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Seleshi T, Alemneh T, Mekonnen D, Tesfaye D, Markos S, Getachew Y, Taddese K, Guteta S. Assessment of subclinical left ventricular systolic and diastolic dysfunction in patients with type 2 diabetes mellitus under follow-up at Tikur Anbessa specialized hospital, Ethiopia: a case-control study. BMC Cardiovasc Disord 2024; 24:201. [PMID: 38582826 PMCID: PMC10998370 DOI: 10.1186/s12872-024-03850-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 03/19/2024] [Indexed: 04/08/2024] Open
Abstract
BACKGROUND Individuals with diabetes mellitus are at increased risk of cardiovascular diseases, which in turn are the most common cause of morbidity and mortality in the diabetic population. A peculiar feature of cardiovascular diseases in this population is that they can have significant cardiac disease while remaining asymptomatic. There is a paucity of data regarding subclinical cardiac imaging features among diabetic adults in Africa, particularly in Ethiopia. This study was conducted to compare the magnitude and spectrum of left ventricular systolic and diastolic dysfunction among asymptomatic type 2 diabetic adults versus a normotensive, non-diabetic control group and to evaluate the determinants of left ventricular diastolic and systolic dysfunction. METHODS This was a case-control study conducted at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. A standard transthoracic echocardiography was done for all study participants with type 2 diabetes mellitus and their normotensive and non-diabetic controls. Structured questionnaires were used to collect demographic and clinical characteristics and laboratory test results. Statistical analysis was done using the SPSS 25.0 software. The data was summarized using descriptive statistics. Bivariate and multivariate analysis was performed to determine the association between variables and echocardiographic parameters. The strength of statistical association was measured by adjusted odds ratios and 95% confidence intervals, with significant differences taken at p < 0.05. RESULTS We analyzed age- and sex-matched 100 participants in the study (diabetic) group and 200 individuals in the control group. Left ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic adults than their sex and age matched controls. Among diabetic individuals, ages of 60 years and above, dyslipidemia, use of Metformin and Glibenclamide, high serum triglyceride level, presence of neuropathy and use of statins correlated significantly with the presence of left ventricular diastolic dysfunction. Chronic kidney disease and neuropathy were determinants of left ventricular systolic dysfunction. CONCLUSION Left ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic patients than their sex- and age-matched controls in our study. We recommend early screening for subclinical left ventricular dysfunction, especially in the elderly and in those with chronic kidney disease, dyslipidemia, and microvascular complications such as neuropathy.
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Affiliation(s)
- Tigist Seleshi
- Department of Internal Medicine, Division of Cardiology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
| | - Theodros Alemneh
- Department of Internal Medicine, Division of Endocrinology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Dufera Mekonnen
- Department of Internal Medicine, Division of Cardiology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Demu Tesfaye
- Department of Internal Medicine, Division of Cardiology, Adama Hospital Medical College, Adama, Ethiopia
| | - Sura Markos
- Department of Internal Medicine, Division of Cardiology, School of Medicine, Hawassa University, Hawassa, Ethiopia
| | - Yitagesu Getachew
- Department of Internal Medicine, Division of Cardiology, Yekatit Hospital Medical College, Addis Ababa, Ethiopia
| | - Konno Taddese
- Department of Internal Medicine, Division of Cardiology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Senbeta Guteta
- Department of Internal Medicine, Division of Cardiology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice. Biomedicines 2023; 11:biomedicines11030662. [PMID: 36979641 PMCID: PMC10045486 DOI: 10.3390/biomedicines11030662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 02/08/2023] [Accepted: 02/11/2023] [Indexed: 02/24/2023] Open
Abstract
Diabetic cardiomyopathy is characterized by abnormal myocardial structure or performance in the absence of coronary artery disease or significant valvular heart disease in patients with diabetes mellitus. The spectrum of diabetic cardiomyopathy ranges from subtle myocardial changes to myocardial fibrosis and diastolic function and finally to symptomatic heart failure. Except for sodium–glucose transport protein 2 inhibitors and possibly bariatric and metabolic surgery, there is currently no specific treatment for this distinct disease entity in patients with diabetes. The molecular mechanism of diabetic cardiomyopathy includes impaired nutrient-sensing signaling, dysregulated autophagy, impaired mitochondrial energetics, altered fuel utilization, oxidative stress and lipid peroxidation, advanced glycation end-products, inflammation, impaired calcium homeostasis, abnormal endothelial function and nitric oxide production, aberrant epidermal growth factor receptor signaling, the activation of the renin–angiotensin–aldosterone system and sympathetic hyperactivity, and extracellular matrix accumulation and fibrosis. Here, we summarize several important emerging treatments for diabetic cardiomyopathy targeting specific molecular mechanisms, with evidence from preclinical studies and clinical trials.
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Insulin Receptors and Insulin Action in the Heart: The Effects of Left Ventricular Assist Devices. Biomolecules 2022; 12:biom12040578. [PMID: 35454166 PMCID: PMC9024449 DOI: 10.3390/biom12040578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/11/2022] [Accepted: 04/12/2022] [Indexed: 02/01/2023] Open
Abstract
This year, 2022, marks the 100th anniversary of the isolation of human insulin and its administration to patients suffering from diabetes mellitus (DM). Insulin exerts many effects on the human body, including the cardiac tissue. The pathways implicated include the PKB/Akt signaling pathway, the Janus kinase, and the mitogen-activated protein kinase pathway and lead to normal cardiac growth, vascular smooth muscle regulation, and cardiac contractility. This review aims to summarize the existing knowledge and provide new insights on insulin pathways of cardiac tissue, along with the role of left ventricular assist devices on insulin regulation and cardiac function.
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Didangelos T, Veves A. Treatment of Diabetic Cardiovascular Autonomic, Peripheral and Painful Neuropathy. Focus on the Treatment of Cardiovascular Autonomic Neuropathy with ACE Inhibitors. Curr Vasc Pharmacol 2020; 18:158-171. [PMID: 31109280 DOI: 10.2174/1570161117666190521101342] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 12/23/2018] [Accepted: 12/31/2018] [Indexed: 12/12/2022]
Abstract
Neuropathies of the peripheral and autonomic nervous systems affect up to half of all people with diabetes mellitus, and are major risk factors for foot ulceration, amputation and cardiovascular dysfunction. Peripheral neuropathies manifest with either painful or painless symptoms, but many patients experience both. Once diagnosed appropriately, painful diabetic neuropathy management presents a unique challenge for physicians and should be considered as a syndrome, clinically distinct from diabetic peripheral neuropathy. The aetiology is multifactorial: metabolic changes in diabetes may directly affect neural tissue and neurodegenerative changes are precipitated by compromised nerve vascular supply. Metabolic changes include the elevated polyol pathway activity, the increased oxidative stress, the formation of advanced glycation and lipoxidation end products, and various pro-inflammatory changes. These mechanisms work in combination and interact in a mutually facilitatory fashion. This review focuses on the current therapies for the management of peripheral and cardiovascular autonomic neuropathy and of painful neuropathy as a distinct entity, based on the current knowledge of diabetic neuropathy. Moreover, the role of ACE inhibition has been explored in the treatment of Cardiovascular Autonomic Neuropathy.
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Affiliation(s)
- Triantafyllos Didangelos
- Diabetes Center, 1st Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, ''AHEPA'' Hospital, Thessaloniki, Greece
| | - Aristidis Veves
- Center for Regenerative Therapeutics, The Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Boston, MA, United States
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Hjortkjær HØ, Jensen T, Hilsted J, Mogensen UM, Corinth H, Rossing P, Køber L, Kofoed KF. Left ventricular remodelling and cardiac chamber sizes in long-term, normoalbuminuric type 1 diabetes patients with and without cardiovascular autonomic neuropathy. J Diabetes Complications 2019; 33:171-177. [PMID: 30355473 DOI: 10.1016/j.jdiacomp.2018.10.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 10/03/2018] [Accepted: 10/09/2018] [Indexed: 01/19/2023]
Abstract
AIMS Type 1 diabetes is associated with increased cardiovascular (CV) morbidity and mortality, and cardiovascular autonomic neuropathy (CAN) is an important CV risk factor. The study aimed to explore associations between CAN and altered cardiac chamber sizes in persons with type 1 diabetes. METHODS This was a cross-sectional study of 71 asymptomatic, normoalbuminuric participants with long-term type 1 diabetes (39 with CAN, determined by >1 abnormal autonomic function test) examined with cardiac multi detector computed tomography scans, which allowed measurements of left ventricular mass and all four cardiac chamber volumes. Cardiac chambers were indexed according to body surface area (ml/m2 or g/m2). RESULTS Persons with and without CAN had mean ± SD age of 57 ± 7 and 50 ± 8 years (p < 0.001) and diabetes duration of 36 ± 11 and 32 ± 9 years (p < 0.05), respectively. Increasing autonomic dysfunction, evaluated by decrease in heart rate variability during deep breathing (in beats per minute), was associated with larger right (-0.5, 95% CI -1.0 to -0.0, p < 0.05) and trend towards larger left (-0.4, 95% CI -0.8-0.0, p < 0.1) ventricular volumes in multivariable linear regression. CONCLUSIONS Our results suggest that impaired autonomic function may be associated with modest enlargement of ventricular volumes; this might be an early sign of progression towards heart failure.
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Affiliation(s)
- Henrik Ø Hjortkjær
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Denmark.
| | - Tonny Jensen
- Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Jannik Hilsted
- Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulrik M Mogensen
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Helle Corinth
- Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Lars Køber
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Klaus F Kofoed
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Radiology, Rigshospitalet, Copenhagen University Hospital, Denmark
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Nakos I, Kadoglou NPE, Gkeka P, Tzallas AT, Giannakeas N, Tsalikakis DG, Katsimpoulas M, Mantziaras G, Kostomitsopoulos N, Liapis CD, Kakisis J. Exercise Training Attenuates the Development of Cardiac Autonomic Dysfunction in Diabetic Rats. In Vivo 2019; 32:1433-1441. [PMID: 30348698 DOI: 10.21873/invivo.11396] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 09/25/2018] [Accepted: 09/27/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND/AIM Exercise training usually complements pharmacological therapy of type 1 diabetes mellitus, however, little is known about its impact on cardiac autonomic neuropathy. Our aim was to evaluate the impact of exercise on electrocardiographic parameters and heart rate variability in diabetic rats. MATERIALS AND METHODS Wistar rats were randomly assigned to four groups (n=12): Sedentary control (SC), sedentary diabetic (SD), exercise control (EC), and exercise diabetic (ED). Diabetes was induced by a single intraperitoneal injection of streptozotocin (45 mg/kg). Exercise groups underwent 8 weeks of training on a treadmill. At the end of the study, echocardiography was performed and continuous electrocardiographic recording was obtained by intra-abdominally implanted telemetric devices. Diabetes induction significantly reduced the heart rate and increased the blood glucose level (p<0.001) and R-wave amplitude (p<0.05). Frequency-domain spectral variables were also analyzed. The SD group had a significantly lower absolute high-frequency component (p<0.05) and higher normalized low-frequency component, as well as low-frequency power divided by the high-frequency power ratio when compared to the SC and EC groups (p<0.05). All these diabetes-related adverse changes in heart rate variability parameters were significantly reversed by exercise training (p<0.05). Overall, our study shows that early initiation of systemic exercise training prevents the development of cardiac autonomic neuropathy in rats with type 1 diabetes mellitus, by favorable change in the balance between parasympathetic and sympathetic activity.
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Affiliation(s)
- Ioannis Nakos
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece
| | - Nikolaos P E Kadoglou
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece.,The Heart Hospital, University College London, London, U.K
| | - Paraskevi Gkeka
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece
| | - Alexandros T Tzallas
- Department of Computer Engineering, School of Applied Technology, Technological Educational Institute of Epirus, Arta, Greece
| | - Nikolaos Giannakeas
- Department of Computer Engineering, School of Applied Technology, Technological Educational Institute of Epirus, Arta, Greece
| | - Dimitrios G Tsalikakis
- Research and Analysis Laboratory, Department of Informatics and Telecommunication Engineering, University of Western Macedonia, Kozani, Greece
| | - Michalis Katsimpoulas
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece
| | - Georgios Mantziaras
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece
| | - Nikolaos Kostomitsopoulos
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece
| | - Christos D Liapis
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece.,Athens Medical Center, Vascular and Endovascular Surgery Clinic, Athens, Greece
| | - John Kakisis
- Biomedical Research Foundation, Center of Clinical, Experimental Surgery, and Translational Research, Academy of Athens, Athens, Greece.,Athens Medical Center, Vascular and Endovascular Surgery Clinic, Athens, Greece
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Toedebusch R, Belenchia A, Pulakat L. Diabetic Cardiomyopathy: Impact of Biological Sex on Disease Development and Molecular Signatures. Front Physiol 2018; 9:453. [PMID: 29773993 PMCID: PMC5943496 DOI: 10.3389/fphys.2018.00453] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 04/11/2018] [Indexed: 12/14/2022] Open
Abstract
Diabetic cardiomyopathy refers to a unique set of heart-specific pathological variables induced by hyperglycemia and insulin resistance. Given that cardiovascular disease (CVD) is the leading cause of death in the world, and type 2 diabetes incidence continues to rise, understanding the complex interplay between these two morbidities and developing novel therapeutic strategies is vital. Two hallmark characteristics specific to diabetic cardiomyopathy are diastolic dysfunction and cardiac structural mal-adaptations, arising from cardiac cellular responses to the complex toxicity induced by hyperglycemia with or without hyperinsulinemia. While type 2 diabetes is more prevalent in men compared to women, cardiovascular risk is higher in diabetic women than in diabetic men, suggesting that diabetic women take a steeper path to cardiomyopathy and heart failure. Accumulating evidence from randomized clinical trials indicate that although pre-menopausal women have lower risk of CVDs, compared to age-matched men, this advantage is lost in diabetic pre-menopausal women, which suggests estrogen availability does not protect from increased cardiovascular risk. Notably, few human studies have assessed molecular and cellular mechanisms regarding similarities and differences in the progression of diabetic cardiomyopathy in men versus women. Additionally, most pre-clinical rodent studies fail to include female animals, leaving a void in available data to truly understand the impact of biological sex differences in diabetes-induced dysfunction of cardiovascular cells. Elegant reviews in the past have discussed in detail the roles of estrogen-mediated signaling in cardiovascular protection, sex differences associated with telomerase activity in the heart, and cardiac responses to exercise. In this review, we focus on the emerging cellular and molecular markers that define sex differences in diabetic cardiomyopathy based on the recent clinical and pre-clinical evidence. We also discuss miR-208a, MED13, and AT2R, which may provide new therapeutic targets with hopes to develop novel treatment paradigms to treat diabetic cardiomyopathy uniquely between men and women.
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Affiliation(s)
- Ryan Toedebusch
- Cardiovascular Medicine Division, Department of Medicine, University of Missouri, Columbia, MO, United States.,Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States
| | - Anthony Belenchia
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States.,Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United States
| | - Lakshmi Pulakat
- Cardiovascular Medicine Division, Department of Medicine, University of Missouri, Columbia, MO, United States.,Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, United States.,Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United States
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Didangelos T, Moralidis E, Karlafti E, Tziomalos K, Margaritidis C, Kontoninas Z, Stergiou I, Boulbou M, Papagianni M, Papanastasiou E, Hatzitolios AI. A Comparative Assessment of Cardiovascular Autonomic Reflex Testing and Cardiac 123I-Metaiodobenzylguanidine Imaging in Patients with Type 1 Diabetes Mellitus without Complications or Cardiovascular Risk Factors. Int J Endocrinol 2018; 2018:5607208. [PMID: 29721015 PMCID: PMC5867537 DOI: 10.1155/2018/5607208] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 01/31/2018] [Indexed: 02/08/2023] Open
Abstract
AIM To compare the cardiovascular autonomic reflex tests (CARTs) with cardiac sympathetic innervation imaging with 123I-metaiodobenzylguanidine (MIBG) in patients with type 1 diabetes mellitus (T1DM). PATIENTS AND METHODS Forty-nine patients (29 males, mean age 36 ± 10 years, mean T1DM duration 19 ± 6 years) without cardiovascular risk factors were prospectively enrolled. Participants were evaluated for autonomic dysfunction by assessing the mean circular resultant (MCR), Valsalva maneuver (Vals), postural index (PI), and orthostatic hypotension (OH). Within one month from the performance of these tests, patients underwent cardiac MIBG imaging and the ratio of the heart to upper mediastinum count density (H/M) at 4 hours postinjection was calculated (abnormal values, H/M < 1.80). RESULTS Twenty-nine patients (59%) had abnormal CARTs, and 37 (76%) patients had an H/M_4 < 1.80 (p = 0.456). MCR, PI, Vals, and OH were abnormal in 29 (59%), 8 (16%), 5 (10%), and 11 (22%) patients, respectively. When using H/M_4 < 1.80 as the reference standard, a cutoff point of ≥2 abnormal CARTs had a sensitivity of 100% but a specificity of only 33% for determining CAN. CONCLUSIONS CARTs are not closely associated with 123I-MIBG measurements, which can detect autonomic dysfunction more efficiently than the former. In comparison to semiquantitative cardiac MIBG assessment, the recommended threshold of ≥2 abnormal CARTs to define cardiovascular autonomic dysfunction is highly sensitive but of limited specificity and is independently determined by the duration of T1DM.
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Affiliation(s)
- Triantafyllos Didangelos
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Efstratios Moralidis
- Laboratory of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece
| | - Eleni Karlafti
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Konstantinos Tziomalos
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Charalambos Margaritidis
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Zisis Kontoninas
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Ioannis Stergiou
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Maria Boulbou
- Department of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Marianthi Papagianni
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | | | - Apostolos I. Hatzitolios
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
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Lee SJ, Jeong SJ, Lee YC, Lee YH, Lee JE, Kim CH, Min KW, Cha BY. Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea. Diabetes Metab J 2017; 41:275-283. [PMID: 28868825 PMCID: PMC5583405 DOI: 10.4093/dmj.2017.41.4.275] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 04/21/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by -3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by -15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by -0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.
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Affiliation(s)
- Sol Jae Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Su Jin Jeong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Yu Chang Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Yong Hoon Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Jung Eun Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Chong Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea.
| | - Kyung Wan Min
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea
| | - Bong Yun Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Mizamtsidi M, Paschou SA, Grapsa J, Vryonidou A. Diabetic cardiomyopathy: a clinical entity or a cluster of molecular heart changes? Eur J Clin Invest 2016; 46:947-953. [PMID: 27600276 DOI: 10.1111/eci.12673] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 09/04/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Although the increasing rate of cardiovascular mortality in patients with diabetes is thought to be due to the coronary atherosclerosis caused mainly by compounding factors such as dyslipidaemia and hypertension, it is now well documented that diabetes alone can lead to a vast array of molecular changes in the heart. DESIGN The aim of this article was to comprehensively review the pathophysiological and molecular changes leading to diabetic cardiomyopathy (DCM), as well as to critically analyse the literature that offers evidence in favour and against the existence of the overt clinical expression of this entity. RESULTS We included in the discussion studies that have revealed the existence of diabetic cardiomyopathy with unique remodelling pattern when compared to other types of cardiomyopathies. On the other hand, several studies debate the existence of clinically discernible cardiomyopathy caused only by diabetes and were also presented and discussed in details. CONCLUSION Clinicians should be aware of DCM when facing patients with diabetes in order both to recognize on time relevant symptoms and to intensively look for and treat other compounding factors, apart from optimal glucose control. Furthermore, the elucidation of the pathophysiological mechanisms leading to DCM could provide new therapeutic targets for heart disease, which will be wonderful for the good of our patients.
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Affiliation(s)
- Maria Mizamtsidi
- Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece
| | - Stavroula A Paschou
- Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece
| | - Julia Grapsa
- Department of Cardiovascular Sciences, Imperial College of London, London, UK
| | - Andromachi Vryonidou
- Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece.
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Felício JS, Koury CC, Carvalho CT, Abrahão Neto JF, Miléo KB, Arbage TP, Silva DD, de Oliveira AF, Peixoto AS, Figueiredo AB, Ribeiro Dos Santos ÂKC, Yamada ES, Zanella MT. Present Insights on Cardiomyopathy in Diabetic Patients. Curr Diabetes Rev 2016; 12:384-395. [PMID: 26364799 PMCID: PMC5101638 DOI: 10.2174/1573399812666150914120529] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 08/27/2015] [Accepted: 09/14/2015] [Indexed: 12/22/2022]
Abstract
The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality.
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Affiliation(s)
- João Soares Felício
- Hospital Universitário João de Barros Barreto - Universidade Federal do Pará, Mundurucus Street, 4487 - Postal Code: 66073-000 - Guamá - Belém - PA - Brazil.
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S M, H R. Left Ventricular Diastolic Dysfunction (LVDD) & Cardiovascular Autonomic Neuropathy (CAN) in Type 2 Diabetes Mellitus (DM): A Cross-Sectional Clinical Study. J Clin Diagn Res 2015; 9:OC18-22. [PMID: 25738018 DOI: 10.7860/jcdr/2015/10509.5497] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 11/11/2014] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Cardiovascular autonomic neuropathy (CAN) is one of the major complications of Diabetes Mellitus (DM) seen in a significant number of patients, which is often ignored and is also least frequently diagnosed. It can be diagnosed by performing five standard non-invasive bedside autonomic function tests based on Cardiovascular reflexes, which are quite cumbersome. Studies have revealed an increase in mortality in the diabetic patients with CAN due to silent cardiac ischemia, sudden cardiac death, arrhythmias. The precursor of diabetic cardiomyopathy is Left ventricular diastolic dysfunction (LVDD). In the present study we are studying the association between LVDD and CAN, in order to identify high mortality risk patients by performing 2D Echo and looking at LVDD instead of performing the cumbersome bedside cardiovascular autonomic function tests. AIMS AND OBJECTIVES To study the association between LVDD and CAN in patients with Type 2 DM. MATERIALS AND METHODS This study is a cross-sectional observational study with a sample size of 100. Both outpatients and inpatients between 35 y and 65 y of age with Type 2 DM coming to Department of General Medicine, KIMS hospital, Bangalore were studied from November 2011 to October 2013.Patients with macrovascular complications, Hypertension, congenital & acquired heart diseases etc. were excluded from the study. The standard five autonomic function tests based on cardiovascular reflexes and 2D Echo were performed. Individual scores for each of the five tests were added to produce Ewing's score. Ewing's score of >2.5 is positive for CAN. STATISTICAL ANALYSIS Chi-square/ Fisher Exact test has been. RESULTS There was a significant association between individual non-invasive bedside tests of Ewing's score and LVDD. Significant association was also seen between LVDD and positive Ewing's score. CONCLUSION Positive Ewing's score is strongly associated with LVDD in patients with Type 2 DM in this study .This suggests that patients with LVDD have CAN and hence, are at increased risk of sudden cardiac death. As bedside tests are cumbersome, patients with LVDD on 2D Echo can be concluded to have CAN.
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Affiliation(s)
- Mythri S
- Post Graduate Student, Department of General Medicine, Kempegowda Institute of Medical Sciences, Rajiv Gandhi University of Health Sciences , Bangalore, India
| | - Rajeev H
- Associate Professor, Department of General Medicine, Kempegowda Institute of Medical Sciences, Rajiv Gandhi University of Health Sciences , Bangalore, India
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Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes 2014; 5:17-39. [PMID: 24567799 PMCID: PMC3932425 DOI: 10.4239/wjd.v5.i1.17] [Citation(s) in RCA: 191] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 12/02/2013] [Accepted: 12/12/2013] [Indexed: 02/05/2023] Open
Abstract
Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.
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Didangelos TP, Arsos G, Karamitsos T, Iliadis F, Papageorgiou A, Moralidis E, Athyros V. Left ventricular systolic and diastolic function in normotensive type 2 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study. Angiology 2013; 65:877-82. [PMID: 24265250 DOI: 10.1177/0003319713510966] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n=24), patients with DAN (n=35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1%±8.2% vs 26.5%±5.1%; P=.031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8±6.3 vs 69.3±3.3 bpm; P<.0001) and a higher rest LV workload (10,072±1165 vs 8606±1075 bpm mm Hg; P<.0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.
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Affiliation(s)
- Triantafyllos P Didangelos
- First Propeudetic Department of Internal Medicine, Diabetes Center, Medical School, Aristotle University of Thessaloniki, "AHEPA'' Hospital, Thessaloniki, Greece
| | - Georgios Arsos
- Laboratory of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece
| | - Theodoros Karamitsos
- Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom
| | - Fotios Iliadis
- First Propeudetic Department of Internal Medicine, Diabetes Center, Medical School, Aristotle University of Thessaloniki, "AHEPA'' Hospital, Thessaloniki, Greece
| | - Athanasios Papageorgiou
- Second Propeudetic Department of Internal Medicine Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
| | - Efstratios Moralidis
- Laboratory of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, "AHEPA" Hospital, Thessaloniki, Greece
| | - Vasilios Athyros
- Second Propeudetic Department of Internal Medicine Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
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Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Investig 2013; 4:4-18. [PMID: 23550085 PMCID: PMC3580884 DOI: 10.1111/jdi.12042] [Citation(s) in RCA: 224] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2012] [Accepted: 11/14/2012] [Indexed: 12/16/2022] Open
Abstract
One of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy. There is now clear evidence that suggests activation of inflammatory cytokines in diabetic patients and that these correlate with abnormalities in sympathovagal balance. Dysfunction of the autonomic system predicts cardiovascular risk and sudden death in patients with type 2 diabetes. It also occurs in prediabetes, providing opportunities for early intervention. Simple tests that can be carried out at the bedside with real-time output of information - within the scope of the practicing physician - facilitate diagnosis and allow the application of sound strategies for management. The window of opportunity for aggressive control of all the traditional risk factors for cardiovascular events or sudden death with intensification of therapy is with short duration diabetes, the absence of cardiovascular disease and a history of severe hypoglycemic events. To this list we can now add autonomic dysfunction and neuropathy, which have become the most powerful predictors of risk for mortality. It seems prudent that practitioners should be encouraged to become familiar with this information and apply risk stratification in clinical practice. Several agents have become available for the correction of functional defects in the autonomic nervous system, and restoration of autonomic balance is now possible.
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Affiliation(s)
- Aaron I Vinik
- The Strelitz Diabetes Research Center and Neuroendocrine Unit, The Department of Medicine and Pathology/Anatomy/Neurobiology, Eastern Virginia Medical School Norfolk, Virginia, USA
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Karayannis G, Giamouzis G, Cokkinos DV, Skoularigis J, Triposkiadis F. Diabetic cardiovascular autonomic neuropathy: clinical implications. Expert Rev Cardiovasc Ther 2013; 10:747-65. [PMID: 22894631 DOI: 10.1586/erc.12.53] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diabetic cardiovascular autonomic neuropathy (DCAN), the impairment of the autonomic balance of the cardiovascular system in the setting of diabetes mellitus (DM), is frequently observed in both Type 1 and 2 DM, has detrimental effects on the quality of life and portends increased mortality. Clinical manifestations include: resting heart rate disorders, exercise intolerance, intraoperative cardiovascular lability, orthostatic alterations in heart rate and blood pressure, QT-interval prolongation, abnormal diurnal and nocturnal blood pressure variation, silent myocardial ischemia and diabetic cardiomyopathy. Clinical tests for autonomic nervous system evaluation, heart rate variability analysis, autonomic innervation imaging techniques, microneurography and baroreflex analysis are the main diagnostic tools for DCAN detection. Aldose reductase inhibitors and antioxidants may be helpful in DCAN therapy, but a regular, more generalized and multifactorial approach should be adopted with inclusion of lifestyle modifications, strict glycemic control and treatment of concomitant traditional cardiovascular risk factors, in order to achieve the best therapeutic results. In the present review, the authors provide aspects of DCAN pathophysiology, clinical presentation, diagnosis and an algorithm regarding the evaluation and management of DCAN in DM patients.
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Effect of cardiovascular autonomic neuropathy (CAN) on left ventricular function in normotensive type 1 diabetic patients: A study by pulsed wave tissue Doppler echocardiography. Egypt Heart J 2012. [DOI: 10.1016/j.ehj.2011.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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Perseghin G, Lattuada G, De Cobelli F, Esposito A, Canu T, Ragogna F, Maffi P, Scifo P, Secchi A, Del Maschio A, Luzi L. Left ventricular function and energy homeostasis in patients with type 1 diabetes with and without microvascular complications. Int J Cardiol 2012; 154:111-5. [PMID: 20926147 DOI: 10.1016/j.ijcard.2010.09.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2010] [Revised: 07/01/2010] [Accepted: 09/05/2010] [Indexed: 11/21/2022]
Abstract
BACKGROUND This study was performed to assess left ventricular (LV) energy metabolism and function in patients with type 1 diabetes with or without overt microvascular complications. METHODS We performed cardiac Magnetic Resonance Imaging (MRI) and (31)P spectroscopy (MRS) in 24 patients with overt microvascular complications and in 15 carefully selected patients without complications in spite of a long duration of the disease (>20 years) and matched for anthropometric features. 31 healthy subjects served as a control group. RESULTS Systolic function was preserved in all study subjects. Patients with overt complications showed a higher LV wall mass/end diastolic volume ratio and altered parameters of diastolic function when compared to patients without complications and to controls. They were also characterized by lower PCr/ATP ratio (a recognized marker of energy metabolism). No effect of HbA1c was detected within groups. CONCLUSIONS In patients with type 1 diabetes 1) overt microvascular complications were associated with altered LV geometry, diastolic function and energy metabolism 2) in patients without complications and duration of disease >20 years no association with these alterations were found despite poor glycemic control. The features of this highly selected subgroup of patients demonstrated that long lasting chronic hyperglycemia per se is not sufficient to induce abnormality of cardiac energy metabolism and that additional yet to be identified (metabolic or genetic) factors must be important contributing factors.
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Affiliation(s)
- Gianluca Perseghin
- Internal Medicine, Section of Nutrition, Istituto Scientifico San Raffaele, Milano, Italy.
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Sacre JW, Franjic B, Jellis CL, Jenkins C, Coombes JS, Marwick TH. Association of cardiac autonomic neuropathy with subclinical myocardial dysfunction in type 2 diabetes. JACC Cardiovasc Imaging 2011; 3:1207-15. [PMID: 21163448 DOI: 10.1016/j.jcmg.2010.09.014] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2010] [Revised: 09/07/2010] [Accepted: 09/13/2010] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The purpose of this study was to investigate the independent association between global cardiac autonomic neuropathy (CAN) and left ventricular (LV) dysfunction in addition to regional associations of LV dysinnervation and function, in patients with type 2 diabetes mellitus (T2DM). BACKGROUND CAN represents a potential mechanism in the etiology of nonischemic diabetic cardiomyopathy. METHODS Clinical measures of CAN based on total spectral power of heart rate variability and cardiac reflex testing and echocardiographic assessment of LV function were performed in 118 patients with type 2 diabetes mellitus. Systolic and diastolic function were defined at rest and peak exercise using peak systolic and peak early diastolic (Em) tissue velocities, calculated in 6 basal- and mid-segments using color tissue Doppler. Iodine 123-metaiodobenzylguanidine imaging was performed in 33 patients to directly quantify global (heart/mediastinum ratio) and regional LV sympathetic integrity. RESULTS Patients with CAN demonstrated higher resting heart rate, systolic and mean blood pressures, aortic stiffness, hemoglobin A(1c), and urine albumin/creatinine ratio, in addition to lower peak heart rate, chronotropic index, and exercise capacity. Diastolic function (Em) was associated with CAN, evidenced by total spectral power (r = 0.42, p < 0.001) and heart/mediastinum ratio (r = 0.41, p = 0.017). Diastolic function (Em) at rest and systolic function (peak systolic tissue velocity) at rest and exercise were significantly reduced in patients with CAN. Furthermore, total spectral power was associated with Em independent of age, hypertension, metabolic factors, and other relevant contributors to LV dysfunction (β = 0.20, p = 0.035). Relative regional tracer deficits indicative of local denervation were predominant in the anterior and lateral walls (p < 0.001). Associations with regional Em, independent of global iodine 123-metaiodobenzylguanidine uptake, were identified exclusively in mid-anterior (β = 0.45, p = 0.01) and mid-lateral walls (β = 0.34, p = 0.03). However, no association was found between regional denervation and systolic or diastolic dyssynchrony. CONCLUSIONS The diastolic dysfunction of type 2 diabetes mellitus shows associations with both regional markers of sympathetic integrity and clinical markers of autonomic neuropathy.
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MESH Headings
- Aged
- Aorta/physiopathology
- Autonomic Nervous System/physiopathology
- Blood Pressure
- Cardiomyopathies/diagnosis
- Cardiomyopathies/etiology
- Cardiomyopathies/physiopathology
- Chi-Square Distribution
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/physiopathology
- Diabetic Neuropathies/etiology
- Diabetic Neuropathies/physiopathology
- Echocardiography, Doppler, Color
- Elasticity
- Exercise Test
- Exercise Tolerance
- Female
- Heart Rate
- Heart Ventricles/innervation
- Humans
- Linear Models
- Male
- Middle Aged
- Myocardial Perfusion Imaging
- Predictive Value of Tests
- Reflex
- Risk Assessment
- Risk Factors
- Tomography, Emission-Computed, Single-Photon
- Ventricular Dysfunction, Left/diagnosis
- Ventricular Dysfunction, Left/etiology
- Ventricular Dysfunction, Left/physiopathology
- Ventricular Function, Left
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Affiliation(s)
- Julian W Sacre
- School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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Stadler M, Theuer E, Anderwald C, Hanusch-Enserer U, Auinger M, Bieglmayer C, Quehenberger P, Bischof M, Kästenbauer T, Wolzt M, Wagner O, Prager R. Persistent arterial stiffness and endothelial dysfunction following successful pancreas-kidney transplantation in Type 1 diabetes. Diabet Med 2009; 26:1010-8. [PMID: 19900233 DOI: 10.1111/j.1464-5491.2009.02817.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Successful simultaneous pancreas-kidney transplantation (SPK) in Type 1 diabetic (T1DM) patients results in improved cardiovascular outcome and survival. However, it is doubtful whether the impairment of cardiovascular and endothelial function in T1DM can be completely reversed. METHODS Pulse-wave velocity, stroke volume, heart rate, serological markers of endothelial dysfunction (soluble intercellular, vascular cell-adhesion molecules, E-selectin, and plasminogen-activator-inhibitor-1) were measured in 10 T1DM patients after SPK with non-diabetic glucose levels, 10 T1DM patients with poor [T1DM>8; glycated haemoglobin (HbA1c)>8%], and 10 with good glucose control (T1DM<7, HbA1c<7%), in 6 non-diabetic patients after kidney transplantation (KT) and 9 non-diabetic control subjects (CON), matching for major anthropometric characteristics. RESULTS Pulse-wave velocity was increased in SPK (P < 0.02 vs. CON, KT, T1DM<7) and in T1DM>8 (P < 0.02 vs. T1DM<7). Systolic blood pressure was increased in SPK (P < 0.05 vs. CON). Stroke volume was reduced in SPK, T1DM>8 and T1DM<7 and KT (P < 0.01 vs. CON). Heart rate was elevated in SPK and in T1DM>8 (P < 0.0003 vs. CON and T1DM<7). In SPK, soluble intercellular and vascular cell-adhesion molecules were 100% and 44% higher (P < 0.03 vs. CON), respectively, while plasminogen-activator-inhibitor-1 was decreased in SPK (P < 0.02 vs. CON). CONCLUSION T1DM patients after SPK experience arterial stiffness, a higher heart-rate and blood pressure, reduced stroke volume and serological signs of endothelial dysfunction. Thus, functional and structural cardiovascular alterations as a result of glucotoxicity, uraemia and hypertension in T1DM might not be completely resolved by SPK.
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Affiliation(s)
- M Stadler
- 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, A-1130 Vienna, Austria.
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Resl M, Hülsmann M, Pacher R, Clodi M. [Heart failure in diabetes]. Wien Med Wochenschr 2009; 159:134-40. [PMID: 19343290 DOI: 10.1007/s10354-009-0645-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2008] [Accepted: 10/03/2008] [Indexed: 01/01/2023]
Abstract
Interactions of glucose metabolism and chronic heart failure have been confirmed by many epidemiologic studies. The association of HbA1c with an increasing risk of heart failure clearly underlines the connection between both diseases. Coronary artery disease (CAD), hypertension and diabetic cardiomyopathy are long-term complications of diabetes mellitus, resulting in diabetic heart failure. Dysfunction of many regulation systems leads to specific diabetic cardiomyopathy, which has been firstly described by Rubler. A reduction in the cardiac expression of the Na-Ca exchanger pump and SERCA2a protein results in an imbalance in cardiac calcium handling. The overactive renin angiotensin aldosteron system (RAAS) also contributes to the impairment of myocardial function. Hyperlipidaemia, hpyerinsulinaemia and hyperglycaemia directly trigger diabetic cardiomyopathy. Generally chronic heart failure is a clinical diagnosis verified by blood tests like NT-proBNP and cardiac ultrasound. Recommendations on treatment of diabetic heart failure are based on subgroup analysis of the large heart failure trials.
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Affiliation(s)
- Michael Resl
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Austria
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Lacigova S, Bartunek L, Cechurova D, Visek J, Gruberova J, Krcma M, Jankovec Z, Rusavy Z, Zourek M. Influence of cardiovascular autonomic neuropathy on atherogenesis and heart function in patients with type 1 diabetes. Diabetes Res Clin Pract 2009; 83:26-31. [PMID: 19013660 DOI: 10.1016/j.diabres.2008.09.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2008] [Revised: 09/03/2008] [Accepted: 09/04/2008] [Indexed: 10/21/2022]
Abstract
AIM Cardiovascular autonomic neuropathy (CAN) increases mortality of patients with type 1 diabetes (Type 1 DM). We set out to find out whether the presence of CAN in asymptomatic, normotensive Type 1 DM affects endothelial function (marker of atherogenesis) and left ventricle function (marker of cardiomyopathy). METHODS Twenty-one Type 1 DM with CAN (Group A) and 35 Type 1 DM without CAN (Group B) were enrolled in the study. None of them suffered from any cardiovascular disease nor advanced chronic complications of diabetes. Both groups were comparable in age, glycemic control, BMI, and blood pressure. Markers of endothelial dysfunction and chronic inflammation were used as indicators of incipient atherogenesis. Left ventricle function was evaluated using echocardiography. RESULTS Both groups did not differ in any parameter of atherogenesis. However we found a statistically significant difference in values characterizing systolic and diastolic left ventricle functions between the groups. CONCLUSIONS CAN is not associated with elevation of markers of endothelial dysfunction and chronic inflammation in normotensive asymptomatic Type 1 DM. However CAN is associated with the impairment of systolic and diastolic left ventricle function and can thus be regarded as one of the risk factors of diabetic cardiomyopathy.
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Affiliation(s)
- Silvie Lacigova
- Department of Diabetology, University Hospital, Charles University in Prague, Faculty of Medicine in Pilsen, Czech Republic.
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Karamitsos TD, Karvounis HI, Didangelos T, Parcharidis GE, Karamitsos DT. Impact of autonomic neuropathy on left ventricular function in normotensive type 1 diabetic patients: a tissue Doppler echocardiographic study. Diabetes Care 2008; 31:325-7. [PMID: 18000173 DOI: 10.2337/dc07-1634] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Cardiovascular autonomic neuropathy (CAN) is one of the most serious complications of diabetes and has been weakly linked with left ventricular (LV) diastolic dysfunction. Previous studies that explored this association either suffer from inadequate definition of CAN or have mainly used conventional Doppler or nuclear techniques to investigate LV diastolic function. Tissue Doppler imaging (TDI) has evolved as a new quantitative tool for the assessment of cardiac systolic function, diastolic function, and the hemodynamics of LV filling. We sought to investigate conventional and TDI-derived indexes of LV systolic and diastolic function in type 1 diabetic patients with and without CAN and also in normal control subjects. Our findings suggest that the presence of CAN seems to have an additive effect on LV diastolic dysfunction in type 1 diabetes.
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Affiliation(s)
- Aaron I Vinik
- Strelitz Diabetes Research Institute, 855 W Brambleton Avenue, Norfolk, VA 23510, USA.
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Karamitsos TD, Karvounis HI, Dalamanga EG, Papadopoulos CE, Didangellos TP, Karamitsos DT, Parharidis GE, Louridas GE. Early diastolic impairment of diabetic heart: The significance of right ventricle. Int J Cardiol 2007; 114:218-23. [DOI: 10.1016/j.ijcard.2006.02.003] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2005] [Revised: 01/22/2006] [Accepted: 02/03/2006] [Indexed: 02/01/2023]
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Weinrauch LA, Berger AJ, Aronson D, Gleason RE, Lee AT, D'Elia JA. Regression of Left Ventricular Hypertrophy in Diabetic Nephropathy: Loss of Parasympathetic Function Predicts Response to Treatment. J Clin Hypertens (Greenwich) 2006; 8:330-5. [PMID: 16687941 PMCID: PMC8109292 DOI: 10.1111/j.1524-6175.2005.04771.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Both left ventricular (LV) hypertrophy and decreased autonomic function are predictors of adverse cardiac events. Patients with diabetic nephropathy have an excess cardiovascular risk. The authors determined heart rate variability from 24-hour ambulatory electrocardiographic recordings and measures of LV mass with systolic and diastolic function from echocardiograms. Patients with diabetic nephropathy (n=16) were seen weekly for insulin and hypertension management. Glycohemoglobin decreased from 9.5+/-0.4% to 8.3+/-0.4% (p=0.01), and advanced glycated end products decreased from 12.1+/-2.2 to 7.4+/-1.2 units (p=0.03). Mean arterial pressure and body weight did not change. Serum creatinine increased (1.8+/-0.1 mg/dL to 2.0+/-0.2 mg/dL; p=0.03). The authors used a panel of markers of baseline heart rate variation to assess autonomic function. When covariance of the heart rate interval results were evaluated, the group below the median was found to have a significant decrease in LV mass, from 230 g to 184 g (p=0.013); the group above the median had an increase (182 g to 193 g; p=0.5329). Baseline covariance of the heart rate interval predicted 12-month changes in LV mass in 13 of 16 patients (predictive accuracy, 81%). Improvement in measures of heart rate variation correlated with a decrease in LV mass. Parallel improvement of LV mass and autonomic function suggests a common mechanism, allowing for prediction of LV mass improvement through analysis of baseline heart rate variation.
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Affiliation(s)
- Larry A Weinrauch
- Joslin Diabetes Center, Boston, Mount Auburn Hospital, and Harvard Medical School, Cambridge, MA, USA.
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Didangelos TP, Arsos GA, Karamitsos DT, Athyros VG, Georga SD, Karatzas ND. Effect of quinapril or losartan alone and in combination on left ventricular systolic and diastolic functions in asymptomatic patients with diabetic autonomic neuropathy. J Diabetes Complications 2006; 20:1-7. [PMID: 16389160 DOI: 10.1016/j.jdiacomp.2005.05.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2005] [Revised: 04/13/2005] [Accepted: 05/03/2005] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To investigate the effect of angiotensin converting enzyme inhibition (ACE-I) or angiotensin receptor blockade (ARB), and their combination, on both diabetic autonomic neuropathy (DAN) and left ventricular (LV) diastolic dysfunction (LVDD) in asymptomatic patients with diabetes mellitus (DM). MATERIALS AND METHODS Sixty-two patients (34 women) with long-term DM (24 with Type 1) and DAN, aged 51.7+/-13.9 years, free of coronary artery disease (CAD) or arterial hypertension (HT) at baseline, were studied for a 12-month period. Diagnosis of DAN was established if two or more of the standard cardiovascular reflex tests (CRT) were abnormal. Patients were randomly allocated to quinapril (20 mg/day), losartan (100 mg/day), or quinapril plus losartan (20 mg/day+100 mg/day). LV systolic and diastolic function was assessed using radionuclide ventriculography (RNV) at baseline and after 12 months of treatment. RESULTS In all three treatment groups, abnormal CRT values were improved. In the quinapril group, the first third filling fraction (1/3FF, 48.9+/-17.8% vs. 39.2+/-12.9% at baseline, P=.005) was increased and the atrial contribution to ventricular filling (25.1+/-6.3 vs. 30.1+/-7.8, P=.027) was reduced in the losartan group; the peak filling rate (PFR) was improved (3.41+/-.62 vs. 3.11+/-.44 volumes/s, P=.05), and in the combination group, the 1/3FF (39.4+/-11.8% vs. 29.6+/-11.9%, P=.018) was markedly increased, while the time to peak filling (TPF; 147+/-42 vs. 184+/-33 ms, P=.02) and the TPF/filling time (TPF/FT; 32.5+/-6.2% vs. 38.2+/-5.7%, P=.016) were reduced. CONCLUSIONS Early ACE-I or ARB improve both DAN and LVDD in asymptomatic patients with Type 1 or 2 DM, after 1 year of treatment. Their combination may be slightly better than monotherapies on DAN and LVDD. The clinical importance of these effects should be validated by larger studies.
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Affiliation(s)
- Triantafillos P Didangelos
- Diabetes Center, 2nd Propedeutic Clinic of Internal Medicine, Hippocration Hospital, Aristotelian University of Thessaloniki, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece.
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Grandi AM, Piantanida E, Franzetti I, Bernasconi M, Maresca A, Marnini P, Guasti L, Venco A. Effect of glycemic control on left ventricular diastolic function in type 1 diabetes mellitus. Am J Cardiol 2006; 97:71-6. [PMID: 16377287 DOI: 10.1016/j.amjcard.2005.07.110] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2005] [Revised: 07/18/2005] [Accepted: 07/18/2005] [Indexed: 11/15/2022]
Abstract
Left ventricular (LV) diastolic dysfunction is a main feature of diabetic heart disease. The aim of this prospective study was to evaluate the influence of glycemic control on diastolic function in type 1 diabetes mellitus. Thirty-six normotensive (24-hour blood pressure <130/80 mm Hg) subjects with inadequately controlled (glycated hemoglobin >7%) type 1 diabetes, without clinically detectable heart disease, were enrolled. After the basal evaluation, insulin therapy was modified to improve glycemic control. Glycated hemoglobin, LV echocardiography, 24-hour blood pressure monitoring, and laboratory tests were repeated after 6 months in all patients and after 12 months in 27 patients. At the basal evaluation, LV anatomy and systolic function were normal in all, and diastolic function was impaired in 14 patients. After 6 months, the mean values of body mass index, 24-hour blood pressure, and LV anatomy and systolic function were unchanged; mean glycated hemoglobin was decreased (p < 0.001), and mean values of diastolic parameters were significantly improved. After 12 months, the mean values of all blood pressure, metabolic, and LV parameters were unchanged. Percent changes of diastolic parameters were inversely correlated with percent changes of glycated hemoglobin, considering changes from the basal to the 6-month evaluation, as well as changes from the 6- to the 12-month evaluation. In conclusion, in normotensive patients with type 1 diabetes, a close relation was found between glycemic control and LV diastolic function, which improves when glycemic control improves. Therefore, diastolic dysfunction can be prevented or reversed, at least partly, by tight glycemic control.
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Affiliation(s)
- Anna M Grandi
- Department of Clinical Medicine, University of Insubria, Insubria, Italy.
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Nathan DM, Cleary PA, Backlund JYC, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353:2643-53. [PMID: 16371630 PMCID: PMC2637991 DOI: 10.1056/nejmoa052187] [Citation(s) in RCA: 3415] [Impact Index Per Article: 170.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease. METHODS The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee. RESULTS During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P< or =0.05) after adjusting for these factors. CONCLUSIONS Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.
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Klein BEK, Klein R, McBride PE, Moss SE, Prineas RJ, Reinke JO. Electrocardiographic abnormalities in individuals with long-duration type 1 diabetes. Diabetes Care 2005; 28:145-7. [PMID: 15616248 DOI: 10.2337/diacare.28.1.145] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Barbara E K Klein
- Department of Ophthalmology and Visual Sciences, University of Wisconsin, School of Medicine, Madison, Wisconsin 53726, USA.
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Johnson BF, Nesto RW, Pfeifer MA, Slater WR, Vinik AI, Chyun DA, Law G, Wackers FJT, Young LH. Cardiac abnormalities in diabetic patients with neuropathy: effects of aldose reductase inhibitor administration. Diabetes Care 2004; 27:448-54. [PMID: 14747227 DOI: 10.2337/diacare.27.2.448] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy. RESEARCH DESIGN AND METHODS Diabetic subjects with neuropathy (n = 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year. RESULTS After 1 year of ARI treatment, there were increases in resting LVEF (P < 0.02), cardiac output (P < 0.03), LV stroke volume (P < 0.004), and exercise LVEF (P < 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P < 0.03), stroke volume (P < 0.02), and end diastolic volume (P < 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group. CONCLUSIONS Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.
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Szczepanska Kostro J, Tolwinska J, Urban M, Gardziejczyk M, Glowińska B. Cardiac Mass and Function, Carotid Artery Intima Media Thickness, Homocysteine and Lipoprotein Levels in Children and Adolescents with Growth Hormone Deficiency. ACTA ACUST UNITED AC 2004. [DOI: 10.1515/jpem.2004.17.10.1405] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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