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.

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.

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.

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.

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).

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.

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).

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.

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.

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.

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.

Brain Mechanisms of Pain and Dysautonomia in Diabetic Neuropathy: Connectivity Changes in Thalamus and Hypothalamus.

CONTEXT: About one-third of diabetic patients suffer from neuropathic pain, which is poorly responsive to analgesic therapy and associated with greater autonomic dysfunction. Previous research on diabetic neuropathy mainly links pain and autonomic dysfunction to peripheral nerve degeneration resulting from systemic metabolic disturbances, but maladaptive plasticity in the central pain and autonomic systems following peripheral nerve injury has been relatively ignored. OBJECTIVE: This study aimed to investigate how the brain is affected in painful diabetic neuropathy (PDN), in terms of altered structural connectivity (SC) of the thalamus and hypothalamus that are key regions modulating nociceptive and autonomic responses. METHODS: We recruited 25 PDN and 13 painless (PLDN) diabetic neuropathy patients, and 27 healthy adults as controls. The SC of the thalamus and hypothalamus with limbic regions mediating nociceptive and autonomic responses was assessed using diffusion tractography. RESULTS: The PDN patients had significantly lower thalamic and hypothalamic SC of the right amygdala compared with the PLDN and control groups. In addition, lower thalamic SC of the insula was associated with more severe peripheral nerve degeneration, and lower hypothalamic SC of the anterior cingulate cortex was associated with greater autonomic dysfunction manifested by decreased heart rate variability. CONCLUSION: Our findings indicate that alterations in brain structural connectivity could be a form of maladaptive plasticity after peripheral nerve injury, and also demonstrate a pathophysiological association between disconnection of the limbic circuitry and pain and autonomic dysfunction in diabetes.

The neuro-restorative effect of adipose-derived mesenchymal stem cell transplantation on a mouse model of diabetic neuropathy.

Diabetic neuropathy (DN) is the most common degenerative complication associated with Diabetes Mellitus. Despite widespread awareness about DN, the only effective treatments are blood glucose control and pain management. The aim of the current study was to determine the effect of intramuscular adipose-derived mesenchymal stem cell (AMSC) transplantation on sciatic nerves in DN using EMG and histological analyses. A total of 27 mice were randomly divided into three groups: control group, DN group and AMSC group. In EMG, CMAP amplitude in the sciatic nerves was lower, but distal latency was higher in the DN group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AMSC group compared with the DN group. Distal latency in the sciatic nerve was lower in the AMSC group compared with the DN group. Histologic examination of the tissues in the animals treated with AMSC showed a remarkable improvement in microscopic morphology. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted AMSC was selectively localized in the sciatic nerves. Transplantation of AMSC increased protein expression of S100, cdk2, NGF and DHH, all of which, interfered with DN onset in sciatic nerves. The findings of the present study suggest that AMSC transplantation improved DN through a signal-regulatory effect on Schwann cells, neurotrophic actions and restoration of myelination.

The relationship between serum 25-hydroxyvitamin-D level and sweat function in patients with type 2 diabetes mellitus.

AIMS: The objective of this study is to explore the relationship between serum 25-hydroxyvitamin-D(25-(OH)2D3) level and sweat function in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study of 1021 patients with T2DM who underwent 25-(OH)2D3 level detections and sweat function tests was carried out. These individuals were divided into deficient groups (n = 154 cases), insufficient groups (n = 593 cases) and sufficient groups (n = 274 cases). Spearman correlation analysis and multivariate stepwise linear regression analysis were implemented to determine the association of 25-(OH)2D3 level and sweat function. RESULTS: The total presence of sweating dysfunction was 38.59%. Patients with a lower level of serum 25-(OH)2D3 had more severe sweat secretion impairment (P < 0.05). As the decrease of serum 25-(OH)2D3 level, the presence of sweating dysfunction increased (P < 0.05). 25-(OH)2D3 level was positively correlated with sweat function parameters, age and duration of T2DM were negatively correlated with sweat function parameter (P < 0.05). Multivariate stepwise linear regression analysis explored a significant association between serum 25-(OH)2D3 level with sweat function (P < 0.05). CONCLUSIONS: Serum 25-(OH)2D3 level was positively correlated with sweat function in patients with T2DM.

Decline in renal function associated with cardiovascular autonomic neuropathy positively coordinated with proteinuria in patients with type 2 diabetes.

AIMS/INTRODUCTION: To investigate the association between cardiovascular autonomic neuropathy (CAN) assessed by the coefficient of variation of the R-R interval and the reduction in the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective observational cohort study enrolled type 2 diabetes patients who had their coefficient of variation of the R-R interval measured on an electrocardiogram from January 2005 to December 2018. CAN was defined using the reference coefficient of variation of the R-R interval value based on age and sex. The primary outcome was set as a 40% eGFR decline from baseline. Regression analyses using the Cox proportional hazards model were carried out to evaluate the association. RESULTS: Of the 831 patients, 118 (14.2%) were diagnosed with CAN. In the analysis of the primary outcome, the median follow-up period was 5.3 years, and 25 (21.2%) patients with CAN and 78 (10.9%) patients without CAN developed a 40% eGFR decline. In the univariate regression analysis, CAN was significantly associated with a 40% eGFR decline (hazard ratio 2.42, 95% confidence interval 1.54-3.80). In the multivariate analysis, CAN remained almost significant after adjusting for the prognostic risk factors for CAN and the decline in the renal function, and an interaction with proteinuria was found. In analyses for the interaction effect between CAN and proteinuria, the presence of CAN synergistically increased the risk of an eGFR decline in patients with macroproteinuria. CONCLUSIONS: CAN strongly increased the risk of a 40% eGFR decline from baseline, especially in type 2 diabetes patients with macroproteinuria.

Electrophysiological Study of the Tibial Nerve Across the Tarsal Tunnel in Distal Symmetric Diabetic Polyneuropathy.

OBJECTIVE: The aim of the study was to demonstrate abnormalities of motor conduction of the tibial nerve across the tarsal tunnel in type 2 diabetes. DESIGN: One hundred twenty-four consecutive patients (mean age = 66.6 yrs, 62.1% male) with distal symmetric diabetic polyneuropathy clinically diagnosed were prospectively enrolled. Nerve conduction studies of deep peroneal, tibial, superficial peroneal, medial plantar, and sural nerves and standard needle electromyography in the lower limbs were performed. Demographic, anthropometric, and clinical findings were collected. RESULTS: Motor conduction velocity of the tibial nerve across tarsal tunnel was slowed in 60.5% of patients; another 4% showed conduction block across tarsal tunnel without reduction of motor conduction velocity. Overall percentage of abnormalities across tarsal tunnel (64.5%) exceeds that of the sensory conduction velocities of proximal sural and superficial peroneal nerves. Abnormal tibial motor conduction velocity across tarsal tunnel represents the most common abnormality among all motor nerve conduction study parameters and significantly correlates with hemoglobin level, diabetic neuropathic index score, and diabetic complications frequency. CONCLUSIONS: Tibial conduction abnormalities across tarsal tunnel are the most sensitive motor parameter in distal symmetric diabetic polyneuropathy, second only to conduction abnormalities of sensory/mixed distal nerves of the feet. The use of nerve conduction studies across tarsal tunnel of the tibial nerve may be useful in the electrophysiological protocol to confirm the diagnosis of distal symmetric diabetic polyneuropathy.

Alterations of tibialis anterior muscle activation pattern in subjects with type 2 diabetes and diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is associated with loss of motor units (MUs), which can cause changes in the activation pattern of muscle fibres. This study investigated the pattern of muscle activation using high-density surface electromyography (HD-sEMG) signals from subjects with type 2 diabetes mellitus (T2DM) and DPN. Thirty-five adults participated in the study: 12 healthy subjects (HV), 12 patients with T2DM without DPN (No-DPN) and 11 patients with T2DM with DPN (DPN). HD-sEMG signals were recorded in the tibialis anterior muscle during an isometric contraction of ankle dorsiflexion at 50% of the maximum voluntary isometric contraction (MVIC) during 30-s. The calculated HD-sEMG signals parameters were the normalised root mean square (RMS), normalised median frequency (MDF), coefficient of variation (CoV) and modified entropy (ME). The RMS increased significantly (p = 0.001) with time only for the DPN group, while the MDF decreased significantly (p < 0.01) with time for the three groups. Moreover, the ME was significantly lower (p = 0.005), and CoV was significantly higher (p = 0.003) for the DPN group than the HV group. Using HD-sEMG, we have demonstrated a reduction in the number of MU recruited by individuals with DPN. This study provides proof of concept for the clinical utility of this technique for identifying neuromuscular impairment caused by DPN.

Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation.

AIMS: Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain. METHODS: We reviewed literature in PubMed published between January 2005 and August 2021. RESULTS AND CONCLUSIONS: In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.