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Current Pain and Headache Reports Jun 2024Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting... (Review)
Review
PURPOSE OF REVIEW
Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting from prolonged exposure to high blood glucose levels. Diabetic neuropathy may cause a range of symptoms, including pain, numbness, muscle weakness, autonomic dysfunction, and foot ulcers, potentially causing significant impairment to the quality of life for those affected. This review article aims to provide a comprehensive overview of the pathophysiology of diabetic neuropathy. The etiology of diabetic neuropathy will be discussed, including risk factors, predisposing conditions, and an overview of the complex interplay between hyperglycemia, metabolic dysregulation, and nerve damage. Additionally, we will explore the molecular mechanisms and pathways of diabetic neuropathy, including the impact of hyperglycemia on nerve function, abnormalities in glucose metabolism, the role of advanced glycation end products (AGEs), and inflammatory and immune-mediated processes. We will provide an overview of the various nerve fibers affected by diabetic neuropathy and explore the common symptoms and complications associated with diabetic neuropathy in the pain medicine field.
RECENT FINDINGS
This review highlights advances in understanding the pathophysiology of diabetic neuropathy as well as reviews potential novel therapeutic strategies and promising areas for future research. In conclusion, this review article aims to shed light on the pathophysiology of diabetic neuropathy, its far-reaching consequences, and the evolving strategies for prevention and management. In understanding the mechanisms of diabetic neuropathy and the ongoing research in this area, healthcare professionals can better serve patients with diabetes, ultimately improving well-being and reducing complications.
Topics: Humans; Diabetic Neuropathies; Risk Factors; Hyperglycemia
PubMed: 38558164
DOI: 10.1007/s11916-024-01243-5 -
Central Nervous System Agents in... Mar 2024One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy...
One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.
PubMed: 38551039
DOI: 10.2174/0118715249278438240325072758 -
Frontiers in Endocrinology 2024The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to...
AIM
The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A ().
METHODS
Eight SNPs in were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated.
RESULTS
The group of individuals with a renal function decline ≥ 5 mL min 1.73 m year presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; = 0.0046). No other significant associations were found.
CONCLUSIONS
This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.
Topics: Humans; Diabetes Mellitus, Type 1; Antioxidants; Melatonin; Receptors, Melatonin; Cross-Sectional Studies; Longitudinal Studies; Kidney
PubMed: 38549765
DOI: 10.3389/fendo.2024.1331012 -
Diabetologia Jun 2024Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation... (Randomized Controlled Trial)
Randomized Controlled Trial
Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial.
AIMS/HYPOTHESIS
Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study.
METHODS
This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function.
RESULTS
Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated.
CONCLUSIONS/INTERPRETATION
Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).
Topics: Humans; Female; Male; Middle Aged; Double-Blind Method; Vagus Nerve Stimulation; Adult; Aged; Transcutaneous Electric Nerve Stimulation; Diabetic Neuropathies; Gastrointestinal Diseases; Diabetes Mellitus, Type 2; Aged, 80 and over; Diabetes Mellitus, Type 1; Treatment Outcome; Young Adult
PubMed: 38546822
DOI: 10.1007/s00125-024-06129-0 -
Autonomic Neuroscience : Basic &... Jun 2024To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS)...
Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study.
PURPOSE
To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state.
METHODS
A cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests.
RESULTS
In CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process.
CONCLUSION
Our data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.
Topics: Humans; Postural Orthostatic Tachycardia Syndrome; Female; Male; Adolescent; Small Fiber Neuropathy; Child; Young Adult; Retrospective Studies; Orthostatic Intolerance; Skin; Adult
PubMed: 38537312
DOI: 10.1016/j.autneu.2024.103163 -
American Journal of Physiology. Heart... May 2024Peripheral artery disease (PAD) is a common vascular disease that primarily affects the lower limbs and is defined by the constriction or blockage of peripheral arteries... (Review)
Review
Peripheral artery disease (PAD) is a common vascular disease that primarily affects the lower limbs and is defined by the constriction or blockage of peripheral arteries and may involve microvascular dysfunction and tissue injury. Patients with diabetes have more prominent disease of microcirculation and develop peripheral neuropathy, autonomic dysfunction, and medial vascular calcification. Early and accurate diagnosis of PAD and disease characterization are essential for personalized management and therapy planning. Magnetic resonance imaging (MRI) provides excellent soft tissue contrast and multiplanar imaging capabilities and is useful as a noninvasive imaging tool in the comprehensive physiological assessment of PAD. This review provides an overview of the current state of the art of MRI in the evaluation and characterization of PAD, including an analysis of the many applicable MR imaging techniques, describing the advantages and disadvantages of each approach. We also present recent developments, future clinical applications, and future MRI directions in assessing PAD. The development of new MR imaging technologies and applications in preclinical models with translation to clinical research holds considerable potential for improving the understanding of the pathophysiology of PAD and clinical applications for improving diagnostic precision, risk stratification, and treatment outcomes in patients with PAD.
Topics: Humans; Peripheral Arterial Disease; Magnetic Resonance Imaging; Animals; Predictive Value of Tests; Prognosis
PubMed: 38517227
DOI: 10.1152/ajpheart.00533.2023 -
Rinsho Shinkeigaku = Clinical Neurology Apr 2024A 52-year-old man had developed hearing loss since childhood, as well as recurrent foot ulcers and osteomyelitis since his forties. He presented with gait disturbance...
A 52-year-old man had developed hearing loss since childhood, as well as recurrent foot ulcers and osteomyelitis since his forties. He presented with gait disturbance and dysarthria that had worsened over four years and a month, respectively. Neurological exams revealed cognitive impairment, proximal weakness of the lower extremities, generalized hyperrflexia, ataxia, sensory disturbances predominant in deep sensation, urinary retention, and gait instability. On nerve conduction study, no sensory nerve action potentials were evoked in the upper and lower limbs. Since his grandmother suffered from similar symptoms, we investigated genetic analysis, which revealed a missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene. He was subsequently diagnosed with hereditary sensory and autonomic neuropathy 1E (HSAN1E). It is important to recognize that increased deep tendon reflex can be observed in HSAN1E.
Topics: Humans; Male; Middle Aged; Hereditary Sensory and Autonomic Neuropathies; Mutation, Missense
PubMed: 38508732
DOI: 10.5692/clinicalneurol.cn-001938 -
International Journal of Applied &... 2024Diagnosing diabetic neuropathy is a challenge at times as it is asymptomatic. Diagnosing diabetic neuropathy involves the use of quantitative sensory testing, nerve...
INTRODUCTION
Diagnosing diabetic neuropathy is a challenge at times as it is asymptomatic. Diagnosing diabetic neuropathy involves the use of quantitative sensory testing, nerve conduction study, and autonomic testing. Tempearture threshold testing (TTT) can aid in diagnosing small fiber neuropathy at early stages. This study aimed to assess the small fiber neuropathy using TTT in diabetes mellitus (DM) and correlate with age, duration of diabetes, and lipid profile.
MATERIALS AND METHODS
The study was commenced after obtaining ethics approval from the institute ethics committee. The study participants included 100 patients with type 2 DM of both genders between the ages of 40 and 65 years. The glycemic status and lipid profile were noted along with physical examination. Neuropathy assessment was done using Michigan Neuropathy Screening Instrument (MNSI) and TTT.
RESULTS
The prevalence of small fiber neuropathy based on TTT was 63%. The lipid profile was similar in both the groups. The MNSI B scale had significantly higher scores in the neuropathy group. In the neuropathy group, the thresholds for hot were significantly greater in all four limbs and cold were significantly lower. Age and years of DM were positively correlated with the neuropathy. Hot threshold in the lower limb had shown a strong positive correlation.
CONCLUSION
The age and duration of diabetes are independent risk factors for diabetic peripheral neuropathy. Small fiber neuropathy is a prequel to the motor neuropathy. Hot threshold testing in the lower limb is more sensitive than cold threshold testing for diagnosing small fiber neuropathy.
PubMed: 38504834
DOI: 10.4103/ijabmr.ijabmr_397_23 -
Health Expectations : An International... Apr 2024Small fibre neuropathy (SFN) is a peripheral neuropathy, leading to neuropathic pain and autonomic dysfunction. An evidence-based standardized patient diagnostic SFN...
Development, validation and feasibility of a Patient Satisfaction Questionnaire for evaluating the quality performance of a diagnostic small fibre neuropathy service: A qualitative study.
INTRODUCTION AND AIM
Small fibre neuropathy (SFN) is a peripheral neuropathy, leading to neuropathic pain and autonomic dysfunction. An evidence-based standardized patient diagnostic SFN service has been implemented in the Netherlands for improving patient-centred SFN care. However, the quality of care of this diagnostic SFN service has never been assessed from a patient perspective. The aim of this study was to develop and validate an SFN-Patient Satisfaction Questionnaire (SFN-PSQ) to measure the quality performance of a standardized diagnostic SFN service.
METHODS
A descriptive qualitative study to create the SFN-PSQ was performed using the (COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. For item generation and content development, domains and/or items from validated PSQs were selected. The content development and content validity were performed using a Delphi method with SFN expert caregivers with different backgrounds. By using the three-step-test method in individual cognitive interviews, the content validity by patients was finalized.
RESULTS
In one online Delphi panel round, the content of the first concept of the SFN-PSQ was validated, which resulted in the second concept of the SFN-PSQ. From July 2019 till March 2020, nine patients consented to participate in the individual cognitive interviews. The most significant changes of the new questionnaire were adding domains and items concerning the waiting list, the diagnostic services and consultation by the hospital psychiatrist. Also, a differentiation was made for both an inpatient and outpatient diagnostic SFN service. Furthermore, the clarity and intelligibility of the domains/items were improved, resulting in an increased comprehension of the SFN-PSQ. Ultimately, the new developed SFN-PSQ consisted of 10 domains and 51 items, suitable for measuring patient satisfaction of the neurological analysis in patients with SFN.
CONCLUSION
Through item generation, expert opinions and interviews with patients, the SFN-PSQ was developed and validated, and feasibility was confirmed. The structure of the questionnaire, based on the logistic and diagnostic SFN pathway, could be used as a model in other hospitals to improve the quality, continuity and access of SFN care and other chronic diseases taking into account potential cross-cultural differences.
PATIENT OR PUBLIC CONTRIBUTION
Caregivers were involved in the item generation and content development of the questionnaire. Patients were directly involved in testing the content validity and feasibility of the SFN-PSQ.
CLINICAL TRIAL REGISTRATION
Not applicable.
Topics: Humans; Patient Satisfaction; Small Fiber Neuropathy; Feasibility Studies; Surveys and Questionnaires; Qualitative Research; Reproducibility of Results
PubMed: 38504460
DOI: 10.1111/hex.14011 -
Journal of Pediatric Gastroenterology... Mar 2024Small fiber neuropathy (SFN) affects the fibers involved in cutaneous and visceral pain and temperature sensation and are a crucial part of the autonomic nervous system....
OBJECTIVES
Small fiber neuropathy (SFN) affects the fibers involved in cutaneous and visceral pain and temperature sensation and are a crucial part of the autonomic nervous system. Autonomic dysfunction secondary to SFN and autoimmune receptor antibodies is being increasingly recognized, and gastrointestinal (GI) manifestations include constipation, early satiety, nausea, vomiting, and diarrhea. Enteric nervous system involvement may be a possible explanation of abnormal GI motility patterns seen in these patients.
METHODS
Children suspected to have SFN based on symptoms underwent skin biopsy at the Child Neurology clinic at Arnold Palmer Hospital for Children, which was processed at Therapath™ Neuropathology. SFN was diagnosed using epidermal nerve fiber density values that were below 5th percentile from the left distal leg (calf) as reported per Therapath™ laboratory.
RESULTS
Twenty-six patients were diagnosed with SFN. Retrospective chart review was performed, including demographic data, clinical characteristics, and evaluation. A majority of patients were white adolescent females. Autonomic dysfunction, including orthostasis and temperature dysregulation were seen in 61.5% of patients (p = 0.124). Somatosensory symptoms, including pain or numbness were seen in 85% of patients (p < 0.001). GI symptoms were present in 85% of patients (p < 0.001) with constipation being the most common symptom seen in 50% of patients. This correlated with the motility testing results.
CONCLUSIONS
Pediatric patients with SFN commonly have GI symptoms, which may be the main presenting symptom. It is important to recognize and look for symptoms of small fiber neuropathy in children with refractory GI symptoms that may explain multisystemic complaints often seen in these patients.
Topics: Female; Adolescent; Humans; Child; Small Fiber Neuropathy; Retrospective Studies; Nerve Fibers; Skin; Gastrointestinal Diseases; Biopsy; Constipation
PubMed: 38504414
DOI: 10.1002/jpn3.12099