TCAs), selective serotonin noradrenaline reuptake inhibitors (SNRIs), anticonvulsants, opiates, membrane stabilizers, the antioxidant alpha lipoic acid, capsaicin etc. Current first-line therapies for DPNP are a TCA, SNRI (such as duloxetine) or anticonvulsants (such as pregabalin or gabapentin), taking into account patient comorbidities and cost. Summary There has recently been a consensus document suggesting an evidence-based protocol for the management of DPNP and this report is highlighted.

Poly(ADP-ribose) polymerase (PARP) activation is emerging as a fundamental mechanism in the pathogenesis of diabetes complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic sensory neuropathy. The experiments were performed in control and streptozotocin-induced diabetic rats treated with or without the PARP inhibitor 1,5-isoquinolinediol (ISO; 3 mg · kg−1 · day−1 i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw-withdrawal and tail-flick tests), mechanical hyperalgesia (von Frey anesthesiometer/rigid filaments and Randall-Sellito tests), tactile allodynia (flexible von Frey filaments), and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine and poly(ADP-ribose) immunoreactivities in the sciatic nerve and increased superoxide formation (hydroxyethidine method) and nitrotyrosine immunoreactivity in vasa ...

Background Peripheral neuropathy is a common complication of diabetes, whereby pain control is the most difficult issue. The outcomes of existing treatment options are far from satisfactory and the results of studies comparing them are indecisive. Hence, we aimed at comparing the effect of treating pain with transcutaneous electrical nerve stimulation (TENS), pregabalin and their combination in patients with painful diabetic neuropathy (PDN), including the quality-of-life aspect.

BACKGROUND Foot problems are a leading cause of hospitalization for patients having diabetes mellitus all over the world. Foot ulcers in diabetes precede 85 % of nontraumatic lower-extremity amputations. Fifteen percent develop foot ulcers during their lifetime. Individuals who develop foot ulcers have a decreased health-related quality of life and consume a lot of healthcare resources. Foot abnormalities is a frequently missed diagnosis and a focus in this area of medical education has never been optimal despite its frequency of presentation. In this study, we wanted to determine clinical and radiographic foot abnormalities in diabetic patients. METHODS A cross-sectional study was carried out on 180 type 2 diabetic patients diagnosed as per ADA definition of diabetes, they were categorized into three groups, the first consisted of 60 diabetic patients without neuropathy or foot ulcers, the second had 60 diabetic patients with neuropathy and the third had 60 diabetic patients with b...

Diabetic neuropathy is a microvascular complication that is one of the causes of mortality and morbidity. An increasing number of studies point to the association of mean platelet volume (MPV) and platelet distribution width (PDW) with microvascular complications in diabetic neuropathy patients. MPV, PDW can therefore be used as simple and cost-effective predictive parameters of platelet activation to monitor and predict the risk of vascular complications. Early diagnosis of neuropathy will ensure significant success in preventing complications.

Using a large US health insurance claims database, we identified all persons aged 18 years or older with 2 or more medical encounters in calendar year 2000 for painful neuropathic disorders (PNDs). We also identified an age-and gender-matched group of patients without PNDs (matched control subjects). We then compared the clinical characteristics and economic costs of PND patients with those of matched control subjects. There were a total of 55,686 patients with PNDs in the study database. The most frequently noted PNDs were back and neck pain with neuropathic involvement (62.3% of PND patients), causalgia (12.1%), and diabetic neuropathy (10.8%). In comparison with matched control subjects, PND patients were more likely to have other pain-related conditions, including fibromyalgia (6.0% vs 0.6% for control subjects), osteoarthritis (13.6% vs 3.6%), and other chronic comorbidities, such as coronary heart disease (13.6% vs 6.5%) and depression (6.4% vs 2.3%). Total calendar year 2000 health care charges were 3-fold higher for PND patients than matched control subjects ($17,355 vs $5,715, respectively). Our results suggest that patients with PNDs are generally in poorer health and have higher health care costs than their peers without these conditions. with PNDs, while relatively few received antiepileptic drugs and tricyclic antidepressants, both of which are often more effective against neuropathic pain. Our study raises questions about the optimality of PND treatment in clinical practice.

Diabetes mellitus (DM) is one of the world's most serious public health issues. Its high morbidity and death contribute to high healthcare costs, particularly in poorer nations. This study uses the cutting-edge mobile lab Cum Labike technology to ascertain the prevalence of diabetes and the risk factors related with it in the rural community. A cross-sectional study with 859 people over the age of 18 was carried out in two rural areas of Delhi. The WHO STEPS technique was employed to gather information on additional variables and socio-demographic parameters. Measurements were made of height, weight, blood sugar, and lipid profile. The semiautomated biochemistry analyzer on the mobile lab Cum Labike was used to gather and test the blood samples. Diabetes affected 4.1% of the participants in the study. Hypercholesterolemia, age, and raised triglycerides were significantly associated with diabetes. Prevention of risk factors, management of complications of these non-communicable diseases are possible if early detection can be made but due to unavailability of diagnostic facilities at cheaper rates most of the patients diagnosed too late. Labike using semiautomated biochemistry analyzer is an innovative technology and has the capacity as a point of care device used for the preventive screening and providing diagnostic services in the remote and rural areas.

Twenty-seven patients with successful transplantation and a control group of 14 patients with early rejection of the pancreas graft but functioning kidney graft were examined in a prospective study for 3 yr. Before transplantation, all patients had long-standing type I diabetes with advanced secondary complications, including end-stage diabetic nephropathy. After transplantation in the patients of both groups, kidney function was almost normal. Mean HbA., levels were normal in the group with pancreas graft survival. In the control group, HbA 1 levels were, on average, 1.5% higher compared with the group with pancreas survival (P = 0.00005). After 3 yr, the patients with functioning pancreas graft showed fewer symptoms (mean difference 1.0 in a symptom score ranging from 0 to 16, P = 0.004) compared with the control group. No statistically significant difference between both groups concerning clinical signs of polyneuropathy could be observed. In the pancreas and kidney transplantation group, peroneal and median nerve conduction velocities increased 7.2 m/s (P < 0.01) and 3.5 m/s (P < 0.05), respectively, whereas no increase was registered in the control group. The change of median and sural sensory nerve conduction velocities, peroneal and median compound muscle action potentials, and sural and median sensory action potentials was insignificant. In conclusion, although the improvement of clinical symptoms and neurophysiological signs of polyneuropathy was modest in the pancreas and kidney transplantation group, our data suggest that successful pancreas transplantation is able not only to halt the progression

Purpose of review-This review will summarize recent findings of the effect of supplemental fatty acids, with an emphasis on omega-3 polyunsaturated fatty acids, as a treatment for diabetic peripheral neuropathy. Recent findings-Pre-clinical studies have provided evidence that treating diabetic rodents with δ linolenic acid (omega-6 18:3) and to a greater extent with eicosapentaenoic and docosahexaenoic acids (omega-3 20:5 and 22:6, respectively) improve and even reverse vascular and neural deficits. Additional studies have shown resolvins, metabolites of eicosapentaenoic and docosahexaenoic acids, can induce neurite outgrowth in neuron cultures and that treating type 1 or type 2 diabetic mice with resolvin D1 or E1 provides benefit for peripheral neuropathy similar to fish oil. Summary-Omega-3 polyunsaturated fatty acids derived from fish oil and their derivatives have anti-inflammatory properties and could provide benefit for diabetic peripheral neuropathy. However, clinical trials are needed to determine whether this statement is true.

The study of diabetic neuropathy has relied primarily on the use of streptozotocin-treated rat and mouse models of type 1 diabetes. This chapter will review the creation and use of other rodent models that have been developed in order to investigate the contribution of factors besides insulin deficiency to the development and progression of diabetic neuropathy as it occurs in obesity, type 1 or type 2 diabetes. Diabetic peripheral neuropathy is a complex disorder with multiple mechanisms contributing to its development and progression. Even though many animal models have been developed and investigated, no single model can mimic diabetic peripheral neuropathy as it occurs in humans. Nonetheless, animal models can play an important role in improving our understanding of the etiology of diabetic peripheral neuropathy and in performing preclinical screening of potential new treatments. To date treatments found to be effective for diabetic peripheral neuropathy in rodent models have failed in clinical trials. However, with the identification of new endpoints for the early detection of diabetic peripheral neuropathy and the understanding that a successful treatment may require a combination therapeutic approach there is hope that an effective treatment will be found.

Patch clamp techniques were used to record whole cell and single channel Na + currents from NB41A3 neuroblastoma cells grown in culture. Cells were grown for two weeks in control medium or medium supplemented with 30 rnM D-glucose of 30 mM L-fucose. Cells exposed to glucose or L-fucose had smaller whole cell Na + currents than cells grown in unsupplemented medium, consistent with earlier studies . Whole cell macroscopic currents showed no change in activation or inactivation kinetics. Single channel current properties and opening probability were also unchanged. The number of [3H]saxitoxin binding sites, and therefore the total number of Na + channels, was not reduced in ceils grown in glucose or L-fucose . Therefore, we conclude that some of the channels must have been rendered nonfunctional by the conditioning media. The finding that single channel properties are not altered suggests that channels become nonfunctional in an all-or-none manner.

Objective: Exploring novel therapeutic approaches for diabetic neuropathy (DN) is crucial, and Ficus carica seed oil (FCSO) emerges as a promising candidate due to its rich composition of fatty acids, phenolics, antioxidants, and anti-inflammatory compounds. This study aimed to investigate the effects of FCSO treatment on the progression of DN. Materials and Methods: Adult male Wistar rats were randomly assigned to control, untreated diabetic, and FCSO-treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg, confirmed by hyperglycemia (>250 mg/ dL). The treatment group received FCSO orally at a dose of 4 mL/kg/day for 5 weeks. Blood glucose was monitored at the initiation and conclusion of the treatment, while insulin and glycated hemoglobin (HbA1c) were assessed at the study's endpoint. The hot plate test was conducted at the 3 rd and 5 th weeks of treatment. Sciatic nerve electrophysiology was performed, followed by biochemical analyses for markers of inflammation and oxidative stress. Results: Diabetes resulted in elevated blood glucose and HbA1c levels, along with decreased insulin levels, indicative of diabetic conditions. Increased oxidative stress and inflammation were observed, alongside reductions in nociceptive response and nerve conduction velocity, indicating DN progression. However, FCSO treatment mitigated these effects, restoring markers to levels comparable to those of normal controls. Conclusion: Early intervention with FCSO appears to counteract the mechanisms leading to DN, exerting neuroprotective and preventive effects. These findings underscore the therapeutic potential of FCSO and highlights its role as a promising treatment against DN.

Background: Peripheral neuropathy and cognitive decline both are very common in diabetics but relationship between them is yet unclear. Hence, this study aimed at assessing the cognitive functions in patients of type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) and compare them with that of patients of T2DM without DPN and apparently healthy controls. Materials and Methods: In this observational cross sectional study eligible T2DM patients were divided into two groups with DPN (25) and without DPN (25) by Nerve conduction velocity (NCV). 25 apparently healthy controls were taken. Cognitive functions were tested by using P300 event related potential. Result: P300 latency on Pz was significantly delayed in the T2DM with DPN as compared to T2DM without DPN (p &lt; 0.05) and controls (p &lt; 0.01). The average latency was also significantly delayed in T2DM with DPN as compared to controls(p &lt; 0.05).A positive correlation between duration of diagnosis of T2DM (...

Diabetic peripheral neuropathy (DPN) impacts up to 50% of diabetic people and is a major cause of illness and death. Its neuropathic symptoms, which can be painful, and insensitivity increase the risk of burns, injuries, and foot ulcers. Several recent studies have identified several risk factors for developing DPN, including obesity, poor glycemic control, diabetes duration, hyperlipidemia, impaired insulin signaling, and lipid oxidation and inflammation. Inspection of the lower limbs is necessary for the diagnosis. Anticonvulsant or tricyclic medications, which are typically used, may be needed. Peripheral neuropathy patients should be treated by a podiatrist and given preventative education since they risk developing insensate foot ulcers. A multidisciplinary approach to preventing and managing foot problems, promptly diagnosing and treating neuropathic pain, and controlling specific cardiometabolic objectives should all be included in treating patients with DPN. The concept of categorizing patients based on different aspects of their pain to enhance analgesic response is being researched, and new drugs are being developed to manage painful DPN.

Background :Diabetes Mellitus, as abbreviated as DM, is a chronic disease characterized by an increase in glucose levels in the blood due to insulin damage, which can reduce the amount of glucose that enters into cells. Administration of black glutinous water soaking can reduce the need for chemical drugs, because with minimal resources it can increase the coverage and extend of nursing services without geographic boundaries.Objectives :This research aimed to determine the effect of black glutinous water soaking on the decrease in blood sugar levels in patient with type 2 diabetes.Methods :Research methods used quasi experimental. The sample consisted of 50 respondents with the inclusion criteria for type 2 DM patients who do not have gangrene complications and the data were analyzed using the Wilcoxon test.Results : The results showed that the most age in patients with type 2 diabetes mellitus is between the ages of 50-59 years (80%). Gender is most women than men, as many as 35 pa...

Oxidative stress has been implicated in pathophysiology of diabetic neuropathy. All the pathways responsible for development of diabetic neuropathy are linked to oxidative stress in one way or the other. In the present study, we have targeted oxidative stress in diabetic neuropathy using resveratrol, a potent antioxidant. Eight weeks streptozotocin-diabetic rats developed neuropathy which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and increased thermal hyperalgesia. The 2-week treatment with resveratrol (10 and 20 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, and hyperalgesia. Resveratrol also attenuated enhanced levels of malondialdehyde (MDA), peroxynitrite and produced increase in catalase levels in diabetic rats. There was marked reduction in DNA fragmentation observed after resveratrol treatment in diabetic rats as evident from decrease in Terminal deoxy...

Introduction: Environmental neuropathy is a major cause of disability in diabetic patients. Pain is a major symptom in neuropathy which appears in more than 30% of diabetic patients. The whole body vibration therapy is one of the non-pharmacological methods in pain control in environmental neuropathy. The present study has been conducted with the aim to investigate the effects of lower limb vibration therapy on controlling the pain of diabetic neuropathy. Methods: The present study is a pre/post interventional research which has been conducted on 36 patients suffering from diabetic neuropathy. The subjects have been introduced into the study with simple sampling. At the beginning of the study, demographic traits and pain severity have been measured and registered by the researcher. Vibration therapy has been done on neuropathic limbs for two weeks. This task has been performed two times a day, each lasting for 10 minutes. Ultimately; after a two-week intervention, the patients' pain severity has been measured again by visual scale. The mean and standard deviation of the participants' age was 52.38±11.61 years. The majority of the participants were female (26 subjects; 72%). The mean and standard deviation of the patients' pain before the vibration therapy was 5.21±1.37 and after three periods of vibration therapy was reduced to 4.30±1.41. In other words, pain severity has been reduced after vibration therapy which had a meaningful difference (p=0.001) using paired T-test. Conclusion: Lower limb vibration therapy can reduce the diabetic neuropathic pain, thus can be utilized as a method of diabetic pain relief.

Aim: To evaluate the effects of a preventive antioxidant treatment of streptozotocin (STZ)-diabetic rats with epigallocatechin gallate (EGCG) in oxidative stress damage and neuronal activation at the spinal cord and in behavioural signs of diabetic neuropathic pain (DNP). Materials and Methods: Three days after STZ injection, the rats initiated a treatment protocol with an aqueous solution of EGCG (2g/L) in the drinking water during 10 weeks. Mechanical nociception was evaluated before and after EGCG treatment using the paw-pressure and von Frey tests. Spinal cords were immunoreacted against 8-hydroxy-2'-deoxyguanosine (marker of oxidative stress damage; 8-OHdG), and double immunoreacted against 8-OHdG and Fos (marker of neuronal activation). Results: STZ rats presented increased oxidative stress damage (immunodetection of 8-OHdG) and higher activation of nociceptive spinal neurons (immunodetection of Fos protein), with a contingent of 8-OHdG-positive neurons also expressing Fos than in age-matched controls. In these animals mechanical hyperalgesia (pawpressure test) and tactile allodynia (von Frey test) were higher than in controls. Treatment with EGCG normalized oxidative stress and neuronal activation to control levels and ameliorated behavioral mechanical nociceptive responses. Conclusions: The beneficial effects of the preventive antioxidant treatment with EGCG at the spinal cord and behavioral signs of DPN indicate that early detection of diabetes allows the onset of antioxidant treatment that can prevent oxidative stress-induced damage to the somatossensory system.

Diabetes is a major health problem with an alarming increasing prevalence, and is the most frequent cause of neuropathy worldwide. Neuropathy affects 50–60% of diabetic patients, being a major life-quality impairment for a quarter of these patients. Diabetic neuropathic pain (DNP) is characterized by spontaneous pain, mechanical hyperalgesia and tactile allodynia and is accompanied by functional and neurochemical changes at the peripheral nerves, spinal cord and supraspinal pain control areas. Regarding the effects of diabetic neuropathy in the central somatossensory system, it was shown that streptozotocin (STZ)-diabetic rats present spontaneous hyperactivity and hyperexcitability of spinal nociceptive neurons, which may be subserving the exacerbated pain responses. The spinal functional changes and pain may be due to increased peripheral input(2), changes in spinal nociceptive modulatory mechanisms and altered supraspinal descending pain modulation. Noradrenergic descending pain m...

Purpose: This randomized, placebo-controlled study examined the effect of vitamin D replacement therapy on neuropathic symptoms and balance in patients with diabetic neuropathic pain and low vitamin D levels. Patients and Methods: Among the 258 patients, the results in a total of 57 volunteers (32 in the treatment and 25 in the control arm) meeting the inclusion criteria are reported. Symptoms of neuropathic pain were assessed using Douleur Neuropathique 4 (DN4) questionnaire, and presence of polyneuropathy (PNP) was determined by performing electromyography (EMG). Balance was assessed using Berg balance test (BBT). After undergoing these examinations, the patients in the treatment group were intramuscularly (IM) injected with 300,000 IU vitamin D in a liquid formulation and those in the placebo group were IM injected with physiological saline. The DN4 and BBT were repeated after 12 weeks, and the results were compared. Results: The patients in the treatment group showed a significant decrease in total DN4 scores from baseline to the study endpoint compared with the patients in the placebo group (p=0.008). The patients in the treatment group also showed a significant increase in BBT scores from baseline to the study endpoint compared with the patients in the placebo group (p=0.001). Furthermore, in subgroup analysis, these patients showed a significant decrease in electric shock and burning sensation scores from baseline to the study endpoint compared with the patients in the placebo group (p=0.006, p=0.001, respectively). In patients with diabetic neuropathic pain, vitamin D levels should be measured and vitamin D replacement therapy should be administered as required to resolve neuropathic symptoms and to improve balance.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) are common comorbid conditions. Life style, particularly diet is a critical component of treatment for these conditions. Register dietitians play a key role in bridging the gap between the science of nutrition and the empowerment of individuals to alter their lifestyles in a healthy manner. A range of dietary manipulations has been reported to reduce risk factors and decrease risk of CVD and CKD outcomes. However, many studies provided food to participants or were limited to adjustment of few specific nutrients. Diet intervention in relation with end-stage renal disease (ESRD) is really complicated topic. As multiple co morbid conditions such as hypertension, CVD, CKD, and diabetes mellitus (DM) are associated with ESRD, which made the scenario really worse while fixing the dose of any diet. Still a lot of research work is required to understand this topic.

Objective: Obesity is a risk factor for calcaneal spur (CS) formation. Diabetes mellitus may contribute to the risk of CS due to the decreased ability of tissue repair and peripheral neuropathy. Thus, we aimed to determine the frequency of CS in asymptomatic obese subjects with and without type 2 diabetes mellitus (T2DM). Also, we tried to find the related factors of CS in patients with T2DM. Material and Methods: Ninety-three obese patients with type-2 diabetes mellitus (T2DM) and 42 obese control subjects without glucose metabolism disturbances were enrolled in the study. A questionnaire was made about the duration of T2DM, age, and occupations of the participants. Physical, laboratory, and x-ray examinations of all cases were made. SPSS 15.0 was used for statistical analyses. Results: Patients with T2DM and control groups were similar in mean age and body mass index (BMI) (p=0.196, p=0.073, respectively). The existence of CS in the T2 diabetic group was significantly higher than in the control group (p=0.023). T2 diabetic patients with CS had significantly higher neuropathy existence, mean age, and BMI than T2 diabetic patients without CS (p=0.001, p=0.016, p=0.043, respectively). There was a positive correlation between the existence of CS and peripheral neuropathy and age (p=0.025, p=0.001, respectively). Increased ratio of CS in obese T2 diabetic patients may be important because of the relation between CS existence and complications of diabetes mellitus. Clinicians should pay more attention to increased frequency of CS in patients with T2DM, to avoid diabetic foot complications and other malformations.

Objectives: To investigate the potential benefits from lightly touching an external supporting device on automatic postural responses to support surface translations, in subjects with profound sensory neuropathy in the feet due to diabetes mellitus (DM-PN). Methods: Eight subjects with DM-PN and 10 age matched controls were tested under randomly ordered conditions of no fingertip touch (NT), light touch (LT; <1 N), and heavy touch (HT, as needed) of a stationary touch plate, during three backward translation velocities of the support surface at 10, 20, and 30 cm/s. Dependent variables included response latencies, CoP velocity, and the slope of the relation between centre of pressure (CoP) velocity and translation velocity as a measure of response scaling. Results: Postural response latencies were significantly longer and scaling of initial response magnitude in proportion to translation velocity was significantly smaller in the DM-PN subjects compared to the control subjects. LT had no significant effect on response latencies of the DM-PN patients. Fingertip touch increased the slope of the scaling of postural response magnitude in both groups. However, DM-PN subjects had to use HT to improve response scaling, whereas control subjects improved scaling with LT as well as HT. LT significantly increased rightward CoP velocity towards the touch plate in all subjects. Conclusions: LT did not reduce the latency or improve the scaling of automatic postural responses in subjects with peripheral neuropathy. The major effect of LT on the automatic postural responses of the DM-PN subjects was in increasing CoP velocity towards the side of the supporting device. HT in neuropathy subjects and LT in age matched control subjects increased the sensitivity of initial postural response scaling, suggesting that somatosensory substitution from a cane in the hand could be used to improve the magnitude of medium latency postural responses to slips and trips.

During the past 12 years, 6 studies reported restoration of sensation and relief of pain in the foot by decompression of the tibial nerve and its distal branches in diabetic neuropathy. Although a positive Tinel sign related to favorable outcomes in some of the reports, this relationship was not evaluated specifically. In this study, the presence of the Tinel sign, positive or negative, over the tibial nerve was recorded in 46 patients with diabetic neuropathy and in 40 patients with idiopathic neuropathy. Outcomes were dichotomized into either a good/excellent or failure/poor category. Postoperative data were analyzed at 1 year. In diabetic neuropathy, the presence of a positive Tinel sign had a sensitivity of 88%, a specificity of 50%, and a positive predictive value of 88% in identifying patients who would have a good/excellent outcome. In idiopathic neuropathy, the presence of a positive Tinel sign had a sensitivity of 95%, a specificity of 56%, and a positive predictive value of 93% in identifying patients who would have a good/excellent outcome. It is concluded that a positive Tinel sign is a reliable indicator of successful outcome from decompression of the tibial nerve in patients with diabetes with symptomatic neuropathy, and in patients with symptomatic idiopathic neuropathy.

The current study was designed to explore whether microRNA-146a and its adapter proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were randomized into control and diabetic groups (n=6). Diabetes was induced by a single-dose injection of nicotinamide (110 mg/kg; i.p.), 15 min before injection of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was evaluated by hot plate and tail emersion tests, 2 months after the injection of streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1, TRAF6, and nuclear factor kappa B (NF-κB) was measured in the sciatic nerve of rats using the real time-PCR method. Moreover, the activity of NF-κB and the concentration of pro-inflammatory cytokines were determined by the ELISA method. In comparison with the control group, a threefold increase in the expression of miR-146a and NF-κB, and a twofold decrease in the expression of TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF-κB activity and the concentration of TNF-α, interleukin 6 (IL-6), and interleukin 1β (IL-1β) in the sciatic nerve of diabetic rats were higher than in those of control counterparts. These results suggest that a defect in the NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.

NAALADase (N‐acetylated‐α‐linked‐acidic dipeptidase; also termed glutamate carboxypeptidase II) is an enzyme that catalyzes hydrolysis of the abundant brain peptide N‐acetyl‐aspartyl‐glutamate (NAAG) to N acetyl‐aspartate (NAA) and glutamate. We have synthesized many potent and selective NAALADase inhibitors from distinct chemical classes. In rodents, selective inhibitors have been shown to increase NAAG and decrease glutamate extracellularly and provide therapeutic benefits in animal models of neurological diseases where excess glutamate neurotransmission has been implicated. Specifically, NAALADase inhibitors exhibit neuroprotection in rats following transient middle cerebral artery occlusion, attenuate neuropathic pain following chronic constrictive injury, prevent nerve conduction velocity deficits and sural nerve degeneration following chronic diabetes in STZ and BB/W rats, and delay clinical symptoms and mortality in the mouse SOD transgenic model of ALS. These biological effe...

Diabetes, one of the most serious and fast growing chronic health conditions, often leads to other serious complications such as neurological, renal, ophthalmic, and heart diseases. Research has shown that more than 85% of diabetic patients develop at least one of these complications. Therefore, studying comorbidities among diabetic patients using association analysis is a worthy research endeavor. Association analysis is a well-known data mining method that aims to reveal the association/affinity patterns/rules among various items (objects or events) that occur together. One of the most critical problems in association analysis is the difficulty with the identification of rare items/patterns. In ordinary association analysis, specifying a large minimum-support leads to not discovering rare rules, while setting a small minimum-support leads to overgenerating rules that may not be strong and beneficial. In this study, we propose a new assessment metric, called adjusted_support, to address this problem. Applying this new metric can retrieve rare patterns without over-generating association rules. To test the proposed metric, we extracted data from a large and feature-rich electronic medical records data warehouse and performed association analysis on the resultant data set that included 492,025 unique patients diagnosed with diabetes and related complications. By applying adjusted_support, we discovered interesting associations among diabetes complications such as neurological manifestations with diabetic arthropathy and gastroparesis; renal manifestations with retinopathy; gastroparesis with ketoacidosis and retinopathy; and skin complications with hyperglycemia, peripheral circulatory disorder, heart disease, and neurological manifestations. We also performed association analysis in various demographic groups at more granular levels. Besides association analysis, we also analyzed the comorbidity situation among different demographic groups of diabetics. Finally, we studied and compared the prevalence of diabetes complications in every demographic group of patients.

Objective: This study aims to experimentally evaluate the impact of 20(S)-ginsenoside Rg3 on the progression of neuropathy induced by streptozotocin (STZ)-induced diabetes. Materials and Methods: Adult male Wistar rats were randomly divided into three groups: control, untreated diabetic, and 20(S)-ginsenoside Rg3-treated diabetic groups (n=6 each). The rats were intraperitoneally injected with a single dose of STZ (50 mg/kg) to induce diabetes, which was verified by the presence of hyperglycemia (>300 mg/dl). Treatment involved administering a daily dose of 20(S)-ginsenoside Rg3 at 5 mg/kg/day through oral gavage for five weeks. Control rats received an equivalent volume of saline phosphate buffer (pH 7.4). Nociceptive alterations were assessed using tail flick and hot plate tests in the fourth week. Distal latency and nerve conduction velocity were measured in vivo from the exposed sciatic nerve in the fifth week. Results: While STZ-induced diabetes led to a significant decline in body weight, an increase in blood glucose levels, and delays in both sensory and motor responses, 20(S)-ginsenoside Rg3 treatment favorably corrected these adverse effects. This treatment effectively alleviated weight loss, lowered blood glucose levels, protected the sciatic nerve, and thus clearly demonstrated a protective role against the progression of neuropathy. Conclusion: Treatment with 20(S)-ginsenoside Rg3 holds the potential to be used as a neuroprotective agent for diabetic neuropathy. It may also exert preventive actions against post-diabetic events at the molecular level, and the mechanisms underlying these actions need further exploration.

Diabetic neuropathy is a condition of impaired nerve function due to complications related to the development of diabetes through various mechanisms. Clinical improvement in diabetic neuropathy patients considers many clinical outcomes, so it requires a multitargeted approach to therapy. Nigella sativa oil is a natural ingredient traditionally used for various conditions related to diabetic neuropathy. It has been partially proven for various essential targets related to diabetic neuropathy, including as an antidiabetic, antidyslipidemic, antioxidant, anti-inflammatory, and neuroprotector. With its multicompound, multitarget capability, N. sativa has the potential as an additional herbal therapy in treating diabetic neuropathy. This review includes a description of diabetic neuropathy and the potential of N. sativa as adjunctive therapy in treating diabetic neuropathy.

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.