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Biomedicine & Pharmacotherapy =... Jun 2022Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy,... (Review)
Review
Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy, diabetic cardiomyopathy and diabetic retinopathy. Diabetic neuropathy is the existence of signs and indications of peripheral nerve damage in patients with diabetes after other causes have been governed out. Diabetic neuropathy is a painful and severe complication of diabetes that affects roughly 20% of people. The development of diabetic neuropathy is regulated by blood arteries that nourish the peripheral nerves and metabolic problems such as increased stimulation of polyol pathway, loss of myo-inositol and enhanced non-enzymatic glycation. It's divided into four types based on where neurons are most affected: autonomic, peripheral, proximal, and focal, with each kind presenting different symptoms like numbing, gastrointestinal disorders, and heart concerns. Pharmacotherapy for neuropathic pain is complex and for many patients, effective treatment is lacking; as a result, scientific proof recommendations are crucial. As a result, the current demand is to give the most vital medications or combinations of drugs that work directly on the nerves to help diabetic neuropathy patients feel less pain without causing any adverse effects. In diabetic neuropathy research, animal models are ubiquitous, with rats and mice being the most typically chosen for various reasons. This review covers the epidemiology, clinical features, pathology, clinical symptom, mechanism of diabetic neuropathy development, diagnosis, screening models of animals, diabetic neuropathy pharmacotherapy.
Topics: Animals; Autonomic Nervous System; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Mice; Neuralgia; Rats; Treatment Outcome
PubMed: 35658222
DOI: 10.1016/j.biopha.2022.113025 -
Medicina (Kaunas, Lithuania) Apr 2023: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without... (Review)
Review
: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). : A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. : Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. : In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.
Topics: Humans; Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Hyperemia; Randomized Controlled Trials as Topic; Non-Randomized Controlled Trials as Topic
PubMed: 37109728
DOI: 10.3390/medicina59040770 -
European Journal of Heart Failure Apr 2022Community-based data on the association between cardiac autonomic neuropathy (CAN) and incident heart failure (HF) in type 2 diabetes are limited. We evaluated the...
AIMS
Community-based data on the association between cardiac autonomic neuropathy (CAN) and incident heart failure (HF) in type 2 diabetes are limited. We evaluated the association of CAN with incident HF in adults with type 2 diabetes.
METHODS AND RESULTS
This analysis included participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without HF at baseline. CAN was assessed by electrocardiogram-based measures of heart rate variability (HRV) and QT interval index (QTI). HRV was measured using standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). CAN was defined using composite measures of the lowest quartile of SDNN and highest quartiles of QTI and heart rate. Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) for HF in relation to various CAN measures. A total of 7160 participants (mean age 62.3 [standard deviation 6.4] years, 40.8% women, 61.9% white) were included. Over a median follow-up of 4.9 years (interquartile range 4.0-5.7), 222 participants developed incident HF. After multivariable adjustment for relevant confounders, lower HRV as assessed by SDNN was associated with a higher risk of HF (aHR for the lowest vs highest quartile of SDNN: 1.70, 95% confidence interval [CI] 1.14-2.54). Participants with CAN (defined as lowest quartile of SDNN and highest quartiles of QTI and heart rate) had a 2.7-fold greater risk of HF (aHR 2.65, 95% CI 1.57-4.48).
CONCLUSIONS
In a large cohort of adults with type 2 diabetes, CAN was independently associated with higher risk of incident HF.
Topics: Adult; Autonomic Nervous System; Diabetes Mellitus, Type 2; Female; Heart; Heart Failure; Heart Rate; Humans; Male; Middle Aged
PubMed: 35064959
DOI: 10.1002/ejhf.2432 -
Arquivos Brasileiros de Cardiologia Apr 2008Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed.... (Review)
Review
Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed. In this review, we discuss the major risk factors for the development and progression of CAN in patients with DM, the natural history of autonomic neuropathy and its impact on cardiovascular disease in DM, as well as the tests for the early diagnosis and staging of CAN in the clinical practice. The bibliographic research was based on two databases: Medline and Tripdatabase, with the following descriptors: diabetic cardiovascular autonomic neuropathy and cardiovascular autonomic neuropathy and diabetes. We selected English and German articles, written between 1998 and 2007. In its initial stages (early and intermediate), CAN may be diagnosed and reversed. However, in advanced cases (severe stage), the only treatment that remains is a symptomatic one. CAN is associated with higher cardiovascular morbidity and mortality rates and poor quality of life in diabetic individuals.
Topics: Autonomic Nervous System Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diagnostic Techniques, Neurological; Early Diagnosis; Female; Humans; Risk Factors; Severity of Illness Index
PubMed: 18516377
DOI: 10.1590/s0066-782x2008000400014 -
International Journal of Molecular... Nov 2020Cardiac autonomic neuropathy (CAN) is one of the earliest complications of type 2 diabetes (T2D), presenting a silent cause of cardiovascular morbidity and mortality.... (Review)
Review
Cardiac autonomic neuropathy (CAN) is one of the earliest complications of type 2 diabetes (T2D), presenting a silent cause of cardiovascular morbidity and mortality. Recent research relates the pathogenesis of cardiovascular disease in T2D to an ensuing chronic, low-grade proinflammatory and pro-oxidative environment, being the hallmark of the metabolic syndrome. Metabolic inflammation emerges as adipose tissue inflammatory changes extending systemically, on the advent of hyperglycemia, to reach central regions of the brain. In light of changes in glucose and insulin homeostasis, dysbiosis or alteration of the gut microbiome (GM) emerges, further contributing to inflammatory processes through increased gut and blood-brain barrier permeability. Interestingly, studies reveal that the determinants of oxidative stress and inflammation progression exist at the crossroad of CAN manifestations, dictating their evolution along the natural course of T2D development. Indeed, sympathetic and parasympathetic deterioration was shown to correlate with markers of adipose, vascular, and systemic inflammation. Additionally, evidence points out that dysbiosis could promote a sympatho-excitatory state through differentially affecting the secretion of hormones and neuromodulators, such as norepinephrine, serotonin, and γ-aminobutyric acid, and acting along the renin-angiotensin-aldosterone axis. Emerging neuronal inflammation and concomitant autophagic defects in brainstem nuclei were described as possible underlying mechanisms of CAN in experimental models of metabolic syndrome and T2D. Drugs with anti-inflammatory characteristics provide potential avenues for targeting pathways involved in CAN initiation and progression. The aim of this review is to delineate the etiology of CAN in the context of a metabolic disorder characterized by elevated oxidative and inflammatory load.
Topics: Animals; Autonomic Nervous System; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus, Type 2; Heart Rate; Humans; Inflammation; Metabolic Diseases
PubMed: 33260799
DOI: 10.3390/ijms21239005 -
BMC Neurology Aug 2016Recent studies have reported that peripheral neuropathy (PN) is common in patients with Parkinson's disease (PD) and raised the possibility that levodopa neurotoxicity...
BACKGROUND
Recent studies have reported that peripheral neuropathy (PN) is common in patients with Parkinson's disease (PD) and raised the possibility that levodopa neurotoxicity is the main culprit.
METHODS
We evaluated the presence of large & small (autonomic) fiber PN in 54 consecutive patients with PD or parkinsonism in a tertiary outpatient clinic from Brazil. Initial PN screening consisted of history/neurological exam and skin wrinkling test (SWT). In addition, we also performed Nerve conduction studies/Electromyography (NCS/EMG) in all patients with PN signs/symptoms and/or abnormal SWT.
RESULTS
Thirty eight patients with PD (10 women, mean age: 63 ± 2.1 years, P < 0.05 versus parkinsonism, mean disease duration: 8 ± 0.8 years) and 16 patients with other forms of parkinsonism [7 women, mean age: 50.1 ± 3.9 years, mean disease duration: 6.9 ± 1.1 years] completed clinical neuromuscular evaluation. SWT was performed in 48 patients (33 PD, 15 parkinsonism). In the PD group, SWT was abnormal in 57.6% of the tested patients (comprising 50% of all PD patients). In the parkinsonism group, SWT was abnormal in 37.5% (comprising 35.3% of all parkinsonism patients). NCS/EMG was performed in 39 patients (26 PD and 13 parkinsonism). Twelve out of the 26 PD (34.2% of all PD) and 4 out of the 13 parkinsonism (23.5% of all parkinsonism) had abnormal NCS/EMG results. Neuropathy prevalence was similar in PD and parkinsonism groups as detected either by NCS/EMG or SWT.
CONCLUSIONS
Large fiber and small (autonomic) fiber PN are common in patients with PD and parkinsonism. The etiology for the neuropathy was likely to be multifactorial and may be secondary to PD itself.
Topics: Age Factors; Aged; Antiparkinson Agents; Autonomic Nervous System Diseases; Autonomic Pathways; Diabetes Complications; Electromyography; Female; Humans; Levodopa; Male; Middle Aged; Neural Conduction; Neuromuscular Junction; Parkinson Disease; Parkinsonian Disorders; Peripheral Nervous System Diseases; Skin
PubMed: 27530902
DOI: 10.1186/s12883-016-0667-3 -
Neurological Sciences : Official... Nov 2022Here , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology.
PURPOSE
Here , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology.
METHODS
Step 1. Patients with prior COVID-19 infection were screened by COMPASS-31 and mTORONTO to create the target population for further evaluation. Step 2. Patients with high scores were invited for a detailed history of their complaints and electrophysiological analysis, which included nerve conduction studies, cutaneous silent period (CSP), and sympathetic skin response (SSR). We also constituted a control group composed of healthy subjects of similar age and sex for electrophysiological analysis.
RESULTS
There were 106 patients, who matched the study criteria. Among them, thirty-eight patients (%35.8) had neuropathic or autonomic complaints or both. Fatigue and headache were significantly more frequent in patients with autonomic and neuropathic complaints. Detailed examination and electrophysiological evaluation were performed in 14 of 38 patients. Neuropathic complaints were patchy and proximally located in the majority. The entire CSP suppression index was higher in the patients (p = 0.002). There was no difference in palmar and plantar SSR between patients and healthy subjects. mTORONTO scores were negatively correlated with palmar and plantar SSR amplitudes, and the correlation was moderate.
CONCLUSION
Neuropathic or autonomic complaints were seen in more than one-third of patients with long-COVID. Neuropathic complaints were generally patchy, proximally predominant, asymmetric, or diffuse. The CSP suppression index was abnormal whereas SSRs were normal.
Topics: Humans; COVID-19; Autonomic Nervous System; Galvanic Skin Response; Diabetic Neuropathies; Skin; Post-Acute COVID-19 Syndrome
PubMed: 35994135
DOI: 10.1007/s10072-022-06350-y -
Frontiers in Endocrinology 2021The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes...
INTRODUCTION
The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care.
PATIENTS AND METHODS
Twenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer, Neuropad-test, Tiptherm, Monofilament, and Rydel-Seiffer tuning fork tests.
RESULTS
T1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer, Neuropad-test, and Monofilament were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 7.9 ± 0.3; left: 7.5 ± 0.9 7.9 ± 0.3, p < 0.05). The Tiptherm-test also identified a significant impairment in T1DM patients (11 sensing failures 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 0, p < 0.01).
CONCLUSION
In this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.
Topics: Adult; Age Factors; Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Hungary; Male; Time Factors; Transition to Adult Care; Young Adult
PubMed: 34512550
DOI: 10.3389/fendo.2021.719953 -
European Stroke Journal Mar 2023There is a dearth of data on the association between cardiac autonomic neuropathy (CAN) with incident stroke among individuals with diabetes mellitus. We evaluated this...
INTRODUCTION
There is a dearth of data on the association between cardiac autonomic neuropathy (CAN) with incident stroke among individuals with diabetes mellitus. We evaluated this association in a large sample of adults with type 2 diabetes.
PATIENTS AND METHODS
Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without atherosclerotic cardiovascular disease at baseline were included. CAN was assessed at baseline by heart rate variability (HRV) indices and QT index (QTI) calculated from 10-s resting electrocardiograms. HRV was assessed using standard deviation of all normal-to-normal R-Rs intervals (SDNN) and root mean square of successive differences between normal-to-normal R-R intervals (rMSSD). CAN was defined based on several composite measures of SDNN, QTI, resting heart rate and peripheral neuropathy. We used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for incident stroke in relation to CAN.
RESULTS
A total of 3493 participants (mean age 62.2 years, 44.5% women, 62.9% White) were included. Over a median follow-up of 5.0 years, 50 stroke cases occurred (incidence rate 3.0/1000 person-years [95% CI 2.2-3.9]). After adjusting for confounders, low HRV was associated with a higher risk of stroke (HR of 2.20 [95% CI 1.23-3.93] and 1.88 [95% CI 1.04-3.41] for low SDNN and rMSSD, respectively). Participants with CAN (defined as lowest quartile of SDNN and highest quartiles of QTI and heart rate) had a 5.7-fold greater risk of stroke (HR 5.70, 95% CI 2.49-13.08).
DISCUSSION AND CONCLUSION
CAN was independently associated with an increased risk of incident stroke in a large cohort of adults with type 2 diabetes.
Topics: Humans; Adult; Female; Middle Aged; Male; Diabetes Mellitus, Type 2; Heart; Autonomic Nervous System; Heart Diseases; Stroke; Primary Dysautonomias
PubMed: 37021204
DOI: 10.1177/23969873221127108 -
Experimental Diabetes Research 2011The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have... (Review)
Review
The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have diabetes, and its prevalence is steadily increasing. The decrease in cardiac mortality in people with diabetes is lagging behind that of the general population. Cardiovascular disease is a broad term which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves, and cardiac rhythm. The ECG offers a quick, noninvasive clinical and research screen for the early detection of cardiovascular disease in diabetes. In this paper, the clinical and research value of the ECG is readdressed in diabetes and in the presence of cardiac autonomic neuropathy.
Topics: Animals; Autonomic Nervous System Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Electrocardiography; Heart; Humans; Vertigo
PubMed: 21747831
DOI: 10.1155/2011/687624