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Having lived through a pandemic and witnessed how regulatory approval processes can evolve rapidly; it is lamentable how we continue to rely on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN. Small (Aδ and C) fibers are key to the genesis of pain, regulate skin blood flow, and play an integral role in the development of diabetic foot ulceration but continue to be ignored. This article challenges the rationale for the FDA insisting on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN. Quantitative sensory testing, intraepidermal nerve fiber density, and especially corneal confocal microscopy remain an after-thought, demoted at best to exploratory secondary endpoints in clinical trials of diabetic neuropathy. If pharma are to be given a fighting chance to secure approval for a new therapy for diabetic neuropathy, the FDA needs to reassess the evidence rather than rely on 'opinion' for the most suitable endpoint(s) in clinical trials of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes. Methods: Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease (T2DM–CKD (n = 25)) and type 2 diabetes without chronic kidney disease (T2DM–no CKD (n = 25)). Ocular surface discomfort assessment, flush tear collection, in-vivo corneal confocal microscopy, and peripheral neuropathy assessment were conducted. Enzyme-linked immunosorbent assays were utilized to ascertain the levels of tear film substance P in collected flush tears. Correlation analysis, hierarchical multiple linear regression analysis, and t-tests or Mann–Whitney U tests were used in the analysis of data for two-group comparisons. Results: There was no substantial difference between the T2DM–CKD and T2DM–no CKD groups for tear film substance P concentration (4.4 (0.2–50.4) and 5.9 (0.2–47.2) ng/mL, respectively; p = 0.54). No difference was observed in tear film substance P concentration between the low-severity peripheral neuropathy and high-severity peripheral neuropathy groups (4.4 (0.2–50.4) and 3.3 (0.3–40.7) ng/mL, respectively; p = 0.80). Corneal nerve fiber length (9.8 ± 4.6 and 12.4 ± 3.8 mm/mm2, respectively; p = 0.04) and corneal nerve fiber density (14.7 ± 8.5 and 21.1 ± 7.0 no/mm2, respectively; p < 0.01) were reduced significantly in the T2DM–CKD group compared to the T2DM–no CKD group. There were significant differences in corneal nerve fiber density (21.0 ± 8.1 and 15.8 ± 7.7 no/mm2, respectively; p = 0.04) and corneal nerve fiber length (12.9 ± 4.2 and 9.7 ± 3.8 mm/mm2, respectively; p = 0.03) between the low- and high-severity peripheral neuropathy groups. Conclusion: In conclusion, no significant difference in tear film substance P concentration was observed between type 2 diabetes with and without CKD. Corneal nerve loss, however, was more significant in type 2 diabetes with chronic kidney disease compared to type 2 diabetes alone, indicating that corneal nerve morphological measures could serve greater utility as a tool to detect neuropathy and nephropathy-related corneal nerve changes. [ABSTRACT FROM AUTHOR]

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Abstract Background This study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases. Methods We identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality. Results Patients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03–1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1–1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03–1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3–1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71–0.87). Conclusions T2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.

Ben Imholz,1 Jack Heijster,1 Abd Tahrani,2 Adriaan Kooy3 1Department of Internal Medicine, ETZ Ziekenhuis, Tilburg, the Netherlands; 2Department of Endocrinology and Diabetes, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 3Department of Internal Medicine, Bethesda Hospital, Treant Care Group, Hoogeveen, the NetherlandsCorrespondence: Ben Imholz, Department of Internal Medicine, ETZ-Location Waalwijk, Kasteellaan 2 5141BM Waalwijk, Tilburg, the Netherlands, Email b.imholz@etz.nlBackground: Painful diabetic peripheral neuropathy (PDPN) is common and difficult to treat with limited treatment options. We assessed the efficacy of frequency rhythmic electromagnetic neural stimulation (FREMS) in patients with PDPN.Methods: An uncontrolled prospective survey of patients with PDPN and pain despite at least two lines of pharmacotherapy. The primary outcome, 50% reduction in pain scores at 1 and/or 3 months post FREMS. FREMS was applied to both legs below the knees using 4 sets of electrodes per leg; the treatment consisted of 10 sessions of 35 min applications given over 14 days. FREMS was repeated every 4 months and patients were followed up for 12 months. Pain was assessed using the neuropathic pain symptom inventory (NPSI) and quality of life (QOL) by the EQ-5D.Results: Out of 336 subjects, 248 patients met the inclusion criteria (56% men), average age and diabetes duration were 65 and 12.6 years respectively. FREMS was associated with a median decrease NPSI of 31% at M1 (range − 100;+93%), and a median decrease of − 37.5% at M3 (range − 100;+250%). The 50% reduction in pain was reached in 80/248 (32.3%) and 87/248 (35.1%) after M1 and M3 respectively. The change in NPSI was accompanied by a decrease in self reported use of opiates of > 50%.Conclusion: FREMS treatment was associated with a significant reduction in pain severity over a three months period in patients who did not have adequate response to pharmacotherapy. Randomised (sham)-controlled trials examining the role of FREMS as a treatment for PDPN in non-responders to pharmacotherapy are needed.Keywords: diabetic neuropathy, electrical stimulation, FREMS, NPSI pain score, quality of life, one-year follow-up

Xiufen Wang,1– 3 Ying Wang,1,2 Li Luo,3 Liuting Tan,4 Wenzhi Cai,1 Ling Chen,1 Wei Ren1 1Department of Nursing, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of the Third Pulmonary Disease, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China; 4Department of Endocrine, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Wei Ren; Ling Chen, Department of Nursing, Shenzhen Hospital, Southern Medical University, 1333 Xinhu Road, Baoan District, Shenzhen, Guangdong Province, 518101, People’s Republic of China, Tel +86-755-23360006, Fax +86-755-23323777, Email renwei196911@163.com; dangdang601@smu.edu.cnIntroduction: Diabetic neurogenic bladder is one of the common complications in patients with diabetic neuropathy. However, studies reporting the prevalence and associated factors of urinary tract infections (UTIs) in patients with diabetic neuropathy are rare. Therefore, the present study aimed to explore the prevalence and influencing factors of UTI in patients with diabetic neuropathy.Methods: A hospital-based cross-sectional study that recruited patients with diabetic neuropathy was conducted from January 2019 to December 2021. Collected data included patient demographic information (age, sex, education level, body mass index), clinical data (duration of diabetes, method of administration), and laboratory tests. Multivariable logistic regression models were used to identify the factors associated with UTI risk. The strength of association was expressed as the odds ratio (OR) and 95% confidence interval (95% CI).Results: A total of 579 patients were recruited (male, 68.2%; overall average age, 57.89 years). Using multivariate analysis with adjustment for confounding factors, female sex (odds ratio [OR]: 4.12; 95% CI: 2.24– 7.60; P < 0.001), hypodermic insulin injection (OR: 2.10; 95% CI: 1.02– 4.35; P = 0.045), chronic kidney disease (OR: 3.12; 95% CI: 1.11– 8.80; P = 0.032), history of UTI (OR = 45.92; 95% CI: 8.62– 244.76; P < 0.001), positive urinary nitrite (OR: 32.87; 95% CI: 7.37– 146.70; P < 0.001), and high residual urine volume (OR: 2.19, 95% CI: 1.17– 4.10; P = 0.014) were independent risk factors for UTI in patients with diabetic neuropathy. Compared with the patients aged < 45 years, UTI prevalence increased 2.91-fold in patients aged 45– 54 years (OR: 3.91; 95% CI: 1.02– 15.03; P = 0.047) and 3.87-fold in those aged ≥ 65 years (OR: 4.87; 95% CI: 1.23– 19.25; P = 0.024).Conclusion: The main findings of this study showed that older age, female sex, hypodermic insulin injection, CKD, history of UTI, and positive urinary nitrite were independent risk factors for UTI in patients with diabetic neuropathy. To minimize the occurrence and resulting disease burden of UTI, knowledge regarding UTI risk factors in patients with diabetic neuropathy is critical to designate interventions.Keywords: epidemiology, prevalence, urinary tract infection, diabetic neuropathy, risk factors

Background: Diabetic Peripheral Neuropathy is one of the most important and significantly prevalent microvascular complications of Diabetes Mellitus. Pyridoxine is a key nutrient for protecting nerve health. The objective of this research is to study the prevalence rate of pyridoxine deficiency in Diabetic neuropathy patients, to understand the correlation between various biochemical and markers of diabetic neuropathy and pyridoxine deficiency. Results: 249 patients were selected for the study based on the selection criteria participants. 51.8% prevalence of pyridoxine deficiency in Diabetic neuropathy patients. The nerve conduction velocity significantly reduced in pyridoxine deficiency cases (p

Background and aim: Natural metabolites are rich in neuroactive and anti-inflammatory phytochemicals. Soapwort or Saponaria officinalis (Sap) has been utilized for its immunomodulatory and ant-rheumatic properties. Thus, the aim is to exploit Sap phytochemically and to investigate Sap isolated active phytochemicals effect to modulate diabetic neuropathy and inflammation, and their possible mechanisms of action. Experimental procedure: Bio-guided chromatographic fractionation and phytochemical isolation of the most abundant Sap phytochemicals utilizing RP-HPLC, 13C, and 1H NMR, in-vivo models of diabetes, diabetic neuropathy, and inflammation were used. Glucometers, HbA1c micro-columns, in-vivo hind-paw edema, tail-flick, hot plate, and Von-Frey filaments methods were utilized to investigate the acute, subchronic, and long term diabetes, inflammation, hyperalgesia, and mechanical allodynia. In-vivo antioxidant, inhibitory alpha-amylase, and alpha-glucosidase, and serum insulin levels, IL-6, IL-10, and TNF-alpha cytokines levels were utilized to investigate Sap mechanisms of action. Results and conclusion: The phytochemical post-hydrolysis RP-HPLC investigation results show six major peaks; Quillaic acid (12.5%), Quillaic acid 22 β-OH (11.25%), Gypsogenin (21.25%), Phytolaccinic acid (18.75%), Phytolaccinic acid (17.50%), and Echynocystic acid (15.10%). The bio-guided chromatographic fractionation investigation utilizing reversed phase HPLC, 13C and 1H NMR has shown that Quillaic acid (QA) is the most abundant and biologically active compound. Sap 20 mg/kg has shown the highest potency in normalization of blood glucose level (BGL) acutely (6-h), subchronically (eight-days), and longer-term (eight-weeks) correlated to Sap 10 and 7 mg/kg, and QA 0.7, 1.0, 2.0 mg/kg. The highest amelioration of diabetic neuropathy (thermal hyperalgesia and mechanical allodynia) was Sap 20 mg/kg. The anti-inflammatory potentials of Sap 20 mg/kg have shown dominance in decreasing carrageenan-induced in-vivo hind-paw edema. The anti-nociceptive mechanism of action might be due to Sap insulin secretagogue and the in-vivo antioxidant potentials. The reduction of IL-6 cytokines and TNF-alpha, along with the elevation of the IL-10 cytokine level might be the underlying Sap anti-inflammatory mechanism. Phytochemically, QA has shown to be the most abundant and biologically active compound in Sap extract. Sap has shown significant (p

Diabetic neuropathy is a common complication of diabetes, but the mechanism remains unclear. Recent studies have shown that inflammation may play a critical role in the development and progression of diabetic neuropathy. In the chronic low-grade inflammatory state of diabetes, the inflammatory signaling pathways in neurons and their surrounding cells are activated and interact with the released inflammatory factors to promote the occurrence of diabetic neuropathy. Advances in the understanding of inflammatory mechanism will facilitate the discovery of the potential therapeutic targets for the development of diabetic neuropathy.

Background: A sedentary lifestyle and an unhealthy diet have considerably increased the incidence of diabetes mellitus worldwide in recent decades, which has generated a high rate of associated chronic complications. Methods: A narrative review was performed in MEDLINE, EMBASES and SciELO databases, including 162 articles. Results: Diabetic neuropathy (DN) is the most common of these complications, mainly producing two types of involvement: sensorimotor neuropathy, whose most common form is symmetric distal polyneuropathy, and autonomic neuropathies, affecting the cardiovascular, gastrointestinal, and urogenital system. Although hyperglycemia is the main metabolic alteration involved in its genesis, the presents of obesity, dyslipidemia, arterial hypertension, and smoking, play an additional role in its appearance. In the pathophysiology, three main phenomena stand out: oxidative stress, the formation of advanced glycosylation end-products, and microvasculature damage. Diagnosis is clinical, and it is recommended to use a 10 g monofilament and a 128 Hz tuning fork as screening tools. Glycemic control and non-pharmacological interventions constitute the mainstay of DN treatment, although there are currently investigations in antioxidant therapies, in addition to pain management. Conclusions: Diabetes mellitus causes damage to peripheral nerves, being the most common form of this, distal symmetric polyneuropathy. Control of glycemia and comorbidities contribute to prevent, postpone, and reduce its severity. Pharmacological interventions are intended to relieve pain.

Impaired rate-dependent depression (RDD) of the spinal H-reflex occurs in diabetic rodents and a sub-set of patients with painful diabetic neuropathy. RDD is unaffected in animal models of painful neuropathy associated with peripheral pain mechanisms and diabetic patients with painless neuropathy, suggesting RDD could serve as a biomarker for individuals in whom spinal disinhibition contributes to painful neuropathy and help identify therapies that target impaired spinal inhibitory function. The spinal pharmacology of RDD was investigated in normal rats and rats after 4 and 8 weeks of streptozotocin-induced diabetes. In normal rats, dependence of RDD on spinal GABAergic inhibitory function encompassed both GABAA and GABAB receptor sub-types. The time-dependent emergence of impaired RDD in diabetic rats was preceded by depletion of potassium-chloride co-transporter 2 (KCC2) protein in the dorsal, but not ventral, spinal cord and by dysfunction of GABAA receptor-mediated inhibition. GABAB receptor-mediated spinal inhibition remained functional and initially compensated for loss of GABAA receptor-mediated inhibition. Administration of the GABAB receptor agonist baclofen restored RDD and alleviated indices of neuropathic pain in diabetic rats, as did spinal delivery of the carbonic anhydrase inhibitor acetazolamide. Pharmacological manipulation of RDD can be used to identify potential therapies that act against neuropathic pain arising from spinal disinhibition.

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

Background: Diabetic neuropathy is one of the most common complications of diabetes mellitus. The aim of this study is to evaluate the Moveo device, a novel device that uses a machine learning (ML) algorithm to detect and track diabetic neuropathy. The Moveo device comprises 4 sensors positioned on the back of the hands and feet accompanied by a mobile application that gathers data and ML algorithms that are hosted on a cloud platform. The sensors measure movement signals, which are then transferred to the cloud through the mobile application. The cloud triggers a pipeline for feature extraction and subsequently feeds the ML model with these extracted features. Methods: The pilot study included 23 participants. Eleven patients with diabetes and suspected diabetic neuropathy were included in the experimental group. In the control group, 8 patients had suspected radiculopathy, and 4 participants were healthy. All participants underwent an electrodiagnostic examination (EDx) and a Moveo examination, which consists of sensors placed on the feet and back of the participant’s hands and use of the mobile application. The participant performs six tests that are part of a standard neurological examination, and a ML algorithm calculates the probability of diabetic neuropathy. A user experience questionnaire was used to compare participant experiences with regard to both methods. Results: The total accuracy of the algorithm is 82.1%, with 78% sensitivity and 87% specificity. A high linear correlation up to 0.722 was observed between Moveo and EDx features, which underpins the model’s adequacy. The user experience questionnaire revealed that the majority of patients preferred the less painful method. Conclusions: Moveo represents an accurate, easy-to-use device suitable for home environments, showing promising results and potential for future usage.

Diabetic neuropathic pain (DNP) is one of the common and severe late-stage complications of diabetes mellitus, which could greatly influence the patients’ quality of life. Patients with DNP often experience spontaneous pain and evoked pain such as mechanical allodynia and thermal hyperalgesia, meaning that their physical and psychological health are severely impaired. Unfortunately, the mechanisms of DNP remain highly elusive, so substantial breakthrough in effective DNP targeted treatments is still clinically challenging. This article will hence summarise the main mechanisms currently known to underlie DNP pathogenesis, along with describing some of the current and potential treatment methods against diabetic neuropathic pain.

IntroductionDiabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes, imposing a significant burden on individuals and healthcare systems worldwide. This study presents a comprehensive analysis of the global research landscape in DN, aiming to provide scientists, funders, and decision-makers with valuable insights into the current state of research and future directions.MethodsThrough a systematic review of published articles, key trends in DN research, including epidemiology, diagnosis, treatment strategies, and gaps in knowledge, are identified and discussed. ResultsThe analysis reveals an increasing prevalence of DN alongside the rising incidence of diabetes, emphasizing the urgent need for effective prevention and management strategies. Furthermore, the study highlights the geographical imbalance in research activity, with a majority of studies originating from high-income countries. DiscussionThis study underscores the importance of fostering international collaboration to address the global impact of DN. Key challenges and limitations in DN research are also discussed, including the need for standardized diagnostic criteria, reliable biomarkers, and innovative treatment approaches. By addressing these gaps, promoting collaboration, and increasing research funding, we can pave the way for advancements in DN research and ultimately improve the lives of individuals affected by this debilitating condition.

Introduction: About 424.9 million people worldwide are affected by Diabetes mellitus. Prevalence among people 20–79 years old in Nepal was 4% in 2017. It is associated with microvascular and macrovascular complications such as peripheral neuropathy leading to risk of foot ulcers and amputation, and impaired sensation in their feet. The study aimed to find the prevalence of vitamin B12 deficiency among metformin-treated type 2 diabetic patients visiting the Department of Medicine of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted in a tertiary care centre between 24 May 2021 to 24 May 2022 after obtaining ethical approval from the Institutional Review Committee. Patients who visited the Department of Medicine and gave informed consent were included in the study. Patients with underlying comorbidities were excluded from the study. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 330 patients, vitamin B12 deficiency was seen in 33 (10%) (6.76-13.24, 95% Confidence Interval). Among them, 27 (81.82%) were male and 6 (18.18%) were female. Conclusions: The prevalence of vitamin B12 deficiency was found to be higher than other studies done in similar settings.

Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide. However, T2DM still remains underdiagnosed and undertreated resulting in poor quality of life and increased morbidity and mortality. Given this ongoing burden, researchers have attempted to locate new therapeutic targets as well as methodologies to identify the disease and its associated complications at an earlier stage. Several studies over the last few decades have identified exosomes, small extracellular vesicles that are released by cells, as pivotal contributors to the pathogenesis of T2DM and its complications. These discoveries suggest the possibility of novel detection and treatment methods. This review provides a comprehensive presentation of exosomes that hold potential as novel biomarkers and therapeutic targets. Additional focus is given to characterizing the role of exosomes in T2DM complications, including diabetic angiopathy, diabetic cardiomyopathy, diabetic nephropathy, diabetic peripheral neuropathy, diabetic retinopathy, and diabetic wound healing. This study reveals that the utilization of exosomes as diagnostic markers and therapies is a realistic possibility for both T2DM and its complications. However, the majority of the current research is limited to animal models, warranting further investigation of exosomes in clinical trials. This review represents the most extensive and up-to-date exploration of exosomes in relation to T2DM and its complications.

Introduction: Indigenous peoples in Canada face a disproportionate burden of diabetes-related foot complications (DRFC), such as foot ulcers, lower extremity amputations (LEA), and peripheral arterial disease. This scoping review aimed to provide a comprehensive understanding of DRFC among First Nations, Métis, and Inuit peoples in Canada, incorporating an equity lens. Methods: A scoping review was conducted based on Arksey and O'Malley refined by the Joanna Briggs Institute. The PROGRESS-Plus framework was utilized to extract data and incorporate an equity lens. A critical appraisal was performed, and Indigenous stakeholders were consulted for feedback. We identified the incorporation of patient-oriented/centered research (POR). Results: Of 5,323 records identified, 40 studies were included in the review. The majority of studies focused on First Nations (92%), while representation of the Inuit population was very limited populations (< 3% of studies). LEA was the most studied outcome (76%). Age, gender, ethnicity, and place of residence were the most commonly included variables. Patient-oriented/centered research was mainly included in recent studies (16%). The overall quality of the studies was average. Data synthesis showed a high burden of DRFC among Indigenous populations compared to non-Indigenous populations. Indigenous identity and rural/remote communities were associated with the worse outcomes, particularly major LEA. Discussion: This study provides a comprehensive understanding of DRFC in Indigenous peoples in Canada of published studies in database. It not only incorporates an equity lens and patient-oriented/centered research but also demonstrates that we need to change our approach. More data is needed to fully understand the burden of DRFC among Indigenous peoples, particularly in the Northern region in Canada where no data are previously available. Western research methods are insufficient to understand the unique situation of Indigenous peoples and it is essential to promote culturally safe and quality healthcare. Conclusion: Efforts have been made to manage DRFC, but continued attention and support are necessary to address this population's needs and ensure equitable prevention, access and care that embraces their ways of knowing, being and acting. Systematic review registration: Open Science Framework https://osf.io/j9pu7, identifier j9pu7. [ABSTRACT FROM AUTHOR]

Background: Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to investigate the potential of C. pepo in attenuation of diabetic neuropathy via using streptozotocin (STZ)-induced diabetes model in male wistar rats. Materials and Methods: Diabetic neuropathy was induced by administration of STZ; 65 mg/kg, i.p. and Nicotinamide (NAD; 230 mg/kg i.p.) and assessed by measuring thermal hyperalgesia, mechanical hyperalgesia and motor nerve conduction velocity (MNCV) in experimental animals. Treatment with different doses of (100, 200 and 400 mg/kg, p.o.) petroleum ether extract of C. pepo (CPE) and hydroethanolic extract of C. pepo (CHE) was started from the 60th day of STZ/NAD administration and continued upto 90th day. Results: CPE and CHE significantly attenuated the behavioural changes including hyperalgesia, allodynia and MNCV linked to diabetic neuropathy. Moreover, the oxidative stress and level of TNF-α, TGF-β and IL-1β was found to be significantly attenuated in experimental animals. Conclusion: Thus C. pepo might ameliorate the progression of diabetic neuropathy via modulation of chronic hyperglycemia and therefore and have therapeutic potential for treatment of diabetic neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Interleukin-9 (IL-9) is a cytokine that has recently been proposed to be associated with type 2 diabetes mellitus (T2DM) risk, but the role it plays in the development of pre-diabetes (PD) and diabetic neuropathy (DN) is unknown. Therefore, this study analyzed serum IL-9 levels in individuals with PD (n = 89), T2DM patients without DN (n = 66), T2DM patients with DN (n = 21), and non-diabetic controls (n = 84) using an ELISA kit. Results: Serum IL-9 levels (median and interquartile range) were significantly lower in the PD (18.9 [12.6–22.1] pg/mL; probability [p] < 0.001) and T2DM (19.4 [16.3–28.0] pg/mL; p = 0.04) groups than in the control group (20.8 [19.4–25.8] pg/mL). Patients with DN also showed lower levels of IL-9 than patients without DN, but the p value was not significant (19.4 [12.5–22.7] vs. 20.6 [17.1–28.1] pg/mL; p = 0.13). IL-9 showed better diagnostic performance in PD and T2DM with DN than in T2DM without DN (area under the curve: 0.699 and 0.702 vs. 0.567, respectively). Moreover, lower levels of IL-9 were significantly associated with PD and DN risks (odds ratio = 0.86 and 0.85, respectively). Conclusions: Serum IL-9 levels were significantly decreased in individuals with PD and patients with T2DM compared with HC. The decrease in IL-9 levels in T2DM patients was more pronounced in patients with DN than in patients without DN. Therefore, low levels of IL-9 can be considered as a potential biomarker associated with an increased risk of PD and DN. [ABSTRACT FROM AUTHOR]

Although diabetic neuropathy is a well-known cause of gastrointestinal motility disorders, it is rare that diabetic neuropathy brings about esophageal obstruction. Here, we report a case with Type 3C diabetes mellitus (DM) lasting over 15 years and repeated esophageal obstruction resulting in chicken-meat-induced esophageal obstruction and candidiasis. This case highlights the importance of management of DM to prevent the development of complications such as diabetic neuropathy and associated symptoms. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes often develop the microvascular complications of diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN), which decrease quality of life and increase mortality. Unfortunately, treatment options for DKD and DPN are limited. Lifestyle interventions, such as changes to diet, have been proposed as non‐pharmacological treatment options for preventing or improving DKD and DPN. However, there are no reported studies simultaneously evaluating the therapeutic efficacy of varying dietary interventions in a type 2 diabetes mouse model of both DKD and DPN. Therefore, we compared the efficacy of a 12‐week regimen of three dietary interventions, low carbohydrate, caloric restriction, and alternate day fasting, for preventing complications in a db/db type 2 diabetes mouse model by performing metabolic, DKD, and DPN phenotyping. All three dietary interventions promoted weight loss, ameliorated glycemic status, and improved DKD, but did not impact percent fat mass and DPN. Multiple regression analysis identified a negative correlation between fat mass and motor nerve conduction velocity. Collectively, our data indicate that these three dietary interventions improved weight and glycemic status and alleviated DKD but not DPN. Moreover, diets that decrease fat mass may be a promising non‐pharmacological approach to improve DPN in type 2 diabetes given the negative correlation between fat mass and motor nerve conduction velocity.Low carbohydrate, caloric restriction, and alternate‐day fasting dietary interventions promoted weight loss, ameliorated glycemic status, and improved diabetic kidney disease (DKD) in a db/db type 2 diabetes mouse model. In contrast, dietary interventions did not impact fat mass or diabetic peripheral neuropathy (DPN). Fat mass negatively correlated with motor nerve conduction velocity, suggesting that diets that decrease fat mass may be promising non‐pharmacological approaches to improve DPN. Image created in BioRender. [ABSTRACT FROM AUTHOR]

Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. Aspirin is an analgesic and antiapoptotic drug used in combination with morphine as an adjuvant in diabetic neuropathy. Our aim in this study was to investigate the effects of aspirin on morphine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. The antinociceptive effects of aspirin (50 mg/kg) and morphine (5 mg/kg) were evaluated by thermal pain tests. Streptozotocin (65 mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats significantly increased the antinociceptive efficacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin significantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin significantly decreased the levels of pro-apoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a significant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case highlights the biomechanical influence of toe amputation on contralateral limb force elevation, possibly through reduced ipsilateral plantar flexor torque production. These findings provide insight into toe amputation‐related compensatory gait mechanics with greater inter‐limb asymmetry, which may increase the risk of musculoskeletal comorbidities, including osteoarthritis in contralateral limb. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a micro vascular disorder that is on a rapid increase in number of diagnosed and undiagnosed cases, and it is estimated that approximately 191 million people may be suffering from this disorder by year 2030. It affects major vital organ and organ systems of the body, and is frequently accompanied with neuropathy, nephropathy, cardiovascular disorders and retinopathy. The quality of life of diabetic patients is significantly impacted by diabetic neuropathy. Aims and Objectives: To investigate the difference in peripapillary retinal nerve fibre layer (RNFL) thickness between normal population and Type-II diabetic patients without diabetic retinopathy using optical coherence tomography. Materials and Methods: Between May 2021 and May 2022, this case control research was conducted at Skims MCH Bemina SRINAGAR. Out of 400 eyes, 200 eyes belonged to healthy people and 200 eyes to Type II diabetics who did not have diabetic retinopathy. Age and gender were the same for both groups. Results: Mean age of study population was 47.05±5.47 years. Mean peripapillary RNFL thickness was 126.98±10.07 µm in Group-A (normal persons), and 120.77±5.41 µm in Group-B (Type-II diabetes). Between the two groups, there was a statistically significant difference in mean RNFL thickness as well as RNFL thicknesses in each quadrant (P=0.001). Conclusion: The diagnosis of any disease based on RNFL thinning must take into consideration the fact that diabetic patients have thin RNFL in comparison to normal persons. [ABSTRACT FROM AUTHOR]

Carpal tunnel syndrome (CTS) is seen in 5% of the population and 14%–30% in diabetics. Although electrophysiological tests are used as the gold standard method in the diagnosis, alternative methods are being studying. We aimed to investigate whether the measurement of median nerve cross-sectional area (CSA) by ultrasound is associated with the presence and severity of CTS. This prospective, cross-sectional observational study includes 128 randomly selected T2DM patients. Electrodiagnostic study was performed for all patients to diagnose CTS. Median nerve CSA were measured with ultrasound examination. The severity of the CTS was determined by Padua method. Among 128 diabetes mellitus (DM) patients, 54 (28%) had CTS and 53 (41%) had diabetic peripheral polyneuropathy. The mean duration of DM was 11.55 years. Median nerve CSAs of the patients were significantly higher in patients with CTS (CTS (−): 10.47 ± 2.67 vs CTS: (+) 12.37 ± 3.17; p < 0.001). Median nerve CSA cutoff value of >10 mm2 predicts the diagnosis of CTS. However, minimal, mild, and moderate CTS groups had similar CSA according to Padua classification (p > 0.05 for all). CSA measurement with ultrasonography can be used as an effective method in diagnosing severe CTS disease. However, median nerve CSA values should not be used to reveal the severity of CTS, in order not to miss the demonstration of minimal, mild, and moderate groups, as well as being an indicator of only the severe CTS group. [ABSTRACT FROM AUTHOR]

Background and objectives: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing diabetic neuropathy (DN)-associated pain are limited and have several side effects. The purpose of the study was to evaluate the antihyperalgesic action of different sildenafil (phosphodiesterase-5 inhibitor) and metformin (antihyperglycemic agent) combinations in alloxan-induced DN. Methods: The study included 100 diabetic mice and 20 non-diabetic mice that were subjected to hot and cold stimulus tests. Furthermore, we determined the influence of this combination on TNF-α, IL-6 and nitrites levels in brain and liver tissues. Results: In both the hot-plate and tail withdrawal test, all sildenafil–metformin combinations administered in our study showed a significant increase in pain reaction latencies when compared to the diabetic control group. Furthermore, all combinations decreased blood glucose levels due to the hypoglycemic effect of metformin. Additionally, changes in nitrite levels and pro-inflammatory cytokines (TNF-α and IL-6) were observed after 14 days of treatment with different sildenafil–metformin combinations. Conclusions: The combination of these two substances increased the pain reaction latency of diabetic animals in a dose-dependent manner. Moreover, all sildenafil–metformin combinations significantly reduced the concentration of nitrites in the brain and liver, which are final products formed under the action of iNOS. [ABSTRACT FROM AUTHOR]

Background: The prevalence of microvascular complications in type 2 diabetes mellitus (T2DM) is increasing. The effect of lipid profiles on diabetic microvascular complications remains debated. This research aimed to study the correlation between lipid profiles and microvascular complications. Methods: This retrospective cross-sectional study included 1096 T2DM patients. The patients were divided into the control, diabetic retinopathy (DR), nephropathy (DKD), and peripheral neuropathy (DPN) groups based on the existence of corresponding complications. The lipid profiles were analyzed, and the effect on complications was assessed by logistic regression. Results: Compared with the control group, the diabetic microvascular complications group had a higher dyslipidemia rate. The rate of high TGs increased significantly with an increasing number of complications. High TG levels contributed to the risk of DKD, DR, and DPN [odds ratios (ORs): 2.447, 2.267, 2.252; 95% confidence interval: 1.648–3.633, 1.406–3.655, 1.472–3.445]. In the age (years) > 55, T2DM duration (years) > 10, and HbA1c (%) ≥ 7 groups, the risk of high TGs was higher for DKD (ORs: 2.193, 2.419, 2.082), DR (ORs: 2.069, 2.317, 1.993), and DPN (ORs: 1.811, 1.405, 1.427). Conclusion: High TG levels increase the risk of diabetic microvascular complications, and patients with older age, longer T2DM duration, and higher HbA1c levels are recommended to keep lipid levels more strictly. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is a loss of distal sensory function in the lower limbs that is accompanied by pain and severe morbidity. The goal of this study was to perform a screening of the MTHFR C677T (A1298C) and BDNF G196A (Val66Met) polymorphisms and determine their possible relationships using biochemical blood tests and clinical presentations of symptoms in Jordanian patients with DPN. PATIENTS AND METHODS: A cross-sectional study was conducted, and medical records were used to identify and recruit patients with DPN and collect their demographic and clinical characteristics. The total neuropathy score (TNSr) was used to assess the severity of sensory symptoms. In addition, direct sequencing was performed after Polymerase Chain Reaction (PCR) amplification to screen the two single nucleotide polymorphisms (SNPs) of interest. RESULTS: Ninety patients with DPN participated in the study. The MTHFR-SNP variant (CT) and (TT) genotypes were identified in 39 (43.3%) and 19 (21.1%) patients, respectively. On the other hand, the BDNF-SNP variant (GA) and (AA) genotypes were identified in 22 (24.4%) and 11 (12.2%) patients, respectively. The distributions of the genotype frequencies of the MTHFR-SNP and BDNF-SNP variants statistically differed between patients with DPN and the control group (p < 0.0001, p < 0.002). Moreover, patients carrying variant genotypes of the two analyzed SNPs were more likely to have unsatisfactory HbA1c levels (> 7 mg/dl, p = 0.029) and moderate to severe symptoms (TNSr score 8-24). CONCLUSIONS: The results of this study show that the MTHFR C>T-677 SNP and the BDNF G>A-196 SNP can be used as genetic risk markers for DPN. Assessing patients’ genetic-metabolic risk profiles is recommended for providing personalized treatment. [ABSTRACT FROM AUTHOR]

Data on the prevalence, clinical features and risk factors associated with paediatric diabetic neuropathy (DN) are scarce. We retrospectively analysed data from the DPV registry, including patients under 20 years of age, treated for type 1 diabetes mellitus (T1D) between 2005 and 2021. Patients with non-diabetic neuropathy were excluded. Data came from centres in Austria, Germany, Luxembourg and Switzerland. 1,121 of the 84,390 patients included had been diagnosed with DN. Univariate analysis showed patients with DN to be older and predominantly female, with a longer duration of T1D, higher insulin dosages per kg and day, lower rates of insulin pump therapy, higher postprandial glucose-, higher HbA1c-and higher cholesterol levels, and higher diastolic and systolic blood pressure values. There was also a larger proportion of smokers and higher prevalence of diabetic retinopathy. Median duration of diabetes at diagnosis of DN was 8.3 years. Multivariable analysis, adjusted for demographics revealed an increased risk for DN among female patients and those who were older, underweight (BMI-SDS), smoked cigarettes or had a longer duration of T1D or higher levels of HbA1c and postprandial blood glucose. The presence of retinopathy and higher cholesterol levels were also linked to increased risk while not-using insulin pump therapy was not. DN can develop after just a short duration of T1D. Prevention may be achieved by a lowering of HbA1c-and postprandial glucose levels through improved glycaemic control. This warrants further investigation. The slight female predominance suggests further hormonal and genetic etiological factors. [ABSTRACT FROM AUTHOR]

Introduction: To date, a multitude of neural circuits within the central nervous system have been recognized for their roles in pain modulation. Notably, the ventrolateral periaqueductal gray (vlPAG) region of the midbrain emerges as a pivotal element within the supraspinal pain modulation network. This region's significance has been thoroughly documented across diverse animal pain models. In our study, we concentrated on exploring the functions of capsaicin receptors in this specific area, particularly their involvement in mediating antinociceptive effects. Methods: In this study, male Wistar rats were utilized to examine the antinociceptive effects of capsaicin when directly administered into the ventrolateral periaqueductal gray (vlPAG) region of the midbrain. The efficacy of this intervention was evaluated using the tail-flick test, conducted five minutes after injection. The research compared the outcomes of intravlPAG capsaicin administration between healthy control rats and those with diabetes. Results: In the control groups, capsaicin induced a swift and temporary analgesic effect, but it did not produce antinociceptive effects in diabetic rats. Conclusion: Acute microinjections of capsaicin failed to elicit significant antinociceptive effects in the diabetic animal group. To derive more precise conclusions, it is advisable to also examine the long-term impacts of these compounds. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, a chronic and progressive condition, was the third most common cause of death in Mexico between January and June 2021. Its most frequent chronic complication is diabetic neuropathy, which has a major impact on the nervous system. A multidisciplinary group of experts met in Mexico City to establish a treatment algorithm considering the symptomatic and etiopathogenic aspects of diabetic neuropathy. A real-time Delphi method with two rounds of interative questions was used. The implementation of the proposed algorithm will allow a comprehensive approach to the diabetic patient with painful and non-painful neuropathy, both in terms of symptoms and etiopathogenesis. This approach provides the opportunity to improve quality of life and achieve reintegration into family and work life. The expert panel recommends thioctic acid as the first line etiopathogenic treatment for diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Background and objectives. Diabetic neuropathy is microvascular complication of diabetes mellitus that attacks the peripheral nervous system and manifested as persistent electrocution pain. Patients with diabetic neuropathy are often found in conditions of vitamin D deficiency. Vitamin D has a neuroprotective effects that plays a role in increasing axonogenesis, preventing nerve degeneration, and is an anti-inflammatory agent that can reduce diabetic neuropathy pain. Determine the effectiveness of additional therapy with Vitamin D 5.000 IU on the reduction of diabetic neuropathy pain in patients with diabetes mellitus at Bethesda Hospital, Yogyakarta. Materials and methods. This study is a Randomized Controlled Trial that has been completed. Data were taken from patients with diabetic neuropathy diagnosed by Diabetic Neuropathy Examination and Diabetic Neuropathy Symptoms at Bethesda Hospital, Yogyakarta. There were 34 subjects involved and divided into two groups: treatment group given symptomatic therapy with additional Vitamin D 5.000 IU and the control group receiving only symptomatical therapy. Furthermore, pain intensity development data using VAS at weeks 0, 4, and 8 were analyzed using non-parametric Mann Whitney test. Results. Both groups experienced a decrease in pain intensity, but the treatment group which was given symptomatic therapy with additional vitamin D 5.000 IU was significantly better as seen from the difference between the VAS rate before and after therapy (p=0.010) (p<0.05). Conclusions. Additional vitamin D 5.000 IU in diabetes mellitus patients with diabetic neuropathic pain can decrease pain intensity better compared to just receiving symptomatic therapy. [ABSTRACT FROM AUTHOR]

Background: Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus (DM) and can lead to a wide array of complications, which are concerning as these are considered a leading cause of disability due to foot ulceration, amputation, gait disturbances, and injuries secondary to falls. Nerve conduction studies (NCS) enable the diagnosis of sensory and motor neuropathy even if the dysfunction is subclinical. This study was conducted to assess the correlation between glycated hemoglobin and duration of diabetes with the parameters of NCS among patients of type 2 DM. Methodology: A cross-sectional study was conducted in a tertiary care center in South India. The study was conducted from November 2022 to February 2023. Sixty patients with type 2 DM who presented to the outpatient department with symptoms of neuropathy were included in the study. Detailed clinical history was taken and clinical examination was done. NCS was conducted in them. The parameters of NCS were correlated with HbA1c and duration of diabetes. The statistical analysis was carried out using the SPSS software version 29.0. Results: Sixty patients with type 2 DM were included in the study. The mean age of type 2 DM patients was 60.92 ± 10.9 years. The mean duration of type 2 DM (in years) was 12.8 ± 6.5. Twenty-three participants (38.3%) had solely an axonal pattern of diabetic neuropathy; whereas 20 (33.3%) participants showed a combined axonal and demyelinating pattern of diabetic neuropathy. There was a significant negative correlation between HbA1c and NCS parameters such as nerve conduction velocity, amplitude, and persistence (p < 0.001); and a significant positive correlation between HbA1c and NCS parameters such as latency and F-wave latency (p < 0.001). There was a significant correlation between parameters of NCSs and duration of DM (p < 0.001). Conclusion: Glycemic control and duration of DM have a significant impact on the nerve conduction parameters. Patients with poor glycemic control have decreased NCS parameters such as velocity, amplitude, and persistence; and increased parameters such as latency and F-wave latency. Strict glycemic control can be reinforced for better management of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

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Background & Objective: Diabetic neuropathy pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite many studies, it remains difficult to treat neuropathic pain. This study aimed to compare the efficacy of duloxetine with high tone power therapy (HTPT) in diabetic peripheral neuropathic pain. Materials & Methods: The study is a single-centre, phase III clinical trial comparing the effect of HTPT versus treatment with duloxetine in diagnosed diabetic neuropathy patients between October 2019 to December 2020. In the case group, the HTPT was used with a four-second duration for 30 minutes daily. This treatment was continued twice a week for 10 sessions. The control group received duloxetine (30 mg/m2 once a day). The treatment response was assessed based on the VAS score. Results: The results showed that in both groups, there was a significant reduction in pain severity. In HTPT group, the average pain decreased from 7.36 to 4.6 and in duloxetine group from 7.7 to 4.8. During 8 measurements after the intervention; decrease in VAS score was higher in HTPT group (5.6) than in duloxetine group (6.5) in the first and fourth times after the intervention (P-Value=0.01). Further analysis demonstrated a positive correlation between pain severity and age so that, the pain also increases with advancing age. Conclusion: The results of the present study showed that both duloxetine and high tone therapies are safe and effective methods for neuropathic pain relief. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has demonstrated potential benefits for neuropathic pains in preclinical studies. This study aimed to assess the efficacy of memantine in the management of peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM). Method: This randomized clinical trial includes 143 diabetic patients (aged between 18 and 75 years) with a confirmed diagnosis of diabetic neuropathy. Patients were randomly assigned to receive memantine 5 mg twice daily for 1 week, followed by 10 mg twice daily plus gabapentin 300 mg daily (n = 72) or just gabapentin 300 mg daily (n = 71) for 8 weeks. The DN4 questionnaire, monofilament, tuning fork, and Tip-therm tests were used to measure neuropathy at baseline and after the 8-week intervention. Results: The mean score of the DN4 questionnaire in the memantine group was significantly lower than the control group (p. value: .001). The number of patients with diabetic neuropathy remarkably decreased in the memantine group at the end of the study based on the performed tests (p. value: .001). Conclusion: Memantine functions as a beneficial agent in the management of diabetic neuropathy, which would significantly improve the quality of life in diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy, retinopathy, and nephropathy) in a cohort of Iranian patients with type 2 diabetes. Methods: For a total population of 3123 patients with type 2 diabetes, a prospective study was designed for 1215 patients with NAFLD and 1908 gender and age-matched control patients without NAFLD. The two groups were followed for a median duration of 5 years for the incidence of microvascular complications. The association between having NAFLD, the level of liver enzymes, aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4) value, and the incidence risk of diabetic retinopathy, neuropathy, and nephropathy were assessed through logistic regression analysis. Results: NAFLD was found to be associated with incidence of diabetic neuropathy and nephropathy (Odds ratio: 1.338 (95% confidence interval: 1.091-1.640) and 1.333 (1.007-1.764), respectively). Alkaline-phosphatase enzyme was found to be associated with higher risks of diabetic neuropathy and nephropathy ((Risk estimate: 1.002 (95% CI: 1.001-1.003) and 1.002 (1.001-1.004), respectively)). Moreover, gamma-glutamyl transferase was associated with a higher risk of diabetic nephropathy (1.006 (1.002-1.009). Aspartate aminotransferase and alanine aminotransferase were inversely associated with the risk of diabetic retinopathy (0.989 (0.979-0.998) and 0.990 (0.983-0.996), respectively). Furthermore, ARPI_T (1), ARPI_T (2), and ARPI_T (3) were shown to be associated with NAFLD (1.440 (1.061-1.954), 1.589 (1.163-2.171), and 2.673 (1.925, 3.710), respectively). However, FIB-4 score was not significantly associated with risk of microvascular complications. Conclusion: Despite the benign nature of NAFLD, patients with type 2 diabetes should be always assessed for NAFLD to ensure early diagnosis and entry into proper medical care. Regular screenings of microvascular complications of diabetes is also suggested for these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to evaluate the neuroprotective efficacy of trimetazidine (TMZ) in a diabetic neuropathy model of the sciatic nerve. MATERIALS AND METHODS: We performed intraperitoneal (IP) single-dose streptozotocin (STZ) injection for a diabetes mellitus neuropathy model in 24 rats; 8 rats were in the control group, and no chemical administration was performed. 24 diabetic rats were randomly divided into 3 groups: Group 1 rats (n = 8; diabetes and saline groups) were given 1 ml/kg saline treatment. Diabetes and trimetazidine (TMZ)-treated rats (n = 8) were given TMZ 10 mg/kg/day i.p. in Group 2. Group 3 rats were given TMZ 20 mg/kg/ day by i.p. for 4 weeks. At the end of the study, EMG and inclined plane testing were used, and blood samples were taken. RESULTS: Amplitudes of CMAP increased significantly in the TMZ treatment group when compared with the group that had been given saline treatment. The latency of CMAP was significantly shortened in the TMZ treatment group as compared to the saline treatment group. When compared to the saline treatment group, 10 mg/kg and 20 mg/kg TMZ treatment significantly reduced HMGB1, Pentraxin-3, TGF-beta, and MDA levels. CONCLUSIONS: We demonstrated the neuroprotective effect of TMZ on diabetic polyneuropathy in rats via modulation of soluble HMGB1. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic neuropathy and diabetic eye disease are well known complications of type 1 diabetes. We hypothesized that chronic hyperglycemia also damages the optic tract, which can be measured using routine magnetic resonance imaging. Our aim was to compare morphological differences in the optic tract between individuals with type 1 diabetes and healthy control subjects. Associations between optic tract atrophy and metabolic measures, cerebrovascular and microvascular diabetic complications were further studied among individuals with type 1 diabetes. Methods: We included 188 subjects with type 1 diabetes and 30 healthy controls, all recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent a clinical examination, biochemical work-up, and brain magnetic resonance imaging (MRI). Two different raters manually measured the optic tract. Results: The coronal area of the optic chiasm was smaller among those with type 1 diabetes compared to non-diabetic controls (median area 24.7 [21.0-28.5] vs 30.0 [26.7-33.3] mm2, p<0.001). In participants with type 1 diabetes, a smaller chiasmatic area was associated with duration of diabetes, glycated hemoglobin, and body mass index. Diabetic eye disease, kidney disease, neuropathy and the presence of cerebral microbleeds (CMBs) in brain MRI were associated with smaller chiasmatic size (p<0.05 for all). Conclusion: Individuals with type 1 diabetes had smaller optic chiasms than healthy controls, suggesting that diabetic neurodegenerative changes extend to the optic nerve tract. This hypothesis was further supported by the association of smaller chiasm with chronic hyperglycemia, duration of diabetes, diabetic microvascular complications, as well as and CMBs in individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: A systematic review was conducted to investigate the prevalence of onychomycosis in patients with diabetes. The association of onychomycosis with risk factors in patients with diabetic foot syndrome was also examined. Methods: The recommendations in the preferred reporting items for systematic reviews and meta‐analysis (PRISMA) checklist were applied, and the included studies were assessed using the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) method. Searches were conducted in October 2022 using PubMed (Medline) and Scopus for clinical studies, clinical trials, comparative studies, observational studies, and randomised clinical trials or controlled clinical trials addressing the prevalence and consequences of onychomycosis in patients with diabetes, diagnoses or treatments. Two authors performed the study selection and data extraction, and any discrepancies between the two reviewers were resolved through discussion with a third reviewer. Results: The systematic review included ten studies that met the inclusion criteria, and these studies enrolled 5664 patients with diabetes. Among these patients, 29.18% had onychomycosis that was mainly caused by Trichophyton rubrum. A significant association was found between the occurrence of onychomycosis and the presence of diabetic neuropathy (p =.012) and elevated glycosylated haemoglobin values (p =.039). There was no significant association between onychomycosis and ulceration (p =.185). Eight studies had a grade 4 level of evidence and a grade C recommendation, and one study had a grade 1b level of evidence and a grade A recommendation. Conclusion: The information described in the literature is insufficient and heterogeneous regarding the association of risk factors and ulceration in patients with diabetic foot compared with developing onychomycosis. There is also a need to implement onychomycosis diagnostic testing instead of relying only on a clinical diagnosis. Additional prospective, randomised, comparative studies are needed to increase the quality of studies in the literature. [ABSTRACT FROM AUTHOR]

Diffuse peripheral neuropathy is a well-known complication of several conditions, whereas many patients have peripheral neuropathy of unknown etiology and pathophyisology. Increased knowledge of mechanisms may provide insight into enteric neuropathy with gastrointestinal dysmotility. The aim of the present systematic review was to identify mechanisms behind diffuse idiopathic peripheral neuropathies in humans. Searches were performed in PubMed, Embase, and Web of Science. Human original and review articles, written in English, describing mechanisms behind diffuse peripheral neuropathy verified by objective examinations were intended to be studied. Articles that described animal models, well-described hereditary diseases, drug-induced neuropathy, pain syndromes, malnutrition, and local neuropathy were excluded. In total, 4712 articles were identified. After scrutinizing titles and abstracts, 633 remained and were studied in full text. After the removal of articles not fulfilling inclusion or exclusion criteria, 52 were finally included in this review. The most frequently described neuropathy was diabetic neuropathy, with a wide range of mechanisms involving mitochondrial dysfunction such as oxidative stress and inflammation. Microvascular changes in diabetes and vasculitis lead to ischemia and secondary oxidative stress with inflammation. Structural changes in neurons and glial cells are observed, with abnormalities in different neurotrophic factors. Neuropathy induced by autoantibodies or immunological mechanisms is described in infectious and systemic inflammatory diseases. Several ion channels may be involved in painful neuropathy. No study identified why some patients mainly develop large fiber neuropathy and others small fiber neuropathy. Metabolic and immunological factors and channelopathy may be considered in diffuse idiopathic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: Diabetes is the most common cause of peripheral neuropathy throughout the world and has negative impact on patient's quality of life. There is no cure and to date several drugs have been used for its symptomatic treatment, including antidepressants and antiepileptics. Neurotec is a herbal medicine (combination of wild star anise, nettle and tansy) that can be potentially effective in the treatment of this disorder. Proposed mechanisms include its effects on increasing nerve conduction velocity and repairing peripheral nerves. Methods: In a single-blind randomized clinical trial from April to September 2018 in Kermanshah of patients referred to Taleghani Hospital Clinic, 100 diabetic patients with sensory complaints, were randomly divided into two groups. The first group received 100 to 300 mg gabapentin (a well-known effective antiepileptic drug) daily and the second group received 100 mg Neurotec daily. At the beginning of the study and at the weeks of 6 and 12, patients were evaluated with DN4 questionnaire and the visual analog scale (VAS) for severity of sensory symptoms including paresthesia and numbness and the results were compared and analyzed. In each serial visit, possible drug side effects were asked from patients and recorded. Results: Neurotec reduced the feeling of coldness, pain, paresthesia and numbness VAS and DN4 scores (P of 0.01,0.05, 0.05, 0.05, 0.001, 0.05 respectively). Neurotec showed a significant advantage over gabapentin in reducing pain intensity and in other parameters the difference between the two groups was not significant. The only significant complication of Neurotec was dyspepsia that could be minimal in patients who receive the drug after a meal. Conversely in the gabapentin group, dizziness, drowsiness, and vertigo were significantly more common (P>0.05). Conclusion: Neurotec can be useful for sensory symptoms of diabetic neuropathy. Its effect on symptomatic therapy is comparable to gabapentin or even better for painful diabetic neuropathies. Its proposed mechanism in neuronal repair needs to be evaluated and can be a potential advantage over symptomatic therapies. Neurotic has no serious side effects. [ABSTRACT FROM AUTHOR]

Painful neuropathy is present in 13% to 35% of diabetic patients, and the reasons for the differential clinical manifestations of painful and painless diabetic neuropathy (DNP) in diabetic patients are unclear. This review focuses on the latest clinical advances. It is observed that gender, diabetes type, glycosylated hemoglobin, and blood lipid levels have certain predictive effects on painful DNP. Clinical attention should be paid to pain and paresthesia caused by small fiber neuropathy. Existing diagnostic Methods have limited differential effect, and active drug treatment is required after the diagnosis of painful DNP is confirmed. Further research on the pathogenesis of painful DNP is required in order to find new therapeutic target. [ABSTRACT FROM AUTHOR]