Diabetic Sensorimotor Polyneuropathy Research Articles

Dietary phytochemical index and its relationship with diabetic sensorimotor polyneuropathy: a case-control study

Phytochemicals are compounds found in fruits, vegetables, whole grains, nuts and legumes that are non-nutritive but have bioactive properties. A high intake of these compounds is essential for optimal health and disease prevention. No study has investigated the association between Dietary Phytochemical Index (DPI) and polyneuropathy in patients with diabetes. This study aimed to examine the association between DPI and Diabetic Sensory-motor Polyneuropathy (DSPN) in a case-control study. In this case-control study, a total of 185 diabetic patients with DSPN (case group) and 185 sex- and age-matched diabetic patients without neuropathy (control group) were enrolled in this study. Participants were 30–60 years old. A validated food frequency questionnaire was used to measure the dietary intake of all participants. Daily energy derived from phytochemical-rich foods was used to calculate the DPI score. Toronto clinical neuropathy score was applied to define DSPN. Anthropometric data and fasting blood glucose levels were measured using standard methods. The Binary logistic regression was used to estimate Crude and multivariable-adjusted OR (95% CI) for DSPN across tertiles of DPI for the whole population. In the crude model, there was a significant trend across the tertile of DPI (OR highest vs. lowest tertile of DPI = 0.33; 95%CI 0.18, 0.52; P-trend < 0.001). After controlling for age, sex, and energy, a significant reverse association was observed between DPI and DSPN (OR highest vs. lowest tertile of DPI = 0.27; 95%CI 0.15, 0·48; P-trend < 0.001). Moreover, after adjusting for a wide range of confounding variables such as energy intake, physical activity, education, smoking status, and HbA1c, participants in the third tertile of DPI had 75% reduced odds for DSPN (95%CI 0.14, 0.45; P-trend < 0.001). Finally in the full adjusted model, after further adjustment for BMI, observed significant association was remained (OR highest vs. lowest tertile of DPI: 0.24; 95% CI 0.13, 0.14; P-trend < 0.001). Higher intakes of phytochemical-rich foods are associated with lower odds of DSPN.

Decompressive nerve surgery associated with low diabetic foot ulcer rate and high-risk bias: A systematic review and meta-analysis.

Diabetic sensorimotor polyneuropathy (DSPN) occurs in 50% of diabetes mellitus (DM) patients. Up to 70% of DM patients incur diabetic foot ulcer(s) (DFU). Of those with DSPN, 20% develop DFU and medical therapy remains challenging. Decompression nerve surgery (DNS) purportedly improves DSPN and DFU. Currently, there is no accurate, pooled DFU incidence post-DNS. Thus, this systematic review meta-analyses DFU incidence post-DNS. Given the 60% global DFU incidence, we hypothesised a lower, pooled DFU incidence following DNS. Two authors searched six databases (MEDLINE/PubMed/Web of Science/Embase/Scopus/Cochrane/Google Scholar) to July 2023 for DNS clinical studies. Primary tracked outcomes were new and recurrent DFU incidence post-DNS. Inclusion criteria: clinical studies, adult DM patients, DNS of tibial nerve(s) at minimum, three-month minimum follow-up, and reported new/recurrent DFU incidence post-DNS. Exclusion criteria: non-clinical, non-human studies. GRADE and MINORS instrument(s) evaluated evidence. With random-effects model, DFU incidence was meta-analysed. For inclusion, 1074 studies were identified and 208 screened. Thirteen studies yielded 2466 and 540 new and recurrent patients with DFU incidence(s) of 1% and 5%, respectively. Primary studies had low-level evidence and high-risk bias, including selection bias using Cochrane Collaboration Bias Risk Tool. A sub-analysis of sample size (new:0% and recurrent:2%) and follow-up length (new:1% and recurrent:7%) produced similar results. Additional analyses based on further co-variables was precluded because of incomplete primary study data. Overall, despite low DFU incidence post-DNS, clinical studies provide too low-level evidence and high-risk bias for any recommendations. Future randomized, control trials may validate DNS for DFU management.

Association of transketolase polymorphisms with diabetic polyneuropathy in the general population: The KORA F4 study.

We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study. In this cross-sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n=394), prediabetes (n=411), and type 2 diabetes (n=147). DSPN was defined by the examination partof the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut-off and two alternative versions extended by touch/pressure perception (TPP) (MNSI>3) and by TPP plus cold perception (MNSI > 4). After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p≤0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI>2: 1.99 (1.16-3.41), MNSI>3: 2.27 (1.26-4.09), and MNSI>4: 4.78 (2.22-10.26); SNP rs9284890 with MNSI>2: 2.43 (1.42-4.16), MNSI>3: 3.46 (1.82-6.59), and MNSI>4: 4.75 (2.15-10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups. The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy.

Current Practice of Podiatrists in Testing for Diabetic Polyneuropathy and Implementing Foot Care (PROTECT Study Survey 2)

AimsPodiatrists constitute a key member of a multidisciplinary foot care team, but their services remain underutilized. We sought to gain insights into the daily practice of podiatrists focusing on screening for and monitoring of diabetic sensorimotor polyneuropathy (DSPN) as well as foot management. MethodsThis cross-sectional survey included 125 podiatrists from 12 federal states across Germany who responded to an online questionnaire. ResultsThe majority of patients treated in podiatry practices were referred by general practitioners and diabetologists. Screening for or follow-up of DSPN was performed by 36% of the respondents at least once a year, by 28% only at initial examination, by 21% only at suspicion, and by 10% basically at each treatment visit. Instruments to assess vibration, touch/pressure, and temperature sensation were used by 81% to 94% of the podiatrists. Previously undiagnosed DSPN and foot ulcers were detected frequently/very frequently (≥6 cases/mo) by 24.0 and 18.4% of the podiatrists, respectively. Almost all podiatrists advised daily self-monitoring of feet and appropriate foot care and >50% gave advice on medical treatment. ConclusionsPodiatrists play an important role in the detection, monitoring, and management of both DSPN and diabetic foot ulcers, suggesting that the utilization of their services should be fostered.

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes

ObjectiveThe objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. MethodsIn 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. ResultsRF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

Ayurvedic Treatment Modalities of Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy is the damage of the nerves due to the uncontrolled diabetes. It can affect any of the neurons can affect any of the neurons. Diabetic distal symmetric sensory and sensorimotor polyneuropathy is the most prevalent type of diabetic neuropathy. The symptoms appear as sensory loss, first in the toes and progressively moving up the legs, fingers, and arms over time. Tingling sensation, Burning sensation, Deep aching pain are other related symptoms. A patient age 54 years with diabetes for past 15 years, hypertension, dyslipidemia, complains of burning sensation of both feet (right&gt;left), numbness, pricking pain, unsteadiness while walking, brownish red discolouration of both lower limbs. The symptoms were gradual in onset. Nerve Conduction Study showed axonal type of motor and sensory affecting peroneal nerve neuropathy. He admitted in Vaidyaratnam Ayurveda College Hospital, done Vibrotherm Neuropathy Analyzer and revealed small and large fibre neuropathy with severe loss of sensations. The main intention of the study is to improve the quality of life of the patient by reducing the symptoms that is disturbing his day today routine. Patient given with anti diabetic Ayurvedic formulations internally. Externally Rookshana, Vatahara, Brimhana treatments were done. After the treatment, Michigan neuropathy screening instrument, diabetic Neuropathy symptom score, Toronto clinical scoring system score were reduced. Neuropathy Analyzer showed mild to moderate loss of sensation. By adopting Prameha hara chikitsa coupled with Vata vyadhihara chikitsa, complications of diabetes can be managed. It is important to focus on diet and regimen since diabetes is a lifestyle disorder and, in ayurveda it is considered as an Anushangi Vyadhi.

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

ABSTRACT 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).

Diabetic Sensorimotor Polyneuropathy: An Overview on Epidemiology, Risk Factors, Classification, Diagnosis, and Treatment.

Diabetic distal symmetric sensorimotor polyneuropathy (DSPN) is a common complication of diabetes with devastating consequences. Hyperglycaemia is the major aetiological factor, while emerging data demonstrate that cardiometabolic risk factors also contribute to its development. Diagnosis of DSPN involves interview of medical and neurological history, foot inspection, and sensory and motor function examination with specific tests such as temperature and pinprick perception for small nerve fibers, and vibration and light touch assessments for large nerve fibers. Management includes optimised glycaemic control, treatment of cardiovascular risk factors, and symptomatic treatment aiming at improving life quality. This article provides an overview on epidemiology, risk factors, classification, diagnosis and current treatment of DSPN.

Prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy in Japanese patients with type 2 diabetes: The Japan Diabetes Complication and its Prevention Prospective study (JDCP study 10).

This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t-test, χ2 -test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio[OR] 1.57, 95% confidence interval [CI] 1.42-1.73), duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39) and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN.

Assessment of MiR-191-5p as a Predictive Marker of Early Diabetic Sensorimotor Polyneuropathy in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Assessment of MiR-191-5p as a Predictive Marker of Early Diabetic Sensorimotor Polyneuropathy in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes

Aims/hypothesisQuantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.MethodsSeventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST.ResultsObjective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve’s FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm2; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=−0.048 [95% CI −0.091, −0.006], p=0.027; SL B=−0.062 [95% CI −0.103, −0.020], p=0.004) and CSA (MH β=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=−0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio).Conclusions/interpretationThe most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN.Trial registrationClinicalTrials.gov NCT03022721Graphical

Sensory Phenotypes Provide Insight Into the Natural Course of Diabetic Polyneuropathy.

The course of diabetic sensorimotor polyneuropathy (DSPN) development, from healthy status to overt DSPN, is poorly understood. We studied the characteristics and longitudinal appearance of lower-extremity sensory phenotypes (healthy, thermal hyperalgesia [TH], mechanical hyperalgesia [MH], and sensory loss [SL]) identified through quantitative sensory testing in individuals with diabetes. There was an increasing severity and patterned order of longitudinal appearance across healthy, TH, MH, and SL phenotypes. SL was most strongly associated with formal DSPN. Our findings provide insight into the natural history of DSPN. Sensory phenotyping can be implemented to identify high-risk individuals and those most likely to benefit from therapeutic interventions.

Diabetic Distal Symmetric Sensorimotor Polyneuropathy: A Proposal of New Electrodiagnostic Evaluation.

Diabetic Distal Symmetric Sensorimotor Polyneuropathy: A Proposal of New Electrodiagnostic Evaluation.

Optimal cut-off value of the Modified Toronto Clinical Neuropathy Score in the diagnosis of polyneuropathy.

The modified Toronto Clinical Neuropathy Score (mTCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy (DSP). To determine the optimal diagnostic cut-off value of the mTCNS in diverse polyneuropathies. Demographics and mTCNS values were retrospectively extracted from an electronic database of 190 patients with polyneuropathy (PNP) and 20 normal controls. Sensitivity, specificity, and likelihood ratios and the area under the receiver operating characteristics (ROC) curve were determined for each diagnosis and different cut-off values of the mTCNS. Patients had clinical, electrophysiological, and functional assessments of their PNP. 43% of PNP was related to diabetes or impaired glucose tolerance. mTCNS was significantly higher in patients with PNP than in those without (15.27±8 vs 0.79±1.4, P = 0.001). The cut-off value for diagnosing PNP was ≥3 (sensitivity 98.4%, specificity 85.7%, positive likelihood ratio 6.88). The area under the ROC curve is 0.987. A value of 3 or more on the mTCNS is recommended for the diagnosis of PNP.

Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.

Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D). Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention. Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both. Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients. https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.

Validity and reliability of the Polish version of the Michigan Neuropathy Screening Instrument

Diabetic sensorimotor polyneuropathy is an important risk factor for foot ulceration and amputation. Thus, patients with diabetes should be screened for this disorder according to local guidelines. An obstacle to the diagnosis of this disease may be the lack of unified diagnostic criteria due to the lack of properly validated scales used for assessment. To validate both sections (A and B) of the Michigan Neuropathy Screening Instrument (MNSI) in Polish (PL) patients with diabetes. A cross-sectional study using a test (A1, B1) and re-test (A2, B2) formula was performed in 80 patients with diabetes. The gold standard used for neuropathy detection was a nerve conduction study (NCS) which was performed in all participants. Reliability of the MNSI-PL was assessed using the Cronbach's alpha, Kuder-Richardson formula 20 (KR-20), split-half reliability, the Gottman split-half tests, and correlation between first and second half was accessed. Stability was assessed using an intraclass correlation coefficient (ICC). For external validation, we used simple linear correlation, binomial regression, and agreement between two different tools using a Bland-Altman plot analysis. The scale was internally consistent (Cronbach's alpha for the full scale: 0.81 for A and 0.87 for B). MNSI-PL scores in test/retest showed high stability (ICC = 0.73 for A and ICC = 0.97 for B). The statistically important correlations between MNSI-PL and NCS were found for B1, B2, and A1 (P < 0.005). The cut-off points of ≥ 3 for section A (sensitivity of 90%-100%; specificity of 33%-40%) and ≥ 2 for section B (sensitivity of 81%-84%; specificity of 60%-70%) were obtained during neuropathy detection. The MNSI-PL is a reliable and valid instrument in screening for diabetic neuropathy.

Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes.

The diagnosis and assessment of neuropathy severity of diabetic sensorimotor polyneuropathy (DSPN) are mainly based on clinical neuropathy scores and electrophysiologic studies. This study aimed to determine whether quantitative thermal testing (QTT) can be used as a screening and follow-up tool for DSPN of prediabetes and type 2 diabetes at baseline and at 1-year follow-up. All patients were assessed using the Toronto Clinical Neuropathy Score (TCNS) and underwent electrophysiological testing, including a nerve conduction study (NCS) and QTT, at baseline and at a 1-year follow-up. The TCNS and the composite scores of nerve conduction were used to assess the severity of DSPN. The DSPN status at the 1-year follow-up was classified as remaining no DSPN, remaining DSPN, regression to no DSPN, or progression to DSPN. Diabetic sensorimotor polyneuropathy was initially diagnosed in 89 patients with prediabetes and type 2 diabetes (22%). The regressed to no DSPN in 29 patients and progressed to DSPN in 20 patients at the 1-year follow-up. TCNS was significantly correlated with composite scores of nerve conduction, hand cold detection threshold (CDT), hand warm detection threshold (WDT), foot CDT, and foot WDT. Stepwise logistic regression demonstrated that the foot CDT (p < 0.0001) was independently associated with the presence of DSPN. The TCNS, composite scores of the nerve conduction, hand WDT, hand CDT, foot WDT, and foot CDT were all statistically significant among the four different DSPN status groups at two different time periods (baseline and the 1-year follow-up). The foot CDT can be used as an initial screening tool for DSPN alternatively. The characteristics of nerve damage after 1 year of DSPN can be progressive or reversible, and the neurological functions of large and small fibers have a parallel trend, which can be objectively measured by NCS and QTT.

Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes.

Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve's FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL). Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage. Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls (p<0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p<0.001 and r=0.6; p<0.001) and sural sensory NCV (r=0.50; p<0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p<0.01 and r=0.3; p<0.01) and lower (r=0.5; p<0.001 and r=0.3; p=<0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p<0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p<0.001 and r= -0.3, p= 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain. This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.

DSPNet: A Self-ONN Model for Robust DSPN Diagnosis From Temperature Maps

Diabetic sensorimotor polyneuropathy (DSPN) leads to pain, diabetic foot ulceration (DFU), amputation, and death. The diagnosis of advanced DSPN to identify those at risk is key to preventing DFU and amputation. Alterations in foot pressure and temperature may help to detect DSPN and the risk of DFU. We have applied a robust machine-learning approach to identify patients with severe DSPN using standing foot temperature maps generated using temperature sensor data. A robust shallow operational neural network model DSPNet is proposed. The study utilized a labeled dataset from the University Hospital Magdeburg, Magdeburg, Germany, consisting of temperature sensor data from eight different points on the foot in seating and standing positions in patients with severe DSPN ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$n =25$ </tex-math></inline-formula> ) and healthy controls ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$n =18$ </tex-math></inline-formula> ). The proposed network achieved an F1 score of 90.3% for identifying patients with DSPN and outperformed current state-of-the-art deep-learning network methods. This is the first of its kind of research where the results confirm that temperature maps are not only effective in the detection of those at high risk of DFU but also in identifying patients with severe DSPN. Such sensors could easily be incorporated into smart insoles.

Composite nerve conduction scores and signs for diagnosis and somatic staging of diabetic polyneuropathy: Mid North American ethnic cohort survey.

In the Diabetes Control and Complications Trial (DCCT), the minimal nerve conduction (NC) criterion for diabetic sensorimotor polyneuropathy (DSPN) was abnormality of NC in more than one peripheral nerve without specifying the attributes of NCs to be evaluated. In the present study, we assess individual and composite scores of NCs meeting the DCCT criterion and signs for improved diagnosis and assessment of DSPN severity. Evaluated were 13 attributes and 6 composite NC scores and signs and symptoms in 395 healthy subjects (HS) and 388 persons with diabetes (DM). Percent abnormality between subjects with DM and HS was remarkably different among individual attributes and the six composite NC scores. For diagnosis of DSPN using the DCCT criterion, assessment of conduction velocities (CVs) and distal latencies (DLs) provided sensitive diagnoses of DSPN. NC amplitudes provided stronger measures of severity. In studied cohorts, DSPN was staged: N0, no NC abnormality using NC score 2 (CVs and DLs), 60.0%; N1, NC abnormality only, 18.4%; N2, NC abnormality and signs of feet or legs, 16.3%; and N3, NC abnormality and signs of thighs, 5.3%. For sensitive and standard diagnosis of DSPN using the DCCT NC criterion, specifically defined composite scores of CVs and DLs, e.g., score 2, is recommended. A composite score of amplitudes, e.g., score 4, provides a stronger measure of neuropathy severity. Also, provided are HS reference values of evaluated attributes of NCs and estimates of staged severity of DSPN of mid North American DM cohorts.