Search

An alteration in circulating miRNAs may have important diagnostic and therapeutic relevance in diabetic neuropathy. Patients with type 2 diabetes mellitus (T2DM) underwent an assessment of neuropathic symptoms using Douleur Neuropathique 4 (DN4), the vibration perception threshold (VPT) using a Neurothesiometer, sudomotor function using the Sudoscan, corneal nerve morphology using corneal confocal microscopy (CCM) and circulating miRNAs using high-throughput miRNA expression profiling. Patients with T2DM, with (n = 9) and without (n = 7) significant corneal nerve loss were comparable in age, gender, diabetes duration, BMI, HbA1c, eGFR, blood pressure, and lipid profile. The VPT was significantly higher (p < 0.05), and electrochemical skin conductance (p < 0.05), corneal nerve fiber density (p = 0.001), corneal nerve branch density (p = 0.013), and corneal nerve fiber length (p < 0.001) were significantly lower in T2DM patients with corneal nerve loss compared to those without corneal nerve loss. Following a q-PCR-based analysis of total plasma microRNAs, we found that miR-92b-3p (p = 0.008) was significantly downregulated, while miR-22-3p (p = 0.0001) was significantly upregulated in T2DM patients with corneal nerve loss. A network analysis revealed that these miRNAs regulate axonal guidance and neuroinflammation genes. These data support the need for more extensive studies to better understand the role of dysregulated miRNAs’ in diabetic neuropathy.

Background and Aims Assessing and monitoring cognitive frailty (CF; coexistence of physical frailty and cognitive impairment) are critical for hemodialysis patients. For administering physical frailty and cognitive assessments, however, clinical settings need to address challenges (e.g., cost, human and technical resources, patient’s fatigue, etc.). This study aims to investigate the feasibility and accuracy of a novel intradialytic cognitive-demanding exercise program based on wearables, called, intradialytic-exergame for screening CF in hemodialysis patients. Method Individuals diagnosed with diabetes and end-stage renal disease requiring hemodialysis (n=28, age: 61.36 ± 6.85 years, 54% female) participated. All participants were assessed for physical frailty using the Fried frailty phenotype method and cognitive impairment using the Mini-Mental State Examination (MMSE). The Fried frailty phenotype method assesses physical frailty, which ranges between 0 and 5 based on five criteria (unintentional weight loss, weakness, slowness, exhaustion, and low physical activity). CF was determined with a frailty phenotype greater than or equal to 1 and a MMSE score less than or equal to 24. The intradialytic-exergame system consists of an inertial wearable sensor and an interactive software installed on a standard laptop. A clinician attaches one wearable sensor to each foot after the participant sits or lies down on a bed (Figure A). While undergoing hemodialysis treatment, the participant performs 15 non-weight-bearing cognitively-demanding dorsiflexion and plantarflexion exercises for each foot. For each exercise, the laptop’s screen displays a target (solid yellow circle) and a cursor (solid red square), which the participant points down for a dorsiflexion motion or up for a plantarflexion motion (Figure B). When the participant successfully puts the cursor in the target, the target disappears, and a new target appears in a different location on the screen (dashed yellow circle shown in Figure B). If the participant moves the cursor to a target in less than 2s, the custom software provides both visual (the target explodes) and auditory (positive sound) feedback as a reward (success). The three outcome measures (Exergame-slowness, frailty, and cognitive performance) were analyzed. Exergame-slowness was computed as an average of the ranges of ankle angular velocity measured by wearable sensors. Linear regression analysis was conducted for the three outcome measures to examine correlations between each outcome measure. Binary logistic regression model was conducted, and its area-under-curve (AUC) was calculated to determine the ability of Exergame-slowness to identify CF. An independent t-test was conducted to compare the differences of Exergame-slowness for CF and non-CF conditions. Significance was defined at the 2-sided p < 0.05 level. Results Five out of 28 participants were identified with CF. Significant correlations were observed between Exergame-slowness and frailty (p = 0.004, R = -0.531), Exergame-slowness and cognitive performance (p = 0.023, R = 0.437), and frailty and cognitive performance (p = 0.015, R = -0.463). The model was significantly reliable (p = 0.012) and its AUC was 0.90. Results indicated that Exergame-slowness was significantly higher (lower velocity) for participants with CF than for those with non-CF (CF: 27.41 ± 3.58 degree/s, non-CF: 34.25 ± 5.24 degree/s, p = 0.010). Conclusion To our knowledge, this is the first study to investigate the feasibility and accuracy of intradialytic-exergame with wearable sensors, as a practical tool for routine screening CF assessment in hemodialysis patients. The results of this study indicate that speed of ankle rotation, measurable using a wearable sensor during a simple intradialytic cognitive-demanding exercise, can be used as a practical digital biomarker for screening CF in hemodialysis patients.

BackgroundCognitive impairment is prevalent but still poorly diagnosed in hemodialysis adults, mainly because of the impracticality of current tools. This study examined whether remotely monitoring mobility performance can help identifying digital measures of cognitive impairment in hemodialysis patients.MethodsSixty-nine hemodialysis patients (age=64.1±8.1years, body mass index=31.7±7.6kg/m2) were recruited. According to the Mini-Mental State Exam, 44 (64%) were determined as cognitive-intact, and 25 (36%) as cognitive-impaired. Mobility performance, including cumulated posture duration (sitting, lying, standing, and walking), daily walking performance (step and unbroken walking bout), as well as postural-transition (daily number and average duration), were measured using a validated pendant-sensor for a continuous period of 24-hour during a non-dialysis day. Motor capacity was quantified by assessing standing balance and gait performance under single-task and dual-task conditions.ResultsNo between-group difference was observed for the motor capacity. However, the mobility performance was different between groups. The cognitive-impaired group spent significantly higher percentage of time in sitting and lying (Cohens effect size d=0.78, p=0.005) but took significantly less daily steps (d=0.69, p=0.015) than the cognitive-intact group. The largest effect of reduction in number of postural-transition was observed in walk-to-sit transition (d=0.65, p=0.020). Regression models based on demographics, addition of daily walking performance, and addition of other mobility performance metrics, led to area-under-curves of 0.76, 0.78, and 0.93, respectively, for discriminating cognitive-impaired cases.ConclusionsThis study suggests that mobility performance metrics could be served as potential digital biomarkers of cognitive impairment among HD patients. It also highlights the additional value of measuring cumulated posture duration and postural-transition to improve the detection of cognitive impairment. Future studies need to examine potential benefits of mobility performance metrics for early diagnosis of cognitive impairment/dementia and timely intervention.

Aim: Charcot foot (CF) is a rare complication of Type 2 diabetes (T2D). Materials & methods: We assessed circulating miRNAs in 17 patients with T2D and acute CF (G1), 17 patients with T2D (G2) and equivalent neuropathy and 17 patients with T2D without neuropathy (G3) using the high-throughput miRNA expression profiling. Results: 51 significantly deregulated miRNAs were identified in G1 versus G2, 37 in G1 versus G3 and 64 in G2 versus G3. Furthermore, we demonstrated that 16 miRNAs differentially expressed between G1 versus G2 could be involved in osteoclastic differentiation. Among them, eight are key factors involved in CF pathophysiology. Conclusion: Our data reveal that CF patients exhibit an altered expression profile of circulating miRNAs

Aims/Introduction The aim of the present study was to identify the extent of small fiber neuropathy in diabetic patients with Charcot neuroarthropathy (CN). Materials and Methods A total of 20 patients with CN were compared with 20 age‐ and diabetes duration‐matched patients with type 2 diabetes and 20 age‐matched control participants. All patients underwent corneal confocal microscopy with quantification of corneal nerve morphology and assessment for vibration perception threshold, and a subset of patients with CN underwent assessment of sudomotor function and neuropathic pain. Results In patients with CN compared with type 2 diabetes patients and control participants, there was a significant reduction in corneal nerve fiber density (14.94 ± 8.23 vs 23.86 ± 7.71, P = 0.004 vs 34.84 ± 9.13, P < 0.001), corneal nerve branch density (18.61 ± 16.7 vs 41.62 ± 22.67, P = 0.032 vs 76.47 ± 38.44, P < 0.001) and corneal nerve fiber length (8.40 ± 4.83 vs 14.87 ± 4.76, P = 0.001 vs 21.24 ± 6.48, P < 0.001), electrochemical skin conductance on the feet (20.57 ± 13.99 vs 61.50 ± 22.26, P < 0.001 vs 76.23 ± 12.01, P < 0.001) and hands (30.86 ± 18.10 vs 61.13 ± 19.14, P = 0.001 vs 68.31 ± 11.96, P < 0.001), and a significant increase in the vibration perception threshold in the feet (38.46 ± 15.10 vs 14.15 ± 10.25, P < 0.001 vs 7.75 ± 4.01, P < 0.001). Conclusions Patients with diabetes and CN have severe large and particularly small fiber neuropathy.

Background: Poor healing is an important contributing factor to amputation among patients with diabetic foot ulcers (DFUs). Physiological stress may slow wound healing and increase susceptibility to infection. Objectives: The objective was to examine the association between heart rate variability (HRV) as an indicator of physiological stress response and healing speed (HealSpeed) among outpatients with active DFUs. Design and Methods: Ambulatory patients with diabetes with DFUs (n = 25, age: 59.3 ± 8.3 years) were recruited. HRV during pre–wound dressing was measured using a wearable sensor attached to participants’ chest. HRVs were quantified in both time and frequency domains to assess physiological stress response and vagal tone (relaxation). Change in wound size between two consecutive visits was used to estimate HealSpeed. Participants were then categorized into slow healing and fast healing groups. Between the two groups, comparisons were performed for demographic, clinical, and HRV derived parameters. Associations between different descriptors of HRV and HealSpeed were also assessed. Results: HealSpeed was significantly correlated with both vagal tone ( r = –.705, P = .001) and stress response ( r = .713, P = .001) extracted from frequency domain. No between-group differences were observed except those from HRV-derived parameters. Models based on HRVs were the highest predictors of slow/fast HealSpeed (AUC > 0.90), while models based on demographic and clinical information had poor classification performance (AUC = 0.44). Conclusion: This study confirms an association between stress/vagal tone and wound healing in patients with DFUs. In particular, it highlights the importance of vagal tone (relaxation) in expediting wound healing. It also demonstrates the feasibility of assessing physiological stress responses using wearable technology in outpatient clinic during routine clinic visits.

Aim: To assess whether DNA methylation of monocytes play a role in the development of acute diabetic Charcot foot (CF). Patients & methods: We studied the whole methylome (WM) of circulating monocytes in 18 patients with Type 2 diabetes (T2D) and acute CF, 18 T2D patients with equivalent neuropathy and 18 T2D patients without neuropathy, using the enhanced reduced representation bisulfite sequencing technique. Results & conclusion: WM analysis demonstrated that CF monocytes are differentially methylated compared with non-CF monocytes, in both CpG-site and gene-mapped analysis approaches. Among the methylated genes, several are involved in the migration process during monocyte differentiation into osteoclasts or are indirectly involved through the regulation of inflammatory pathways. Finally, we demonstrated an association between methylation and gene expression in cis- and trans-association.

Objective: The objective was to report patterns of physical activity and their relationship to wound healing success in patients with diabetic foot ulcers protected with removable or irremovable offloading devices. Methods: Forty-nine people with diabetic foot ulcers were randomized to wear either a removable cast walker (RCW) or an irremovable instant total contact cast (iTCC). Primary outcome measures included change in wound size, physical activities including position (ie, sitting, standing, lying) and locomotion (speed, steps, etc). Outcomes parameters were assessed on weekly basis until wound healing or until 12 weeks. Results: A higher proportion of patients healed at 12 weeks in the iTCC group ( P = .038). Significant differences in activity were observed between groups starting at week 4. RCW patients became more active than the iTCC group (75% higher duration of standing, 100% longer duration of walking, and 126% longer unbroken walking bout, P < .05). Overall, there was an inverse association between rate of weekly wound healing and number of steps taken per day ( r < –.33, P < .05) for both groups. RCW patients had a significant inverse correlation between duration of daily standing and weekly rate of healing ( r = –.67, P < .05). Standing duration was the only significant predictor of healing at 12 weeks. Conclusion: The results from this study suggest significant differences in activity patterns between removable and irremovable offloading devices. These patterns appear to start diverging at week 4, which may indicate a decline in adherence to offloading. Results suggest that while walking may delay wound healing, unprotected standing might be an even more unrealized and sinister culprit.

Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. This study examined whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48&ndash, 64 years) and older adults (65+ years). One hundred and ninety-six subjects (age = 66.2 &plusmn, 9.1 years, body-mass-index = 30.1 &plusmn, 6.4 kg/m2, female = 56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n = 38) and without HD (Mid-age HD&minus, n = 40), older adults with diabetes undergoing HD (Older HD+, n = 36) and without HD (Older HD&minus, n = 37), and non-diabetic older adults (Older DM&minus, n = 45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p &lt, 0.050). Among people with diabetes, HD+ had significantly worsened gait and balance when comparing to HD&minus, (Cohen&rsquo, s effect size d = 0.63&ndash, 2.32, p &lt, 0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d = 2.32, p &lt, 0.001). Results suggested that deterioration in normalized gait speed among HD+ was negatively correlated with age (r = &minus, 0.404, p &lt, 0.001), while this correlation was diminished among HD&minus, Interestingly, results also suggested that poor gait among Older HD&minus, is related to poor ankle stability, while no correlation was observed between poor ankle stability and poor gait among Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among HD&minus, people with diabetes, poor ankle stability described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visit. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention.

Background: Balance, mobility, falls, and foot problems are serious detriments for the diabetic patients undergoing hemodialysis (HD) treatment. In addition, the HD process often leaves them too fatigued to engage in any physical activity or daily exercise, further deteriorating their motor functions. Exercise would be effective for this population. However, due to the time availability, post-dialysis fatigue, as well as limitation of transportation to exercise facility, the conventional exercise is impractical. Objective: We are developing an interactive foot and ankle exercise game that can be played during HD sessions to improve mobility and balance, as well as reduce foot problems. In this study, we examined the feasibility and effectiveness of this innovative wearable sensor based non-weight bearing exercise (Exergame) to improve daily physical activity in diabetic patients undergoing HD treatment. Methods: Thirty-three diabetic subjects receiving HD treatment were recruited and randomized into an intervention group (IG: n = 15, age = 62.2 ± 7.6 years, BMI = 29.1 ± 6.1 kg/m2) and a control group (CG: n = 18, age = 66.6 ± 8.7 years, BMI = 32.5 ± 9.0 kg/m2). Both groups underwent a 4-week ankle and foot exercise program (30 minutes per session, two sessions per week) during HD process. The IG received exercise via the Exergame program, which uses wearable sensors attached on subject's feet. The subject's 3-dementional ankle and foot movements were visualized in real-time on a computer screen placed in front of him/her. The subject played some game-like tasks by moving and rotating the foot and ankle. The difficulty level of the task was gradually increased depends on ability of the subject (like a game) from a simple flexion-extension movement to more complex movements including medial-lateral movement with different range of motion. The CG received traditional foot and ankle exercise without technology. Daily physical activity data was assessed for 48 hours (day and night) at baseline and post 4-week exercise, using a validated wearable sensor (PAMSysTM). Daily physical activity was quantified by duration spent in each main posture (i.e. lying, sitting, standing, and walking) and activities (e.g. postural transition, sedentary behavior, etc). Results: All IG subjects achieved to complete all exercise tasks indicating the feasibility of the Exergame platform. No adverse event or difficulty were reported indicating practicality of the exercise program. None subject in the IG was dropped out during the 4-week exercise program. Low dropout rate may indicate acceptability of the proposed Exergame platform. At the end of intervention, subjects in the IG were more active than subjects in the CG. In summary, the IG performed 53% more posture transitions to walking (Cohen's d effect size = 0.5) and 39% more posture transitions between sitting and walking (d = 0.5), when compared to the CG. Subjects in the IG also had significant less sedentary behavior than subjects in the CG. In summary, subjects in the IG spent 5% less time on sitting and lying (p = 0.049, d = 0.7), as well as 47% more time on standing and walking (p = 0.049, d = 0.7), when compared to subjects in the CG. Conclusions: This study demonstrated feasibility, acceptability, and effectiveness of an innovative Exergame program to improve daily physical activity in diabetic patients undergoing HD treatment. The key innovation of the proposed intervention is its practicality to be done during HD process, which could address the limitations of prior exercise interventions in HD patients, for example the low adherence of therapeutic exercise. Further studies should be addressed to confirm the observation with larger sample sizes.

Background: Poor balance, falls, and foot problems are serious detriments for the diabetic patients due to the obesity and diabetic foot ulcer. In addition, for the diabetic patients undergoing hemodialysis (HD) treatment, the HD process often leaves them too fatigued to engage in any physical activity or daily exercise, further deteriorating their motor functions and increasing risk of falling. Exercise would be effective for this population. However, due to the time availability, post-dialysis fatigue, as well as limitation of transportation to exercise facility, the conventional exercise for this population is impractical. Objective: We are developing an interactive foot and ankle exercise game that can be played during HD sessions to improve foot region blood flow, as well as reduce foot problems. In this study, we examined the feasibility and effectiveness of this innovative wearable sensor based non-weight bearing exercise (Exergame) to improve postural balance in diabetic patients undergoing HD treatment. Methods: Sixty diabetic subjects receiving HD treatment were recruited and randomized into an intervention group (IG: n = 29, age = 63.3 ± 7.9 years, BMI = 31.2 ± 6.5 kg/m2, female = 41%) and a control group (CG: n = 31, age = 66.5 ± 10.7 years, BMI = 32.3 ± 8.2 kg/m2, female = 55%). Both groups underwent a 4-week ankle and foot exercise program (30 minutes per session, two sessions per week) during HD process. The IG received exercise via the Exergame program, which uses wearable sensors attached on subject's feet. The subject's 3-dementional ankle and foot movements were visualized in real-time on a computer screen placed in front of him/her. The subject performed some game-like tasks by moving and rotating the foot and ankle. The difficulty level of the task was gradually increased depending on ability of the subject (like a game) from a simple flexion-extension movement to more complex movements including medial-lateral movement with different range of motion. The CG received traditional foot and ankle exercise without any technology. Postural balance was assessed in the semi-tandem test. Balance tests were performed at baseline and conclusion of the program, under both eyes-open and eyes-closed conditions. Balance parameters included ankle sway and hip sway in anterior-posterior (AP) direction (degree), medial-lateral (ML) direction (degree), as well as in area (degree2). Results: All IG subjects achieved to complete all exercise tasks indicating the feasibility of the Exergame platform. No adverse event or difficulty were reported indicating practicality of the exercise program. None subject in the IG was dropped out during the 4-week exercise program. Low dropout rate may indicate acceptability of the proposed Exergame platform. Under eyes-open condition, the IG had significant ankle sway reduction in the AP direction (Cohens’ d effect size = 0.55, p = 0.037), when comparing with the CG. At conclusion, the AP direction ankle sway reduced 18% in the IG, while in the CG it increased 58%. More significant improvements of postural balance were observed under eyes-closed condition. When comparing with the CG, the IG had significant ankle and hip sway reductions in both AP and ML directions, as well as in area (p

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

Objective: This study aimed to validate a smart-textile based on fiber-optics for simultaneous measurement of plantar temperature, pressure, and joint angles in patients with diabetic peripheral neuropathy (DPN). Methods: After in-vitro validation in the laboratory, 33 eligible subjects with DPN were recruited (age: 58 ± 8 years, BMI: 31.5 ± 8 kg/m2) for assessing plantar pressure and temperature during habitual gait-speed in a clinical-setting. All participants were asked to walk at their habitual speed while wearing a pair of sensorized socks made from highly flexible fiber optics (SmartSox). An algorithm was designed to estimate temperature, pressure, and toe range of motion from optical wavelength generated from SmartSox. To validate the device, results from thermal stress response (TSR) using thermography and peak pressure measured by computerized pressure insoles (F-Scan) were used as gold standards. Results: In laboratory and under controlled conditions, the agreements for parameters of interest were excellent ( r > .98, P = .000), and no noticeable cross-talks between measurements of temperature, angle, and pressure were observed. During clinical data acquisition, a significant correlation was found for pressure profile under different anatomical regions of interest between SmartSox and F-Scan ( r = .67, P < .050) as well as between thermography and SmartSox ( r = .55, P < .050). Conclusion: This study demonstrates the validity of an innovative smart textile for assessing simultaneously the key parameters associated with risk of foot ulcers in patients with DPN. It may empower clinicians to objectively stratify foot risk and provide timely care. Another study is warranted to validate its clinical application in preventing limb threating problems in patients with DPN.

Objective: This study examined the impact of shoe closure on plantar thermal stress response (TSR), which is known to be a surrogate of shear stress and skin perfusion. It is aimed to explore potential impact of shoe closure on increasing risk factors associated with plantar ulcers in people with diabetic peripheral neuropathy (DPN). Methods: Fifteen eligible subjects were enrolled. The left foot was used as a reference and fitted to a self-adjusted and habitual lace-tightening method by each subject. The right foot was used as a test closure and fitted into three lace closure conditions: loose, tight, and preset optimal closure (reel clutch, BOA technology). Thermal images were taken after 5 minutes of acclimatization (pre-trial) and immediately after 200 walking steps in each shoe closure condition (post-trial). TSR was calculated from the thermal images. Results: TSR was significantly higher in the test closure with loose (70.24%, P = .000) and tight (66.85%, P = .007) and lower (−206.53%, P = .000) in the preset optimal closure when compared to the reference closure. Only lace closure conditions affected TSR with no significant impact from age, BMI, and gender in our sample in a multivariable regression model. Conclusion: The results from this study suggest that shoelace closure technique can have a profound effect on TSR. It therefore stands to reason that optimal lace closure may have an impact in reducing risk of plantar ulcers in people with DPN. Interestingly, results revealed that even a self-adjusted lace closure may not be necessarily optimal and a preset closure setting like reel clutch might ultimately be recommended to minimize risk. Further study is warranted to confirm or refute these interesting results.

Objective: People with diabetic peripheral neuropathy (DPN) often exhibit deteriorations in motor-performance mainly due to lack of plantar-sensation. The study explored effectiveness of plantar electrical-stimulation therapy to enhance motor-performance among people with DPN. Design and methods: Using a double-blinded model, 28 volunteers with DPN (age: 57.8 ± 10.2 years) were recruited and randomized to either intervention (IG: n = 17) or control (CG: n = 11) group. Both groups received identical plantar-stimulation devices for six weeks of daily use at home; however, only the IG devices were set to deliver stimulation. Balance (ankle, hip, and center of mass [COM] sway) and gait (stride velocity [SV], stride time [ST], stride length [SL], and cadence) were measured using validated wearable sensors. Outcomes were assessed at baseline and at six-week. Clinical assessment including vascular as measured by ankle-brachial-index (ABI) and plantar-sensation as quantified by vibratory plantar threshold (VPT) were also measured at baseline and six weeks. Results: No difference were observed between groups for baseline characteristics ( P > .050). Posttherapy, ankle and COM sway with eyes open were significantly improved ( P < .05, Cohen’s effect size d = 0.67-0.76) in the IG with no noticeable changes in CG. All gait parameters were significantly improved in the IG with highest effect size observed for cadence ( d = 1.35, P = .000). Results revealed improvement in VPT ( P = .004, d = 1.15) with significant correlation with stride velocity improvement ( r = .56, P = .037). ABI was improved in the IG in particulate among those with ABI>1.20 ( P = .041, d = 0.99) Conclusion: This study suggests that daily home use of plantar electrical-stimulation may be a practical means to enhance motor-performance and plantar-sensation in people with DPN.

Diabetic foot complications are common, costly, and difficult to treat. Peripheral neuropathy, repetitive trauma, and peripheral vascular disease are common reasons that lead to ulcers, infection, and hospitalization. Individuals with diabetes presenting with foot infection require optimal medical and surgical management to accomplish limb salvage and prevent amputation; aggressive short-term and meticulous long-term care plans are required. Multiple classification systems have been recommended to ease the understanding and the management of these infections. Multi-disciplinary approach is the mainstay for a successful management. Such teams typically include multiple medical, surgical, and nursing specialties across a variety of public and private health care systems. This article is an overview in how to medically and surgically approach the diabetic foot infection with emphasis in soft tissue infection.

Background Nearly all amputations in people with diabetes are preceded by a foot ulcer. It has been reported that stress is an important risk factor for slower wound healing and susceptibility to infection. The purpose of this study was to objectively monitor physiological stress response in patients with diabetic foot ulcer (DFU) during a clinical visit for wound dressing change. Methods Physiological stress was continuously monitored in 20 patients (Age: 56.7 ± 12.2 years) with DFU for duration of approximately 45 min including waiting, dressing change and post-dressing period. Stress was quantified using a custom algorithm based on standard deviation of R-R intervals, heart rate variability (HRV). To identify the change in level of stress, change in HRV was compared to baseline HRV. Medium and high-stress periods were defined when HRV was in the range of 60–85% and below 60% of baseline HRV, respectively. Results During the entire time of visit medium and high stress episodes happened for 28 ± 12.6% and 16 ± 18% of the time respectively. Further analyses of wound dressing time revealed that medium and high stress episodes were experienced for 47 ± 24% and 18.3 ± 27% of dressing time respectively. In addition, the duration of medium stress was significantly increased in average by 66% (difference = 21.8%, p = 0.002, 95%CI [7.5, 29.5]%) during dressing change compared to entire period of clinic visit. Conclusions This pilot study shows that patients with DFU experience moderate to high stress while visiting a wound clinic, which may negatively impact wound healing outcomes. In particular, the highest stressful condition was during wound dressing change, which may be related to painful dressing or perception of pain. Further investigation is required to explore association between quantified stress and outcomes of wound healing. In addition, future studies need to explore benefit of stress management in enhancing the outcomes of wound healing in patients with diabetes.

Wound moisture is known to be a key parameter to ensure optimum healing conditions in wound care. This study tests the moisture content of wounds in normal practice in order to observe the moisture condition of the wound at the point of dressing change. This study is also the first large‐scale observational study that investigates wound moisture status at dressing change. The WoundSense sensor is a commercially available moisture sensor which sits directly on the wound in order to find the moisture status of the wound without disturbing or removing the dressing. The results show that of the 588 dressing changes recorded, 44·9% were made when the moisture reading was in the optimum moisture zone. Of the 30 patients recruited for this study, 11 patients had an optimum moisture reading for at least 50% of the measurements before dressing change. These results suggest that a large number of unnecessary dressing changes are being made. This is a significant finding of the study as it suggests that the protocols currently followed can be modified to allow fewer dressing changes and less disturbance of the healing wound bed.

Background: Individuals with diabetic peripheral neuropathy frequently experience concomitant impaired proprioception and postural instability. Conventional exercise training has been demonstrated to be effective in improving balance but does not incorporate visual feedback targeting joint perception, which is an integral mechanism that helps compensate for impaired proprioception in diabetic peripheral neuropathy. Methods: This prospective cohort study recruited 29 participants (mean ± SD: age, 57 ± 10 years; body mass index [calculated as weight in kilograms divided by height in meters squared], 26.9 ± 3.1). Participants satisfying the inclusion criteria performed predefined ankle exercises through reaching tasks, with visual feedback from the ankle joint projected on a screen. Ankle motion in the mediolateral and anteroposterior directions was captured using wearable sensors attached to the participant’s shank. Improvements in postural stability were quantified by measuring center of mass sway area and the reciprocal compensatory index before and after training using validated body-worn sensor technology. Results: Findings revealed a significant reduction in center of mass sway after training (mean, 22%; P = .02). A higher postural stability deficit (high body sway) at baseline was associated with higher training gains in postural balance (reduction in center of mass sway) (r = −0.52, P < .05). In addition, significant improvement was observed in postural coordination between the ankle and hip joints (mean, 10.4%; P = .04). Conclusions: The present research implemented a novel balance rehabilitation strategy based on virtual reality technology. The method included wearable sensors and an interactive user interface for real-time visual feedback based on ankle joint motion, similar to a video gaming environment, for compensating impaired joint proprioception. These findings support that visual feedback generated from the ankle joint coupled with motor learning may be effective in improving postural stability in patients with diabetic peripheral neuropathy. (J Am Podiatr Med Assoc 103(6): 498–507, 2013)

Background : There are several applications of electrical stimulation described in medical literature to accelerate wound healing and improve cutaneous perfusion. This is a simple technique that could be incorporated as an adjunctive therapy in plastic surgery. The objective of this review was to evaluate the results of randomized clinical trials that use electrical stimulation for wound healing. Method : We identified 21 randomized clinical trials that used electrical stimulation for wound healing. We did not include five studies with treatment groups with less than eight subjects. Results : Electrical stimulation was associated with faster wound area reduction or a higher proportion of wounds that healed in 14 out of 16 wound randomized clinical trials. The type of electrical stimulation, waveform, and duration of therapy vary in the literature. Conclusion : Electrical stimulation has been shown to accelerate wound healing and increase cutaneous perfusion in human studies. Electrical stimulation is an adjunctive therapy that is underutilized in plastic surgery and could improve flap and graft survival, accelerate postoperative recovery, and decrease necrosis following foot reconstruction. Keywords : diabetic foot ulcer; electric stimulation therapy; treatment outcome; perfusion; infection (Published: 16 September 2013) Citation: Diabetic Foot & Ankle 2013, 4 : 22081 - http://dx.doi.org/10.3402/dfa.v4i0.22081

Background and Aim: In the United States alone, diabetic limb complications and amputations are estimated to cost $17 billion. Significant risk factors that may lead to amputation of the diabetic foot include ineffective wound healing and infection of a wound or ulcer. Previous studies have shown that wound healing is slowed and patient's susceptibility to infection is increased when a patient is under chronic stress. To date, objective measures of stress have not been used to determine if stress affects the rate at which wounds heal. Our study used novel real-time monitoring of patient's heart rate variability to objectively determine the stress levels of patients visiting a surgery clinic for wound dressing changes. The wound healing rates of patients with high stress levels were compared to healing rates of low-stress individuals to assess the effect of stress on rates of wound healing among diabetics with a history of foot ulceration. Methods: Twenty patients (age: 56.7 ± 12.2 years) with diabetic foot ulcers were equipped with a chest-worn sensor (Bioharness 3, Zephyr Technology Corp., Annapolis, MD) during their 45-minute appointments where the patients’ wound was re-dressed. The chest sensor contained a uni-channel ECG recorder, and a novel algorithm was developed to determine heart rate variability from sensor output. Low frequency (0.04 to 0.15 Hz) HRV signals were isolated from high frequency signals (0.15 to 0.40 Hz), and the ratio of their amplitudes was used as a measure of stress. Patients were categorized as low-stress if the ratio of the signals was less than 1, and were otherwise categorized as high-stress individuals. Regardless of classification, each patient's wound size (length, width, depth) was recorded at baseline and in follow-up visits. High and low-stress patients were compared to see if wound sizes decreased more rapidly in either group. Results: Results indicate that patients with low levels of stress reduced their wound size by 79% between baseline and the first follow-up appointment (1.36 mm3 to 0.28 mm3). In contrast, patients with high levels of stress had adverse outcomes, with their wound sizes increasing nearly four times between baseline and follow-up (0.17 mm3 vs 0.84 mm3). Although high stress individuals had smaller wound sizes than low stress individuals initially (0.17 mm3 vs. 1.36 mm3, p 3 vs. 0.28 mm3, p = 0.10). Conclusion: Our research proposes that an individual's stress level can be objectively measured using an algorithm that processes ECG data from a single body-worn sensor that is lightweight and comfortable to wear. The stress levels measured with our algorithm are predictive of positive clinical outcomes. Specifically, individuals with low levels of recorded stress at baseline have faster healing rates and greater reductions in wound size by their second clinical appointment. This indicates that real-time patient stress monitoring using body-worn sensors may help clinicians identify risk factors that prolong wound healing times. In addition, it can be inferred that managing stress in diabetic patients will quicken the pace of wound healing. Surprisingly, however, our results suggest that initial wound sizes are not good indicators of stress levels in patients during initial clinical appointments. In fact, wound sizes of high stress individuals were significantly lower than low-stress individuals at baseline.

SUMMARY As clinicians, we have been searching for objective and widely available outcome measures for our care. We also prefer these measuring processes not to burden our busy clinics or patients’ time. With this in mind, it seems that there are many challenges to treating patients with diabetes. Some of these are well recognized and some are not. For example, we know that balance deterioration affects this population. In addition, individuals with diabetes are more vulnerable to any minor trauma than a healthy individual. Any minor trauma causes a major wound, which can be very dangerous for this population. Thus preventive strategies for reducing the risk of falls in diabetes should be considered even before geriatric age. Evaluation of the risk of falling is a necessary step towards the provision of preventive measures. This paper reviews and provides a comprehensive outlook of current development and possible emerging technologies for addressing balance instability in diabetes.

Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m2) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m2) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-controlslope = 1.23±1.06×10-2 cm2/sec, P

Background: Individuals with diabetic peripheral neuropathy (DPN) have deficits in sensory and motor skills leading to inadequate proprioceptive feedback, impaired postural balance and higher fall risk. Objective: This study investigated the effect of sensor-based interactive balance training on postural stability and daily physical activity in older adults with diabetes. Methods: Thirty-nine older adults with DPN were enrolled (age 63.7 ± 8.2 years, BMI 30.6 ± 6, 54% females) and randomized to either an intervention (IG) or a control (CG) group. The IG received sensor-based interactive exercise training tailored for people with diabetes (twice a week for 4 weeks). The exercises focused on shifting weight and crossing virtual obstacles. Body-worn sensors were implemented to acquire kinematic data and provide real-time joint visual feedback during the training. Outcome measurements included changes in center of mass (CoM) sway, ankle and hip joint sway measured during a balance test while the eyes were open and closed at baseline and after the intervention. Daily physical activities were also measured during a 48-hour period at baseline and at follow-up. Analysis of covariance was performed for the post-training outcome comparison. Results: Compared with the CG, the patients in the IG showed a significantly reduced CoM sway (58.31%; p = 0.009), ankle sway (62.7%; p = 0.008) and hip joint sway (72.4%; p = 0.017) during the balance test with open eyes. The ankle sway was also significantly reduced in the IG group (58.8%; p = 0.037) during measurements while the eyes were closed. The number of steps walked showed a substantial but nonsignificant increase (+27.68%; p = 0.064) in the IG following training. Conclusion: The results of this randomized controlled trial demonstrate that people with DPN can significantly improve their postural balance with diabetes-specific, tailored, sensor-based exercise training. The results promote the use of wearable technology in exercise training; however, future studies comparing this technology with commercially available systems are required to evaluate the benefit of interactive visual joint movement feedback.

Background: Undetected repeated foot loading and temperature changes during walking in diabetic patients with peripheral neuropathy significantly increases risk of foot ulceration. Early detection of inflammation due to foot temperature and pressure changes from walking has shown to be a potentially effective strategy in prevention of foot ulcers. Therefore, a clinically feasible assessment of these changes is vital to measure pre-ulcerative inflammation and predict DFUs. The current study is aimed to validate effectiveness of an innovative fiber optics embedded smart textile for simultaneous measurement of plantar pressure and temperature. Methods: The study recruited 21 diabetic patients (Age: 57.8±7.9 years, BMI: 31.6±8.0 kg/m2, VPT: 26.8±15 volt, 68% diagnosed with peripheral neuropathy) at high risk for foot ulcers from Wound and Diabetic Foot Center at Hamad Medical Co. Doha. A series of sensors were juxtaposed on the length of an optical fiber integrated in a comfortable sock (Novinoor LLC, IL) for measuring temperature and pressure changes under anatomical regions of the heel, midfoot, 1st and 5th metatarsal heads, and big toe based on changes in wavelength of light. A thermal image was acquired after five-minute temperature acclimation before walking for validating temperature changes. Participants walked 200 steps to induce thermal stress and follow up thermal image was acquired. Participants also wore F-scan insoles (TekScan®Inc) during walk for pressure validation. Results: All the recruited patients perceived the device as comfortable. A significant correlation was observed between both pressure (r=0.67, p

Background: Inadequate blood flow can increase risk of foot ulceration in diabetics. Exercise training can improve lower extremity blood flow in diabetes, however, the intensity of exercise should be taken into account for this population is they are at high risk for developing foot ulcers. Aim: The aim of the present study is to explore the immediate effect of a tailored low impact virtual reality exercise training on lower extremity blood flow in patients with diabetic peripheral neuropathy. We hypothesize that tailored exercise specifically designed for diabetes will induce sufficient muscle activation in order to improve blood flow. Methods: Eight patients (Age: 64.3±10.2 years, BMI 32.6±6.3) with diagnosed DPN (HbA1c: 7.3±1.2) participated in a single 45 minute session for low-impact virtual reality based balance training exercise. Changes in blood flow were quantified by Ankle Brachial Index (ABI) recorded pre- and post-training. Systolic blood pressures were determined at the brachial, posterior tibial, and dorsalis pedis arteries using a 10 MHz handheld Doppler. Results: Non-parametric Wilcoxon Signed Rank test revealed a strong but non-significant reduction in ABI from single session virtual reality training. The values dropped from 1.28 to 1.22 (4.7% reduction, p = 0.173). Conclusion: The initial results show that a tailored low impact exercises for diabetes can improve blood flow, which may reduce the risk for diabetic foot ulceration. Future studies should confirm these findings in a larger pool of patients with 8-12 week exercise training in order to explore the long term effect on exercise on blood flow. Funding Source: QNRF NPRP 4-1025-3-276

Gait-related fall risk is the leading cause of mortality among patients with diabetes, especially those older than 65 years. Deterioration in balance and loss of protective sensation in lower extremities contribute significantly to fall risk in patients with diabetic peripheral neuropathy (DPN). This study aimed to explore the impact of neuropathy and foot ulcer on gait.We recruited 39 participants (age, 56.9 ± 8.2 years; body mass index, 29.6.3 ± 4.7 kg/m2), including 15 DPN patients without foot ulcers, 16 DPN patients with foot ulcers, and 8 healthy aged-matched controls. Patients with active foot ulcers wore an offloading device during gait examination, including removable cast walker.Results suggest that neuropathy alters gait mainly by increasing gait initiation, gait variability (coefficient of variation of gait velocity), and double support (DS) time, while reducing knee range of motion and center of mass sway (p.05). Interestingly, the presence of foot ulcer does not impact gait velocity (p.1) but enhances some of the gait parameters such as gait variability and DS time.This study demonstrates that neuropathy deteriorates gait, but the presence of foot ulcers does not alter gait parameters further than neuropathy. In addition, patients with foot ulcers demonstrated a better gait compared with DPN patients without ulcers. We speculate that offloading footwear may be enhancing the somatosensory feedback from sensate skin, thereby positively affecting gait parameters. A study with a larger sample is required to explore the effect of prescribed footwear in the DPN population in order to validate the findings of this research study.

Background: Individuals with diabetes have a higher risk of falls and fall-related injuries. People with diabetes often develop peripheral neuropathy (DPN) as well as nerve damage throughout the body. In particular, reduced lower extremity proprioception due to DPN may cause a misjudgment of foot position and thus increase the risk of fall. Objective: An innovative virtual obstacle-crossing paradigm using wearable sensors was developed in an attempt to assess lower extremity position perception damage due to DPN. Methods: 67 participants (age 55.4 ± 8.9, BMI 28.1 ± 5.8) including diabetics with and without DPN as well as aged-matched healthy controls were recruited. Severity of neuropathy was quantified using a vibratory perception threshold (VPT) test. The ability of perception of lower extremity was quantified by measuring obstacle-crossing success rate (OCSR), toe-obstacle clearance (TOC), and reaction time (TR) while crossing a series of virtual obstacles with heights at 10% and 20% of the subject’s leg length. Results: No significant difference was found between groups for age and BMI. The data revealed that DPN subjects had a significantly lower OCSR compared to diabetics with no neuropathy and controls at an obstacle size of 10% of leg length (p < 0.05). DPN subjects also demonstrated longer TR compared to other groups and for both obstacle sizes. In addition, TOC was reduced in neuropathy groups. Interestingly, a significant correlation between TR and VPT (r = 0.5, p < 10–3) was observed indicating a delay in reaction with increasing neuropathy severity. The delay becomes more pronounced by increasing the size of the obstacle. Using a regression model suggests that the change in TR between obstacle sizes of 10% and 20% of leg length is the most sensitive predictor for neuropathy severity with an odds ratio of 2.70 (p = 0.02). Conclusion: The findings demonstrate proof of a concept of virtual-reality application as a promising method for objective assessment of neuropathy severity, however a further study is warranted to establish a stronger relationship between the measured parameters and neuropathy.

Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT) as a function of graduated walking activity to quantify thermal responses during the first 200 steps.Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot).Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P=0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps.Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course.

Background & Objectives: Charcot neuroarthropathy (CN) is a devastating complication of diabetes. It has two-fold higher rate of major amputation compared to those without CN. Unfortunately, to date, there is no pathological marker or diagnostic criterion for it and diagnosis relies on pattern recognition and clinical intuition. Not surprisingly, the diagnosis can be missed up to 95% of the time and the average diagnostic delay has been estimated at almost 7 months. Recent studies reported asymmetric plantar temperature differences secondary to inflammation as a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. Methods: Fifteen individuals with acute CN and 17 age-matched non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The plantar temperature (PT) response as a function of number of steps was examined using a validated wearable sensor technology. A custom image processing toolbox was designed to characterize the plantar temperature response to activity. Results: During initial activity, the PT was reduced in all participants, but the temperature drop for the non-affected foot was 1.9 times greater than the affected side in CN group (p=0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions: The observed differential thermal response to walking initiation between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between activity dosing and thermal response. It may also lead to a valuable insight into identifying an "inflammatory trigger" that may ultimately provide an early warning sign or increased sensitivity for subsequent unilateral or bilateral CN development or clinical expression of foot ulcer. These results also support that managing modulating duration of continuous steps and or prolonged standing during daily activity could be helpful for reducing the trauma in patients with CN or patients at risk of diabetic foot ulcer.

Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes that affects nerve functions and may occur in 25% of patients with 10 or more years of diabetes and up to 50% with 20 years of diabetes. Patients with DPN experience a high incidence of injuries while walking and have a low level of perceived safety. In certain cases the impaired judgment - mainly due to impaired proprioceptive feedback - can cause obstacle collision leading to falls and injuries. The subtle early findings that are indicative of postural instability are difficult to accurately assess from a clinical examination, and gait laboratory assessment is not currently available or practical. Thus, unfortunately, many patients that are "at risk for falls" are undiagnosed. Objectives: An innovative virtual obstacle crossing (VOC) paradigm using wearable sensors was developed in attempts to detect lower extremity nerve damage due to DPN. Methods: Sixty-eight participants including diabetes with no, moderate and severe neuropathy and aged-matched healthy controls were recruited. Severity of neuropathy was quantified using vibratory perception threshold (VPT) values. The ability of perception of lower extremity was quantified by measuring the rate of obstacle crossing success (OCS), reaction time (TR), and foot position while crossing a series of virtual obstacles with various heights. Results: Results suggest VOC test allows separating between groups. All proposed parameters were significantly deteriorated by increasing neuropath severity (p

Background: People with diabetes-related peripheral neuropathy (DPN) frequently suffer from concomitant postural instability that can lead to falls, fractures, depression, anxiety, and decreased quality of life. Exercise has been demonstrated to be effective in improving balance. However, high demands of conventional balance programs might overtax DPN patients' ability to perform exercises correctly. This might in turn reduce motivation or increase risk of diabetic foot ulcers. In addition, conventional training regimes do not incorporate visual feedback, which is of key importance for compensating the impaired proprioceptive feedback due to DPN. In this study, we examined the effectiveness of an innovative ankle exercise program based on virtual reality for improving postural control among DPN patients. Methods: A novel ankle reaching exercise program was developed based on virtual reality and body worn sensors. Twenty-nine eligible DPN subjects (Age:57±10 years; BMI: 55.9±11.1 kg/m2) were asked to perform a set of point-to-point ankle reaching tasks while receiving real-time video game style feedback from ankle joint motion. The ankle motion in medial-lateral and anterior-posterior was measured using a set of wearable sensors attached to the subject's shank. To evaluate the benefit of this paradigm for improving postural control, a validated technology based on body worn sensors was used to examine balance at baseline and after training. Postural control was quantified by measuring the area of center of mass sway (COM) and reciprocal compensatory index (RCI). Results: Our findings revealed a significant reduction in COM post-training in average by 16% (p= 0.03). A negative correlation (r= -0.46; p< 0.05) was observed between baseline COM and the magnitude of COM reduction post-training suggesting a larger exercise benefit for those who have higher postural control deficit. A similar association was observed between neuropathy severity and magnitude of exercise benefit. In addition, a significant improvement was observed in RCI in average by 11.3% (p< 0.005). Conclusions: The current research has implemented a novel balance training paradigm that provides real-time visual feedback from ankle joint motion in order to incorporate joint proprioception in balance training. Our findings support that motor learning based on real-time feedback from ankle joint motion is effective in improving postural stability among DPN patients.