Effects of Computer-based Balance Exercises on Balance, Pain, Clinical Presentation and Nerve Function in Patients With Diabetic Peripheral Neuropathy: A Randomized Controlled Study.

OBJECTIVE: To evaluate the use of a computer-based biodex balance exercise system (BBS) on balance, neuropathic pain, clinical presentation and nerve function in patients with diabetic peripheral neuropathy (DPN). METHODS: A total of 32 participants with DPN were randomly assigned in a 1:1 ratio to an intervention group (IG) or control group (CG). The IG performed exercises using the BBS twice weekly for 8 weeks, while CG were informed regarding diabetes self-management. At baseline and after study completion, participants underwent balance (postural stability and fall risk) and neuropathic pain assessment (DN4 questionnaire) and were screened using the Michigan Neuropathy Screening Instrument and nerve conduction test. RESULTS: Among the baseline participants, 14 in the IG and 13 in the CG completed the study. Balance training improved postural stability (overall, p<0.001), fall risk (p<0.001), neuropathic pain (p=0.01) and symptoms (p<0.001), and clinical presentation (p=0.02), but not nerve function, within the IG. At follow-up, IG displayed significantly improved stability (p<0.001) and fall risk (p=0.02) and decreased neuropathic symptoms (p=0.01) compared to the CG. CONCLUSION: Computer-based balance exercises improve balance, pain, and clinical presentation of DPN, but not nerve function, in patients with DPN. CLINICALTRIALS: gov ID: NCT05255497.

[To determine the value of iMAX, a new electrodiagnostic method, and its application in the evaluation of peripheral motor nerve excitability].

Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.

Undiagnosed and Untreated Peripheral Complications of Diabetes: Findings from a Pilot Study on Diabetes-Related Foot Diseases (DFD) in Patients with Glycemic Disorders.

BACKGROUND Diabetes-related foot disease (DFD) is a serious complication of diabetes, increasing the risk of amputation. Coimplications are preventable, but most diabetics do not receive proper screening and treatment, despite indications. This study was a pilot screening of diabetes-related foot disease in a group of people with glycemic disorders. MATERIAL AND METHODS We recruited 143 volunteers over 40 years of age. In the final analysis, we included 85 people diagnosed with glycemic disorders (diabetes or prediabetes), for whom we performed a total of 170 foot measurements. We screened for peripheral artery disease using: foot pulse, ankle-brachial index (manual and automatic), toe-brachial index, and transcutaneous oxygen pressure (TcPO2). To screen for diabetic peripheral neuropathy, we used indicators of loss of protective sensation: pressure perception and temperature perception, and plantar pressure distribution. RESULTS A history of diabetes was reported by 26 (30.6%) of the subjects. Disorders of at least 1 foot occurred in 20 (66.7%) subjects with diagnosed diabetes and in 10 (17%) subjects declaring no diabetes. Higher risk and DFD category were correlated with duration of diabetes (r=0.68, p=0.007), glycemic levels (r=0.56, p=0.001), age (r=0.57, p=0.007), and the presence of other diabetes complications. The best predictor of risk in DFD was manual ABI, p=0.001; followed by automatic ABI, p=0.006. CONCLUSIONS Our results showed that peripheral complications of diabetes, such as DFD, often remain undiagnosed and untreated despite the high risk of developing ulcers. There is a need for multi-center screening studies.

Can the 128-Hz tuning fork be an alternative to the biothesiometer for diabetic peripheral neuropathy screening? A cross-sectional study in a tertiary hospital in East India.

INTRODUCTION: Diabetic neuropathy is frequently underdiagnosed and undertreated. Logistic problems accompany the routine use of the biothesiometer. Hence, we attempted to find a more easily available alternative. RESEARCH DESIGN AND METHODS: 149 patients with diabetes visiting the outpatient endocrinology clinic were assessed for vibration sense using a 128-Hz tuning fork (absolute timing method) and a biothesiometer. A reading of >25 V on the biothesiometer (known as vibration perception threshold or VPT) was taken as the diagnostic criterion for severe neuropathy while >15 V was used as an indicator of the mild form. The sensitivity and specificity were calculated by constructing the receiver operating characteristic curve (ROC). A p value of <0.05 was considered as statistically significant. RESULTS: The timed tuning fork (TTF) test showed a statistically significant correlation with the VPT measurements (r=-0.5, p=0.000). Using the VPT findings as a reference, a timed tuning fork cut-off of 4.8 s was 76% sensitive and 77% specific in diagnosing mild neuropathy while absent tuning fork sensation demonstrated 70% sensitivity and 90% specificity in detecting severe neuropathy. CONCLUSIONS: The tuning fork test demonstrated significant sensitivity and specificity in diagnosing diabetic peripheral neuropathy when compared against the biothesiometer. A cut-off of 4.8 s can be a useful indicator of the early stages of onset of the condition.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Retention of Improved Plantar Sensation in Patients with Type II Diabetes Mellitus and Sensory Peripheral Neuropathy after One Month of Vibrating Insole Therapy: A Pilot Study.

Sensory peripheral neuropathy is a common complication of diabetes mellitus and the biggest risk factor for diabetic foot ulcers. There is currently no available treatment that can reverse sensory loss in the diabetic population. The application of mechanical noise has been shown to improve vibration perception threshold or plantar sensation (through stochastic resonance) in the short term, but the therapeutic use, and longer-term effects have not been explored. In this study, vibrating insoles were therapeutically used by 22 participants, for 30 min per day, on a daily basis, for a month by persons with diabetic sensory peripheral neuropathy. The therapeutic application of vibrating insoles in this cohort significantly improved VPT by an average of 8.5 V (p = 0.001) post-intervention and 8.2 V (p < 0.001) post-washout. This statistically and clinically relevant improvement can play a role in protection against diabetic foot ulcers and the delay of subsequent lower-extremity amputation.

Implementation of surface mechanomyography as a novel approach for objective evaluation of phasic muscle stretch reflexes in people with type 2 diabetes.

INTRODUCTION: Diabetic peripheral neuropathy is the most common complication of diabetes producing metabolic disruptions in the peripheral nervous system. Alteration in the predictable nature of tendon reflexes is the most common indicator suggesting the possibility of diabetic neuropathy. Evaluation of tendon reflexes is a part of various clinical scoring systems that assess neuropathy. The conventional reflex grading scales are subjective, lack temporal data, and have high inter-rater variability. Hence, an indigenous quantification tool was developed to evaluate the tendon reflexes in order to assess diabetic peripheral neuropathy. MATERIALS AND METHODS: A cross-sectional study was carried out in 140 healthy volunteers and 140 patients with type 2 diabetes. The mean age of controls and diabetics (49.1 ± 8.9, 50.7 ± 7.5) years, weight (66.9 ± 9.4, 69.8 ± 11.5) kilograms and BMI (24.5 ± 3.8, 26.1 ± 4.7), respectively. All of them are subjected to evaluation of tendon reflexes using the reflex quantification tool comprised of surface mechanomyography and electrogoniometry that can provide various static and dynamic variables of tendon reflex. RESULTS: The dynamic variables such as reflex amplitude, muscle velocity and angular velocity were significantly low in diabetic patients (p: <0.001) whereas latency and duration (p: <0.001) were prolonged. Furthermore, no significant difference was observed in the application of tendon striking force (p: 0.934) among the participants. CONCLUSION: The current study demonstrates that the proposed reflex quantification tool provides several dynamic variables of patellar tendon reflex, which are significantly affected and altered in diabetic patients suggesting the involvement of peripheral neurons.

Do you mind the role of spinal sensory block duration in a crucial endocrine disorder of diabetes mellitus? A prospective observational study.

OBJECTIVE: Diabetes mellitus, per se, is a global health concern, which is often accompanied by complications such as diabetic neuropathy. This prospective observational study purposed to assess the durations of spinal sensory block and motor blocks in individuals with and without diabetes mellitus who had undergone spinal anesthesia. METHODS: This study incorporated 80 cases, which were evenly divided into spinal sensory block without diabetes mellitus and spinal sensory block with diabetes mellitus. Various parameters were recorded at different time points, including heart rate, mean arterial blood pressure, SpO2, and spinal block characteristics. Notable measures included maximum spinal sensory block onset time, time to reach the 10th thoracic vertebra (T10), maximal spinal sensory block, time for Bromage scores, and block regression while controlling for age-related variations. RESULTS: Patients in the diabetic group exhibited extended block durations, with significant differences in heart rate noted at specific time points. Regarding the spinal block characteristics, the "maximum onset of SSB" and the "time to reach the T10" were more prolonged in the SSBwDM without significance. Maximum sensory spinal sensory block did not differ. However, some cases in the SSBwDM displayed blocks extending up to the T6. The times to achieve Bromage motor block scores 1-3 were shorter in SSBwDM and lost significance regarding age. Notably, the regression time was longer in SSBwDM, which held significance for both parameters. CONCLUSION: Diabetic cases commonly encounter prolonged block durations post-subarachnoid intervention, potentially linked to nerve sensitivity, age-related changes, and glycemic control. As such, attenuated local doses for diabetic neuropathic cases may enhance early mobilization, attenuate thromboembolic events, and expedite gastrointestinal recovery.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

OBJECTIVE: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Artificial intelligence-enhanced electrocardiogram analysis for identifying cardiac autonomic neuropathy in patients with diabetes.

AIM: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN). MATERIALS AND METHODS: We used motif and discord extraction techniques, alongside long short-term memory networks, to analyse 12-lead, 10-s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10-fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC). RESULTS: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91-0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54-0.81). CONCLUSION: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large-scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated.

High serum levels of CCL11/Eotaxin-1 are associated with diabetic sensorimotor polyneuropathy and peripheral nerve function but not with cardiac autonomic neuropathy in people with type 2 diabetes.

AIMS: To investigate whether higher serum CCL11/Eotaxin-1, a biomarker for aging and neurodegenerative and neuroinflammatory disorders, is associated with diabetic sensorimotor polyneuropathy (DSPN), peripheral nerve dysfunction, and cardiac autonomic neuropathy in people with type 2 diabetes. METHODS: This cross-sectional study included 106 patients with type 2 diabetes and 40 healthy controls, matched for the age and sex distribution of the diabetes group as a whole. The CC chemokines CCL11/Eotaxin-1 and CCL22/MDC were measured in fasting serum samples. DSPN and peripheral nerve function were assessed by neurological examination and nerve conduction studies, and cardiac autonomic function, by heart rate variability (HRV) and corrected QT (QTc) time. The cardio-ankle vascular index (CAVI) was measured as a marker for arterial stiffness. RESULTS: Serum CCL11/Eotaxin-1 levels were significantly higher in diabetic patients than in healthy controls (183 ± 63.5 vs. 113.1 ± 38.5 pg/ml, p < 0.001), but serum CCL22/MDC levels were not significantly different between the two groups. In the diabetes group, the serum CCL11/Eotaxin-1 level was positively correlated with ulnar and sural nerve conduction velocities (p = 0.0009, p = 0.0208, respectively) and sensory nerve action potential (p = 0.0083), and CAVI (p = 0.0005), but not with HRV indices or QTc time, and serum CCL22/MDC was not significantly correlated with any indices of nerve conduction. In a model adjusted for age and duration of diabetes, serum CCL11/Eotaxin-1 was still associated with ulnar nerve conduction velocity (p = 0.02124). Serum CCL11/Eotaxin-1, but not CCL22/MDC, was significantly higher in patients with than in those without DSPN (208.2 ± 71.6 vs. 159.1 ± 45.1 pg/ml, respectively; p < 0.0001). CONCLUSIONS: Serum CCL11/Eotaxin-1 is elevated in patients with DSPN and is associated with peripheral nerve dysfunction, in particular sensory nerve conduction velocity, suggesting that serum CCL11/Eotaxin-1 may be a potential biomarker for DSPN. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000040631).

The effects of vibrating shoe insoles on standing balance, walking, and ankle-foot muscle activity in adults with diabetic peripheral neuropathy.

BACKGROUND: Peripheral neuropathy is one of the most common complications of type 2 diabetes, which can lead to impaired balance and walking. Innovative footwear devices designed to stimulate foot sensory receptors, such as vibrating insoles, could offer a new route to improve motor impairments in people with diabetic peripheral neuropathy (DPN). RESEARCH QUESTION: Does wearing vibrating insoles for the first time alter measures of balance, walking, and ankle-foot muscle activity, in people with DPN? METHODS: A randomised cross-over study was conducted with 18 ambulant men and women with a diagnosis of DPN. Participants performed tests of standing balance (Bertec® force platform) under four conditions (foam/firm surface, eyes open/closed) and level-ground walking (GAITRite® instrumented walkway), whilst wearing vibrating and non-vibrating (control) insoles on two separate occasions (one insole/session). Electromyography (EMG) was used to assess soleus, medial gastrocnemius, tibialis anterior, peroneus longus activity during balance tests. Outcomes included centre of pressure (CoP) sway, EMG amplitude, spatiotemporal gait patterns, and Timed Up and Go test. One sample t-tests were used to explore %differences in outcomes between insole conditions. RESULTS: Wearing vibrating insoles led to a reduction (improvement) in CoP elliptical area, when standing on a foam surface with eyes closed, relative to non-vibrating insoles (P=0.03). Applying perceptible vibrations to the soles of the feet also reduced the EMG amplitude in soleus (P=0.01 and P=0.04) and medial gastrocnemius (P=0.03 and P=0.09) when standing with eyes closed on firm and foam surfaces. SIGNIFICANCE: Our findings of signs of improved balance and altered muscle activity with suprasensory vibrating insoles provides new insights into how these devices can be used to inform innovative rehabilitation approaches in individuals with DPN. This will be strengthened by further research into possible clinical benefits of these devices - given that the effects we detected were small with uncertain clinical meaning.

Diabetic Neuropathy: Pathophysiology Review.

PURPOSE OF REVIEW: Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting from prolonged exposure to high blood glucose levels. Diabetic neuropathy may cause a range of symptoms, including pain, numbness, muscle weakness, autonomic dysfunction, and foot ulcers, potentially causing significant impairment to the quality of life for those affected. This review article aims to provide a comprehensive overview of the pathophysiology of diabetic neuropathy. The etiology of diabetic neuropathy will be discussed, including risk factors, predisposing conditions, and an overview of the complex interplay between hyperglycemia, metabolic dysregulation, and nerve damage. Additionally, we will explore the molecular mechanisms and pathways of diabetic neuropathy, including the impact of hyperglycemia on nerve function, abnormalities in glucose metabolism, the role of advanced glycation end products (AGEs), and inflammatory and immune-mediated processes. We will provide an overview of the various nerve fibers affected by diabetic neuropathy and explore the common symptoms and complications associated with diabetic neuropathy in the pain medicine field. RECENT FINDINGS: This review highlights advances in understanding the pathophysiology of diabetic neuropathy as well as reviews potential novel therapeutic strategies and promising areas for future research. In conclusion, this review article aims to shed light on the pathophysiology of diabetic neuropathy, its far-reaching consequences, and the evolving strategies for prevention and management. In understanding the mechanisms of diabetic neuropathy and the ongoing research in this area, healthcare professionals can better serve patients with diabetes, ultimately improving well-being and reducing complications.

Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial.

AIMS/HYPOTHESIS: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS: This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).

Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study.

OBJECTIVE: This study investigated the effects of vibrating insoles on dynamic balance and gait quality during level and stair walking and explored the influence of vibration type and frequency in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Twenty-two men with DPN were assessed for gait quality and postural and dynamic balance during walking and stair negotiation using a motion capture system and force plates across seven vibratory insole conditions (Vcs) versus a control (Ctrl) condition (insole without vibration). Vibration was applied during standing and walking tasks, and 15-min rest-stop periods without vibration were interposed between conditions. Repeated measures test conditions were randomized. The primary outcomes were gait speed and dynamic balance. RESULTS: Gait speed during walking significantly improved in all Vcs compared with Ctrl (P < 0.005), with Vc2, Vc4, and Vc6 identified as the most effective. Gait speed increased (reflecting faster walking) during stair ascent and descent in Vc2 (Ctrl vs. Vc2 for ascent 0.447 ± 0.180 vs. 0.517 ± 0.127 m/s; P = 0.037 and descent 0.394 ± 0.170 vs. 0.487 ± 0.125 m/s; P = 0.016), Vc4 (Ctrl vs. Vc4 for ascent 0.447 ± 0.180 vs. 0.482 ± 0.197 m/s; P = 0.047 and descent 0.394 ± 0.170 vs. 0.438 ± 0.181 m/s; P = 0.017), and Vc6 (Ctrl vs. Vc6 for ascent 0.447 ± 0.180 vs. 0.506 ± 0.179 m/s; P = 0.043 and descent 0.394 ± 0.170 vs. 0.463 ± 0.159 m/s; P = 0.026). Postural balance improved during quiet standing with eyes closed in Vc2, Vc4, Vc6, and Vc7 (P < 0.005). CONCLUSIONS: Vibrating insoles are an effective acute strategy for improving postural balance and gait quality during level walking and stair descent in individuals with DPN. These benefits are particularly evident when the entire plantar foot surface is stimulated.

Neuromuscular electrical stimulation for the treatment of diabetic sensorimotor polyneuropathy: A prospective, cohort, proof-of-concept study.

OBJECTIVE: To assess a potential efficacy signal, safety and feasibility of neuromuscular electrical stimulation (NMES) therapy as an adjunct to standard care in patients with diabetic sensorimotor polyneuropathy (DSPN). METHODS: In this single-centre, prospective, cohort, proof-of-concept study, 25 patients with DSPN consented to at least one daily 30-minute NMES therapy session (Revitive® IX) for 10 weeks, with 20 patients completing the study. The primary outcome measure was nerve conductivity assessed using a nerve conduction study of the sural, superficial peroneal, common peroneal and tibial nerves at 10 weeks compared to baseline. Secondary outcomes included superficial femoral artery (SFA) haemodynamics during NMES therapy compared to rest and quality-of-life at 10 weeks compared to baseline. RESULTS: At 10 weeks, there were significant increases in sural sensory nerve action potential amplitude and conduction velocity (p < 0.001), superficial peroneal sensory nerve action potential amplitude (p = 0.001) and conduction velocity (p = 0.002), common peroneal nerve conduction velocity (p = 0.004) and tibial nerve compound muscle action potential amplitude (p = 0.002) compared to baseline. SFA volume flow and time-averaged mean velocity significantly increased (p ≤ 0.003) during NMES compared to rest. Patient-reported Michigan Neuropathy Screening Instrument scores significantly decreased (p = 0.028) at 10 weeks compared to baseline. Three unrelated adverse events occurred, and 15 participants adhered to treatment. CONCLUSIONS: NMES therapy as an adjunct to standard care for 10 weeks significantly increased lower limb nerve conductivity in patients with DSPN and may be beneficial in the treatment of DSPN.

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study.

OBJECTIVE: The study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. METHODS: Participants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. RESULTS: Participants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

Which scale is more useful to detect diabetic neuropathic pain?: A cross-sectional study.

BACKGROUND: Diabetic neuropathy is one of the most common causes of neuropathic pain. LANSS, sLANSS, DN4 and painDETECT are scales which are commonly used worldwide. There are not many studies comparing these screening tools in specific neuropathic pain subgroups. The aim of this study is to compare the utilities of LANSS, sLANSS, DN4 and PainDETECT for the diagnosis of diabetic neuropathic pain. METHODS: One hundred-one individuals without diabetic neuropathic pain were included in control group, 102 patients with diabetic neuropathic pain to DNP group. LANSS, sLANSS, DN4 and painDETECT scores of the groups were compared. RESULTS: The difference between the groups was significant for all questionnaires and for all questions/titles they included. DN4 had the highest sensitivity and painDETECT had the highest specificity. CONCLUSIONS: All questionnaires seemed to be useful for detecting diabetic neuropathic pain. DN4 had a high specificity and sensitivity. PainDETECT, also had a high sensitivity and specificity when cut off value was accepted more than 12.

Correlation Analysis and Intervention Study on Disturbance of Lipid Metabolism and Diabetic Peripheral Neuropathy.

OBJECTIVE: To explore the significance and clinical value of dynamic monitoring of lipid metabolism indexes in patients with diabetic peridiabetic lesions. METHODS: A total of 192 patients with type 2 diabetes (T2DM) treated in our hospital from October 2019 to July 2021 were divided into two groups according to whether they were complicated with peripheral neuropathy (DPN). The patients in the observation group were randomly assigned into group A (n = 45) and group B (n = 45) according to the method of random number table. The patients were assigned into control group (n = 102) and observation group (n = 90), and the patients in the observation group were randomly divided into two groups (n = 45). All the patients in the three groups were given routine hypoglycemic treatment, and group B was observed to dynamically monitor the indexes of lipid metabolism and regulate blood lipids on the basis of routine hypoglycemic treatment. The indexes of lipid metabolism, including total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C), were detected before treatment. The receiver operating curve (ROC) was applied to elucidate the efficacy of TC, TG, and HDL-C and LDL-C in predicting peripheral neuropathy (DPN) in patients with T2DM. The indexes of lipid metabolism and neurological function of patients were determined after the treatment. The difference was considered to be statistically significant (P < 0.05). RESULTS: In contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, with HDL-C significantly lower. ROC curve analysis indicated that the area under the curve (AUC) of serum TG level to predict peripheral neuropathy in patients with T2DM was 0.753 (95% CI = 0.604 - 0.901, P = 0.007). When the Youden index reached the maximum (0.677), with corresponding sensitivity and specificity 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L, the AUC of serum TC level for predicting peripheral neuropathy in patients with T2DM was 0.851 (95% CI = 0.735 ~ 0.967P < 0.001); when the Youden index reaches its maximum (0.750), with the sensitivity and specificity 84.44% and 92.06%, respectively, and the critical value is 4.52 mmol/L, the AUC of predicting peripheral neuropathy in patients with T2DM by serum LDL-C level was 0.799 (95% CI = 0.52 ~ 0.946, P = 0.001); when the Youden index reaches its maximum (0.706), with sensitivity and specificity 80.58% and 87.24%, respectively, and the critical value is 3.36 mmol/L, the AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727 (95% CI = 0.568 ~ 0.886P = 0.014). When the Youden index reached the maximum (0.640), the sensitivity and specificity were 74.56% and 83.25%, respectively, the critical value is 1.51 mmol/L. The AUC in predicting DPN in patients with T2DM was 0.919 (95% CI = 0.839 ~ 0.978P < 0.001); when the Jordan index reached the maximum (0.786), the sensitivity and specificity were 91.75% and 95.82%, respectively. Compared with group A, the levels of serum TG, TC, and LDL-C in group B decreased significantly, while the level of HDL-C increased (P < 0.05). The motor nerve conduction velocity and sensory nerve conduction velocity of median nerve and peroneal nerve in group B were higher than those in group A (P < 0.05). CONCLUSION: Diabetic patients with severe lipid metabolic disorders have a higher risk of DPN. Combined detection of lipid metabolism indexes such as TC, TG, and HDL-C and LDL-C is effective in predicting diabetic patients with DPN. In clinic, through dynamic monitoring of lipid metabolism indexes, we can actively regulate the level of blood lipids in patients with T2DM, which can delay the occurrence and development of DPN to a certain extent, as well as improving the prognosis of patients with diabetes.

What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.