Diabetic Distal Symmetric Polyneuropathy Research Articles

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.

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.

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.

Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment.

Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.

Udgharshana (an Ayurvedic therapeutic intervention) in improving vibration perception threshold in diabetic distal symmetric polyneuropathy: An observation

Diabetic Distal Symmetrical Polyneuropathy (DSPN), affects the sensation of vibration, a major risk factor for diabetic foot ulcers that raises the likelihood of lower limb amputation among the diabetic population. The effectiveness of existing therapeutic approaches in its management is limited, necessitating exploring alternative therapy approaches. A 61-year-old female, a known Type 2 Diabetic for five years, presented with complaints of numbness and tingling sensation in bilateral lower limbs below the knee joint associated with aching pain in the bilateral foot region for the last two years. On assessment, she was found to be positive on the Michigan Neuropathy Screening Instrument that indicates the probable diagnosis of diabetic DSPN. The patient was treated with an Ayurvedic topical therapeutic intervention, Udgharshana (~therapeutic coarse powder massage) with a combination of Triphala (~a polyherbal Ayurvedic formulation) powder and Dhanyamla (~fermented sour liquid prepared from gruel of husked grains). Improvement in clinical features was observed on Neuropathy Total Symptom Score-6 and in Semmes-Weinstein monofilament reading in the bilateral foot (right 7/10 vs. 9/10 and left 7/10-10/10). The intervention also improved the vibration perception threshold bilaterally (right 31.5V vs. 20.1V; left 30.5V vs. 22.8V). Inferring the observations, it is suggested that early disease management of diabetic DSPN with Ayurveda might arrest further disease progression and help in reversing the pathogenesis, with a positive effect on improving vibration perception threshold.

Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy.

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes. Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (α-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction. Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency.

Declining Incidence Rates of Distal Symmetric Polyneuropathy in People With Type 1 and Type 2 Diabetes in Denmark, With Indications of Distinct Patterns in Type 1 Diabetes.

It is not known if incidence rates for diabetic distal symmetric polyneuropathy (DSPN) are decreasing, as they are for other diabetic complications. Here, we investigated incidence rates of DSPN in type 1 and type 2 diabetes in a large population-based study. In the period 1996 to 2018, 19,342 individuals were identified at a Danish tertiary diabetes center. Vibration perception threshold was assessed by biothesiometry and repeated throughout the study. Exclusion of prevalent DSPN cases or missing data left data on 9,473 individuals for analysis of DSPN using a cutoff of >25 V and on 2,783 individuals for analysis using an age-, sex-, and height-specific cutoff. Poisson regression analysis was used to model incidence rates of DSPN for both cutoff types and separately for diabetes types. Covariates were sex, age, diabetes duration, and calendar time. Incidence rates (95% CI) of DSPN decreased from 1996 to 2018 (e.g., from 4.78 [3.60-6.33]/100 person-years [PY] to 1.15 [0.91-1.47]/100 PY for 40-year-old men with type 1 diabetes and from 16.54 [11.80-23.18]/100 PY to 8.02 [6.63-9.69]/100 PY for 60-year-old men with type 2 diabetes, when using >25 V as the cutoff value). Analyses using age-, sex-, and height-specific cutoff values demonstrated similar incidence patterns by calendar time without sex differences. For type 1 diabetes, decreasing incidence rates were seen with older age. Incidence rates for DSPN are declining in type 1 and type 2 diabetes, possibly due to improved diabetes treatment. This causality remains to be explored. Distinct age-related patterns indicate that the pathophysiology of DSPN may differ between diabetes types.

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

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

Ultra-high performance liquid chromatography coupled to tandem mass spectrometry-based metabolomics study of diabetic distal symmetric polyneuropathy.

Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression. Plasma metabolite profiles were obtained by the ultra-high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups. Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6-acetyllysine, N-acetylhistidine, N,N,N-trimethyl-alanylproline betaine, cysteine, 7-methylguanine, N6-carbamoylthreonyladenosine, pseudouridine, 5-methylthioadenosine, N2,N2-dimethylguanosine, aconitate and C-glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism. The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further.

Three genes expressed in relation to lipid metabolism considered as potential biomarkers for the diagnosis and treatment of diabetic peripheral neuropathy

Diabetic neuropathy is one of the most common chronic complications and is present in approximately 50% of diabetic patients. A bioinformatic approach was used to analyze candidate genes involved in diabetic distal symmetric polyneuropathy and their potential mechanisms. GSE95849 was downloaded from the Gene Expression Omnibus database for differential analysis, together with the identified diabetic peripheral neuropathy-associated genes and the three major metabolism-associated genes in the CTD database to obtain overlapping Differentially Expressed Genes (DEGs). Gene Set Enrichment Analysis and Functional Enrichment Analysis were performed. Protein–Protein Interaction and hub gene networks were constructed using the STRING database and Cytoscape software. The expression levels of target genes were evaluated using GSE24290 samples, followed by Receiver operating characteristic, curve analysis. And Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the target genes. Finally, mRNA-miRNA networks were constructed. A total of 442 co-expressed DEGs were obtained through differential analysis, of which 353 expressed up-regulated genes and 89 expressed down-regulated genes. The up-regulated DEGs were involved in 742 GOs and 10 KEGG enrichment results, mainly associated with lipid metabolism-related pathways, TGF-β receptor signaling pathway, lipid transport, and PPAR signaling pathway. A total of 4 target genes (CREBBP, EP300, ME1, CD36) were identified. Analysis of subject operating characteristic curves indicated that CREBBP (AUC = 1), EP300 (AUC = 0.917), ME1 (AUC = 0.944) and CD36 (AUC = 1) may be candidate serum biomarkers for DPN. Conclusion: Diabetic peripheral neuropathy pathogenesis and progression is caused by multiple pathways, which also provides clinicians with potential therapeutic tools.

Diabetic neuropathy: Pathogenesis and evolving principles of management

The global rise of prediabetes and diabetes has spawned an epidemic of complications associated with these conditions. Neuropathy is the most common consequence, with distal symmetric polyneuropathy (DSP) being the most prevalent. Diabetic neuropathy (DN) is a debilitating consequence of diabetes mellitus resulting in the highest morbidity and death, besides imposing a substantial financial burden on the patient. Loss of sensory function commencing distally in the lower limbs, accompanied by discomfort and considerable morbidity, characterizes diabetic neuropathy. The clinical evaluation and therapeutic options for diabetic peripheral neuropathy are multifaceted. At least fifty percent of people with diabetes acquire diabetic neuropathy over time. Good glycemic control halts the evolution in individuals with Type 1 diabetes mellitus. These results have prompted fresh attempts to comprehend the origin and develop new guidelines for prevention and treatment. New recommendations have also been established for the treatment of painful DN using separate classes of medications, with an emphasis on avoiding the use of opioids. Although our comprehension of the intricacies of diabetic neuropathy has progressed significantly over the past decade, the unique processes driving the neuropathy in type 1 and type 2 diabetes remain unexplained. Currently, glycemic control and pain management are the only effective therapies. While glucose management significantly reduces neuropathy development in type 1 diabetics, the effect is considerably lower in type 2 diabetics. Evidence supports the use of anticonvulsants and antidepressants for diabetic peripheral neuropathy pain treatment. However, the absence of disease-modifying medications for diabetic DSP necessitates the identification of unrecognized modifiable risk factors. It is imperative to identify the ‘missed’ risk factors and targets, allowing comprehensive, individualized care for patients.

Motor Nerve Conduction Slowing in Diabetic Distal Symmetrical Polyneuropathy: A Novel Approach (P11-8.011)

<h3>Objective:</h3> To evaluate the use of novel regression equations to investigate the profile of conduction slowing in diabetic distal symmetric polyneuropathy (DSP). <h3>Background:</h3> Conduction slowing beyond what is expected from pure axonal loss have been reported in diabetic DSP and have been attributed to an additional demyelinating component. Conventional nerve conduction studies do not allow for a clear distinction between pure axonal loss and loss of large fibers with contributing demyelination. <h3>Design/Methods:</h3> Electrodiagnostic data from CIDP patients was plotted, transformed and linear regression analysis was performed to create confidence intervals to determine abnormal nerve conduction ranges of distal latency (DL), conduction velocity (CV) and F latency for compound muscle action potential (CMAP). These ranges were then used to evaluate abnormal nerve conduction values in 219 patients with diabetic DSP and 219 non-diabetic axonal DSP. <h3>Results:</h3> The mean CV was significantly slower in diabetic DSP than in non-diabetic DSP groups for all tested nerves. There was a significantly higher number of patients fulfilling the regression equation above criteria in the diabetic group compared to the axonal non-diabetic group (47.0% vs. 23.3%; p &lt; 0.0001). There are significantly more patients with more than 2 motor nerves with CV in the demyelinating range in the diabetic DSP group compared to the axonal non-diabetic group (25.6% vs. 7.8%; p &lt; 0.0001). Furthermore, there are significantly more patients that fulfilled an additional criteria of at least one motor nerve with the corresponding F response in the demyelinating range by AAN criteria in the diabetic DSP group compared to the axonal non-diabetic group (21.0% vs. 4.1%; p &lt; 0.0001). <h3>Conclusions:</h3> Regression analysis identified conduction slowing in diabetic DSP, beyond what is expected from exclusive axonal loss. Combining regression analysis for conduction slowing with adequate clinical evaluation may improve the identification of demyelination in diabetic DSP. <b>Disclosure:</b> Mr. Jaffry has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Mandava has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Trivedi has nothing to disclose. Mr. Ors has nothing to disclose. Ms. Faiz has nothing to disclose. Ankit Pahwa has nothing to disclose. Dr. Patel has nothing to disclose. Abu Nasar, MD has nothing to disclose. Dr. Sander has received personal compensation for serving as an employee of Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Law firm. Dr. Souayah has received publishing royalties from a publication relating to health care.

Novel Biomarker for Demyelination in Diabetic Distal Symmetric Polyneuropathy: A Prospective Study (P11-8.006)

<h3>Objective:</h3> To develop a new strategy to identify acquired demyelination in diabetic distal symmetric polyneuropathy (DSP). <h3>Background:</h3> Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds what is expected from pure axonal loss and can be attributed to additional acquired demyelination. <h3>Design/Methods:</h3> We prospectively studied CV and urine secretory phospholipase A2 (sPLA2) activity in 90 diabetic DSP patients divided into 2 groups A and B with and without at least one motor nerve with CV slowing in the demyelination range by AAN criteria. sPLA2 activity was tested in 46 healthy controls. In parallel, we studied CV in these diabetic patients using a regression analysis that we developed and validated from data from 114 CIDP patients. <h3>Results:</h3> Mean urine sPLA2 activity was significantly higher in diabetic groups compared to healthy controls, (942.9 ± 977.97 vs. 591.6 ± 390.15, pmol/min/ml p &lt; 0.05), and was significantly higher in group A compared to B, (1328.3 ± 1274.21 vs. 673.8 ± 576.93 pmol/min/ml, p = 0.0014). The number of patients with elevated sPLA2 activity and have more than 2 motor nerves with CV slowing in the AAN or regression analysis ranges was significantly higher in patients of group A compared to group B (35.1% vs. 5.7%, p = 0.0005). Furthermore, 13.5% in diabetic DSP group A and no patient in diabetic DSP group B fulfilled an additional criteria of more than one motor nerve with CV slowing in the demyelinating range with the corresponding F response in the demyelinating range by AAN criteria. <h3>Conclusions:</h3> To the best of our knowledge, the present study is the first to use a combination of regression analysis of electrodiagnostic data and a urine biological marker of inflammation to identify a subgroup of diabetic DSP with significant contribution of acquired demyelination and neuroinflammation in diabetic nerve injury. <b>Disclosure:</b> Mr. Jaffry has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Mandava has nothing to disclose. Mr. Trivedi has nothing to disclose. Mr. Ors has nothing to disclose. Ms. Faiz has nothing to disclose. Dr. Patel has nothing to disclose. Ankit Pahwa has nothing to disclose. Hongxin Chen has nothing to disclose. Timothy Cunningham has received intellectual property interests from a discovery or technology relating to health care. Dr. Sander has received personal compensation for serving as an employee of Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Sander has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Law firm. Dr. Souayah has received publishing royalties from a publication relating to health care.

Obstetric Neuropathy in Diabetic Patients: The "Double Hit Hypothesis".

The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal damage during the delivery process. However, the anatomical and pathophysiological mechanisms are not well understood. Our overarching hypothesis in this review paper is that pregnant women who are diabetic have a damaged peripheral nervous system, constituting the "first hit" hypothesis. The delivery process itself-the "second hit"-can produce neurological damage to the mother. Women with diabetes mellitus (DM) are at risk for neurological damage during both hits, but the cumulative effects of both "hits" pose a greater risk of neurological damage and pathophysiological changes during delivery. In our analysis, we introduce the different steps of our concept paper. Subsequently, we describe each of the topics. First, we outline the mechanisms by which diabetes acts as a detrimental variable in neuropathy by focusing on the most common form of diabetic neuropathy, diabetic distal symmetrical polyneuropathy, also known as distal sensorimotor neuropathy. The possible role of macrosomia in causing diabetic neuropathy and obstetric neurological injury is discussed. Second, we describe how vaginal delivery can cause various obstetrical neurological syndromes and pathophysiological changes. Third, we highlight the risk of obstetric neuropathy and discuss anatomical sites at which lesions may occur, including lesions during delivery. Fourth, we characterize the pathophysiological pathways involved in the causation of diabetic neuropathy. Finally, we highlight diabetic damage to sensory vs. motor nerves, including how hyperglycemia causes different types of damage depending on the location of nerve cell bodies.