Bone Marrow-Derived Mesenchymal Stem Cells Improve the Functioning of Neurotrophic Factors in a Mouse Model of Diabetic Neuropathy

Diabetic neuropathy is one of the most frequent and troublesome complications of diabetes. Although there has been a continuous increase in the incidence of diabetic neuropathy, treatments have yet to be found that effectively treat diabetic neuropathy. Neurotrophic factors are proteins that promote the survival of specific neuronal populations. They also play key roles in the regeneration of peripheral nervous system. Recent evidence from diabetic animal models and human diabetic subjects suggest that reduced availability of neurotrophic factors may contribute to the pathogenesis of diabetic neuropathy. One way to reverse this effect is to take advantage of the finding that bone marrow derived mesenchymal stem cells (BM-MSCs) promote peripheral nerve repair and the functioning of neurotrophic factors. Therefore, we speculated that treatment with BM-MSCs could be a viable therapeutic strategy for diabetic neuropathy. The present study was designed to examine the possible beneficial effect of BM-MSCs on functions of neurotrophic factors in diabetic neuropathy. To assess this possibility, we used an in vivo streptozotocin-induced diabetic neuropathy mouse model. Quantitative real-time polymerase-chain reacion showed that BM-MSCs significantly increase expression levels of neurotrophic factors. Also, BM-MSCs ameliorated nerve conduction velocity in streptozotocin-treated mice. These results may help to elucidate the mechanism by which BM-MSCs function as a cell therapy agent in diabetic neuropathy

Plantar Pressure Distribution Patterns During Gait in Diabetic Neuropathy Patients with a History of Foot Ulcers

OBJECTIVE: To investigate and compare the influence of a previous history of foot ulcers on plantar pressure variables during gait of patients with diabetic neuropathy. INTRODUCTION: Foot ulcers may be an indicator of worsening diabetic neuropathy. However, the behavior of plantar pressure patterns over time and during the progression of neuropathy, especially in patients who have a clinical history of foot ulcers, is still unclear. METHODS: Subjects were divided into the following groups: control group, 20 subjects; diabetic neuropathy patients without foot ulcers, 17 subjects; and diabetic neuropathy patients with at least one healed foot ulcer within the last year, 10 subjects. Plantar pressure distribution was recorded during barefoot gait using the Pedar-X system. RESULTS: Neuropathic subjects from both the diabetic neuropathy and DNU groups showed higher plantar pressure than control subjects. At midfoot, the peak pressure was significantly different among all groups: control group (139.4±76.4 kPa), diabetic neuropathy (205.3±118.6 kPa) and DNU (290.7±151.5 kPa) (p=0.008). The pressure-time integral was significantly higher in the ulcerated neuropathic groups at midfoot (CG: 37.3±11.4 kPa.s; DN: 43.3±9.1 kPa.s; DNU: 68.7±36.5 kPa.s; p=0.002) and rearfoot (CG: 83.3±21.2 kPa.s; DN: 94.9±29.4 kPa.s; DNU: 102.5±37.9 kPa.s; p=0.048). CONCLUSION: A history of foot ulcers in the clinical history of diabetic neuropathy subjects influenced plantar pressure distribution, resulting in an increased load under the midfoot and rearfoot and an increase in the variability of plantar pressure during barefoot gait. The progression of diabetic neuropathy was not found to influence plantar pressure distribution

The Effects of Dietary and Lifestyle Management on Diabetic Neuropathy

Numerous patients who have uncontrolled diabetes have developed complications associated with diabetic neuropathy. The apparent knowledge deficit and noncompliance have led to the development of clinical concerns related to improving patient outcomes. This scholarly project assesses the effects of dietary, weight, and exercise management on improving diabetic neuropathy symptoms. The debilitating effects of diabetes continue to affect numerous people each day. Uncontrolled diabetes can create innumerable complications, including diabetic neuropathy. Appropriate nutrition associated with accountability, monitoring, and proper education can alleviate the progression of uncontrolled diabetes. Assessment of the improvement of diabetic neuropathy with dietary and exercise management is examined among a group of twelve participants selected randomly

ASSOCIATION OF SERUM HOMOCYSTEINE IN DIABETIC NEUROPATHY

Aims and Objectives: The main aim of the study was to find out the association of serum homocysteine (HCY) in diabetic neuropathy patients. Methods: All the patients who were diagnosed with Type II diabetes mellitus will be included. Their serum levels of fasting blood sugar, postprandial blood sugar, glycated hemoglobin, and associated blood parameters will be assessed. Diabetic neuropathy will be confirmed using nerve conduction testing, electromyography, and quantitative sensory testing with clinically correlated. The serum HCY levels will be measured and correlated with other blood parameters. Results: Of 1000 patients, 46 were Type I diabetic and 954 were Type II. The prevalence of neuropathy in diabetic patients was 156. Mean serum HCY without diabetic neuropathy was 6.8+2.9 and serum HCY with diabetic neuropathy was 21.6+0.29 and p value was found to be 0.0017. The correlation between serum HCY and diabetic neuropathy was found to be 14.5 with p=0.001. Conclusion: There has been a significant increase of HCY in diabetic patients. It can be clearly seen that elevated serum HCY level has led to some of the complications of diabetic neuropathy

Novel insights on diagnosis, cause and treatment of diabetic neuropathy: Focus on painful diabetic neuropathy

Diabetic neuropathy is common, under or misdiagnosed, and causes substantial morbidity with increased mortality. Defining and developing sensitive diagnostic tests for diabetic neuropathy is not only key to implementing earlier interventions but also to ensure that the most appropriate endpoints are employed in clinical intervention trials. This is critical as many potentially effective therapies may never progress to the clinic, not due to a lack of therapeutic effect, but because the endpoints were not sufficiently sensitive or robust to identify benefit. Apart from improving glycaemic control, there is no licensed treatment for diabetic neuropathy, however, a number of pathogenetic pathways remain under active study. Painful diabetic neuropathy is a cause of considerable morbidity and whilst many pharmacological and nonpharmacological interventions are currently used, only two are approved by the US Food and Drug Administration. We address the important issue of the ‘placebo effect’ and also consider potential new pharmacological therapies as well as nonpharmacological interventions in the treatment of painful diabetic neuropathy

Prevalence of risk factors promoting Diabetic neuropathy .

Diabetic neuropathy is the worst consequence of diabetes mellitus leading to nerve dysfunction that is the cause of several complications such as pain, loss of sensitivity, damage to body systems, foot ulcers, morbidity and amputations etc. The aim of the present work was to study the prevalence of risk factors and occurrence of diabetic neuropathy in patients with diabetes, and how much diabetic neuropathy complications affect the life of diabetic patients

Corneal Sensitivity as a Potential Marker of Diabetic Neuropathy

Diabetes mellitus (DM) is a complex and chronic metabolic disorder leading to many complications. One of the most common complications of DM is diabetic neuropathy. There are many studies exploring corneal sensitivity as a potential marker of diabetic neuropathy. This review aims to explore association between corneal sensitivity and diabetic neuropathy. In diabetic neuropathy, corneal sensitivity is impaired due to low level of corneal nerve trophic factors, impaired sensory nerve fibers, and lost communication of dendtritic cell. In diabetic patients, this condition can be assessed by several techniques, such as Cochet Bonnet aesthesiometry, non-contact corneal aesthesiometry, and confocal microscopy. Few promising therapeutic targets for impaired corneal sensitivity include stem cell and growth factor therapy that can be used to prevent complication in patient with diabetic neurotrophic keratopathy. Impaired corneal sensitivity serve as a potential marker of diabetic neuropathy. Doctors, opthalmologists and internists, should anticipate the possibility of observing the following changes in diabetic patients with neuropathy by using corneal sensitivity assessment test

Sympathetic Blocks Provided Sustained Pain Relief in a Patient with Refractory Painful Diabetic Neuropathy

The sympathetic nervous system has been implicated in pain associated with painful diabetic neuropathy. However, therapeutic intervention targeted at the sympathetic nervous system has not been established. We thus tested the hypothesis that sympathetic nerve blocks significantly reduce pain in a patient with painful diabetic neuropathy who has failed multiple pharmacological treatments. The diagnosis of small fiber sensory neuropathy was based on clinical presentations and confirmed by skin biopsies. A series of 9 lumbar sympathetic blocks over a 26-month period provided sustained pain relief in his legs. Additional thoracic paravertebral blocks further provided control of the pain in the trunk which can occasionally be seen in severe diabetic neuropathy cases, consequent to extensive involvement of the intercostal nerves. These blocks provided sustained and significant pain relief and improvement of quality of life over a period of more than two years. We thus provided the first clinical evidence supporting the notion that sympathetic nervous system plays a critical role in painful diabetic neuropathy and sympathetic blocks can be an effective management modality of painful diabetic neuropathy. We concluded that the sympathetic nervous system is a valuable therapeutic target of pharmacological and interventional modalities of treatments in painful diabetic neuropathy patients

Serum Level Changes of Neurotrophin-3 After Performing Diabetic Foot Exercise in Diabetic Neuropathy

The research aimed to determine the pattern of changes in serum levels of NT-3 in the improvement of diabetic neuropathy, after doing diabetic foot exercise. A true experimental study with randomaized pre – post test control trial. A total of 36 subjects meeting the inclusion and exclusion criteria were included in the exercise group or the control one with age matched systematic random sampling method. Exercise group had a significant improvement on the score of ABI (p.0.002), systolic blood pressure (p.0.014), diastolic blood pressure (p.0.055), DNS (p.0.01), DNE (p.0.001) and increased of serum level of NT-3 (p.0.049). Control group had result respectively on ABI (p.0.131), systolic blood pressure (p.0.668), diastolic blood pressure (p.0.216), DNS (p.1.00), DNE (p.0.543), and increase of NT-3 (p.0.264). The comparation results of the two groups had a significant different on the score of ABI (p.0.01), systolic blood pressure (p.0.01), diastolic blood pressure (p.0.01), DNS (p.0.01), DNE (p.0.01), and increased of NT-3 (p.0.01). Diabetic foot exercise had a peripheral affect on a clinically significant improvement based on ABI scores, systolic and diastolic blood pressure, DNS and DNE, and increase of serum level of NT-3

High Plasma Tnf-? Levels And Mononuclear Cells Inos And Tnf-? Expression AS Risk Factors For Painful Diabetic Neuropathy

Painful Diabetic Neuropathy (PDN) is one of the most common and annoyingcomplications of diabetes mellitus. The pathogenesis of PDN is complex and still unclear.Recently it has become clear that nitric oxide (NO) and proinflammatory cytokines playan important role in the pathogenesis and maintenance of pain in PDN. Based on thisphenomenon, this study was conducted to investigate whether the cytokine tumornecrosis factor-alpha (TNF-?) and NO, in this case inducible Nitric Oxide Synthase(iNOS), play a role in PDN pathogenesis.The study was carried in two steps. The first step was a cross sectional and thesecond step was a case-control study. The study was performed in 110 type-2 diabeticpatients. The plasma TNF-? levels were determined by ELISA while the expression ofTNF-? and iNOS in mononuclear cells were analyzed immunohistochemically.Of 110 subjects, 59 patients suffered from Painful DN (case) and the remaining51 patients were Painless DN (control). Cross sectionally, plasma TNF-? levels andimmunoreactivity for iNOS and TNF-? were higher in patients with more severe pain inthe Visual Analog Scale (VAS). There were statistically significant differences (p <0.05) between mild and severe pain in regard to TNF-? level (15.24 pg/ml ± 5.42 vs.20.44 pg/ml ± 10.34 ); to iNOS immunoreactivity (9.72 % ± 8.61 vs. 15.6% ± 11.84); andto TNF-? immunoreactivity (13.0 % ± 9. 48 vs. 20.44% ± 11.75).The case control study showed that TNF-? had an odd ratio of 5.053 [CI 95%(2.241-11.392); p < 0.001]. TNF-? immunoreactivity of 4.125 [CI 95% (1.805-9.425); p< 0.001]; and iNOS immunoreactivity of 3.546 [CI 95% (1.613-7.795); p = 0.002]. There were correlations between TNF-? level, TNF-? and iNOS immunoreactivity andVAS with coefficient correlation: 0.330; 0.285 and 0.275 (p < 0.05) respectively.It is concluded that Diabetic Neuropathy patients with high TNF-? levels, iNOSand TNF-? immunoreactivity of mononuclear cells have higher risk for painful DN thanpainless DN. The higher TNF-? level, iNOS and TNF-? immunoreactivity the moresevere was the pain. This supports the hypothesis that TNF-? and iNOS have role inPDN pathogenesis. The results of this research could be applied as a basic for furtherresearch in pursuit of better management of PDN