Evaluation Of Diabetic Neuropathy Research Articles

Deciphering the Neuroprotective Role of Glucagon-like Peptide-1 Agonists in Diabetic Neuropathy: Current Perspective and Future Directions.

Diabetic neuropathy is referred to as a subsequential and debilitating complication belonging to type 1 and type 2 diabetes mellitus. It is a heterogeneous group of disorders with a particularly complex pathophysiology and also includes multiple forms, ranging from normal discomfort to death. The evaluation of diabetic neuropathy is associated with hyperglycemic responses, resulting in an alteration in various metabolic pathways, including protein kinase C pathway, polyol pathway and hexosamine pathway in Schwann and glial cells of neurons. The essential source of neuronal destruction is analogous to these respective metabolic pathways, thus identified as potential therapeutic targets. These pathways regulating therapeutic medications may be used for diabetic neuropathy, however, only target specific drugs could have partial therapeutic activity. Various antidiabetic medications have been approved and marketed, which possess the therapeutic ability to control hyperglycemia and ameliorate the prevalence of diabetic neuropathy. Among all antidiabetic medications, incretin therapy, including Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, are the most favorable medications for the management of diabetes mellitus and associated peripheral neuropathic complications. Besides enhancing glucose-evoked insulin release from pancreatic β-cells, these therapeutic agents also play a vital role to facilitate neurite outgrowth and nerve conduction velocity in dorsal root ganglion. Furthermore, incretin therapy also activates cAMP and ERK signalling pathways, resulting in nerve regeneration and repairing. These effects are evidently supported by a series of preclinical data and investigations associated with these medications. However, the literature lacks adequate clinical trial outcomes related to these novel antidiabetic medications. The manuscript emphasizes the pathogenesis, current pharmacological approaches and vivid description of preclinical and clinical data for the effective management of diabetic neuropathy.

Dose vitamin D supplementations improve peripheral diabetic neuropathy? A before-after clinical trial

ObjectivePeripheral neuropathy is a common complication of diabetes mellitus. This study was set to assess the effect of vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes (T2DM). Materials and methodsThis study was a quasi-experimental trial in Yazd diabetic research center. Sixty T2DM subjects (30–65 years old) with painful diabetic neuropathy enrolled in this study from March 2017 till April 2018. Patients received weekly 50000 IU of vitamin D3 for 12 weeks orally. Evaluation of diabetic neuropathy was performed by using Michigan Neuropathy Screening Instrument (MNSI) before and after trial. Also fasting plasma glucose, HbA1c, calcium and vitamin D checked before and after the trial. SPSS version 20 software was used for statistical analysis. P ≤ 0.05 was considered to be statistically significant. ResultsAmong 60 T2DM patients, 58 completed the study. Most of them (53.4%) were male. At the end of study, HbA1c, vitamin D, MNSI (both questionnaire and physical examination) improved that is statistically significant (p-value: <0.001). ConclusionOral supplementation of vitamin D 3 (50,000 IU) once weekly for 12 weeks was associated with improvement in the serum level of vitamin D and significant decrease in the symptoms and sign of diabetic neuropathy. So serum vitamin D level should be checked in persons with diabetic neuropathy and low levels of it should be corrected in order to reducing neuropathy severity.

The role of ultrasound in the diagnosis and evaluation of diabetic neuropathy in nerve roots of the foot

Background Neuropathies are characterized by a progressive loss of nerve fiber function. Diabetic peripheral neuropathy is the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after exclusion of other causes. The diagnosis of diabetic neuropathy is based primarily on characteristic symptoms and is confirmed with nerve conduction studies (NCS), which are time-consuming, slightly invasive, and occasionally not well tolerated for repeated evaluations. In contrast, ultrasonographic (US) examinations can be performed to assess peripheral nerves with less discomfort and have already been used for the evaluation of several disorders of the peripheral nervous system such as carpal tunnel syndrome. Patients and methods A total of 50 patients were included in the study, with 40 patients with type 2 diabetes and 10 controls. All cases underwent clinical history, local clinical examination, NCS, and real-time high-resolution US. Ultrasound examination The patients were examined in supine position, and the foot was bolstered with a pillow to expose the anterior and medial portion of the lower leg and foot. The transducer was placed immediately above the medial malleolus to locate the tibial nerve in the transverse (short axis) and the longitudinal (long axis) views. The 5.0–12.0-MHz multifrequency linear array probe was used for tibial nerve scanning. The instrument used was Philips HD3 ultrasound scanner. Result There was a statistically significant difference between case and controls regarding US cross-sectional area done for right and left tibial nerves, with high mean among cases (0.18±0.02 and 0.17±0.02, respectively). There was a statistically significant difference between US and NCS. There was no statistically significant difference between the two groups regarding the other measurements. Conclusion High-resolution US can be used as adjuvant tool for the NCS for diabetic patients suspected to have neuropathy.

Corneal confocal microscopy: Recent progress in the evaluation of diabetic neuropathy.

The present brief review discusses recent progress with corneal confocal microscopy for the evaluation of diabetic sensorimotor polyneuropathy. Corneal confocal microscopy is a new, non-invasive and reproducible diagnostic modality, and it can also be easily applied for patient follow up. It enables new perspectives of studying the natural history of diabetic sensorimotor polyneuropathy, severity of nerve fiber pathology and documenting early nerve fiber regeneration after therapeutic intervention. It shows moderate to high sensitivity and specificity for the timely diagnosis of diabetic sensorimotor polyneuropathy. Currently, corneal confocal microscopy is mainly used in specialized centers, but deserves more widespread application for the assessment of diabetic sensorimotor polyneuropathy. Finally, further progress is required in terms of technical improvements for automated nerve fiber quantification and for analysis of larger images.

Usefulness of ratio of motor nerve conduction velocity to F-wave conduction velocity in diabetic neuropathy

Background: Diabetic poly neuropathy, a common complication of diabetes, is diagnosed by symptoms, signs, physical examination, nerve conduction studies, and other neuro-physiological methods. Although nerve conduction studies are useful in the diagnosis and evaluation of diabetic neuropathy, there are difficulties in using them for the differential diagnosis of peripheral neuropathy because the pathological changes of diabetic neuropathy are varied. Aims & Objective: To investigate the usefulness of a new parameter, the ratio of motor nerve conduction velocity to F-wave conduction velocity (M/F ratio), for the differential diagnosis of diabetic neuropathy. Materials and Methods: Nerve conduction studies were conducted in 100 patients with diabetic neuropathy during the period of December 2012 to February 2013, 45 non diabetic patients with peripheral neuropathy, and 25 normal control participant. Non diabetic patients with neuropathy were grouped by clinical diagnosis as follows: segmental demyelination (n = 15), axonal neuropathy (n = 11), alcoholic poly neuropathy (n = 5), and other poly neuropathy (n = 14). Motor nerve conduction velocity (MCV) of post-tibial nerves, sensory nerve conduction velocity (SCV) of sural nerves, and F-wave conduction velocity (FWCV) of post-tibial nerves were measured by standardized techniques. The M/F ratio was calculated from these measurements. Results: The motor conduction velocity (MCV) and sensory conduction velocity (SCV) of diabetic patients were significantly slower and the M/F ratio was significantly lower than those of normal participants: MCV, 43.7 ± 5.4 vs. 47.1 ± 2.9 m/s, P < 0.001; SCV, 44.7 ±11.1 vs. 48.3 ± 5.7 m/s, P < 0.05; M/F ratio, 0.84 ± 0.09 vs. 0.90 ± 0.06, P < 0.001. The FWCV of non-diabetic patients with neuropathy was significantly slower (40.0 ± 6.3 vs. 48.3 ± 4.0 m/s, P < 0.001) and the M/F ratio was significantly higher (1.04 ± 0.12, P < 0.001) than that of normal participants, respectively. Although MCV, SCV, and FWCV were correlated with age in normal control participants, the M/F ratio was independent of age in the diabetic as well as the non-diabetic patients with neuropathy. Conclusion: Results suggest that the M/F ratio, which is influenced by the neuronal damages in the distal segment of peripheral nerves, is useful in the differential diagnosis of diabetic neuropathy.

Effect of Fluoxetine on an Experimental Model of Diabetes-induced Neuropathic Pain Perception in the Rat.

The aim of the present study was to study the effect of chronic treatment (9 weeks) of fluoxetine (20 mg/kg p.o.) a selective serotonin reuptake inhibitor on blood glucose level and in prevention of diabetic neuropathic pain perception. Evaluation of diabetic neuropathy was performed after 9 weeks of single injection of streptozotocin (70 mg/kg i.v.) in rats. Blood glucose level, glycated haemoglobin, grip strength, pain sensitivity and threshold in diabetic rats were measured at the end of 9 weeks. The results of the present study indicate that the 9 weeks treatment of fluoxetine demonstrates hypoglycemic effect; it marked decreases the blood glucose level in diabetic treated animals. There was also decrease in the grip strength in diabetic rat indicates to induction of neuropathy or nerve damage. Fluoxetine increase the grip strength of diabetic rats. There was also found loss of pain perception in diabetes rats which measured using hot plate and tail flick methods. Fluoxetine increases the licking time and withdrawal latency in hot plate and tail flick test respectively indicates the presence of pain perception and prevention of nerve damage demonstrates its protective effect in diabetic neuropathy. Our study concludes the chronic treatment of fluoxetine significantly decreases the glycemic level as well as it protected from the development of diabetic neuropathy.

Evaluation of diabetic neuropathy using the tone-entropy analysis, a noninvasive method to estimate the autonomic nervous function

It is clinically important to diagnose diabetic neuropathy at the early stage. In this study, the toneentropy analysis of electrocardiogram was applied to diabetic patients to evaluate its usability in the screening of diabetic neuropathy. Consecutive 102 diabetic patients were invited to the study. Electrocardiogram was obtained and analyzed for the tone and the entropy using an original software developed previously. Nerve conduction velocity (NCV) was examined on the median, the posterior tibial and the sural nerves. Patients were divided into quartile subpopulations according to the NCVs in the analysis. Both the tone and the entropy significantly correlated with NCVs, while coefficient of variation in R-R intervals did not show a significant correlation. The correlation was most significant between the entropy and the NCV on the sural nerve. When a multivariate analysis (ordinary regression) was applied to examine independent effects of the factors influencing the NCV on the sural nerve, the entropy was the most potent independent factor (beta = 1.14 +/- 0.32, P = 0.0004) along with sex (beta = 0.43 +/- 0.19, P = 0.02) and BMI (beta = 0.11 +/- 0.05, P = 0.04). The tone-entropy analysis on electrocardiogram may be a promising non-invasive screening method for diabetic neuropathy.

Evaluation Of Diabetic Neuropathy Through The Quantitation Of Cutaneous Nerves

The significance and usefulness of immunohistochemically quantitated cutaneous nerves in the evaluation of diabetic neuropathy was examined in biopsied skins of the calf from healthy subjects (n = 12) and non‐insulin dependent diabetic patients (n = 32) with diabetic sensory neuropathy. Skin samples were immunostained with antibodies against protein gene product (PGP) 9.5, a pan‐axonal marker. A quantitative analysis to determine nerve fiber (NF) number and nerve lengths (NLs) was performed on nerve fibers of the epidermis and the dermis and on nerves surrounding sweat glands. Nerve function tests were performed on the biopsied sites and erythrocyte aldose reductase level was determined by enzyme‐linked immunosorbent assay. Numbers of epidermal NFs, NLs of epidermis and dermis and NL around sweat glands were significantly decreased in diabetic patients compared with control subjects (P&lt;0.001, P&lt;0.001, P &lt; 0.01, P &lt; 0.01, respectively). NL of epidermis showed a significant correlation with NL of dermis (P &lt; 0.01). Sural nerve conduction velocity was significantly correlated with NL of dermis (P &lt; 0.05). Patients with higher AR level (&gt; 10.8 (average in 555 diabetic patients) ng/mgHb) possessed a shorter NL of dermis NFs than those with lower AR level (&gt; 10.8) (P &lt; 0.05). These findings suggest that the quantitation of cutaneous nerves in biopsied skin samples provides important information about diabetic neuropathy and may improve the understanding of the pathophysiology of sensory nerve terminals in diabetic neuropathy.

Electrophysiologic evaluation of diabetic neuropathy after intensive insulin therapy

Electrophysiologic evaluation of diabetic neuropathy after intensive insulin therapy

Pathological Definition and Evaluation of Diabetic Neuropathy and Clinical Correlations

Diabetic neuropathy is a major complication of diabetes mellitus affecting to an equal extent type 1 and type 2 patients. Various mechanisms including metabolic and vascular abnormalities have been proposed to explain the progressive pathological changes that occur in peripheral nerve. Regardless of the precise mechanisms, structural abnormalities lead to functional changes which eventually result in the clinical manifestations of diabetic neuropathy. Possible interventions that may influence the progressive disease process include intensive insulin therapy and aldose reductase inhibitors. This article reviews the proposed pathogenetic mechanisms underlying diabetic neuropathy, their effects on nerve histomorphometric changes and ultrastructure typical of diabetic neuropathy, and potential therapeutic interventions and their impact on disease progression.

Auditory Brainstem and Middle Latency Evoked Responses in the Clinical Evaluation of Diabetes

The measurement of auditory brainstem evoked responses and middle latency evoked responses may improve the evaluation of diabetic neuropathy. Twenty diabetic patients were studied (12 males, 8 females), aged 21 to 63 years with normal hearing, together with 20 age- and sex-matched normal subjects (10 males, 10 females). Auditory brainstem evoked responses were induced by rarefaction clicks of 0.1 ms at a repetition rate of 21.1 CPS and an intensity of 75 dB hearing level. Middle latency evoked responses were induced with clicks of 0.1 ms, a repetition rate of 7.7 CPS and an intensity of 75 dB hearing level. Diagnostic criteria were: a I-V interval latency shift greater than 2SD of the control group for the auditory brainstem evoked response test or the interval difference of wave V greater than 0.2 ms. Middle latency evoked response was diagnostic if the latency of the Pa component was greater than 2SD of normals. Twenty-five per cent of subjects had retrocochlear impairment (absence of I wave) even in the absence of symptoms. The combined technique of auditory brainstem evoked response and middle latency evoked response improved the detection rate of central nervous system dysfunction. Auditory brainstem response is important for detecting desynchronization of the auditory response, whereas middle latency evoked response detects abnormalities in the more rostral regions of the central nervous system. In conclusion, there is a role for auditory brainstem evoked response and middle latency evoked response in the global assessment of diabetic neuropathy.

Peripheral nerve responses during ischemia in the evaluation of diabetic neuropathy

The stability of sensory conduction and evoked potentials during ischemia has been used in the evaluation of diabetic neuropathy and diabetic control (Hgb A1C). Six newly diagnosed juvenile diabetics were studied at diagnosis and 3 to 12 months later. In three patients in good control, ischemic "resistance" became normal. In three patients in poor control, resistance remained increased; two of these three experienced a 10%-20% slowing in conduction velocity. Similar relationships between control and ischemic resistance are found in long-term diabetics. These data suggest that abnormal ischemic resistance may herald the onset of an electrical and clinical neuropathic state.