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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 -
Current Therapeutic Research, Clinical... 2020The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular... (Review)
Review
BACKGROUND
The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular (CV) events (myocardial infarction, stroke, or CV mortality), lower-extremity amputations, and end-stage renal disease. Microvascular complications include retinopathy, autonomic and peripheral neuropathy, nephropathy, and diabetic ulcers. Major CV outcomes trials that were by the Food and Drug Administration for all new antihyperglycemia medications for patients at high risk for CV events were recently completed for all 4 US-marketed dipeptidyl peptidase-4 (DPP-4) inhibitors.
OBJECTIVE
To present a comprehensive review of the clinical trials that evaluate macrovascular and microvascular complications reported with DPP-4 inhibitors in patients with type 2 diabetes mellitus.
METHODS
In this review, we analyzed published articles in PubMed and Ovid databases between January 2008 and September 2019 that evaluated the effect of DPP-4 inhibitors on macrovascular and microvascular complications in patients with type 2 diabetes mellitus.
RESULTS
A total of 18 studies, which included randomized controlled trials and meta-analyses were assessed. Current evidence demonstrates that the addition of DPP-4 inhibitors to standard antihyperglycemic and CV risk reduction treatment has not shown CV benefit relative to placebo in contrast to recently published studies for other medications within the glucagon-like peptide 1 agonist and sodium-glucose co-transporter 2 inhibitor classes. Notably, the potential risk for heart failure hospitalizations may exist for saxagliptin, and this effect is not extrapolated as a class effect. Based on our review, DPP-4 inhibitors may not influence microvascular complications in patients with diabetes. However, some studies have shown that saxagliptin and linagliptin may slow down the progression of albuminuria in patients with type 2 diabetes mellitus. The overall quality of the studies included in this review was high due to the inclusion of randomized controlled trials and meta-analyses.
CONCLUSIONS
DPP-4 inhibitors were found to have a neutral effect on macrovascular and microvascular complications, with the exception of saxagliptin, which may increase the risk for heart failure hospitalizations.
PubMed: 32817765
DOI: 10.1016/j.curtheres.2020.100596 -
Journal of Clinical Medicine Feb 2020Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or... (Review)
Review
Diabetic foot is the most frequent disorder among the chronic complications of diabetes, happening in 25% of patients. Objective clinical outcome measures are tests or clinical instruments that provide objective values for result measurement. The aim of this study was to carry out a systematic review of specific objective clinical outcome measures focused on the assessment and monitoring of diabetic foot disorders. The databases used were PubMed, CINAHL, Scopus, PEDro, Cochrane, SciELO and EMBASE. Search terms used were foot, ankle, diabet*, diabetic foot, assessment, tools, instruments, objective outcome measures, valid*, reliab*. Because of the current published evidence, diabetic neuropathy assessment via sudomotor analysis, cardiovascular autonomic neuropathy and peripheral vascular disease detection by non-invasive electronic devices, wound 3D dimensional measurement, hyperspectral imaging for ulcer prediction and the probe-to-bone test for osteomyelitis diagnosis were highlighted in this study.
PubMed: 32102313
DOI: 10.3390/jcm9020602 -
Immunosuppressive treatment for peripheral neuropathies in Sjogren's syndrome - a systematic review.Romanian Journal of Internal Medicine =... Mar 2020Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no...
BACKGROUND
Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS.
METHODS
The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG).
RESULTS
A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35.5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%). IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic.
CONCLUSION
There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.
Topics: Adrenal Cortex Hormones; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Peripheral Nervous System Diseases; Rituximab; Sjogren's Syndrome
PubMed: 31527298
DOI: 10.2478/rjim-2019-0022 -
Clinical Autonomic Research : Official... Sep 2019Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic...
BACKGROUND
Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic dysfunction in patients with hereditary ATTR amyloidosis.
METHODS
A systematic review of the natural history and clinical trials of patients with ATTR amyloidosis was performed. Alternative surrogate markers of autonomic function were analyzed to understand the prevalence and outcome of autonomic dysfunction.
RESULTS
Patients with early-onset disease displayed autonomic dysfunction more distinctively than those with late-onset disease. The nutritional status and some autonomic items in the quality-of-life questionnaires were used to assess the indirect progression of autonomic dysfunction in most studies. Gastrointestinal symptoms and orthostatic hypotension were resent earlier than urogenital complications. Once symptoms were present, their evolution was equivalent to the progression of the motor and sensory neuropathy impairment.
CONCLUSION
The development of autonomic dysfunction impacts morbidity, disease progression, and mortality in patients with hereditary ATTR amyloidosis.
Topics: Amyloid Neuropathies, Familial; Autonomic Nervous System Diseases; Humans
PubMed: 31473866
DOI: 10.1007/s10286-019-00630-y -
Cancer Chemotherapy and Pharmacology Sep 2019Vincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy,...
PURPOSE
Vincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy, possibly including both peripheral sensory and motor nerves, autonomic nervous functions, and the central nervous system. This dose-limiting side-effect can diminish quality of life and, furthermore, cause discontinuation of vincristine treatment. The present review elucidates the current knowledge regarding vincristine-induced neuropathy in hematologic malignancies, focusing on neuropathy assessment, clinical and molecular predictive markers, drug-drug interference, prevention, and treatment.
METHODS
This review is conducted by a systematic search strategy for the identification of relevant literature in the PubMed and Embase databases.
RESULTS
No clinical parameters displayed convincing potential as predictors of vincristine-induced neuropathy; however, preexisting neuropathy was consistently reported to be associated with an increased risk of neurotoxicity. In contrast, molecular markers, including polymorphisms in genes involved in the pharmacodynamics and pharmacokinetics of vincristine, displayed great potential as predictive markers of neuropathy incidence and severity. Furthermore, antifungal drugs, such as itraconazole and voriconazole, decrease the metabolism of vincristine and consequently lead to severe neuropathy when co-administered with vincristine, underscoring why fluconazole should be the antifungal drug of choice.
CONCLUSION
Reports from the 71 included studies clearly emphasize the lack of consistency in neuropathy assessment, grading systems, and reporting, making it difficult to interpret results between studies. Thus, truer clinical and molecular markers could emerge if the consistency of neuropathy detection and reporting increases by the use of conventional standardized neuropathy assessment tools and grading scales.
Topics: Antineoplastic Agents, Phytogenic; Drug-Related Side Effects and Adverse Reactions; Hematologic Neoplasms; Humans; Neurotoxicity Syndromes; Prognosis; Vincristine
PubMed: 31214762
DOI: 10.1007/s00280-019-03884-5 -
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 -
Journal of Clinical Neurology (Seoul,... Jan 2019Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive...
BACKGROUND AND PURPOSE
Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive sensorimotor and autonomic polyneuropathy. This systematic literature review and meta-analysis evaluated the efficacy and safety of tafamidis in TTR-FAP patients, with the aim of improving the evidence-based medical evidence of this treatment option for TTP-FAP.
METHODS
A systematic search of the English-language literature in five databases was performed through to May 31, 2018 by two reviewers who independently extracted data and assessed the risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias.
RESULTS
The meta-analysis identified six relevant studies. The tafamidis group showed smaller changes from baseline in the Neuropathy Impairment Score-Lower Limbs [mean difference (MD)=-3.01, 95% confidence interval (CI)=-3.26 to -2.75, <0.001] and the Norfolk Quality of Life-Diabetic Neuropathy total quality of life score (MD=-6.67, 95% CI=-9.70 to -3.64, <0.001), and a higher modified body mass index (MD=72.45, 95% CI=69.41 to 75.49, <0.001), with no significant difference in total adverse events [odds ratio (OR)=0.69, 95% CI=0.35 to 1.35, =0.27]. The incidence of adverse events did not differ between tafamidis and placebo treatment except for fatigue (OR=0.13, 95% CI=0.02 to 0.72, =0.02) and hypesthesia (OR=0.16, 95% CI=0.03 to 0.92, =0.04).
CONCLUSIONS
This systematic review and meta-analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life. The rates of adverse events did not differ between the patients in the tafamidis and placebo groups. Tafamidis might be a safer noninvasive option for patients with TTR-FAP.
PubMed: 30618225
DOI: 10.3988/jcn.2019.15.1.108 -
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 -
Frontiers in Neuroscience 2018Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.
PubMed: 29670504
DOI: 10.3389/fnins.2018.00203