Distal Symmetric Polyneuropathy Research Articles

Pathogenic Mechanisms of Diabetic Neuropathy

Diabetes stands as the predominant cause of peripheral neuropathy, and diabetic neuropathy (DN) is an early-onset and most frequent complication of diabetes. Distal symmetric polyneuropathy is the major form of DN; however, various patterns of nerve injury can manifest. Growing evidence suggests that hyperglycemia-related metabolic disorders in neurons, Schwann cells, and vascular endothelial cells play a major role in the development and progression of DN; however, its pathogenesis and development of disease-modifying therapies warrant further investigation. Herein, recent studies regarding the possible pathogenic factors of DN (polyol and other collateral glycolysis pathways, glycation, oxidative stress, Rho/Rho kinase signaling pathways, etc.) and therapeutic strategies targeting these factors are introduced.

Novel strategy: Identifying new markers for demyelination in diabetic distal symmetrical polyneuropathy

ObjectiveTo develop a novel strategy for identifying acquired demyelination in diabetic distal symmetrical polyneuropathy (DSP). BackgroundMotor nerve conduction velocity (CV) slowing in diabetic DSP exceeds expectations for pure axonal loss thus implicating superimposed acquired demyelination. MethodsAfter establishing demyelination confidence intervals by regression analysis of nerve conduction data from chronic inflammatory demyelinating polyneuropathy (CIDP), we prospectively studied CV slowing in 90 diabetic DSP patients with and without at least one motor nerve exhibiting CV slowing (groups A and B) into the demyelination range by American Academy of Neurology (AAN) criteria respectively and 95 amyotrophic lateral sclerosis (ALS) patients. Simultaneously, secretory phospholipase A2 (sPLA2) activity was assessed in both diabetic groups and 46 healthy controls. ResultsNo ALS patient exhibited CV slowing in more than two motor nerves based on AAN criteria or the confidence intervals. Group A demonstrated a significantly higher percentage of patients as compared to group B fulfilling the above criteria, with an additional criterion of at least one motor nerve exhibiting CV slowing in the demyelinating range and a corresponding F response in the demyelinating range by AAN criteria (70.3 % vs. 1.9 %; p < 0.0001). Urine sPLA2 activity was increased significantly in diabetic groups as compared to healthy controls (942.9 ± 978.0 vs. 591.6 ± 390.2 pmol/min/ml, p < 0.05), and in group A compared to Group B (1328.3 ± 1274.2 vs. 673.8 ± 576.9 pmol/min/ml, p < 0.01). More patients with elevated sPLA2 activity and more than 2 motor nerves with CV slowing in the AAN or the confidence intervals were identified in group A as compared to group B (35.1 % vs. 5.7 %, p < 0.001). Furthermore, 13.5 % of patients in diabetic DSP Group A, and no patients in diabetic DSP Group B, fulfilled an additional criterion of more than one motor nerve with CV slowing into the demyelinating range with its corresponding F response into the demyelinating range by AAN criteria. ConclusionA combination of regression analysis of electrodiagnostic data and a urine biological marker of systemic inflammation identifies a subgroup of diabetic DSP with superimposed acquired demyelination that may respond favorably to immunomodulatory therapy.

Contemporary prevalence of diabetic neuropathies in individuals with type 1 and type 2 diabetes in a Danish tertiary outpatient clinic

BackgroundPopulation-based prevalence estimates of distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN) are scares. Here we present neuropathy estimates and describe their overlap in a large cohort of people with type 1 and type 2 diabetes. MethodsIn a large population of outpatient participants, DPN was assessed using vibration perception threshold, sural nerve function, touch, pain and thermal sensation. Definite DPN was defined by the Toronto Consensus Criteria. Painful DPN was defined by Douleur Neuropathique 4 Questions. DAN measures were: cardiovascular reflex tests, electrochemical skin conductance, and gastroparesis cardinal symptom index. ResultsWe included 822 individuals with type 1 (mean age (±SD) 54 ± 16 years, median [IQR] diabetes duration 26 [15–40] years) and 899 with type 2 diabetes (mean age 67 ± 11 years, median diabetes duration 16 [11−22] years).Definite DPN was prevalent in 54 % and 68 %, and painful DPN was in 5 % and 15 % of type 1 and type 2 participants, respectively. The prevalence of DAN varied between 6 and 39 % for type 1 and 9–49 % for type 2 diabetes. DPN without other neuropathy was present in 45 % with T1D and 50 % with T2D. ConclusionThe prevalence of DPN and DAN was high. DPN and DAN co-existed in only 50 % of cases.

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

ObjectiveWe 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 methodsCross-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. ResultsWe 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. ConclusionsA 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.

Perceived Stress and its Association with Sleep Quality in Patients with Neuropathic Pain and Distal Symmetric Polyneuropathy (P3-11.020)

Perceived Stress and its Association with Sleep Quality in Patients with Neuropathic Pain and Distal Symmetric Polyneuropathy (P3-11.020)

Natural History of Acquired Demyelination in Diabetic Distal Symmetric Polyneuropathy (P9-11.014)

Natural History of Acquired Demyelination in Diabetic Distal Symmetric Polyneuropathy (P9-11.014)

Regression Equation Analysis Enhances Detection of Conduction Slowing Beyond Exclusive Axonal Loss in Diabetic Distal Symmetrical Polyneuropathy (P1-11.012)

Regression Equation Analysis Enhances Detection of Conduction Slowing Beyond Exclusive Axonal Loss in Diabetic Distal Symmetrical Polyneuropathy (P1-11.012)

Identification of New Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing: A Prospective Proteomics Analysis (P8-11.003)

Identification of New Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing: A Prospective Proteomics Analysis (P8-11.003)

Is There an Association Between Serum Neurofilament Light Chain Levels and Conduction Slowing in Type 2 Diabetic Distal Symmetrical Polyneuropathy? (P3-4.003)

Is There an Association Between Serum Neurofilament Light Chain Levels and Conduction Slowing in Type 2 Diabetic Distal Symmetrical Polyneuropathy? (P3-4.003)

Clinical and Biological Markers of Conduction Slowing in Diabetic Distal Symmetrical Polyneuropathy: A Prospective Study (P8-11.012)

Clinical and Biological Markers of Conduction Slowing in Diabetic Distal Symmetrical Polyneuropathy: A Prospective Study (P8-11.012)

Lipidomic Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing (P8-11.015)

Lipidomic Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing (P8-11.015)

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.

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

IntroductionDiabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methodsIn adults with type 1...

Cognitive decline and diabetes in the clinical setting

Objective. The aim of our study was to evaluate the prevalence of cognitive decline in patients with diabetes in the clinical setting and to identify patient characteristics directly associated with this condition. patients with diabetes in the clinical setting and to identify patient characteristics directly associated with this condition.&#x0D; Methods. In our cross-sectional study, we applied the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to determine cognitive function in 172 diabetic patients, in the clinical setting. We included 120 patients with type 2 diabetes (T2DM), 42 cases with type 1 diabetes (T1DM) and 10 patients with confirmed secondary diabetes (SDM). The mean age of the participants was 62.4 years (±1.01, min: 26 years, Max: 87 years), with median diabetes duration of 15±11.8 years.&#x0D; Results. More than half (55.23%) of the subjects presented cognitive deterioration, which was diabetes type-specific (p&lt;0.05). Mild forms affected mostly T1DM and SDM cases (31.5% and 30% vs. T2DM: 14.5%, p=0.00), whereas moderate cognitive decline was more predominant in T2DM (21.9% vs. T1DM: 7.1%, p=0.1). A higher prevalence of severe cognitive impairment was present in T1DM (14.5% vs. T2DM: 8.7%, p=0.1).&#x0D; The middle-aged category (40-64 years) was characterized by a more significant reduction of cognitive function in comparison with other age groups (p=0.02).&#x0D; No gender-related difference in the prevalence of cognitive decline was found (female: 45.83% vs male: 45.71%, p=0.98), although severe forms were significantly more suggestive for men (15.27% vs. 4.18%, p=0.04).&#x0D; Diabetic ketoacidosis (DKA) at admission was more frequently associated with cognitive deterioration, in comparison with hypoglycemic events (p=0.03).&#x0D; In T2DM, cognitive decline (p=0.006, r=-0.342) was associated with the presence of anemia.&#x0D; In T2DM women, treatment with calcium-channel blockers facilitated cognitive decrement (p=0.01, r=-0.339), whereas in men, therapy for distal symmetric polyneuropathy resulted in higher MMSE/ MoCA test scores (p=0.00, r=0.72).&#x0D; In T1DM, a higher glycemic burden evidenced by increased HbA1c (p=0.03, r=- 0.364) and glycemia at admission (p=0.01, r=-0.389) was suggestive to a more severe form of cognitive impairment. Distal symmetrical polyneuropathy (p=0.05, r=-0.305) and diabetic retinopathy (p=0.03, r=-0.102) was often co-occurring with cognitive decline.&#x0D; Cognitive deterioration was associated with insulin therapy (p=0.05, r=-0.232).&#x0D; Conclusion. The prevalence of cognitive decline is high in the diabetic population. Risk stratification must start at diagnosis and physicians should follow disease progression periodically, with special attention attributed to T1DM and the middle-aged population.

Current Concepts in the Molecular Mechanisms and Management of Diabetic Neuropathy by Pharmacotherapeutics and Natural Compounds.

One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.

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.

Association of vitamin D deficiency and subclinical diabetic peripheral neuropathy in type 2 diabetes patients.

Diabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients. This cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level < 50 nmol/L. 1620 (44.6%) patients had subclinical DPN and they were further divided into subgroups: distal symmetric polyneuropathy (DSPN) (n=685), mononeuropathy (n=679) and radiculopathy (n=256). Compared with non-DPN, DPN group had significantly lower level of 25(OH)D (P < 0.05). In DPN subtypes, only DSPN patients had significantly lower levels of 25(OH)D (36.18 ± 19.47 vs. 41.03 ± 18.47 nmol/L, P < 0.001) and higher proportion of vitamin D deficiency (78.54% vs. 72.18%, P < 0.001) than non-DPN. Vitamin D deficiency was associated with the increased prevalence of subclinical DPN [odds ratio (OR) 1.276, 95% confidence interval (CI) 1.086-1.501, P = 0.003] and DSPN [OR 1. 646, 95% CI 1.31-2.078, P < 0.001], independent of sex, age, weight, blood pressure, glycosylated hemoglobin, T2DM duration, calcium, phosphorus, parathyroid hormone, lipids and renal function. The association between vitamin D deficiency and mononeuropathy or radiculopathy was not statistically significant. A negative linear association was observed between 25(OH)D and subclinical DSPN. Vitamin D deficiency maintained its significant association with subclinical DSPN in all age groups. Vitamin D deficiency was independently associated with subclinical DSPN, rather than other DPN subtypes.

Micro-vascular complications of post-transplant diabetes mellitus in renal transplant recipients- an observational study

IntroductionThe incidence of post-transplant diabetes mellitus (PTDM) ranges from 2.5% to 20% in kidney transplant recipients. Diabetic retinopathy (DR), diabetic kidney disease (DKD), and distal symmetric polyneuropathy (DSPN) are the microvascular complications frequently seen in both type 1 and 2 diabetes mellitus (DM). However, the data regarding these complications in patients with PTDM is lacking. MethodA retrospective and prospective observational study of PTDM conducted at a tertiary care hospital from November 2018 to December 2020. 115 kidney transplant recipients who had PTDM of ≥5 years duration were included and analysed. ResultsThe mean duration of PTDM was 8.8 ± 3.0 years, and the mean of all available HbA1c values was 7.0 ± 0.9%. while none of the patients had evidence of diabetic retinopathy on direct ophthalmoscopy, 37.4% of patients (n = 43) had DSPN and this was associated with the duration of PTDM and age. The mean estimated glomerular filtration rate (eGFR) was 59.24 ± 21.82 ml/min/1.73m2, and patients had a median proteinuria of 620 mg/day (IQR 1290). Out of 115 patients, 20% of them (n = 23) underwent graft kidney biopsy, and 10 biopsies were diagnosed as de-novo DKD. Patients with biopsy proven DKD had a mean PTDM duration of 143.3 ± 52.4 months; a mean HbA1c level of 7.9 ± 1.3%; a mean eGFR of 44.8 ± 21.8 ml/min; and a median proteinuria of 2653 mg (IQR 2758). An additional analysis of all 23 biopsied patients showed that HbA1c level and degree of proteinuria were significantly associated with de-novo DKD. ConclusionPTDM in transplant patients had milder microvascular complications than usually expected in Type 1/2 diabetes in non-transplant patients. DR was not strongly associated with DKD in PTDM patients. Furthermore, de-novo DKD development was associated with poor glycaemic control and increased proteinuria.

Characteristics of bone metabolism in the male patients with diabetic neuropathy.

This study aimed to evaluate the characteristics of bone metabolism and fracture risk in the type 2 diabetes mellitus (T2DM) patients with distal symmetric polyneuropathy (DSPN). A total of 198 T2DM individuals were recruited from January 2017 to December 2020. Patients with DSPN were evaluated by strict clinical and sensory thresholds. Biochemical parameters and bone mineral density (BMD) were measured. The BMD, bone turnover markers, and probability of fracture were compared between two groups, and the factors related to BMD and probability of hip fracture in 10 years were further explored. Compared with type 2 diabetes mellitus without distal symmetric polyneuropathy (T2DN-) patients, type 2 diabetes mellitus with distal symmetric polyneuropathy (T2DN+) patients had lower level of cross-linked C-telopeptide (CTX) (0.32 ± 0.19 vs 0.38 ± 0.21 ng/mL, p = 0.038) and higher level of bone-specific alkaline phosphatase (BALP) (15.28 ± 5.56 vs 12.58 ± 4.41 μg/mL, p = 0.003). T2DN+ patients had higher BMD of lumbar L1-L4 (1.05 ± 0.19 vs 0.95 ± 0.37, p = 0.027) and higher probability of hip fracture (0.98 ± 0.88 vs 0.68 ± 0.63, p = 0.009) as compared to T2DN- individuals. Univariate correlation analysis showed that BALP level (coefficient (coef) = -0.054, p = 0.038), CTX level (coef = -2.28, p = 0.001), and hip fracture risk (coef = -1.02, p < 0.001) were negatively related to the BMD of L1-L4. As for the risk of hip fracture evaluated by WHO Fracture Risk Assessment Tool (FRAX), age (coef = 0.035, p < 0.001), use of insulin (coef = 0.31, p =0.015), and levels of BALP (coef = 0.031, p = 0.017) and CTX (coef = 0.7, p = 0.047) were positively related to the risk of hip fracture. Multivariate regression analysis showed that CTX level (coef = -1.41, p = 0.043) was still negatively related to BMD at the lumbar spine. This study indicates that T2DM patients with DSPN have special bone metabolism represented by higher BALP level and lower CTX level which may increase BMD at the lumbar spine.

Spectrum of Diabetic Neuropathy: New Insights in Diagnosis and Treatment.

Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.