Quantitative Tactile Examination Using Shape Memory Alloy Actuators for the Early Detection of Diabetic Neuropathy

Diabetic neuropathy (DPN) is asymptomatic in its early phases but can cause serious complications as it progresses. Most DPN tests are cumbersome and produce only qualitative assessments, and simpler approaches that yield quantitative results are needed. Techniques that allow patients to perform examinations themselves would be especially valuable. In this study, we focused on quantifying the decline in tactile sensation associated with DPN and developed a measurement device that used a thin shape memory alloy (SMA) wire as the actuator. An ON/OFF pulse current caused the wire to shrink and expand. This vibration was amplified by a round-headed pin, allowing even DPN patients with reduced tactile sensitivity to detect the stimuli generated when lightly touching the pin with their fingertips. The tactile stimuli were ranked into 30 levels of intensity. A key advantage of the device is that it can be used by patients themselves, returning quantified results within minutes. Although developed for DPN, the method can be applied to the detection of peripheral neuropathy in general

Comparison of vascular and neurological parameters between diabetic subjects without diabetic foot ulceration or amputation and those with either foot ulceration or a lower extremity amputation : a pilot study

Background: It is likely that lower limb ulceration, lower limb amputation, or their absence in diabetic subjects, indicate varying degrees of long-term diabetes and its complications, and that measures of atherosclerosis and neuropathy would reflect these differences. Objectives: To determine feasibility and, based on our results, make sample size estimates for future study: By comparing peripheral and central vasculature between diabetic subjects with lower extremity ulcers, diabetic subjects with lower extremity amputation and a group of diabetics without these complications — through evaluating toe blood pressure (TBP), toe-brachial index (TBI) and pulse wave velocity (PWV); also, by comparing peripheral and autonomic nervous system integrity between these groups — through sensory, nerve conduction, needle-examination and autonomic function assessment. Study design: A cross-sectional, descriptive and comparative pilot study. Setting: Pretoria Academic Hospital. Participants: Three groups of ten patients consecutively selected from diabetes and diabetic foot clinics — ten with chronic lower extremity ulcers, ten with healed lower extremity amputations and ten diabetic controls. Methods: Assessment of peripheral and autonomic neuropathy included evaluation of 5.07/10-g monofilament sensation, vibration perception (using a 128Hz tuning fork), nerve conduction and electromyography, cutaneous autonomic response and heart rate variability (expressed as an Expiration: Inspiration (E:I)-ratio). For evaluation of vascular status, we obtained the photo-plethysmographically-derived TBI and assessed carotid-femoral (CF) and carotid-radial (CR) PWV. Sample sizes for future studies were calculated through a nomogram for three-group comparisons, ANOVA, simulation and log-transformation of non-parametric data. Results: Absence of vibration perception in at least one leg, with significant p-values of 0.000 at toe-, and 0.027 at medial malleolus- level, occurred more frequently in the amputation, than in the control group. For the total bilateral monofilament count a statistically significant difference between groups was demonstrated (p-value 0.043). Peripheral neuropathy based on abnormality of at least one conduction attribute in at least two distinct nerves, the E:I-ratio, assessment of cutaneous autonomic responses and TBI, by worsening across groups, seemed to display a correlation with severity of lower limb complications, but without statistically significant results. For CF- and CR PWV, the lowest values were observed in the amputation group. Sample size calculations based on our TBP, TBI, vibration and monofilament results, lead to a proposed equal group size of between 34 and 103 for future three-group comparisons using these outcomes measures. Should PWV be included, the group size would have to be between 160 and 222. Conclusions: This study confirmed the usefulness of monofilament sensation and vibration perception assessment in identifying diabetic patients with differing degrees of lower extremity risk. Also, due to the large differences between groups, it demonstrated the effectiveness of these measures to display differences between groups, even in the event of very small sample sizes. The tendencies to worsen across the three groups, of the E:I -ratio, peripheral neuropathy based on nerve conduction, and the TBI, will have to be re-examined in a study with larger sample size. In order to demonstrate statistically significant CF- and CR PWV results, a larger sample size may also be required.Dissertation (MSc (Clinical Epidemiology))--University of Pretoria, 2007.Clinical Epidemiologyunrestricte

Effectiveness of Lower Extremity Weight Bearing Training along with the Conventional Training to Improve Balance, Vibration Perception and Ankle Mobility in Diabetic Peripheral Neuropathy Patients: A Quasi Experimental study

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a condition which challenging the quality of life of the patients. According to the world health organization report, 108 million persons had diabetes during 1980s; 422 million persons had diabetes in the year 2014. The global prevalence of diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in the adult population. Mostly the diabetic patients are sedentary in their life style, inactivity contribute the deconditioning of the skin, uncontrolled hyperglycemia and lowering the tolerance for weight bearing activities. Historically these patients are advised to avoid more stress to the plantar tissues to avoid foot ulceration, but moderate lower extremity weight bearing exercises help to improve the patient mobility without increase the risk of foot ulcers. A progressive program may preserve the lower extremity muscles, improve sensory perception and functional balance. AIM AND OBJECTIVE: To study the effect of lower extremity weight bearing training along with conventional training on static balance using sharpen Romberg test, on dynamic balance using TUG test, on vibration perception using biothesiometer and active range of motion using universal goniometer among Diabetic peripheral neuropathy patients. METHODOLOGY: Quasi-experimental research design with purposive sampling technique was employed. 300 Type 2 diabetic patients were selected. Patients who have diabetic history more than 10years, age between 40-65 years, MNSI score >2 and vibratory perception between 15-50V were included. Thirty patients fulfilled the inclusion criteria and they were randomly allocated in to two group. Group A (Experimental) received Lower extremity weight bearing training along with conventional training and group B (control) received the same conventional training alone. Post-test measures of thirty patients were taken after 8 weeks of treatment. OUTCOME MEASURES: Static balance using sharpen Romberg test, dynamic balance using TUG test, Vibratory perception using biothesiometer and Active range of motion using Universal goniometer are used. RESULTS: The data was analyzed using ‘t’ test at 5% level of significance. The homogeneity is maintained between two groups. The experimental group that receive Lower extremity weight bearing training along with conventional training had significant improvement in both static balance (t stat=26.89), dynamic balance (t stat=27.8), vibration perception in right foot (t stat=12.07), left foot (t stat=16.74) and active ankle range of motion than the control group that receive only conventional training. CONCLUSION: The results of this study conclude that lower extremity weight bearing training enhance balance both static and dynamic, vibration perception and active ankle range of motion among diabetic peripheral neuropathy patients

Evaluating non-invasive cytokine sampling to detect diabetic peripheral neuropathy : a proof-of-concept study

Diabetic Peripheral Neuropathy (DPN) is the most common form of peripheral neuropathy worldwide. However, there are limited treatments for DPN, thus early diagnosis and prevention are essential. A large component of the pathophysiology of diabetes and DPN is based on the presence of inflammation that consequently leads to the complications associated with DPN. The focus of this proof-of-concept study is investigating the link between local inflammatory factors on the skin and comparing them to the circulating cytokines in the blood. This will provide insight into whether the same cytokines associated with DPN that have been previously identified in the blood – mainly Interleukin-6 (IL-6), Interluekin-1 (IL-1), Interleukin-8 (IL-8), Tumour Necrosis Factor Alpha (TNF-α), C-Reactive Protein (CRP) and Interkeukin-10 (IL-10) – are also present on the skin of people with diagnosed peripheral neuropathy. Twenty-five participants with diabetes were recruited to undergo both functional and objective assessments to determine DPN diagnosis and severity: the Michigan Neuropathy Screening Instrument (MNSI) in conjunction with Quantitative Sensory Testing (QST), and nerve conduction testing. Sebum from the foot and blood samples were collected from participants and analysed by an external lab. While there were no statistically significant results due to the small sample size, this pilot study provided some direction for future research with a larger sample size. Finding an association between local inflammatory factors on the skin and those circulating in the blood might provide an opportunity for the development of a localised, skin sebum test that is non-invasive, inexpensive, and accessible for a more reliable, measurable, and standardised diagnostic tool for DPN

Advances in Screening, Early Diagnosis and Accurate Staging of Diabetic Neuropathy

This is the final version. Available on open access from Frontiers Media via the DOI in this recordThe incidence of both type 1 and type 2 diabetes is increasing worldwide. Diabetic peripheral neuropathy (DPN) is among the most distressing and costly of all the chronic complications of diabetes and is a cause of significant disability and poor quality of life. This incurs a significant burden on health care costs and society, especially as these young people enter their peak working and earning capacity at the time when diabetes-related complications most often first occur. DPN is often asymptomatic during the early stages; however, once symptoms and overt deficits have developed, it cannot be reversed. Therefore, early diagnosis and timely intervention are essential to prevent the development and progression of diabetic neuropathy. The diagnosis of DPN, the determination of the global prevalence, and incidence rates of DPN remain challenging. The opinions vary about the effectiveness of the expansion of screenings to enable early diagnosis and treatment initiation before disease onset and progression. Although research has evolved over the years, DPN still represents an enormous burden for clinicians and health systems worldwide due to its difficult diagnosis, high costs related to treatment, and the multidisciplinary approach required for effective management. Therefore, there is an unmet need for reliable surrogate biomarkers to monitor the onset and progression of early neuropathic changes in DPN and facilitate drug discovery. In this review paper, the aim was to assess the currently available tests for DPN’s sensitivity and performance.National Institute for Health Research (NIHR

Risk assessment tool for diabetic neuropathy.

Peripheral neuropathy is one of the serious complications of diabetes. Symptoms such as tingling and loss of touch sensation are commonly associated with the early stages of neuropathy causing numbness in the feet. Early detection of this condition is necessary in order to prevent the progression of the disease. Out of many detection techniques vibration perception is becoming the gold standard for neuropathy assessment. Devices like tuning fork, Biothesiometer and Neurothesiometer use this technology but require an operator to record and manually interpret the results. The results are user-dependent and are not consistent. To overcome these limitations, a platform-based device “VibraScan” was developed that can be self-operated and results displayed on a user interface. The development of the device is based on studying the effect of the vibration on the human subject by identifying the receptors responsible for sensation. The requirement of generating vibration was achieved by selecting a specific actuator that creates vibration perpendicular to the contact surface. The battery operated VibraScan is wirelessly controlled by software to generate vibration for determining the vibration perception threshold (VPT). Care has been taken while developing the user interface for human safety with the vibration intensity. The device can be operated without any assistance and results are automatically interpreted in terms of severity level indicated similar to the traffic-light classification. In order to provide consistent results with the existing devices a study was undertaken between Neurothesiometer and VibraScan with 20 healthy subjects. The results were compared using Bland-Altman plot and a close agreement was found between the two measurements. VibraScan accurately measures VPT based on the perceived vibration threshold, however, it does not predict any risk associated with neuropathy. In order to supplement this device with the progression of neuropathy a risk assessment tool was developed for automated prediction of neuropathy based on the clinical history of patients. The smart tool is based on the research related to the risk factors of diabetic neuropathy which was studied and analysed using summarised patient data. Box-Cox regression was used with the response variable (VPT) and a set of clinical variables as potential predictors. Significant predictors were: age, height, weight, urine albumin to creatinine ratio (ACR), HbA1c, cholesterol and duration of diabetes. Ordinary Least Squares Regression was then used with logarithmic (VPT) and the significant predictor set (Box-Cox transformed) to obtain additional fit estimates. With the aim to improving the precision of VPT prediction, a simulated patient data set (n = 4158) was also generated using the mean and the covariance of the original patient variables, but with reduced standard errors. For clinical or patient use, providing direct knowledge of VPT was considered less helpful than providing a simple risk category corresponding to a range of VPT values. To achieve this, the continuous scale VPT was recoded into three categories based on the following clinical thresholds in volts (V): low risk (0 to 20.99 V), medium risk (21 to 30.99 V) and high risk (≥ 31 V). Ordinal Logistic Regression was then used with this categorical outcome variable to confirm the original predictor set. Having established the effectiveness of this “classical” baseline, attention turned to Neural Network modelling. This showed that a carefully tuned Neural Network based Proportional Odds Model (NNPOM) could achieve a classification success >70%, somewhat higher than that obtained with the classical modelling. A version of this model was implemented in the VibraScan risk assessment tool. Integrating VibraScan and the risk assessment software has created a comprehensive diagnostic tool for diabetic neuropathy