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PloS One 2018Cardiac autonomic neuropathy in type 2 dibetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. Heart rate variability (HRV) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac autonomic neuropathy in type 2 dibetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. Heart rate variability (HRV) is the gold standard to measure cardiac autonomic neuropathy. We aimed to conduct a systematic review and meta-analysis to evaluate the impact of T2DM on HRV parameters.
METHODS
The PubMed, Cochrane Library, Embase and Science Direct databases were searched on 1st October 2017 using the keywords "diabetes" AND ("heart rate variability" OR "HRV"). Included articles had to report HRV parameters in T2DM patients and healthy controls measured during 24 hours with a Holter-electrocardiogram. Measurements of HRV retieved were: RR-intervals (or Normal to Normal intervals-NN), standard deviation of RR intervals (SDNN), percetange of adjacent NN intervals differing by more than 50 milliseconds (pNN50), square root of the mean squared difference of successive RR intervals (RMSSD), total power, Low Frequency (LF), High Frequency (HF) and LF/HF ratio, as per Task Force recommendations.
RESULTS
We included twenty-five case-control studies with 2,932 patients: 1,356 with T2DM and 1,576 healthy controls. T2DM patients had significantly (P<0.01) lower RR-intervals (effect size = -0.61; 95%CI -1.21 to -0.01), lower SDNN (-0.65; -0.83 to -0.47), lower RMSSD (-0.92; -1.37 to -0.47), lower pNN50 (-0.46; -0.84 to -0.09), lower total power (-1.52; -2.13 to -0.91), lower LF (-1.08; -1.46 to -0.69]), and lower HF (-0.79; -1.09 to -0.50). LF/HF did not differ between groups. Levels of blood glucose and HbA1c were associated with several HRV parameters, as well as Time from diagnosis of T2DM.
CONCLUSIONS
T2DM was associated with an overall decrease in the HRV of T2DM patients. Both sympathetic and parasympathetic activity were decreased, which can be explained by the deleterious effects of altered glucose metabolism on HRV, leading to cardiac autonomic neuropathy.
Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Heart Rate; Humans; Male; Middle Aged; Regression Analysis; Risk Factors
PubMed: 29608603
DOI: 10.1371/journal.pone.0195166 -
PloS One 2021Cardiac autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), that can be measured through heart rate variability (HRV)-known to be decreased... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), that can be measured through heart rate variability (HRV)-known to be decreased in T2DM. Physical exercise can improve HRV in healthy population, however results are under debate in T2DM. We conducted a systemic review and meta-analysis to assess the effects of physical exercise on HRV in T2DM patients.
METHOD
PubMed, Cochrane, Embase, and ScienceDirect databases were searched for all studies reporting HRV parameters in T2DM patients before and after exercise training, until September 20th 2020, without limitation to specific years. We conducted random-effects meta-analysis stratified by type of exercise for each of the HRV parameters: RR-intervals (or Normal to Normal intervals-NN), standard deviation of RR intervals (SDNN), percentage of adjacent NN intervals varying by more than 50 milliseconds (pNN50), root mean square of successive RR-intervals differences (RMSSD), total power, Low Frequency (LF), High Frequency (HF) and LF/HF ratio. Sensitivity analyses were computed on studies with the highest quality.
RESULTS
We included 21 studies (9 were randomized) for a total of 523 T2DM patients: 472 had an exercise training and 151 were controls (no exercise). Intervention was endurance (14 studies), resistance (2 studies), endurance combined with resistance (4 studies), and high intensity interval training (HIIT) (4 studies). After exercise training, all HRV parameters improved i.e. an increase in SDNN (effect size = 0.59, 95%CI 0.26 to 0.93), RMSSD (0.62, 0.28 to 0.95), pNN50 (0.62, 0.23 to 1.00), HF (0.58, -0.16 to 0.99), and a decrease in LF (-0.37, -0.69 to -0.05) and LF/HF (-0.52, -0.79 to -0.24). There were no changes in controls. Stratification by type of exercise showed an improvement in most HRV parameters (SDNN, RMSSD, pNN50, LF, HF, LF/HF) after endurance training, whereas mostly LF/HF was improved after both resistance training and HIIT. Supervised training improved most HRV parameters. Duration and frequency of training did not influence the benefits on HRV.
CONCLUSION
Exercise training improved HRV parameters in T2DM patients which may reflect an improvement in the activity of the autonomic nervous system. The level of proof is the highest for endurance training. Supervised training seemed beneficial.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Endurance Training; Exercise; Female; Heart; Heart Rate; High-Intensity Interval Training; Humans; Male; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 33999947
DOI: 10.1371/journal.pone.0251863 -
Journal of Personalized Medicine Mar 2021Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes... (Review)
Review
BACKGROUND
Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, sensory levels and at the level of autonomic nervous system in diabetic patients, there is not a systematic approach regarding the differences in neuropathy between the major variants of diabetes, e.g., type 1 and 2 diabetes at both neurological and molecular level.
DATA SOURCES
we systematically (Medline, Scopus, and Cochrane databases) evaluated the literature related to the difference of neuropathy in type 1 and 2 diabetes, differences in molecular biomarkers. Study characteristics: seventeen articles were selected based on pre-defined eligibility criteria.
CONCLUSIONS
both superficial sensitivity (primarily thermal sensitivity to cold) and deep sensitivity (such as vibratory sensitivity), have been reported mainly in type 2 diabetes. Cardiac autonomic neuropathy is one of the diabetic complications with the greatest impact at a clinical level but is nevertheless one of the most underdiagnosed. While for type 1 diabetes patients most neuropathy alterations have been reported for the Valsalva maneuver and for the lying-to-standing test, for type 2 diabetes patients, alterations have been reported for deep-breathing test and the Valsalva test. In addition, there is a greater sympathetic than parasympathetic impairment, as indicated by the screening tests for autonomic cardiac neuropathy. Regarding subclinical inflammation markers, patients with type 2 diabetes showed higher blood levels of inflammatory markers such as high-sensitivity C-reactive protein, proinflammatory cytokines IL-6, IL-18, soluble cell adhesion molecules and E-selectin and ICAM-1, than in type 1 diabetes patients. By contrast, the blood levels of adiponectin, an adipocyte-derived protein with multiple paracrine and endocrine activities (anti-inflammatory, insulin-sensitizing and proangiogenic effects) are higher in type 1 than in type 2 diabetic patients. This review provides new insights into the clinical differences in type 1 and 2 diabetes and provide future directions in this research field.
PubMed: 33810048
DOI: 10.3390/jpm11030230 -
Clinical Autonomic Research : Official... Aug 2019Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary... (Review)
Review
PURPOSE
Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary interventions in patients with diabetes and diabetic neuropathy have multiple beneficial effects and are generally low risk, which makes lifestyle interventions an attractive treatment option. We reviewed the literature on the effects of physical activity and dietary interventions on length-dependent peripheral neuropathy and cardiac autonomic neuropathy in diabetes.
METHODS
The electronic database PubMed was systematically searched for original human and mouse model studies examining the effect of either dietary or physical activity interventions in subjects with diabetes, prediabetes, or metabolic syndrome.
RESULTS
Twenty studies are included in this review. Fourteen studies were human studies and six were in mice. Studies were generally small with few controlled trials, and there are no widely agreed upon outcome measures.
CONCLUSIONS
Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models, and there are promising data that they may also ameliorate diabetic neuropathy in humans. It has been known for some time that lifestyle interventions can prevent the development of diabetic neuropathy in type 2 diabetes mellitus subjects. However, there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy. In addition to the observed clinical value of lifestyle interventions, there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems, including the peripheral nerve. However, data from randomized controlled trials are needed.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet, Healthy; Exercise; Humans; Overweight; Risk Reduction Behavior
PubMed: 31076938
DOI: 10.1007/s10286-019-00607-x -
BMJ Open Diabetes Research & Care Dec 2021We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2... (Meta-Analysis)
Meta-Analysis Review
We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2 diabetes through a systematic review and meta-analysis. This systematic review and meta-analysis was registered with PROSPERO (CRD42020216305) and was conducted with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological criteria. CAN was defined on the basis of 1 (early/possible CAN) or ≥2 (definite CAN) positive autonomic function tests as per the Toronto Consensus guidelines. Studies included those with prospective CVE or mortality data. Methodological variables/risk of bias were assessed using ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) and RoB-2 (Risk-Of-Bias tool for randomized trials) appraisal tools. Electronic database searches yielded 18 467 articles; 84 articles were screened full-text, 26 articles fulfilled the inclusion criteria for quantitative synthesis. Sixteen studies from patients with (n=2875) and without (n=11 722) CAN demonstrated a pooled relative risk (RR) of 3.16 (95%CI 2.42 to 4.13; p<0.0001) of future CVE in favour of CAN. Nineteen studies provided all-cause mortality data from patients with (n=3679) and without (n=12 420) CAN, with a pooled RR of 3.17 (95%CI 2.11 to 4.78; p<0.0001) in favour of CAN. The risk of both future CVE and mortality was higher in type 1 compared with type 2 diabetes and with a definite CAN (vs possible CAN) diagnosis. Three studies were considered to have risk of serious bias. This study confirms the significant association between CAN and CVE and all-cause mortality. The implementation of population-based CAN screening will identify a subgroup with disproportionately higher cardiovascular and mortality risk that will allow for earlier targeted intervention.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Mass Screening; Prognosis
PubMed: 34969689
DOI: 10.1136/bmjdrc-2021-002480 -
Cancer Treatment and Research... 2021This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and...
This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and patterns described in studies of children who received neurotoxic chemotherapy to treat cancer. PubMed, CINAHL, PsycINFO, and Embase were searched for articles published 2009 - 2019, yielding 861. Forty-two papers met the eligibility criteria, including 31 that described characteristics and patterns of vincristine-induced CIPN. Fifty-seven percent of articles were of low to moderate quality; measurement flaws were the most common limitations. The reported CIPN incidence varies widely (2.8%-100%) depending on risk factors (e.g., race) and the measurement approach. Incidence rates of sensory, motor, autonomic CIPN, and pain were 12-28%, 50-72%, 0.8-83% and 5.7-44%, respectively. The evidence suggests that sensory and motor neuropathy, pain, and functional deficits are common and can persist into adulthood. Caucasian race is a risk factor and, contrary to prior thinking, cumulative chemotherapy dosage alone does not predict CIPN severity. The influence of other risk factors is less clear, and studies to date have not explored potential interactions among race, genetics, age, sex, drug metabolism, and nutritional status, among other factors.
Topics: Antineoplastic Agents; Child; Humans; Peripheral Nervous System Diseases
PubMed: 34225104
DOI: 10.1016/j.ctarc.2021.100420 -
Diabetology International Jul 2023Cardiovascular autonomic neuropathy (CAN) is a debilitating complication of diabetes mellitus. To date, there is no systematic review on all the available drug... (Review)
Review
BACKGROUND
Cardiovascular autonomic neuropathy (CAN) is a debilitating complication of diabetes mellitus. To date, there is no systematic review on all the available drug treatments for CAN in diabetic patients, except for one review focusing on aldose reductase inhibitors.
OBJECTIVE
To evaluate available drug treatment options for CAN in diabetic patients.
METHODS
A systematic review was conducted with a search of CENTRAL, Embase, PubMed and Scopus from database inception till 14th May 2022. Randomised controlled trials (RCTs) of diabetic patients with CAN that investigated the effect of treatment on blood pressure, heart rate variability, heart rate or QT interval were included.
RESULTS
Thirteen RCTs with a total of 724 diabetic patients with CAN were selected. There was a significant improvement in the autonomic indices of diabetic patients with CAN given angiotensin-converting enzyme inhibitor (ACEI) for 24 weeks (<0.05) to two years (<0.001), angiotensin-receptor blocker (ARB) for one year (<0.05), single dose of beta blocker (BB) (<0.05), omega-3 polyunsaturated fatty acids (PUFAs) for three months (<0.05), alpha-lipoic acid (ALA) for four months ( < 0.05) to six months (=0.048), vitamin B12 in combination with ALA, acetyl L‑carnitine (ALC), superoxide dismutase (SOD) for one year (=0.001) and near significant improvement in the autonomic indices of diabetic patients with CAN given vitamin E for four months ( = 0.05) compared to the control group. However, there was no significant improvement in the autonomic indices of patients given vitamin B12 monotherapy ( ≥ 0.05).
CONCLUSION
ACEI, ARB, BB, ALA, omega-3 PUFAs, vitamin E, vitamin B12 in combination with ALA, ALC and SOD could be effective treatment options for CAN, while vitamin B12 monotherapy might be unlikely to be recommended for the treatment of CAN due to its lack of efficacy.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13340-023-00629-x.
PubMed: 37397902
DOI: 10.1007/s13340-023-00629-x -
Diabetologia Feb 2021Cardiac autonomic neuropathy (CAN) is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular...
AIMS/HYPOTHESIS
Cardiac autonomic neuropathy (CAN) is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular mortality. Several studies have highlighted the increased prevalence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose). Considering the exponential rise of prediabetes, we aimed to determine the prevalence of CAN through a systematic literature review.
METHODS
This systematic review was registered with PROSPERO (CRD42019125447). An electronic literature search was performed using MEDLINE, EMBASE, PubMed, Web of Science, Scopus and Cochrane databases. Published full text, English language articles that provide CAN prevalence data of studies in individuals with prediabetes and aged over 18 years were included. Prevalence data for normal glucose tolerance and diabetes were also extracted from the selected articles, if present. All articles were screened by two independent reviewers using a priori criteria. Methodological quality and risk of bias were evaluated using a critical appraisal tool.
RESULTS
Database searches found 4500 articles; subsequently, 199 full text articles were screened, 11 of which fulfilled the inclusion criteria (4431 total participants, 1730 people with prediabetes, 1999 people with normal glucose tolerance [NGT] and 702 people with predominantly type 2 diabetes). Six of the selected studies reported definite CAN prevalence data (9-39%). Only a single large population-based study by Ziegler et al (KORA S4 study, 1332 participants) determined definite CAN based on two or more positive autonomic function tests (AFTs), with a mean prevalence of 9% in all prediabetes groups (isolated impaired glucose tolerance 5.9%; isolated impaired fasting glucose 8.1%; impaired fasting glucose plus impaired glucose tolerance 11.4%), which was higher than NGT (4.5%). This study is most likely to provide a reliable population-specific estimate of CAN in prediabetes. There was a higher than expected prevalence of CAN in prediabetes (9-38%) when compared with normal glucose tolerance (0-18%) within the same studies (n = 8). There was a wide prevalence of possible CAN based on one positive AFT (n = 5). There was heterogeneity between the studies with variations in the definition of CAN, methodology and characteristics of the populations, which likely contributed to the diversity of prevalence estimates. The overall risk of bias was low.
CONCLUSIONS/INTERPRETATION
There is a higher than expected prevalence of CAN in prediabetes. Early detection of CAN in prediabetes through population screening needs careful consideration in view of the excess morbidity and mortality risk associated with this condition. Graphical abstract.
Topics: Autonomic Nervous System Diseases; Diabetic Neuropathies; Glucose Intolerance; Humans; Prediabetic State; Prevalence
PubMed: 33164108
DOI: 10.1007/s00125-020-05316-z -
Respiratory Care Dec 2015Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and... (Review)
Review
Cardiovascular autonomic neuropathy is one of the factors implicated in the high morbidity and mortality rate in patients with COPD. Thus, several studies and nonsystematic reviews have increasingly reported autonomic function impairment in these subjects. For a better understanding, this systematic review was performed to evaluate not only the evidence for autonomic function impairment, but also factors influencing it. The results of the studies reviewed showed a strong level of evidence to support the impairment of heart rate variability in the time domain. A similar evidence level was also found to support impairment in baroreceptor sensitivity and muscle sympathetic nerve activity. Furthermore, this review identified physical activity level, muscle function, and circadian rhythm as the major influencing factors (strong evidence) of autonomic function in subjects with COPD. However, no definite conclusion could be reached for factors such as dyspnea, anxiety, body composition, pulmonary function, age, breathing frequency, ventilatory effort, quality of life, and disease severity due to limited, conflicting, or lack of existing evidence. The results of this review highlight relevant clinical messages for clinicians and other health-care providers regarding the role autonomic function can play as an important physiological marker for prognostication and stratification. Hence, autonomic function outcomes should be identified and considered during management of patients with COPD. Moreover, this review can serve as basis for future research aimed at assessing the interventions for autonomic function abnormalities in these patients.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Circadian Rhythm; Heart Rate; Humans; Motor Activity; Muscles; Pressoreceptors; Pulmonary Disease, Chronic Obstructive
PubMed: 26487747
DOI: 10.4187/respcare.04174 -
Respiratory Medicine Aug 2018Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and... (Review)
Review
BACKGROUND
Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia.
METHODS
We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
RESULTS
Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy.
CONCLUSIONS
Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
Topics: Bronchoalveolar Lavage; Bronchoscopy; Brugada Syndrome; Consensus; Deglutition Disorders; Dysautonomia, Familial; Evidence-Based Practice; Humans; New York; Pneumonia, Aspiration; Polysomnography; Prospective Studies; Respiration Disorders; Respiratory Function Tests
PubMed: 30053970
DOI: 10.1016/j.rmed.2018.06.017