A thermoregulation model to detect diabetic peripheral neuropathy

BackgroundDiabetic foot disease is associated with physiological and biomechanical abnormalities in the foot that increase risk for ulceration. The objective was to assess MRI changes in the composition of sub-calcaneal fat pad tissue and its association with plantar pressure during walking. MethodsFourteen people with diabetes and peripheral neuropathy and five age-matched healthy controls underwent T1-weighted sagittal plane spin-echo Dixon MRI of the rearfoot. Dixon Chemical Shift Imaging was used to create fat-only and water-only images from which the fat signal fraction in a defined ROI of the sub-calcaneal fat pad was calculated. Barefoot plantar pressure distribution during walking was assessed and associated with fat pad outcomes. FindingsMean ± SD fat signal fraction was significantly lower in the neuropathic subjects than in the healthy controls (0.55 ± 0.11 vs. 0.72 ± 0.03, p < 0.005), and was explained by a lowering in fat signal (R2 0.87), more than an increase in water signal (R2 0.32). Mean ± SD peak pressure at the heel was 391 ± 119 kPa for the neuropathic subjects and 325 ± 53 kPa for the healthy controls (non-significantly different). Fat signal fraction and peak pressure were significantly inversely correlated (r = −0.59, p < 0.01). InterpretationDixon chemical shift MRI showed a reduced fat signal fraction in sub-calcaneal fat pad tissue in people with diabetic neuropathy. Both neuropathic and non-neuropathic factors may be attributed to this outcome. Fat pad function also seems to be compromised, as indicated by an associated increase in peak plantar pressures. This may increase risk for foot ulceration.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic syndrome marked by hyperglycemia due to absolute or relative deficiency of insulin hormone. Diabetic neuropathy is a complication of both type 1 and type 2 diabetes. Although pain is one of the most dominant symptoms of diabetic neuropathy, its pathophysiological mechanisms yet unknown. Toxic effects of high glucose levels play an important role in the development of this complication. METHODOLOGY: Data was collected through the questionnaire regarding Clinical findings, medical records, weight, age, family history, different habits, and psychogenic behavior. All the patients with the mentioned diseases are included in this study, excluding the mentally ill patients and the pregnant women. RESULT: The result of the present study showed that diabetic neuropathy is the most common complication of diabetes mellitus. It has been observed that most of the patients due to lack of awareness are suspected to the elevated or extreme blood sugar level which leads to neuropathy. Due to the Diabetic Peripheral Neuropathy (DPN) most of the patients suffering from foot problems, foot ulcers and then amputations. Lack of awareness, lack of health management, obesity, blood pressure changes, less care plays a key role in increasing the chances of diabetic neuropathy. COCLUSION: Diabetic neuropathy had very bad influence on a person’s health and daily activities. The Patient education programs need to emphasize on large scale. The ultimate aim of this study is the foot care education for people with the diabetes and to prevent foot ulcers and amputation.

The aim of this article was to present results of warm immersion recovery test in the diabetic foot with neuropathy using a liquid crystal-based contact thermography system. It is intended to provide a 'proof of concept' for promoting the role of supplementary thermal assessment techniques and evidence-based diagnosis of diabetic neuropathy. A total of 81 subjects from the outpatient department of MV Hospital for Diabetes, India, were assessed using a liquid crystal thermography system. Each subject was assigned to one of three study groups, that is diabetic neuropathy, diabetic non neuropathy and non diabetic healthy. The room temperature and humidity were consistently maintained at 24 degrees C and less than 50%, respectively, with air conditioning. The right foot for each subject was located on the measurement platform after warm immersion in water at 37 degrees C. Whole-field thermal images of the plantar foot were recorded for 10 minutes. Local measurements at the most prevalent sites of ulceration, that is metatarsal heads, great toe and heel, show highest temperature deficit after recovery for diabetic neuropathy group. The findings of the current study support the ones of a previous study by the authors, which used cold immersion recovery test for the neuropathic assessment of the diabetic foot. A temperature deficit between the recovery and the baseline temperature for the neuropathic group suggests degeneration of thermoreceptors. Thermal stimulus tests can be useful to validate the nutritional deficits' (during plantar loading and thermal stimulus) contribution in foot ulceration.

Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4years later in patients with type 1 diabetes. At baseline, 188 patients (age 51years, diabetes duration 22years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p < 0.0005). In the multivariate analysis, a 1 SD higher skin autofluorescence at baseline was associated with an increased risk of signs of neuropathy (OR = 2.68, p = 0.01). All of the neurological tests were significantly altered in the highest quartile of the baseline sAF (>2.4AU) compared with the lowest quartiles after multivariate adjustment. This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd.

AimsAbnormalities in the oculomotor system may represent an early sign of diabetic neuropathy and are currently poorly studied. We designed an eye-tracking-based test to evaluate oculomotor function in patients with type 1 diabetes.MethodsWe used the SRLab—Tobii TX300 Eye tracker®, an eye-tracking device, coupled with software that we developed to test abnormalities in the oculomotor system. The software consists of a series of eye-tracking tasks divided into 4 classes of parameters (Resistance, Wideness, Pursuit and Velocity) to evaluate both smooth and saccadic movement in different directions. We analyzed the oculomotor system in 34 healthy volunteers and in 34 patients with long-standing type 1 diabetes.ResultsAmong the 474 parameters analyzed with the eye-tracking-based system, 11% were significantly altered in patients with type 1 diabetes (p < 0.05), with a higher proportion of abnormalities observed in the Wideness (24%) and Resistance (10%) parameters. Patients with type 1 diabetes without diabetic neuropathy showed more frequently anomalous measurements in the Resistance class (p = 0.02). The classes of Velocity and Pursuit were less frequently altered in patients with type 1 diabetes as compared to healthy subjects, with anomalous measurements mainly observed in patients with diabetic neuropathy.ConclusionsAbnormalities in oculomotor system function can be detected in patients with type 1 diabetes using a novel eye-tracking-based test. A larger cohort study may further determine thresholds of normality and validate whether eye-tracking can be used to non-invasively characterize early signs of diabetic neuropathy.Trial: NCT04608890.

PurposeTo evaluate the relationship of neuroretinal layer thickness with sensitive measures of cardiovascular autonomic neuropathy in diabetic patients with non‐proliferative diabetic retinopathy (NPDR).MethodsTwenty‐seven eyes of 27 patients with type 1 diabetes presenting with mild‐to‐moderate NPDR were compared to 27 healthy control (HC) eyes matched for age and gender. The total macular volume (TMV) and the volumes of individual neurosensory layers in the macula were analysed from spectral domain optical coherence tomography using automated layer segmentation. Cardiovascular autonomic regulation was assessed by short‐term power spectrum analysis of heart rate variability (HRV) before, during and after an orthostatic challenge.ResultsThe patients had an age of 46 ± 12 years and diabetes since 28 ± 9 years. Diastolic and mean arterial pressure was lower in the patients compared to HCs. TMV (r = 0.58, p = 0.002), inner plexiform layer volume (IPLV; r = 0.39, p = 0.047) and inner nuclear layer volume (INLV; r = 0.60, p = 0.001) were associated with reduced recovery of low‐frequency (LF) spectral power of HRV after orthostatic load in diabetic patients but not in HCs. The response of LF spectral power during the orthostatic manoeuvre was blunted in patients compared to HCs (p = 0.02). Diabetes duration was negatively associated with TMV and INLV, whereas IPLV was significantly reduced in eyes with moderate NPDR compared to HCs.ConclusionThe results indicate a correlation between inner retinal tissue loss and diminished autonomic regulation in type 1 diabetic patients with mild‐to‐moderate NPDR. The observed changes can be interpreted as congruent early signs of retinal and systemic neuropathy in diabetes.

BackgroundDiabetic peripheral neuropathy (DPN) is a prevalent and serious complication of diabetes mellitus, impacting the nerves in the limbs and leading to symptoms like pain, numbness, and diminished function. While the exact molecular and immune mechanisms underlying DPN remain incompletely understood, recent findings indicate that mitochondrial dysfunction may play a role in the advancement of this diabetic condition.MethodsTwo RNA transcriptome datasets (codes: GSE185011 and GSE95849), comprising samples from diabetic peripheral neuropathy (DPN) patients and healthy controls (HC), were retrieved from the Gene Expression Omnibus (GEO) database hosted by the National Center for Biotechnology Information (NCBI). Subsequently, differential expression analysis and gene set enrichment analysis were performed. Protein–protein interaction (PPI) networks were constructed to pinpoint key hub genes associated with DPN, with a specific emphasis on genes related to mitochondria and peripheral neuropathy disease (PND) that displayed differential expression. Additionally, the study estimated the levels of immune cell infiltration in both the HC and DPN samples. To validate the findings, quantitative polymerase chain reaction (qPCR) was employed to confirm the differential expression of selected genes in the DPN samples.ResultsThis research identifies four hub genes associated mitochondria or PN. Furthermore, the analysis revealed increased immune cell infiltration in DPN tissues, particularly notable for macrophages and T cells. Additionally, our investigation identified potential drug candidates capable of regulating the expression of the four hub genes. These findings were corroborated by qPCR results, reinforcing the credibility of our bioinformatics analysis.ConclusionsThis study provides a comprehensive overview of the molecular and immunological characteristics of DPN, based on both bioinformatics and experimental methods.

Diabetic peripheral neuropathy (DPN) is one of the most common complications, which occurs in 50–70% of people with Type 2 diabetes mellitus (T2DM). The disease usually affects the peripheral nerves and can cause loss of sensation in the feet, leading to impaired body equilibrium during quiet stance and gait, and elevated risk of falls. A total of 38 non-insulin-dependent T2DM adults (mean age 53.21 ± 7.74 years) – 18 with DPN and 20 without DPN, and 20 age- and sex-matched controls took part in the study. The DPN group was selected with standard clinical criteria and a Bulgarian version of the Michigan neuropathy screening instrument. Postural stability was evaluated with static posturography under two visual conditions (eyes open and eyes closed) on firm and soft support. Both diabetic groups exhibited significantly higher postural instability compared with the healthy controls, as well as stronger visual dependence. While standing on firm support, subjects with DPN exhibited significantly higher postural instability than those without DPN in the closed eyes condition only, whereas when standing on soft support, their postural stability was significantly more impaired compared with the diabetic subjects without DPN in both experimental conditions (open and closed eyes). A better understanding of the changes in postural stability in persons with T2DM would contribute to early diagnostics, rehabilitation and prevention of DPN.

Diabetic peripheral neuropathy (DPN) is a primary cause of diabetic foot, early detection of DPN is essential. This study aimed to construct a machine learning model for DPN diagnosis based on microcirculatory parameters, and identify the most predictive parameters for DPN. Our study involved 261 subjects, including 102 diabetics with neuropathy (DMN), 73 diabetics without neuropathy (DM), and 86 healthy controls (HC). DPN was confirmed by nerve conduction velocity and clinical sensory tests. Microvascular function was measured by postocclusion reactive hyperemia (PORH), local thermal hyperemia (LTH), and transcutaneous oxygen pressure (TcPO<inf>2</inf>). Other physiological information was also investigated. Logistic regression (LR) and other machine learning (ML) algorithms were used to develop the model for DPN diagnosis. Kruskal-Wallis Test (non-parametric) were performed for multiple comparisons. Several performance measures, such as accuracy, sensitivity and specificity, were used to access the efficacy of the developed model. All the features were ranked based on the importance score to find features with higher DPN predictions. There was an overall decrease in microcirculatory parameters in response to PORH and LTH, as well as TcPO<inf>2</inf>, in DMN group compared to DM group and HC group. Random forest (RF) was found to be the best model, and achieved 84.6% accuracy along with 90.2% sensitivity and 76.7% specificity. RF_PF% of PORH was the main predictor of DPN. In addition, diabetic duration was also an important risk factor. PORH Test is a reliable screening tool for DPN, which can accurately distinguish DPN from diabetics using RF.

Background:Mechanical noise may improve somatosensation at the dorsal side of the foot,but the effect at the plantar side of the foot, the side most at risk forfoot ulceration, is unknown. Moreover, techniques used in research so farhave several problems that limit applicability in daily practice.Piezoelectric actuators may provide mechanical noise with better clinicalapplicability. We assessed the effects of piezoelectric actuators generatingmechanical noise on the vibration perception threshold (VPT) at the plantarside of the foot in people with diabetic neuropathy.Methods:Double-blind within-subjects design in a controlled laboratory settingincluding participants with diabetic neuropathy (N = 40; 18 male; mean age69.6 years; mean duration of diabetes 14.1 years; mean BMI 30.5). VPT wasmeasured at three plantar foot locations with and without mechanical noiseapplied via piezoelectric actuators.Results:Mechanical noise improved VPT at metatarsophalangeal joint (MTP) 1 (left39.3V vs 43.5V; right 39.0 vs 42.6 V), MTP5 (left 37.5V vs 41.7V; right34.5V vs 40.8V) and the heel (left 40.0V vs 44.0V; right 39.3V vs 41.0V),all P < .001.Conclusions:Mechanical noise improves VPT at the plantar side of the foot in people withdiabetic neuropathy. This is an important step for further development ofinsoles using mechanical noise that may have the potential to improve VPTand decrease the risk of foot ulceration.

Aim of the studyHigh-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy.Material and methods75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs.ResultsThe mean cross sectional area (22.63 +/− 2.66 mm2) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score (p < 0.001). The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/− 1.72 mm2) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/− 1.01 mm2 and 0.30 mm respectively).ConclusionThe cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

Introduction – The pathogenetic vision of diabetes mellitus has changed in the last few years, with inflammatory and autoimmunity pathways playing roles in the development and progression of diabetic complications. This study was conducted to investigate whether inflammation and/or autoimmunity are associated with the pathogenesis of human diabetic peripheral neuropathy. Methods – A cross-sectional analysis was initially conducted to explore the population of patients with diabetes mellitus in the Kingdom of Bahrain. The demographics of patients diagnosed with diabetes mellitus in the Royal Medical Services-Bahrain Defence Force Hospital were randomly collected from 500 record cards. Case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 patients with diabetes mellitus without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the levels of pro-inflammatory markers and autoimmune markers between the three groups. Secondary analysis investigated the correlations between the level of markers and sample demographics and neurological manifestations. Due to the limited time and financial resources available, this research was considered as a pilot/exploratory study encouraging further investigations to take place in the near future. Results – From the 500 sample initially selected, 48% were male (n=242) and 52% (n= 258) were female. The mean age was 55 ± 14 years and the mean BMI was 35 ± 9 kg/m². Type I DM was present in 8% (n=38) only as opposed to 92% (n=462) who had type II DM. From the sample randomly selected, 76% of the patients had other medical complications, the commonest being peripheral neuropathy; 26% (n=186) followed by vascular insufficiency; 20% (n=141). Case control analysis demonstrated very highly significant differences between the three groups in the levels of IL-6, IL-8 and IL-1β (p<0.001), highly significant differences in the levels of TNF-α, IFN-ɤ (p<0.01), and a significant difference in the levels of CRP (p<0.05). Highly significant differences between the percentages of positive and negative autoimmune antibodies (ANA) between the three groups were observed. The odds of positive values of ANAs in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis detected a number of significant relationships between the levels of pro-inflammatory markers and sample demographics. Highly significant correlations were found to be associated with neurological characteristics in the neuropathy group at the levels of CRP, IL-8, and IL-1β. Conclusion – The present study demonstrated that human peripheral diabetic neuropathy is associated with increased biochemical markers of inflammation and autoimmunity. Furthermore, painful neuropathy may be associated with further increase in inflammation. These results indicate that inflammation and autoimmunity may be important contributors in the development of peripheral neuropathy in diabetes mellitus. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers.

Diabetic neuropathy is a chronic, progressive neurodegenerative complication of diabetes mellitus, arising primarily from prolonged hyperglycemia and metabolic dysregulation. It is among the most prevalent and debilitating long-term sequelae of diabetes, affecting a significant proportion of individuals with poor glycemic control over extended durations. Prolonged exposure to high blood sugar levels causes inflammation, oxidative stress, and decreased blood flow to peripheral nerves. Over time, this causes nerve malfunction and degeneration, resulting in a variety of symptoms that can significantly disrupt a person’s everyday life. Diabetic neuropathy usually affects the lower limbs, especially the feet and legs, although it can also affect the hands and arms in some circumstances. Beyond physical discomfort and problems, diabetic neuropathy has a substantial impact on a person’s overall quality of life. Chronic pain and limited movement can cause psychological anguish, anxiety, depression, and incapacity. The loss of sensation also raises the risk of falls and accidents, jeopardizing independence and daily functioning. As a result, people with this condition require ongoing medical care, such as blood sugar management, pain control, and preventive steps to avoid complications. This case study illustrates the effective use of Ayurvedic treatment in managing diabetic neuropathy in a 60-year-old male with poorly controlled type 2 diabetes mellitus. The patient presented with gradually worsening symptoms such as tingling, burning sensations, muscle weakness, and sensory deficits, particularly in the hands and feet. A neurological assessment revealed classic signs of peripheral neuropathy, including muscle wasting, absent ankle reflexes, and bilateral foot drop. The patient underwent a 2-month Ayurvedic treatment protocol, which included Ekangveer Rasa , Mahayograj Guggulu , Rasnadi Kashaya , and daily Sarvanga Abhyanga with Til taila , complemented by prescribed dietary and lifestyle practices ( pathya ). Following this regimen, the patient showed a significant improvement in clinical symptoms along with better blood sugar regulation, most notably, a reduction in postprandial glucose levels from 299 mg/dL to 171 mg/dL. This case highlights the potential of Ayurvedic interventions to alleviate neuropathic symptoms and enhance quality of life in diabetic patients.

Grip force control and hand dexterity are impaired in individuals with diabetic peripheral neuropathy.

As the most common chronic complication of diabetes mellitus (DM), diabetic peripheral neuropathy (DPN) seriously affects the quality of life of DM patients. So, it is of great significance for the diagnosis and treatment of DPN. In recent years, there have been numerous studies on pathogenesis and biomarkers of DM, but there are few studies on the biomarkers of DPN. This research is intended to identify abnormal metabolic pathways, search for potential biomarkers of DPN, and provide a metabolic basis for the diagnosis and mechanism of DPN. Serum samples from 23 healthy controls (HC), 42 DM patients and 30 DPN patients and urine samples from 42 HC, 40 DM patients, and 30 DPN patients were collected. UPLC-Q-TOF/MS was used to analyze the samples. Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least squares discriminant analysis (OPLS-DA) and further evaluated by receiver operating characteristic analysis (ROC). The biomarkers were then enriched and pathway analyzed. 12 potential DPN biomarkers were identified from patient's serum. 11 potential DPN biomarkers were identified from the patient's urine. Among them, the diagnostic ability of gluconic acid, lipoic acid, sphinganine, bilirubin, sphingosine and 4-hydroxybenzoic acid was increased by ROC analysis. Potential biomarkers suggest that the disorder of DPN metabolism may be linked to sphingolipid metabolism. This research laid a theoretical foundation for the diagnosis and pathogenesis of DPN.