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Okamoto LE, Urechie V, Rigo S, Abner JJ, Giesecke M, Muldowney JAS, Furlan R, Shibao CA, Shirey-Rice JK, Pulley JM, Diedrich A, Biaggioni I. Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine. Hypertension 2024; 81:2237-2247. [PMID: 39109428 PMCID: PMC11483201 DOI: 10.1161/hypertensionaha.124.23035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 07/22/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND A subset of patients with postural tachycardia syndrome (POTS) are thought to have a primary hyperadrenergic cause. We assessed clinical biomarkers to identify those that would benefit from sympatholytic therapy. METHODS We measured sympathetic function (supine muscle sympathetic nerve activity, upright plasma norepinephrine, and blood pressure responses to the Valsalva maneuver) in 28 patients with POTS (phenotyping cohort) to identify clinical biomarkers that are associated with responsiveness to the central sympatholytic guanfacine in a separate uncontrolled treatment cohort of 38 patients that had received guanfacine clinically for suspected hyperadrenergic POTS (HyperPOTS). RESULTS In the phenotyping cohort, an increase in diastolic blood pressure (DBP) >17 mm Hg during late phase 2 of the Valsalva maneuver identified patients with the highest quartile of resting muscle sympathetic nerve activity (HyperPOTS) with 71% sensitivity and 85% specificity. In the treatment cohort, patients with HyperPOTS, identified by this clinical biomarker, more often reported clinical improvement (85% versus 44% in nonhyperadrenergic; P=0.016), had better orthostatic tolerance (∆Orthostatic Hypotension Daily Activities Scale: -1.9±0.9 versus 0.1±0.5; P=0.032), and reported less chronic fatigue (∆PROMIS Fatigue Short Form 7a: -12.9±2.7 versus -2.2±2.2; P=0.005) in response to guanfacine. CONCLUSIONS These results are consistent with the concept that POTS is caused by a central sympathetic activation in a subset of patients, which can be identified clinically by an exaggerated DBP increase during phase 2 of the Valsalva maneuver and improved by central sympatholytic therapy. These results support further clinical trials to determine the safety and efficacy of guanfacine in patients with POTS enriched for the presence of this clinical biomarker.
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Affiliation(s)
- L E Okamoto
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
| | - V Urechie
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
| | - S Rigo
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
| | - J J Abner
- Vanderbilt Institute for Clinical and Translational Research, Nashville, TN (J.J.A., J.K.S.-R., J.M.P.)
| | - M Giesecke
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
| | - J A S Muldowney
- Division of Cardiovascular Medicine, Department of Medicine (J.A.S.M.), Vanderbilt University Medical Center, Nashville, TN
| | - R Furlan
- Department of Biomedical Sciences, Humanitas University, Milan, Italy (R.F.)
- Internal Medicine, IRCCS Humanitas Research Hospital, Milan, Italy (R.F.)
| | - C A Shibao
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
| | - J K Shirey-Rice
- Vanderbilt Institute for Clinical and Translational Research, Nashville, TN (J.J.A., J.K.S.-R., J.M.P.)
| | - J M Pulley
- Vanderbilt Institute for Clinical and Translational Research, Nashville, TN (J.J.A., J.K.S.-R., J.M.P.)
| | - A Diedrich
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN (A.D.)
| | - Italo Biaggioni
- Vanderbilt Autonomic Dysfunction Center, Division of Clinical Pharmacology (L.E.O., V.U., S.R., M.G., C.A.S., A.D., I.B.), Vanderbilt University Medical Center, Nashville, TN
- Department of Pharmacology (I.B.), Vanderbilt University Medical Center, Nashville, TN
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Padovani C, Arruda RMDC, Phillips S, Sampaio LMM. Cardiac autonomic activity, endothelial function and physical fitness in type 2 diabetic patients. REVISTA CIÊNCIAS EM SAÚDE 2022. [DOI: 10.21876/rcshci.v12i3.1279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Objective: To investigate the association between cardiac autonomic activity, endothelial function, and physical fitness in patients with type 2 diabetes mellitus (T2DM). Methods: Twenty-seven patients with T2DM were studied, with a mean age of 57 ± 9 years and a mean disease duration of 7.4 ± 5 years. The assessment of physical fitness was performed using the Shuttle Walking Test (SWT), cardiac autonomic modulation by heart rate variability (HRV), and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery through ultrasound imaging. Results: The main finding of this study was that some HRV indices (SDNN, RMSSD, and HF) were significantly correlated with endothelial function in individuals with T2DM, with R values between 0.51 and 0.57 (p < 0, 05), for all relationships. Additionally, an association was found between the distance covered in the SWT and the basal diameter of the brachial artery (R = 0.59; p = 0.01). Conclusion: Our data demonstrate that some HRV indices are associated with DMF, indicating an interaction between these two systems. Furthermore, our findings suggest a correlation between physical fitness and endothelial function in individuals with T2DM.
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Mueller B, Figueroa A, Robinson-Papp J. Structural and functional connections between the autonomic nervous system, hypothalamic-pituitary-adrenal axis, and the immune system: a context and time dependent stress response network. Neurol Sci 2022; 43:951-960. [PMID: 35034231 DOI: 10.1007/s10072-021-05810-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/03/2021] [Indexed: 01/17/2023]
Abstract
The autonomic nervous system (ANS), hypothalamic-pituitary-adrenal (HPA) axis, and immune system are connected anatomically and functionally. These three systems coordinate the central and peripheral response to perceived and systemic stress signals. Both the parasympathetic and sympathetic components of the autonomic nervous system rapidly respond to stress signals, while the hypothalamic-pituitary-adrenal axis and immune system have delayed but prolonged actions. In vitro, animal, and human studies have demonstrated consistent anti-inflammatory effects of parasympathetic activity. In contrast, sympathetic activity exerts context-dependent effects on immune signaling and has been associated with both increased and decreased inflammation. The location of sympathetic action, adrenergic receptor subtype, and timing of activity in relation to disease progression all influence the ultimate impact on immune signaling. This article reviews the brain circuitry, peripheral connections, and chemical messengers that enable communication between the ANS, HPA axis, and immune system. We describe findings of in vitro and animal studies that challenge the immune system with lipopolysaccharide. Next, neuroimmune connections in animal models of chronic inflammatory disease are reviewed. Finally, we discuss how a greater understanding of the ANS-HPA-immune network may lead to the development of novel therapeutic strategies that are focused on modulation of the sympathetic and parasympathetic nervous system.
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Affiliation(s)
- Bridget Mueller
- Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Box 1139, New York City, NY, 10029, USA.
| | - Alex Figueroa
- University of Texas at Southwestern Medical School, Dallas, TX, USA
| | - Jessica Robinson-Papp
- Department of Neurology, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Box 1139, New York City, NY, 10029, USA
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Levine TD, Bellaire B, Gibbons C, Freeman R. Cutaneous alpha-synuclein deposition in postural tachycardia patients. Ann Clin Transl Neurol 2021; 8:908-917. [PMID: 33764697 PMCID: PMC8045934 DOI: 10.1002/acn3.51347] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/14/2021] [Accepted: 03/02/2021] [Indexed: 11/11/2022] Open
Abstract
Objective To report a case series of patients with neuropathic POTS and cutaneous phosphorylated alpha‐synuclein (P‐SYN) deposition on skin biopsy and compare these to neuropathic POTS patients without P‐SYN deposition. Methods The medical history, physical examination findings, autonomic function testing, and skin biopsy neuropathology of patients under the age of 50 with a postural tachycardia and a diagnosis of POTS were retrospectively reviewed. Included patients completed the composite autonomic severity score (COMPASS 31), the Wood Mental Fatigue Inventory, the Epworth Sleepiness scale, the REM Behavior Disorder Questionnaire, the Patient‐Reported Outcomes Measurement Information System (PROMIS‐10), and the Gastroparesis Cardinal Symptom Index. Results Of 296 patients seen with POTS, 22 patients with suspected neuropathic POTS had skin biopsies performed during their evaluation. Seven of 22 patients had P‐SYN present on skin biopsy, while 15 individuals did not. Those with P‐SYN on biopsy: (1) were more likely to be male; (2) had features of REM sleep behavioral disorder; (3) reported less sleepiness and cognitive impairment; and (4) noted greater symptoms of gastroparesis. On autonomic testing, the group with P‐SYN deposition was more likely to have a hypertensive response to tilt‐table testing and abnormal QSART responses. Interpretation Phosphorylated alpha‐synuclein deposition is present in some postural tachycardia patients with neuropathic features. Individuals with a postural tachycardia and cutaneous phosphorylated alpha‐synuclein deposition may be distinguished from other patients with neuropathic POTS.
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Affiliation(s)
| | | | - Christopher Gibbons
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Roy Freeman
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Wegeberg AM, Lunde ED, Riahi S, Ejskjaer N, Drewes AM, Brock B, Pop-Busui R, Brock C. Cardiac vagal tone as a novel screening tool to recognize asymptomatic cardiovascular autonomic neuropathy: Aspects of utility in type 1 diabetes. Diabetes Res Clin Pract 2020; 170:108517. [PMID: 33096186 DOI: 10.1016/j.diabres.2020.108517] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 10/08/2020] [Accepted: 10/09/2020] [Indexed: 12/25/2022]
Abstract
AIMS To test the performance of the cardiac vagal tone (CVT) derived from a 5-minute ECG recording compared with the standardized cardiovascular autonomic reflex tests (CARTs). METHODS Cross-sectional study included 56 well-phenotyped adults with type 1 diabetes (19-71 years, 2-54 years disease-duration). Autonomic testing included: standardized CARTs obtained with the VAGUS™, CVT, and indices of heart rate variability (HRV) obtained at 24- and 120-hour, and electrochemical skin conductance assessed with SUDOSCAN®. ROC AUC and cut-off values were calculated for CVT to recognize CAN based on ≥ 2 (established CAN, n = 7) or 1 (borderline CAN, n = 9) abnormal CARTs and compared to HRV indices and electrochemical skin conductance. RESULTS Established CAN: The cut-off CVT value of 3.2LVS showed 67% sensitivity and 87% specificity (p = 0.01). Indices of HRV at either 24-hour (AUC > 0.90) and 120-hour (AUC > 0.88) performed better than CVT. Borderline CAN: The cut-off CVT value of 5.2LVS indicated 88% sensitivity and 63% specificity (p = 0.07). CVT performed better than HRV indices (AUC < 0.72). Electrochemical skin conductance (AUC:0.63-0.72) had lower sensitivity and specificity compared with CVT. CONCLUSIONS Implementation of CVT with a clinically applicable cut-off value may be considered a quicker and accessible screening tool which could ultimately decrease the number of unrecognized CAN and initiate earlier prevention initiatives.
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Affiliation(s)
- Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, and Clinical Institute, Aalborg University, Aalborg, Denmark
| | - Elin D Lunde
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Sam Riahi
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, and Clinical Institute, Aalborg University, Aalborg, Denmark; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Niels Ejskjaer
- Steno Diabetes Center North Denmark, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, and Clinical Institute, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg, Denmark
| | | | - Rodica Pop-Busui
- Department of Internal Medicine, Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, USA
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, and Clinical Institute, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg, Denmark.
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Robinson-Papp J, Astha V, Nmashie A, Sharma SK, Kim-Schulze S, Murray J, George MC, Morgello S, Mueller BR, Lawrence SA, Benn EK. Sympathetic function and markers of inflammation in well-controlled HIV. Brain Behav Immun Health 2020; 7:100112. [PMID: 34589872 PMCID: PMC8474355 DOI: 10.1016/j.bbih.2020.100112] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/14/2020] [Accepted: 07/19/2020] [Indexed: 01/14/2023] Open
Abstract
PURPOSE HIV-associated autonomic neuropathy (HIV-AN) is common and may be associated with both sympathetic and parasympathetic dysfunction. Sympathetic nervous system (SNS) dysfunction occurs on a continuum of hyper-to hypo-adrenergic function, and may be a mediator between psychological stress and chronic inflammation. We sought to describe patterns of SNS dysfunction in people living with HIV, and to determine whether SNS dysfunction is associated with markers of systemic inflammation (focusing on IL-6 and TNF-α) and pain and anxiety. METHODS Forty-seven people with well-controlled HIV and without confounding medical conditions or medications completed the Medical Outcomes Survey (MOS-HIV), quantification of a panel of 41 plasma cytokines/chemokines, and a standardized, non-invasive autonomic reflex screen (ARS). Adrenergic baroreflex sensitivity (BRSA) was calculated from the ARS as a measure of SNS function. RESULTS Pain (46%) and anxiety (52%) were commonly reported on the MOS-HIV. BRSA was reduced in 30% of participants and elevated in 9% with the latter occurring only in participants with normal to mild HIV-AN. BRSA was significantly associated with IL-6, but not with TNF-α, pain or anxiety. Exploratory analyses also revealed positive associations of BRSA with numerous other cytokines with no significant inverse associations. CONCLUSION Higher BRSA, indicative of a more hyperadrenergic state, can be part of the spectrum of early HIV-AN, and may be associated with elevations in multiple cytokines including IL-6. These associations do not appear to be driven by stressors such as pain or anxiety.
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Affiliation(s)
| | - Varuna Astha
- Icahn School of Medicine at Mount Sinai, Center for Scientific Diversity, Center for Biostatistics & Department of Population Health Science and Policy, United States
| | - Alexandra Nmashie
- Icahn School of Medicine at Mount Sinai, Department of Neurology, United States
| | - Sandeep K. Sharma
- Icahn School of Medicine at Mount Sinai, Department of Neurology, United States
- Icahn School of Medicine at Mount Sinai, Center for Scientific Diversity, Center for Biostatistics & Department of Population Health Science and Policy, United States
| | - Seunghee Kim-Schulze
- Icahn School of Medicine at Mount Sinai, Human Immune Monitoring Center, United States
| | - Jacinta Murray
- Icahn School of Medicine at Mount Sinai, Department of Neurology, United States
| | | | - Susan Morgello
- Icahn School of Medicine at Mount Sinai, Department of Neurology, United States
| | - Bridget R. Mueller
- Icahn School of Medicine at Mount Sinai, Department of Neurology, United States
| | - Steven A. Lawrence
- Icahn School of Medicine at Mount Sinai, Center for Scientific Diversity, Center for Biostatistics & Department of Population Health Science and Policy, United States
- Columbia University Mailman School of Public Health, Department of Biostatistics, United States
| | - Emma K.T. Benn
- Icahn School of Medicine at Mount Sinai, Center for Scientific Diversity, Center for Biostatistics & Department of Population Health Science and Policy, United States
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Goldstein DS, Cheshire WP. Roles of catechol neurochemistry in autonomic function testing. Clin Auton Res 2018; 28:273-288. [PMID: 29705971 DOI: 10.1007/s10286-018-0528-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 04/10/2018] [Indexed: 12/14/2022]
Abstract
Catechols are a class of compounds that contain adjacent hydroxyl groups on a benzene ring. Endogenous catechols in human plasma include the catecholamines norepinephrine, epinephrine (adrenaline), and dopamine; the catecholamine precursor DOPA, 3,4-dihydroxyphenylglycol (DHPG), which is the main neuronal metabolite of norepinephrine; and 3,4-dihydroxyphenylacetic acid (DOPAC), which is the main neuronal metabolite of dopamine. In the diagnostic evaluation of patients with known or suspected dysautonomias, measurement of plasma catechols is rarely diagnostic but often is informative. This review summarizes the roles of clinical catechol neurochemistry in autonomic function testing.
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Affiliation(s)
- David S Goldstein
- Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike MSC-1620, Building 10 Room 8N260, Bethesda, MD, 20892-1620, USA.
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Allawi AAD. Prediction of autonomic neuropathy in chronic kidney disease (stage 5) Iraqi patients (case control study). Diabetes Metab Syndr 2017; 11 Suppl 2:S969-S973. [PMID: 28757390 DOI: 10.1016/j.dsx.2017.07.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 07/16/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND The presence of autonomic neuropathy in association with end stage chronic kidney disease have not yet been established. An extending studies need to evaluate the presence of autonomic neuropathy in different stages of chronic kidney disease. OBJECTIVES To estimate the prevalence rate of autonomic neuropathy in stage 5 chronic kidney disease. METHODS 35 patients with end stage CKD were selected (patient group), compared with 100 person had CKD of different stages other than stage 5 CKD (control group). A sequence of questionnaires (6 questions) were applied to both groups, followed by testing for postural hypotension using as a complementary test for ANP with the cold immersion test. Any subject failed to show an increment in BP was labeled as having test positive and hence having ANP. RESULTS The distribution of ANP according to the questionnaire was higher in the patient's group than the controls (p<0.0001). Postural hypotension was more in patients versus the control (p 0.026). The Cold immersion test was positive in 23 subject in patients (65.7%) than the control only 11 subject (11%), (p<0.0001).
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Affiliation(s)
- Ali Abdulmajid Dyab Allawi
- Department of Internal Medicine, Baghdad College of Medicine, University of Baghdad, Baghdad Teaching Hospital, Baghdad, Iraq.
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Seposo XT, Dang TN, Honda Y. How Does Ambient Air Temperature Affect Diabetes Mortality in Tropical Cities? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2017; 14:ijerph14040385. [PMID: 28379204 PMCID: PMC5409586 DOI: 10.3390/ijerph14040385] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 03/16/2017] [Accepted: 03/28/2017] [Indexed: 12/20/2022]
Abstract
Diabetes is well-known as one of the many chronic diseases that affect different age groups. Currently, most studies that evaluated the effects of temperature on diabetes mortality focused on temperate and subtropical settings, but no study has been conducted to assess the relationship in a tropical setting. We conducted the first multi-city study carried out in tropical cities, which evaluated the temperature–diabetes relationship. We collected daily diabetes mortality (ICD E10–E14) of four Philippine cities from 2006 to 2011. Same period meteorological data were obtained from the National Oceanic and Atmospheric Administration. We used a generalized additive model coupled with a distributed lag non-linear model (DLNM) in determining the relative risks. Results showed that both low and high temperatures pose greater risks among diabetics. Likewise, the study was able to observe the: (1) high risk brought about by low temperature, aside from the largely observed high risks by high temperature; and (2) protective effects in low temperature percentile. These results provide significant policy implications with strategies related to diabetes risk groups in relation to health service and care strategies.
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Affiliation(s)
- Xerxes T Seposo
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba City 305-8577, Japan.
| | - Tran Ngoc Dang
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba City 305-8577, Japan.
- Department of Environmental Health, Faculty of Public Health, University of Medicine and Pharmacy, Ho Chi Minh City 70000, Vietnam.
| | - Yasushi Honda
- Faculty of Health and Sports Sciences, University of Tsukuba, Tsukuba City 305-8577, Japan.
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Kang SJ, Ko KJ, Baek UH. Effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in type 2 diabetes mellitus patients. J Phys Ther Sci 2016; 28:2088-93. [PMID: 27512271 PMCID: PMC4968512 DOI: 10.1589/jpts.28.2088] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 04/07/2016] [Indexed: 01/05/2023] Open
Abstract
[Purpose] This study evaluated the effects of 12 weeks combined aerobic and resistance
exercise on heart rate variability in patients with Type 2 diabetes mellitus. [Subjects
and Methods] The subjects were 16 female patients with Type 2 diabetes mellitus selected
among the participants of a chronic disease management exercise class at C Region Public
Health Center in South Korea. Subjects were randomly assigned to the exercise group (n=8;
age, 55.97 ± 7.37) or the control group (n=8; age, 57.53 ± 4.63) The exercise group
performed aerobic and resistance exercises for 60 minutes per day, 3 times per week for 12
weeks. Anthropometric measurements, biochemical markers, physical fitness, and heart rate
variability were examined. [Results] After 12 weeks of exercise, weight, body fat
percentage, waist circumference, blood glucose, insulin resistance, glycated hemoglobin
level, systolic blood pressure, and diastolic blood pressure significantly decreased and
cardiorespiratory fitness and muscular strength significantly increased in the exercise
group. Although heart rate variability measures showed favorable changes with the exercise
program, none were significant. [Conclusion] Although the exercise program did not show
notable changes in heart rate variability in patients with Type 2 diabetes within the
timeframe of the study, exercise may contribute to the prevention and control of
cardiovascular autonomic neuropathy.
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Affiliation(s)
- Seol-Jung Kang
- Department of Physical Education, Changwon National University, Republic of Korea
| | - Kwang-Jun Ko
- Department of Sports Medicine, National Fitness Center, Republic of Korea
| | - Un-Hyo Baek
- Department of Sports Science, College of Natural Science, Kyungnam University, Republic of Korea
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Abstract
BACKGROUND Plasma catecholamine influences autonomic function and control, but there are few reports correlating them. In this study, 47 individuals (mean age, 38 years) were studied: 19 diabetes mellitus (DM) patients with gastroparesis, 16 with liver disease and 12 control subjects. METHODS Noninvasive autonomic function was assessed for sympathetic adrenergic functions as peripheral vasoconstriction in response to cold stress test and postural adjustment ratio (PAR) and cholinergic function as Valsalva ratio, represented by change in R-R intervals. Measurements were compared by analysis of variance and Spearman's correlation, and results were reported as mean ± standard error. RESULTS Plasma norepinephrine (1902.7 ± 263.3; P = 0.001) and epinephrine (224.5 ± 66.5; P = 0.008) levels, as well as plasma dopamine levels (861.3 ± 381.7), and total plasma catecholamine levels were highest for patients with liver disease, who also had significant negative correlation between norepinephrine level and vasoconstriction (P = 0.01; r = -0.5), PAR1 (P = 0.01; r = -0.5), sympathetic adrenergic functions (P = 0.005; r = -0.6), total autonomic index (P = 0.01-0.5) and total autonomic function (P = 0.01; r = -0.2) and also negative correlation between epinephrine plasma level and total autonomic function (P = 0.04; r = 0.4). DM patients were next highest in norepinephrine level (133.26 ± 7.43), but lowest for plasma catecholamine; a positive correlation between dopamine level and PAR1 (P = 0.008; r = 0.6) was also seen in this group. Plasma dopamine levels and spider score correlated negatively (P = 0.04; r = -0.5) and total plasma catecholamine positively with encephalopathy (P = 0.04; r = 0.5) in patients with liver disease. CONCLUSIONS Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with DM and liver disease, with no significant correlation seen for cholinergic function.
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Malabu UH, Vangaveti VN, Kennedy RL. Disease burden evaluation of fall-related events in the elderly due to hypoglycemia and other diabetic complications: a clinical review. Clin Epidemiol 2014; 6:287-94. [PMID: 25152631 PMCID: PMC4140240 DOI: 10.2147/clep.s66821] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
A hypoglycemia-induced fall is common in older persons with diabetes. The etiology of falls in this population is usually multifactorial, and includes microvascular and macrovascular complications and age-related comorbidities, with hypoglycemia being one of the major precipitating causes. In this review, we systematically searched the literature that was available up to March 31, 2014 from MEDLINE/PubMed, Embase, and Google Scholar using the following terms: hypoglycemia; insulin; diabetic complications; and falls in elderly. Hypoglycemia, defined as blood glucose <4.0 mmol/L (70 mg/dL) requiring external assistance, occurs in one-third of elderly diabetics on glucose-lowering therapies. It represents a major barrier to the treatment of diabetes, particularly in the elderly population. Patients who experience hypoglycemia are at a high risk for adverse outcomes, including falls leading to bone fracture, seizures, cognitive dysfunction, and prolonged hospital stays. An increase in mortality has been observed in patients who experience any one of these events. Paradoxically, rational insulin therapy, dosed according to a patient’s clinical status and the results of home blood glucose monitoring, so as to achieve and maintain recommended glycemic goals, can be an effective method for the prevention of hypoglycemia and falls in the elderly. Contingencies, such as clinician-directed hypoglycemia treatment protocols that guide the immediate treatment of hypoglycemia, help to limit both the duration and severity of the event. Older diabetic patients with or without underlying renal insufficiency or other severe illnesses represent groups that are at high risk for hypoglycemia-induced falls and, therefore, require lower insulin dosages. In this review, the risk factors of falls associated with hypoglycemia in elderly diabetics were highlighted and management plans were suggested. A target hemoglobin A1c level between 7% and 8% seems to be more appropriate for this population. In addition, the first-choice drugs should have good safety profiles and have the lowest probability of causing hypoglycemia – such as metformin (in the absence of significant renal impairment) and incretin enhancers – while other therapies that may cause more frequent hypoglycemia should be avoided.
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Affiliation(s)
- Usman H Malabu
- School of Medicine and Dentistry, James Cook University, QLD, Australia
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Cannillo M, Frea S, Fornengo C, Toso E, Mercurio G, Battista S, Gaita F. Berberine behind the thriller of marked symptomatic bradycardia. World J Cardiol 2013; 5:261-264. [PMID: 23888197 PMCID: PMC3722425 DOI: 10.4330/wjc.v5.i7.261] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 06/05/2013] [Accepted: 06/19/2013] [Indexed: 02/06/2023] Open
Abstract
Patients with chronic aortic dissections are at high risk of catheter-induced complications. We report a Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman referred to our hospital for the onset of fatigue and dyspnoea upon exertion after he started berberine to treat hypercholesterolaemia. An electrocardiogram showed sinus bradycardia (45 bpm), first-degree atrioventricular block, and competitive junctional rhythm. An ergometric stress test showed slightly reduced chronotropic competence and the presence of runs of competitive junctional rhythm, atrial tachycardia, and sinus pauses in the recovery. After 10 d of wash-out from berberine, the patient experienced a complete resolution of symptoms, and an ergometric stress test showed good chronotropic competence. An electrocardiogram Holter showed a latent hypervagotonic state. This is the first case report that shows that berberine could present certain side effects in hypervagotonic people, even in the absence of a situation that could cause drug accumulation. Therefore, berberine’s use should be carefully weighed in hypervagotonic people due to the drug’s bradycardic and antiarrhythmic properties, which could became proarrhythmic, exposing patients to potential health risks.
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Peltier AC, Bagai K, Artibee K, Diedrich A, Garland E, Elasy T, Shi Y, Wang L, Feldman EL, Robertson D, Malow BA. Effect of mild hyperglycemia on autonomic function in obstructive sleep apnea. Clin Auton Res 2012; 22:1-8. [PMID: 21796355 PMCID: PMC3925507 DOI: 10.1007/s10286-011-0131-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2010] [Accepted: 06/08/2011] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Obstructive sleep apnea (OSA) has been hypothesized to cause a hypersympathetic state, which may be the mechanism for the increased incidence of cardiovascular disease in OSA. However, there is a high prevalence of hyperglycemia in OSA patients, which may also contribute to autonomic dysfunction. METHODS Thirty-five patients with OSA and 11 controls with average body mass index (BMI) of 32.0 ± 4.6 underwent polysomnography, glucose tolerance testing, autonomic function tests, lying and standing catecholamines, overnight urine collection, and baseline ECG and continuous blood pressure measurements for spectral analysis. A linear regression model adjusting for age and BMI was used to analyze spectral data, other outcome measures were analyzed with Kruskal-Wallis test. RESULTS Twenty-three OSA patients and two control patients had hyperglycemia (based on 2001 American Diabetes Association criteria). Apnea-hypopnea index (AHI) correlated with total power and low frequency (LF) power (r = 0.138, 0.177, p = 0.031; and r = 0.013) but not with the LF/high frequency (HF) ratio (p = 0.589). Glucose negatively correlated with LF systolic power (r = -0.171, p = 0.038) but not AHI (p = 0.586) and was marginally associated with pnn50, total power, LF, and HF power (p ranged from 0.07 to 0.08). CONCLUSION These data suggest that patients with OSA and mild hyperglycemia have a trend towards lower heart rate variability and sympathetic tone. Hyperglycemia is an important confounder and should be evaluated in studies of OSA and autonomic function.
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Affiliation(s)
- Amanda C Peltier
- Division of Neuromuscular Disorders, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
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Lindenberger M, Olsen H, Lanne T. Impaired compensatory response to hypovolaemic circulatory stress in type 1 diabetes mellitus. Diab Vasc Dis Res 2011; 8:136-42. [PMID: 21562065 DOI: 10.1177/1479164111404576] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Diabetes mellitus is associated with decreased haemodynamic stability and reduced tolerance to hypovolaemia. Compensatory haemodynamic responses during experimental hypovolaemia in type 1 diabetes patients with (DMR+) and without (DMR-) retinopathy as well as healthy controls (C) were studied. Lower body negative pressure created hypovolaemic circulatory stress. Volumetric techniques were used to assess the compensatory capacitance response (redistribution of peripheral venous blood to the central circulation) and to assess capillary fluid absorption from tissue to blood. The compensatory capacitance response was 1/3 lower in DMR+ compared with C (p = 0.002) and DMR- (p = 0.01). Net capillary fluid absorption was reduced by one-third in DMR- and DMR+ compared with C (each p < 0.05). Type 1 diabetes patients with retinopathy demonstrate reduced mobilisation of peripheral venous blood to the central circulation. Furthermore, type 1 diabetes patients present with impaired capillary fluid absorption, which in combination with potentially decreased sympathetic vasoconstriction impedes cardiovascular homeostasis during acute hypovolaemic stress.
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Affiliation(s)
- Marcus Lindenberger
- Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Sweden.
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Affiliation(s)
- J-Y Choi
- Department of Neurology, Korea University Medical Centre, Korea University College of Medicine, Seoul, Republic of Korea
| | - K Oh
- Department of Neurology, Korea University Medical Centre, Korea University College of Medicine, Seoul, Republic of Korea
| | - W-K Seo
- Department of Neurology, Korea University Medical Centre, Korea University College of Medicine, Seoul, Republic of Korea
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Chuang KJ, Coull BA, Zanobetti A, Suh H, Schwartz J, Stone PH, Litonjua A, Speizer FE, Gold DR. Particulate air pollution as a risk factor for ST-segment depression in patients with coronary artery disease. Circulation 2008; 118:1314-20. [PMID: 18779445 PMCID: PMC2751595 DOI: 10.1161/circulationaha.108.765669] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND The association of particulate matter (PM) with cardiovascular morbidity and mortality is well documented. PM-induced ischemia is considered a potential mechanism linking PM to adverse cardiovascular outcomes. METHODS AND RESULTS In a repeated-measures study including 5979 observations on 48 patients 43 to 75 years of age, we investigated associations of ambient pollution with ST-segment level changes averaged over half-hour periods measured in the modified V(5) position by 24-hour Holter ECG monitoring. Each patient was observed up to 4 times within 1 year after a percutaneous intervention for myocardial infarction, acute coronary syndrome without infarction, or stable coronary artery disease without acute coronary syndrome. Elevation in fine particles (PM(2.5)) and black carbon levels predicted depression of half-hour-averaged ST-segment levels. An interquartile increase in the previous 24-hour mean black carbon level was associated with a 1.50-fold increased risk of ST-segment depression > or =0.1 mm (95% CI, 1.19 to 1.89) and a -0.031-mm (95% CI, -0.042 to -0.019) decrease in half-hour-averaged ST-segment level (continuous outcome). Effects were greatest within the first month after hospitalization and for patients with myocardial infarction during hospitalization or with diabetes. CONCLUSIONS ST-segment depression is associated with increased exposure to PM(2.5) and black carbon in cardiac patients. The risk of pollution-associated ST-segment depression may be greatest in those with myocardial injury in the first month after the cardiac event.
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Affiliation(s)
- Kai Jen Chuang
- Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA
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Shibao C, Raj SR, Gamboa A, Diedrich A, Choi L, Black BK, Robertson D, Biaggioni I. Norepinephrine Transporter Blockade With Atomoxetine Induces Hypertension in Patients With Impaired Autonomic Function. Hypertension 2007; 50:47-53. [PMID: 17515448 DOI: 10.1161/hypertensionaha.107.089961] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Atomoxetine, a selective norepinephrine transporter blocker, could increase blood pressure by elevating norepinephrine concentration in peripheral sympathetic neurons. This effect may be masked in healthy subjects by central sympatholytic mechanisms. To test this hypothesis we studied the pressor effect of 18 mg of atomoxetine (pediatric dose) in 21 patients with damage of the central (10 subjects) and peripheral (11 subjects) autonomic nervous system. Atomoxetine was administered in a randomized, crossover, placebo-controlled fashion, and blood pressure and heart rate were measured at baseline and for 60 minutes after drug intake. Atomoxetine acutely increased seated and standing systolic blood pressure in patients with central autonomic failure by 54+/-26 (mean+/-standard deviation; P=0.004) and 45+/-23 mm Hg (P=0.016), respectively, as compared with placebo. At the end of the observation period the mean seated systolic blood pressure in the atomoxetine group was in the hypertensive range (149+/-26, range 113 to 209 mm Hg). However, in patients with peripheral autonomic failure, atomoxetine did not elicit a pressor response; seated and standing systolic blood pressure increased by 4+/-18 mm Hg (P=0.695) and 0.6+/-8 mm Hg (P=0.546) with atomoxetine as compared with placebo. In conclusion, atomoxetine induces a dramatic increase in blood pressure in patients with central autonomic failure even at very low doses. These findings suggest that a functional central sympatholytic pathway is essential to avoid hypertension in patients treated with this drug. Caution should be exercised when this medication is used in patients with milder form of autonomic impairment.
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Affiliation(s)
- Cyndya Shibao
- Department of Medicine, Division of Clinical Pharmacology, and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN 37212, USA
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Shibao C, Gamboa A, Diedrich A, Dossett C, Choi L, Farley G, Biaggioni I. Acarbose, an α-Glucosidase Inhibitor, Attenuates Postprandial Hypotension in Autonomic Failure. Hypertension 2007; 50:54-61. [PMID: 17515447 DOI: 10.1161/hypertensionaha.107.091355] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Postprandial hypotension is an important clinical condition that predisposes to syncope, falls, angina, and cerebrovascular events. The magnitude of the fall in blood pressure after meals depends on enteric glucose availability. We hypothesized that acarbose, an α-glucosidase inhibitor that decreases glucose absorption in the small intestine, would attenuate postprandial hypotension. Acarbose or placebo was given 20 minutes before a standardized meal in 13 patients with postprandial hypotension in the setting of autonomic failure (age: 65±2.64 years; body mass index: 25±1.08 kg/m
2
; supine plasma norepinephrine: 110±26.6 pg/mL). Four patients were studied in a single-blind protocol and 9 patients in a double-blind, randomized, crossover fashion. Patients were studied supine, and blood pressure, heart rate, and neuroendocrine parameters were obtained at baseline and for 90 minutes after meal intake. After adjusting for potential confounders, acarbose significantly attenuated the postprandial fall in systolic and diastolic blood pressures by 17 mm Hg (95% CI: 7 to 28;
P
=0.003) and 9 mm Hg (95% CI: 5 to 14;
P
=0.001), respectively. Furthermore, acarbose effectively reduced plasma levels of insulin, a known vasodilator, by 11 μU/mL (95% CI: 5 to 18;
P
=0.001) compared with placebo. After adjusting for insulin levels, the attenuation of postprandial hypotension by acarbose remained significant, indicating that additional mechanisms contribute to this effect. In conclusion, 100 mg of acarbose successfully improved postprandial hypotension in patients with severe autonomic failure. This effect is not explained solely by a reduction in insulin levels.
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Affiliation(s)
- Cyndya Shibao
- Department of Medicine, Division of Clinical Pharmacology and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN 37212, USA
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Peltier AC, Consens FB, Sheikh K, Wang L, Song Y, Russell JW. Autonomic dysfunction in obstructive sleep apnea is associated with impaired glucose regulation. Sleep Med 2007; 8:149-55. [PMID: 17236808 DOI: 10.1016/j.sleep.2006.06.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2006] [Revised: 06/02/2006] [Accepted: 06/09/2006] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Autonomic dysfunction has been theorized to be responsible for the increased risk of cardiovascular disease in obstructive sleep apnea (OSA). Previous studies did not control for the presence of impaired glucose regulation (IGR, comprising impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes) which is also associated with abnormalities in autonomic function. METHODS Thirty-two patients were recruited for the study. Patients underwent autonomic testing consisting of heart rate response to deep breathing, valsalva maneuver, tilt-up, and quantitative sudomotor axon reflex testing. Polysomnography (PSG) and a 2-h oral glucose tolerance test were performed. Results were analyzed with logistic regression, with age, race, body mass index (BMI), and gender as covariates. RESULTS Nineteen of 24 patients with OSA had abnormal glucose (79%, p=0.04) compared to two of nine patients without OSA. The correlation between IGR, OSA and total autonomic dysfunction was similar (p=.10 for IGR, p=0.06 for OSA). However, cardiac autonomic function was more strongly associated with IGR than OSA (p=.10 vs. 0.50). Age was a significant confounder, as glucose correlated with adrenergic autonomic dysfunction significantly when age was removed from the model (p=0.006). CONCLUSIONS The presence of IGR may be a confounding factor in studies of autonomic function in OSA. Larger studies are needed to delineate whether OSA is directly associated with autonomic dysfunction or whether the previously described association between dysautonomia and OSA may have been due to glucose dysregulation.
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Affiliation(s)
- Amanda C Peltier
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
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Asil T, Utku U, Balci K, Uzunca I. Changing cerebral blood flow velocity by transcranial Doppler during head up tilt in patients with diabetes mellitus. Clin Neurol Neurosurg 2007; 109:1-6. [PMID: 16675103 DOI: 10.1016/j.clineuro.2006.03.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2005] [Revised: 03/20/2006] [Accepted: 03/23/2006] [Indexed: 10/24/2022]
Abstract
OBJECTIVE Diabetes mellitus is an independent risk factor for poor prognosis in patients with ischemic stroke. It is known that diabetes mellitus directly affects cerebral vasculature as a secondary, long-term complication of cerebral circulation, and causes cerebral blood flow abnormalities. The abnormalities of cerebral autoregulation also poorly affects the prognosis of ischemic stroke. In this study, we aimed to show the cerebral autoregulation with transcranial Doppler (TCD) ultrasound in diabetic patients with autonomic nervous system abnormalities, determined with electrophysiological studies. MATERIAL AND METHOD Twenty healthy controls and 39 patients, who had at least 2 years of diabetes mellitus, were evaluated (age ranges: 42-75 years). The patients were divided into two groups according to sympathetic skin response and R--R interval variation studies: (1) patients with autonomic neuropathy; (2) patients without autonomic neuropathy. Blood flow velocities were measured during supine position and after the patients were raised upright position on head up tilt table. Arterial blood pressures and heart rates were also evaluated. RESULTS Mean blood flow velocities of diabetic patients with autonomic neuropathy were found more decreased at 90s after the patients were raised upright position. DISCUSSION Autonomic neuropathy due to diabetes mellitus affects cerebral autoregulation, and by this way cerebral perfusion loses protection against hemodynamical changes.
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Affiliation(s)
- Talip Asil
- University of Trakya, Faculty of Medicine, Department of Neurology, 22030 Edirne, Turkey.
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Maurer MS, Burcham J, Cheng H. Diabetes mellitus is associated with an increased risk of falls in elderly residents of a long-term care facility. J Gerontol A Biol Sci Med Sci 2005; 60:1157-62. [PMID: 16183956 DOI: 10.1093/gerona/60.9.1157] [Citation(s) in RCA: 183] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Diabetes mellitus is common among elderly persons, with several potential complications that could contribute to falls. However, diabetes mellitus is not widely recognized as an important risk factor for falls among elderly persons. Accordingly, the purpose of the current study was to determine whether diabetes is an independent risk factor for falls in elderly residents of a long-term care facility. METHODS Ours was a prospective cohort study of 139 elderly (88 +/- 7 years, range 70-105 years), Caucasian (97%) residents (women, 84%) of a long-term care facility. Inclusion criteria were age > or = 60 years, ability to rise from a seated position, informed consent obtained from participant or guardian. Multiple domains were assessed for the association with falls including: clinical diagnoses; medication use; orthostatic changes in blood pressure, gait, or balance; cognitive/mental status; general well being; activities of daily living; affect/behavior; range of motion and/or ambulation; and communication. Diabetes mellitus was determined by use of hypoglycemic agents. Time to first fall was determined by review of daily New York State mandated "Incident and Accident" reports. RESULTS Over the follow-up period (mean 299 days), 49 participants (35%) experienced a fall. The fall incidence rate for the participants with and without diabetes mellitus was 78% and 30%, respectively (p <.001). The significant unadjusted hazard ratios of fall risk factors included diabetes mellitus, Berg Balance Scale score <45, number of medications, angiotensin-converting enzyme (ACE) inhibitors, hypertension, use of assistive device, inability to independently move a wheelchair, and use of antidepressants, with the latter two factors being protective. In multivariate analysis, only diabetes (adjusted hazard ratio 4.03; 95% confidence interval, 1.96-8.28) and gait and balance (adjusted hazard ratio 5.26; 95% confidence interval, 1.26-22.02) were significantly and independently associated with an increased risk of falls. CONCLUSIONS Our results suggest that diabetes mellitus is an independent fall risk factor among elderly nursing home residents.
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Affiliation(s)
- Mathew S Maurer
- Columbia University, College of Physicians and Surgeons, Clinical Cardiovascular Research Lab for the Elderly, Allen Pavilion, 5141 Broadway, 3 Field West, Room 035, New York, NY 10034, USA.
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Abstract
We discuss 2 cases presenting clinically with disabling orthostatic hypotension and severe supine hypertension. This is a common presentation of autonomic failure, and one that challenges conventional treatment. Clinical findings of isolated autonomic failure were the most prominent manifestation in case 1, whereas a movement disorder was the key finding in case 2. The differential diagnosis and treatment of orthostatic hypotension is discussed from a pathophysiological approach. Understanding of the underlying mechanisms of disorders of the autonomic nervous system is fundamental for an effective management of these patients and provides insight into more common disorders such as essential hypertension.
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Affiliation(s)
- Cyndya Shibao
- Division of Clinical Pharmacology, Department of Medicine and Pharmacology, and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tenn 37212, USA
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El-Atat F, McFarlane SI, Sowers JR. Diabetes, hypertension, and cardiovascular derangements: Pathophysiology and management. Curr Hypertens Rep 2004; 6:215-23. [PMID: 15128475 DOI: 10.1007/s11906-004-0072-y] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Hypertension frequently coexists with diabetes mellitus, occurring twice as frequently in diabetic as in nondiabetic persons. It accounts for up to 75% of added cardiovascular disease (CVD) risk in people with diabetes, contributing significantly to the overall morbidity and mortality in this high-risk population. Patients with hypertension are two times more prone to have diabetes than are normotensive persons. Hypertension substantially increases the risk for coronary heart disease (CHD), stroke, retinopathy, and nephropathy. In patients with type 2 diabetes, hypertension usually clusters with the other components of the cardiometabolic syndrome, such as microalbuminuria, central obesity, insulin resistance, dyslipidemia, hypercoagulation, increased inflammation, and left ventricular hypertrophy (LVH). In type 1 diabetes, hypertension often occurs subsequent to the development of diabetic nephropathy. Hypertension in people with diabetes is characterized by volume expansion, increased salt sensitivity, isolated systolic blood pressure (BP) elevation, loss of the nocturnal dipping of BP and pulse, and increased propensity toward orthostatic hypotension and albuminuria. Among the treatment strategies tested in hypertensive diabetic persons, low-density lipoprotein (LDL)-cholesterol lowering to less than 100 mg/dL and aggressive BP control to less than 130/80 mm Hg have proven effective in CVD risk reduction. The combination of two or more drugs is usually necessary to achieve the target BP.
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Affiliation(s)
- Fadi El-Atat
- Department of Internal Medicine, University of Missouri-Columbia, MA410 Health Science Center, One Hospital Drive, Columbia, MO 65212, USA
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