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Healthcare (Basel, Switzerland) Jun 2024Diabetic autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), especially in patients with long-term, poorly controlled diabetes. This study... (Review)
Review
BACKGROUND
Diabetic autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), especially in patients with long-term, poorly controlled diabetes. This study investigates the effects of exercise on autonomic nervous system activity in T2DM patients over time.
METHODS
A literature review using MEDLINE, Embase, Cochrane Library, Scopus, and PubMed identified studies assessed via heart rate variability. Papers were categorized into three groups: immediate effects (within 60 min), short-term effects (2-3 months), and long-term effects (over 4 months).
RESULTS
Nine articles with 161 T2DM patients were included in the meta-analysis. RMSSD changes after exercise were -4.3 ( = 0.227), 8.14 ( < 0.001), and 4.17 ( = 0.002) for the immediate, short-term, and long-term groups, respectively. LF/HF ratio changes were 0.21 ( = 0.264), -3.04 ( = 0.102), and -0.05 ( = 0.006) for the respective groups. Meta-regression indicated age, male gender, and exercise duration were associated with increased RMSSD, with coefficients of 2.36 ( = 0.001), 13.76 ( = 0.008), and 1.50 ( = 0.007), respectively. Age positively correlated with the LF/HF ratio, with a coefficient of 0.049 ( = 0.048).
CONCLUSIONS
Regular exercise (≥3 times per week) for over 2 months increases parasympathetic activity in T2DM patients, while sympathetic activity decreases significantly after 4 months. Further study is needed to validate these findings.
PubMed: 38921350
DOI: 10.3390/healthcare12121236 -
Journal of Neurology Jun 2024Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as...
Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif 'ACAAG'.
PubMed: 38916676
DOI: 10.1007/s00415-024-12519-6 -
The American Journal of Gastroenterology Jun 2024We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint...
Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction and Autoimmune markers (JAG-A): Clinical Associations and Response to Intravenous Immunoglobulin Therapy.
INTRODUCTION
We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD).
METHODS
AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder (AIDX) with at least one positive seromarker of autoimmunity or at least two positive seromarkers by themselves. Three cohorts were studied: (a) Retrospective (n = 300); (b) Prospective validation cohort (n =133); and (c) Treatment cohort (n=40), administered open-label intravenous immunoglobulin (IVIG).
RESULTS
AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had AIDX. Significantly more patients with AIM had elevations of C-reactive protein (31% versus 15%, p<0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% versus 29%; p<.001), small fiber neuropathy (20% versus 9%; p=.002).8) and HLADQ8 positivity (24% versus 13%, p=.01). JH/HSD patients were more likely to have AIM (43% versus 15%, p=.001) along with more severe autonomic and gastrointestinal symptom scores. IVIG treatment was associated with robust improvement in pain, gastrointestinal and autonomic symptoms but adverse events were experienced by 62% patients.
CONCLUSIONS
Autoimmune markers and autonomic dysfunction are common in patients with unexplained gastrointestinal symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov, NCT04859829.
PubMed: 38912927
DOI: 10.14309/ajg.0000000000002910 -
Endocrine Practice : Official Journal... Jun 2024To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of ΔHR/ΔSBP, index of cardiac baroreflex function, in...
OBJECTIVES
To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of ΔHR/ΔSBP, index of cardiac baroreflex function, in identifying neurogenic OH.
METHODS
In 208 participants with T2D, we performed three heart rate based cardiovascular reflex tests (HR-CARTs) and OH test and assessed clinical history and variables. We defined OH as a systolic blood pressure (BP) fall ≥20 and ≥30 mmHg with supine BP <140 and ≥140 mmHg, respectively, and early and confirmed CAN based on 1 and 2 abnormal HR-CARTs. In participants with OH, we measured ΔHR/ΔSBP, using data from the lying to standing and OH test, and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN).
RESULTS
OH was present in 25 participants and associated with lower HR-CARTs (P=0.01), higher HbA1c (P=0.0048), presence of CAN (P=0.0058), retinopathy (P=0.037), and peripheral vascular disease (P=0.0056), absence of hypertension (P=0.0008) and physical activity (P=0.0214), but not with interfering drugs and beta-blockers. In a multiple logistic regression, HR-CAN was the main independent determinant of OH (odds ratio: 4.74) with physical activity and hypertension (odds ratio: 0.16 and 0.23) (R2=0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (AUC: 0.816±0.087), and at the cut-off of 0.5 bpm/mmHg a sensitivity of 100% and specificity of 63.2%.
CONCLUSION
CAN is still the main determinant of OH in T2D but does not explain all its variance with contribution of comorbidities and physical inactivity. The index ΔHR/ΔSBP might represent a useful clinical tool to identify neurogenic OH.
PubMed: 38908717
DOI: 10.1016/j.eprac.2024.06.008 -
Scientific Reports Jun 2024Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction....
Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.
Topics: Animals; MicroRNAs; Astrocytes; Mice; Septins; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Male; Neuralgia; Disease Models, Animal
PubMed: 38906977
DOI: 10.1038/s41598-024-65096-z -
Endocrine Jun 2024Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this...
BACKGROUND
Previous studies have shown that increasing body mass index (BMI) was associated with decreased hypoglycemia in type 2 diabetes, but it remains uncertain whether this finding could be applied to patients with and without cardiac autonomic neuropathy (CAN).
METHODS
The study included 7789 participants with type 2 diabetes from action to control cardiovascular risk in diabetes (ACCORD) trail. CAN was defined as SDNN < 8.2 ms and RMSSD < 8.0 ms. Obesity was defined as BMI ≥ 30 kg/m. Outcomes were identified as severe hypoglycemia requiring any assistance (HAA) or requiring medical assistance (HMA). We assessed the association between obesity and severe hypoglycemia in type 2 diabetes with or without CAN using COX regression models adjusted for baseline characteristics.
RESULTS
Over a median follow-up of 4.7 years, a total of 893 participants developed HAA and 584 participants developed HMA. Compared with non-obesity, obesity was associated with lower risk of severe hypoglycemia (HAA: hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.38-0.68, P < 0.001; HMA: HR 0.57, 95% CI 0.40-0.82, P = 0.002) in CAN present group, but not in CAN absent group (HAA: HR 0.98, 95% CI 0.83-1.16, P = 0.830; HMA: HR 0.97, 95% CI 0.79-1.19, P = 0.754). Similarly, increasing BMI was associated with reduced severe hypoglycemic events in participants with CAN, but not in participants without CAN.
CONCLUSIONS
CAN modifies the association between obesity and hypoglycemia in type 2 diabetes. Type 2 diabetic individuals with CAN who are under weight control should pay attention to hypoglycemic events.
TRIAL REGISTRY
http://www.
CLINICALTRIALS
gov . Unique identifier: NCT00000620.
PubMed: 38904908
DOI: 10.1007/s12020-024-03728-0 -
Immunological Medicine Jun 2024Postural orthostatic tachycardia syndrome (POTS) is characterized by exaggerated orthostatic tachycardia in the absence of orthostatic hypotension. The pathophysiology... (Review)
Review
Postural orthostatic tachycardia syndrome (POTS) is characterized by exaggerated orthostatic tachycardia in the absence of orthostatic hypotension. The pathophysiology of POTS may involve hypovolemia, autonomic neuropathy, a hyperadrenergic state, and cardiovascular deconditioning, any of which can co-occur in the same patient. Furthermore, there is growing evidence of the role of autoimmunity in a subset of POTS cases. In recent years, investigators have described an increased rate of autoimmune comorbidities as evidenced by the finding of several types of neural receptor autoantibody and non-specific autoimmune marker in patients with POTS. In particular, the association of the disease with several types of anti-G protein-coupled receptor (GPCR) antibodies and POTS has frequently been noted. A previous study reported that autoantibodies to muscarinic AChRs may play an important role in POTS with persistent, gastrointestinal symptoms. To date, POTS is recognized as one of the sequelae of coronavirus disease 2019 (COVID-19) and its frequency and pathogenesis are still largely unknown. Multiple autoantibody types occur in COVID-related, autonomic disorders, suggesting the presence of autoimmune pathology in these disorders. Herein, we review the association of anti-GPCR autoantibodies with disorders of the autonomic nervous system, in particular POTS, and provide a new perspective for understanding POTS-related autoimmunity.
PubMed: 38900132
DOI: 10.1080/25785826.2024.2370079 -
Neurogastroenterology and Motility Jun 2024Enteric neuropathies are characterized by abnormalities of gut innervation, which includes the enteric nervous system, inducing severe gut dysmotility among other... (Review)
Review
Enteric neuropathies are characterized by abnormalities of gut innervation, which includes the enteric nervous system, inducing severe gut dysmotility among other dysfunctions. Most of the gastrointestinal tract is innervated by the vagus nerve, the efferent branches of which have close interconnections with the enteric nervous system and whose afferents are distributed throughout the different layers of the digestive wall. The vagus nerve is a key element of the autonomic nervous system, involved in the stress response, at the interface of the microbiota-gut-brain axis, has anti-inflammatory and prokinetic properties, modulates intestinal permeability, and has a significant capacity of plasticity and regeneration. Targeting these properties of the vagus nerve, with vagus nerve stimulation (or non-stimulation/ pharmacological methods), could be of interest in the therapeutic management of enteric neuropathies.
PubMed: 38873822
DOI: 10.1111/nmo.14842 -
Reviews in the Neurosciences Jun 2024Small fiber neuropathy (SFN) is a peripheral nerve condition affecting thin myelinated Aδ and unmyelinated C-fibers, characterized by severe neuropathic pain and other... (Review)
Review
Small fiber neuropathy (SFN) is a peripheral nerve condition affecting thin myelinated Aδ and unmyelinated C-fibers, characterized by severe neuropathic pain and other sensory and autonomic symptoms. A variety of medical disorders can cause SFN; however, more than 50% of cases are idiopathic (iSFN). Some investigations suggest an autoimmune etiology, backed by evidence of the efficacy of IVIG and plasma exchange. Several studies suggest that autoantibodies directed against nervous system antigens may play a role in the development of neuropathic pain. For instance, patients with CASPR2 and LGI1 antibodies often complain of pain, and and studies support their pathogenicity. Other antibodies have been associated with SFN, including those against TS-HDS, FGFR3, and Plexin-D1, and new potential targets have been proposed. Finally, a few studies reported the onset of SFN after COVID-19 infection and vaccination, investigating the presence of potential antibody targets. Despite these overall findings, the pathogenic role has been demonstrated only for some autoantibodies, and the association with specific clinical phenotypes or response to immunotherapy remains to be clarified. The purpose of this review is to summarise known autoantibody targets involved in neuropathic pain, putative attractive autoantibody targets in iSFN patients, their potential as biomarkers of response to immunotherapy and their role in the development of iSFN.
PubMed: 38865989
DOI: 10.1515/revneuro-2024-0027 -
Endocrine Jun 2024To analysis the change of electrogastrogram (EGG) in patients with type 2 diabetes mellitus (T2DM), and evaluate the prevalence of abnormal gastric electrical rhythm...
AIM
To analysis the change of electrogastrogram (EGG) in patients with type 2 diabetes mellitus (T2DM), and evaluate the prevalence of abnormal gastric electrical rhythm (AGER) and its relative influencing factors.
METHODS
A total of 65 patients with T2DM hospitalized at the Second Affiliated Hospital of Soochow University from Dec. 2020 to Dec. 2021 were included in the cross-sectional study. General information, clinical data, and medical history data of all study subjects, including name, gender, body mass index (BMI), duration of diabetes, anti-diabetic therapies, high blood pressure (HBP) history, smoking history, and medication history, were completely collected. The results of laboratory tests, including biochemical parameters, glycosylated hemoglobin (HbA1c), fasting C-peptide, 2 h postprandial C-peptide, 24 h urine total protein (24 hUTP), urine microalbumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were recorded. EGG, Gastroparesis Cardinal Symptom Index (GCSI), gastric emptying ultrasound, fundus examination, carotid artery ultrasonography, cardiac autonomic function test, heart rate variability (HRV) were all examined and recorded as well. According to the results of EGG, the subjects were divided into normal gastric electrical rhythm (NGER) group and abnormal gastric electrical rhythm (AGER) group.
RESULTS
(1) Fasting blood glucose (FBG), HbA1c, the presence of diabetic peripheral neuropathy (DPN) and diabetic cardiac autonomic neuropathy (DCAN) were significantly higher in the AGER group (p < 0.05). Low frequency (LF) and high frequency (HF), the indicators of HRV, were significantly lower in the AGER group (p < 0.05). In addition, the prevalence of feeling excessively full after meals, loss of appetite, and stomach or belly visibly larger after meals of gastrointestinal symptoms of gastroparesis were significantly higher in the AGER group (p < 0.05). Multiple logistic regression analysis showed that FBG and the prevalence of DCAN were the independent risk factors.
CONCLUSION
AGER was associated with high FBG and the presence of DCAN. EGG examination is recommended for patients with gastrointestinal symptoms and clues of DCAN.
PubMed: 38861116
DOI: 10.1007/s12020-024-03908-y