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Leon-Mercado L, Gautron L. Sympathetic NPY boosts thermogenic adipocytes. Am J Physiol Endocrinol Metab 2025; 328:E44-E45. [PMID: 39606907 DOI: 10.1152/ajpendo.00377.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 11/19/2024] [Accepted: 11/19/2024] [Indexed: 11/29/2024]
Affiliation(s)
- Luis Leon-Mercado
- Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States
| | - Laurent Gautron
- Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States
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Caturano A, Galiero R, Vetrano E, Sardu C, Rinaldi L, Russo V, Monda M, Marfella R, Sasso FC. Insulin-Heart Axis: Bridging Physiology to Insulin Resistance. Int J Mol Sci 2024; 25:8369. [PMID: 39125938 PMCID: PMC11313400 DOI: 10.3390/ijms25158369] [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: 07/01/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin-heart axis, focusing on insulin's multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin-angiotensin-aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin-heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (R.G.); (E.V.); (C.S.); (R.M.)
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy;
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (R.G.); (E.V.); (C.S.); (R.M.)
| | - Erica Vetrano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (R.G.); (E.V.); (C.S.); (R.M.)
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (R.G.); (E.V.); (C.S.); (R.M.)
| | - Luca Rinaldi
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, Università degli Studi del Molise, 86100 Campobasso, Italy;
| | - Vincenzo Russo
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA;
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Marcellino Monda
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy;
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (R.G.); (E.V.); (C.S.); (R.M.)
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (R.G.); (E.V.); (C.S.); (R.M.)
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Tang Y, Ang L, Jaiswal M, Dillon BR, Esfandiari NH, Shah HS, Spino C, Plunkett C, Perkins BA, Pop-Busui R, Doria A. Cardiovascular Autonomic Neuropathy and Risk of Kidney Function Decline in Type 1 and Type 2 Diabetes: Findings From the PERL and ACCORD Cohorts. Diabetes 2024; 73:751-762. [PMID: 37467433 PMCID: PMC11043059 DOI: 10.2337/db23-0247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/29/2023] [Indexed: 07/21/2023]
Abstract
Results of previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among people with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N = 469) and with type 2 diabetes (T2D) from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (N = 7,973). Baseline CAN was ascertained with electrocardiogram-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss of ≥5 mL/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed-effects, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 mL/min/1.73 m2/year (95% CI -1.93 to -0.37; P = 4.0 × 10-3) in PERL and 0.34 mL/min/1.73 m2/year (95% CI -0.49 to -0.19; P = 6.3 × 10-6) in ACCORD. This translated to 2.11 (95% CI 1.23-3.63; P = 6.9 × 10-3) and 1.39 (95% CI 1.20-1.61; P = 1.1 × 10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (hazard ratio 2.60 [95% CI 1.15-5.45], P = 0.02, in PERL and hazard ratio 1.54 [95% CI 1.28-1.84], P = 3.8 × 10-6, in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help with development of new therapies to prevent kidney function decline in patients with diabetes. ARTICLE HIGHLIGHTS
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Affiliation(s)
- Yaling Tang
- Research Division, Joslin Diabetes Center, Boston, MA
- Department of Medicine, Harvard Medical School, Boston, MA
| | - Lynn Ang
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Mamta Jaiswal
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Brendan R. Dillon
- Department of Medicine, NYU Grossman School of Medicine, New York, NY
| | - Nazanene H. Esfandiari
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Hetal S. Shah
- Research Division, Joslin Diabetes Center, Boston, MA
- Department of Medicine, Harvard Medical School, Boston, MA
| | - Cathie Spino
- Statistical Analysis of Biomedical and Educational Research (SABER), University of Michigan, Ann Arbor, MI
| | - Cindy Plunkett
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Bruce A. Perkins
- Division of Endocrinology, University of Toronto, Toronto, Canada
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Alessandro Doria
- Research Division, Joslin Diabetes Center, Boston, MA
- Department of Medicine, Harvard Medical School, Boston, MA
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Julián MT, Pérez-Montes de Oca A, Julve J, Alonso N. The double burden: type 1 diabetes and heart failure-a comprehensive review. Cardiovasc Diabetol 2024; 23:65. [PMID: 38347569 PMCID: PMC10863220 DOI: 10.1186/s12933-024-02136-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 01/15/2024] [Indexed: 02/15/2024] Open
Abstract
Heart failure (HF) is increasing at an alarming rate, primary due to the rising in aging, obesity and diabetes. Notably, individuals with type 1 diabetes (T1D) face a significantly elevated risk of HF, leading to more hospitalizations and increased case fatality rates. Several risk factors contribute to HF in T1D, including poor glycemic control, female gender, smoking, hypertension, elevated BMI, and albuminuria. However, early and intensive glycemic control can mitigate the long-term risk of HF in individuals with T1D. The pathophysiology of diabetes-associated HF is complex and multifactorial, and the underlying mechanisms in T1D remain incompletely elucidated. In terms of treatment, much of the evidence comes from type 2 diabetes (T2D) populations, so applying it to T1D requires caution. Sodium-glucose cotransporter 2 inhibitors have shown benefits in HF outcomes, even in non-diabetic populations. However, most of the information about HF and the evidence from cardiovascular safety trials related to glucose lowering medications refer to T2D. Glycemic control is key, but the link between hypoglycemia and HF hospitalization risk requires further study. Glycemic variability, common in T1D, is an independent HF risk factor. Technological advances offer the potential to improve glycemic control, including glycemic variability, and may play a role in preventing HF. In summary, HF in T1D is a complex challenge with unique dimensions. This review focuses on HF in individuals with T1D, exploring its epidemiology, risk factors, pathophysiology, diagnosis and treatment, which is crucial for developing tailored prevention and management strategies for this population.
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Affiliation(s)
- María Teresa Julián
- Department of Endocrinology and Nutrition, Hospital Germans Trias i Pujol, Badalona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
| | - Alejandra Pérez-Montes de Oca
- Department of Endocrinology and Nutrition, Hospital Germans Trias i Pujol, Badalona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Josep Julve
- Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain
- Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Nuria Alonso
- Department of Endocrinology and Nutrition, Hospital Germans Trias i Pujol, Badalona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
- Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
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Dai ZC, Chen JX, Zou R, Liang XB, Tang JX, Yao CW. Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease. Front Immunol 2023; 14:1213473. [PMID: 37809091 PMCID: PMC10552262 DOI: 10.3389/fimmu.2023.1213473] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 09/06/2023] [Indexed: 10/10/2023] Open
Abstract
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
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Affiliation(s)
| | | | | | | | - Ji-Xin Tang
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Diseases of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Cui-Wei Yao
- Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Diseases of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
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Bell DSH. Detecting and treating the protean manifestations of diabetic autonomic neuropathy. Diabetes Obes Metab 2023; 25:1162-1173. [PMID: 36748121 DOI: 10.1111/dom.15004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/17/2023] [Accepted: 02/02/2023] [Indexed: 02/08/2023]
Abstract
The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic.
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Belli M, Barone L, Bellia A, Sergi D, Lecis D, Prandi FR, Milite M, Galluccio C, Muscoli S, Romeo F, Barillà F. Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients? Int J Mol Sci 2022; 23:ijms232314598. [PMID: 36498924 PMCID: PMC9737325 DOI: 10.3390/ijms232314598] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 11/19/2022] [Accepted: 11/20/2022] [Indexed: 11/24/2022] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.
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Affiliation(s)
- Martina Belli
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
- Cardiovascular Imaging Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Lucy Barone
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Alfonso Bellia
- Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Domenico Sergi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Dalgisio Lecis
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Francesca Romana Prandi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
- Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Marialucia Milite
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Chiara Galluccio
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Saverio Muscoli
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Francesco Romeo
- Department of Departmental Faculty of Medicine, UniCamillus-Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy
| | - Francesco Barillà
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
- Correspondence:
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Potential Roles of Anti-Inflammatory Plant-Derived Bioactive Compounds Targeting Inflammation in Microvascular Complications of Diabetes. Molecules 2022; 27:molecules27217352. [PMID: 36364178 PMCID: PMC9657994 DOI: 10.3390/molecules27217352] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus (DM) is a group of metabolic disorders, the characteristics of which include chronic hyperglycemia owing to defects in insulin function, insulin secretion, or both. Inflammation plays a crucial role in DM pathogenesis and innate immunity in the development of microvascular complications of diabetes. In addition, hyperglycemia and DM mediate a proinflammatory microenvironment that can result in various microvascular complications, including diabetic nephropathy (DNP), diabetic neuropathy (DN), and diabetic retinopathy (DR). DNP is a major cause of end-stage renal disease. DNP can lead to albuminuria, decreased filtration, mesangium expansion, thickening of the basement membrane, and eventually renal failure. Furthermore, inflammatory cells can accumulate in the interstitium and glomeruli to deteriorate DNP. DN is another most prevalent microvascular complication of DM and the main cause of high mortality, disability, and a poor quality of life. DNs have a wide range of clinical manifestations because of the types of fiber dysfunctions and complex structures of the peripheral nervous system. DR is also a microvascular and multifactorial disease, as well as a major cause of visual impairment globally. Pathogenesis of DR is yet to be fully revealed, however, numerous studies have already confirmed the role of inflammation in the onset and advancement of DR. Despite evidence, and better knowledge regarding the pathogenesis of these microvascular complications of diabetes, there is still a deficiency of effective therapies. Bioactive compounds are mainly derived from plants, and these molecules have promising therapeutic potential. In this review, evidence and molecular mechanisms regarding the role of inflammation in various microvascular complications of diabetes including DNP, DN, and DR, have been summarized. The therapeutic potential of several bioactive compounds derived from plants in the treatment of these microvascular complications of diabetes has also been discussed.
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Blonde L, Umpierrez GE, Reddy SS, McGill JB, Berga SL, Bush M, Chandrasekaran S, DeFronzo RA, Einhorn D, Galindo RJ, Gardner TW, Garg R, Garvey WT, Hirsch IB, Hurley DL, Izuora K, Kosiborod M, Olson D, Patel SB, Pop-Busui R, Sadhu AR, Samson SL, Stec C, Tamborlane WV, Tuttle KR, Twining C, Vella A, Vellanki P, Weber SL. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract 2022; 28:923-1049. [PMID: 35963508 PMCID: PMC10200071 DOI: 10.1016/j.eprac.2022.08.002] [Citation(s) in RCA: 234] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
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Affiliation(s)
| | | | - S Sethu Reddy
- Central Michigan University, Mount Pleasant, Michigan
| | | | | | | | | | | | - Daniel Einhorn
- Scripps Whittier Diabetes Institute, La Jolla, California
| | | | | | - Rajesh Garg
- Lundquist Institute/Harbor-UCLA Medical Center, Torrance, California
| | | | | | | | | | | | - Darin Olson
- Colorado Mountain Medical, LLC, Avon, Colorado
| | | | | | - Archana R Sadhu
- Houston Methodist; Weill Cornell Medicine; Texas A&M College of Medicine; Houston, Texas
| | | | - Carla Stec
- American Association of Clinical Endocrinology, Jacksonville, Florida
| | | | - Katherine R Tuttle
- University of Washington and Providence Health Care, Seattle and Spokane, Washington
| | | | | | | | - Sandra L Weber
- University of South Carolina School of Medicine-Greenville, Prisma Health System, Greenville, South Carolina
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Pop-Busui R, Januzzi JL, Bruemmer D, Butalia S, Green JB, Horton WB, Knight C, Levi M, Rasouli N, Richardson CR. Heart Failure: An Underappreciated Complication of Diabetes. A Consensus Report of the American Diabetes Association. Diabetes Care 2022; 45:1670-1690. [PMID: 35796765 PMCID: PMC9726978 DOI: 10.2337/dci22-0014] [Citation(s) in RCA: 197] [Impact Index Per Article: 65.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 03/29/2022] [Indexed: 02/03/2023]
Abstract
Heart failure (HF) has been recognized as a common complication of diabetes, with a prevalence of up to 22% in individuals with diabetes and increasing incidence rates. Data also suggest that HF may develop in individuals with diabetes even in the absence of hypertension, coronary heart disease, or valvular heart disease and, as such, represents a major cardiovascular complication in this vulnerable population; HF may also be the first presentation of cardiovascular disease in many individuals with diabetes. Given that during the past decade, the prevalence of diabetes (particularly type 2 diabetes) has risen by 30% globally (with prevalence expected to increase further), the burden of HF on the health care system will continue to rise. The scope of this American Diabetes Association consensus report with designated representation from the American College of Cardiology is to provide clear guidance to practitioners on the best approaches for screening and diagnosing HF in individuals with diabetes or prediabetes, with the goal to ensure access to optimal, evidence-based management for all and to mitigate the risks of serious complications, leveraging prior policy statements by the American College of Cardiology and American Heart Association.
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Affiliation(s)
- Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - James L. Januzzi
- Cardiology Division, Massachusetts General Hospital, and Cardiometabolic Trials, Baim Institute for Clinical Research, Boston, MA
| | - Dennis Bruemmer
- Center for Cardiometabolic Health, Section of Preventive Cardiology and Rehabilitation, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH
| | - Sonia Butalia
- Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Alberta, Canada
| | - Jennifer B. Green
- Division of Endocrinology and Duke Clinical Research Institute, Department of Medicine, Duke University Medical Center, Durham, NC
| | - William B. Horton
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA
| | - Colette Knight
- Inserra Family Diabetes Institute, Hackensack University Medical Center, Hackensack Meridian School of Medicine, Hackensack, NJ
| | - Moshe Levi
- Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC
| | - Neda Rasouli
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO
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Rivera-Mancilla E, Villanueva-Castillo B, Altamirano-Espinoza AH, Manrique-Maldonado G, Villalón CM. Prospective role of α2A/2B/2C-adrenoceptor subtypes in the modulation of cardioaccelerator sympathetic tone in an experimental model of diabetes. Eur J Pharmacol 2022; 929:175138. [DOI: 10.1016/j.ejphar.2022.175138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 06/28/2022] [Accepted: 06/30/2022] [Indexed: 11/15/2022]
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12
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Dysregulated Epicardial Adipose Tissue as a Risk Factor and Potential Therapeutic Target of Heart Failure with Preserved Ejection Fraction in Diabetes. Biomolecules 2022; 12:biom12020176. [PMID: 35204677 PMCID: PMC8961672 DOI: 10.3390/biom12020176] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/12/2022] [Accepted: 01/18/2022] [Indexed: 02/01/2023] Open
Abstract
Cardiovascular (CV) disease and heart failure (HF) are the leading cause of mortality in type 2 diabetes (T2DM), a metabolic disease which represents a fast-growing health challenge worldwide. Specifically, T2DM induces a cluster of systemic metabolic and non-metabolic signaling which may promote myocardium derangements such as inflammation, fibrosis, and myocyte stiffness, which represent the hallmarks of heart failure with preserved ejection fraction (HFpEF). On the other hand, several observational studies have reported that patients with T2DM have an abnormally enlarged and biologically transformed epicardial adipose tissue (EAT) compared with non-diabetic controls. This expanded EAT not only causes a mechanical constriction of the diastolic filling but is also a source of pro-inflammatory mediators capable of causing inflammation, microcirculatory dysfunction and fibrosis of the underlying myocardium, thus impairing the relaxability of the left ventricle and increasing its filling pressure. In addition to representing a potential CV risk factor, emerging evidence shows that EAT may guide the therapeutic decision in diabetic patients as drugs such as metformin, glucagon-like peptide‑1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 inhibitors (SGLT2-Is), have been associated with attenuation of EAT enlargement.
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Bjerre-Christensen T, Winther SA, Tofte N, Theilade S, Ahluwalia TS, Lajer M, Hansen TW, Rossing P, Hansen CS. Cardiovascular autonomic neuropathy and the impact on progression of diabetic kidney disease in type 1 diabetes. BMJ Open Diabetes Res Care 2021; 9:9/1/e002289. [PMID: 34645614 PMCID: PMC8515448 DOI: 10.1136/bmjdrc-2021-002289] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 09/26/2021] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION We investigated the association between cardiovascular autonomic neuropathy (CAN) and decline in kidney function in type 1 diabetes. RESEARCH DESIGN AND METHODS We included 329 persons with type 1 diabetes. CAN was assessed by cardiovascular reflex tests (CARTs): heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuvre. Two or more pathological CARTs defined CAN diagnosis. Outcomes were yearly change in albuminuria or yearly change in estimated glomerular filtration rate (eGFR). An endpoint of eGFR decline >30%, development of end-stage kidney disease (ESKD) or death was examined.Associations were assessed by linear and Cox regression. RESULTS Participants were aged 55.2 (9.4) years, 52% were male, with a diabetes duration of 40.1 (8.9) years, HbA1c of 7.9% (62.5 mmol/mol), eGFR 77.9 (27.7) mL/min/1.73 m2, urinary albumin excretion rate of 14.5 (7-58) mg/24 hours, and 31% were diagnosed with CAN.CAN was associated with a 7.8% higher albuminuria increase per year (95% CI: 0.50% to 15.63%, p=0.036) versus no CAN. The endpoint of ESKD, all-cause mortality and ≥30% decline in eGFR was associated with CAN (HR=2.497, p=0.0254). CONCLUSION CAN and sympathetic dysfunction were associated with increase in albuminuria in individuals with type 1 diabetes suggesting its role as a potential marker of diabetic kidney disease progression.
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Affiliation(s)
| | | | - Nete Tofte
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | | | - Tarunveer S Ahluwalia
- Department of Biology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Maria Lajer
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | | | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Salvatore T, Pafundi PC, Galiero R, Albanese G, Di Martino A, Caturano A, Vetrano E, Rinaldi L, Sasso FC. The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms. Front Med (Lausanne) 2021; 8:695792. [PMID: 34277669 PMCID: PMC8279779 DOI: 10.3389/fmed.2021.695792] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/07/2021] [Indexed: 12/12/2022] Open
Abstract
Individuals with diabetes mellitus (DM) disclose a higher incidence and a poorer prognosis of heart failure (HF) than non-diabetic people, even in the absence of other HF risk factors. The adverse impact of diabetes on HF likely reflects an underlying “diabetic cardiomyopathy” (DM–CMP), which may by exacerbated by left ventricular hypertrophy and coronary artery disease (CAD). The pathogenesis of DM-CMP has been a hot topic of research since its first description and is still under active investigation, as a complex interplay among multiple mechanisms may play a role at systemic, myocardial, and cellular/molecular levels. Among these, metabolic abnormalities such as lipotoxicity and glucotoxicity, mitochondrial damage and dysfunction, oxidative stress, abnormal calcium signaling, inflammation, epigenetic factors, and others. These disturbances predispose the diabetic heart to extracellular remodeling and hypertrophy, thus leading to left ventricular diastolic and systolic dysfunction. This Review aims to outline the major pathophysiological changes and the underlying mechanisms leading to myocardial remodeling and cardiac functional derangement in DM-CMP.
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Affiliation(s)
- Teresa Salvatore
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Pia Clara Pafundi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Gaetana Albanese
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Anna Di Martino
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Erica Vetrano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
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Yehya YM, Hussein AM, Ezam K, Eid EA, Ibrahim EM, Sarhan MAFE, Elsayed A, Sarhan ME. Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model. Endocr Metab Immune Disord Drug Targets 2021; 20:464-478. [PMID: 31544705 DOI: 10.2174/1871530319666190809150921] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 06/16/2019] [Accepted: 07/04/2019] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats. METHODS Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks). RESULTS In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density. CONCLUSION RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.
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Affiliation(s)
- Yomna M Yehya
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Abdelaziz M Hussein
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Khaled Ezam
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Elsayed A Eid
- Department of internal Medicine and endocrinology, Delta University, Gamasa, Egypt
| | - Eman M Ibrahim
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed A F E Sarhan
- Medical Biochemistry Department, Faculty of Medicine, Mansoura, University, Mansoura, Egypt
| | - Aya Elsayed
- Medical Experimental Research Centre, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed E Sarhan
- Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Role of peripheral 5-HT5A receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats. Sci Rep 2020. [DOI: 10.1155/2013/313917] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Abstract5-HT inhibits cardiac sympathetic neurotransmission in normoglycaemic rats, via 5-HT1B, 5-HT1Dand 5-HT5Areceptor activation. Since type 1 diabetes impairs the cardiac sympathetic innervation leading to cardiopathies, this study aimed to investigate whether the serotonergic influence on cardiac noradrenergic control is altered in type 1 diabetic rats. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by electrical preganglionic stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT1B, 5-HT1Dand 5-HT5Areceptor expression in the stellate ganglion from normoglycaemic and diabetic rats. In the diabetic group, i) i.v. continuous infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT1/5Aagonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT1A), CP 93,129 (5-HT1B), PNU 142633 (5-HT1D), or LY344864 (5-HT1F); ii) SB 699551 (5-HT5Aantagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT5Areceptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT5Areceptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.
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García-Pedraza JÁ, Hernández-Abreu O, Morán A, Carretero J, García-Domingo M, Villalón CM. Role of peripheral 5-HT 5A receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats. Sci Rep 2020; 10:19358. [PMID: 33168874 PMCID: PMC7652863 DOI: 10.1038/s41598-020-76298-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/16/2020] [Indexed: 01/15/2023] Open
Abstract
5-HT inhibits cardiac sympathetic neurotransmission in normoglycaemic rats, via 5-HT1B, 5-HT1D and 5-HT5A receptor activation. Since type 1 diabetes impairs the cardiac sympathetic innervation leading to cardiopathies, this study aimed to investigate whether the serotonergic influence on cardiac noradrenergic control is altered in type 1 diabetic rats. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by electrical preganglionic stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT1B, 5-HT1D and 5-HT5A receptor expression in the stellate ganglion from normoglycaemic and diabetic rats. In the diabetic group, i) i.v. continuous infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT1/5A agonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT1A), CP 93,129 (5-HT1B), PNU 142633 (5-HT1D), or LY344864 (5-HT1F); ii) SB 699551 (5-HT5A antagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT5A receptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT5A receptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.
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Affiliation(s)
- José Ángel García-Pedraza
- Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Biomedical Research Institute of Salamanca (IBSAL), 37007, Salamanca, Spain
| | - Oswaldo Hernández-Abreu
- Department of Pharmacobiology, Cinvestav-Coapa, Czda. Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, Mexico City, Mexico
| | - Asunción Morán
- Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Biomedical Research Institute of Salamanca (IBSAL), 37007, Salamanca, Spain
| | - José Carretero
- Laboratory of Neuroendocrinology, Department of Human Anatomy and Histology, Faculty of Medicine, University of Salamanca, Neurosciences Institute of Castilla y León (INCyL), Salamanca, Spain.,Laboratory of Neuroendocrinology and Obesity, IBSAL, Salamanca, Spain
| | - Mónica García-Domingo
- Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, Biomedical Research Institute of Salamanca (IBSAL), 37007, Salamanca, Spain
| | - Carlos M Villalón
- Department of Pharmacobiology, Cinvestav-Coapa, Czda. Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, Mexico City, Mexico.
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Petry D, Mirian de Godoy Marques C, Brum Marques JL. Baroreflex sensitivity with different lags and random forests for staging cardiovascular autonomic neuropathy in subjects with diabetes. Comput Biol Med 2020; 127:104098. [PMID: 33152669 DOI: 10.1016/j.compbiomed.2020.104098] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/22/2020] [Accepted: 10/25/2020] [Indexed: 10/23/2022]
Abstract
Impaired baroreflex sensitivity (BRS) may indicate cardiovascular autonomic neuropathy (CAN), which often remains undiagnosed during the initial course of diabetes mellitus. The baroreflex mechanism can be considered negative feedback because of baroreflex delay, the time delay between a change in blood pressure and the counteracting heart rate response. This work sought to analyze BRS considering lags from 1 to 10 RR intervals. We hypothesized that diabetic patients with subclinical CAN (SCAN) have a detectable delay in autonomic nervous system activity and that this would differ from patients without CAN (NCAN) and with established CAN (ECAN). In the first stage, 30 patients were included in an exploratory analysis using the Principal Component Analysis. Six indexes related to the BRS delay were proposed and considered significant for staging diabetic patients. Three indexes allowed for the differentiating of patients with and without CAN, and three indexes distinguished subjects with SCAN from subjects with NCAN or ECAN. Then, in the second stage, a random forest model was developed with 72 subjects, using the variables selected in the first stage. It was possible to detect SCAN, and to point out those subjects with the potential to change the CAN stage, allowing for the tracking of CAN progression. The model achieved a sensitivity of 96% and specificity of 100% to detect SCAN. Thus, the BRS analysis considering delayed reaction in the dynamics of heart rate variability may contribute to an accurate screening tool to staging CAN, in addition to indicating patients with most insidious disease progress.
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Affiliation(s)
- Daiana Petry
- Institute of Biomedical Engineering, Department of Electrical and Electronic Engineering, Federal University of Santa Catarina, Florianópolis, SC, Brazil; Department of Environmental Engineering, State University of Santa Catarina, Lages, SC, Brazil.
| | | | - Jefferson Luiz Brum Marques
- Institute of Biomedical Engineering, Department of Electrical and Electronic Engineering, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
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Zobel EH, Winther SA, Hasbak P, von Scholten BJ, Holmvang L, Kjaer A, Rossing P, Hansen TW. Myocardial flow reserve assessed by cardiac 82Rb positron emission tomography/computed tomography is associated with albumin excretion in patients with Type 1 diabetes. Eur Heart J Cardiovasc Imaging 2020; 20:796-803. [PMID: 30535392 PMCID: PMC6587116 DOI: 10.1093/ehjci/jey174] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/22/2018] [Accepted: 10/30/2018] [Indexed: 11/14/2022] Open
Abstract
AIMS To evaluate myocardial flow reserve (MFR) and coronary artery calcium (CAC) in persons with Type 1 diabetes with or without albuminuria and in non-diabetic controls. MFR reflects the function of large epicardial arteries and myocardial microcirculation. CAC represents structural aspects of atherosclerosis. In addition, we evaluated the association of MFR and CAC with retinopathy, another microvascular complication. METHODS AND RESULTS Cross-sectional study in Type 1 diabetes, stratified by normoalbuminuria (NORMO; n = 30) and macroalbuminuria (MACRO; n = 30), and in non-diabetic controls (n = 30). MFR (pharmacological stress flow/rest flow) was evaluated by cardiac 82Rb positron emission tomography/computed tomography. MFR was similar in patients with NORMO and controls (3.1 ± 0.79 vs. 3.0 ± 0.79; P = 0.74). Patients with MACRO had lower (impaired) MFR when compared with NORMO (2.1 ± 0.92 vs. 3.1 ± 0.79; P < 0.0001). The CAC score [median (interquartile range)] was higher in NORMO when compared with controls [72 (22-247) vs. 0 (0-81), P = 0.03], and comparable between MACRO and NORMO. MFR was comparable in patients with diabetes and simplex or no retinopathy (n = 24 and n = 12, 2.8 ± 0.84 vs. 3.3 ± 0.77, P = 0.11), but lower in proliferative (n = 24) compared with simplex retinopathy (2.1 ± 0.97 vs. 2.8 ± 0.84, P = 0.02). The CAC score was comparable between groups of retinopathy. CONCLUSION Myocardial microvascular function was comparable in non-diabetic controls and patients with Type 1 diabetes and NORMO; but impaired in the presence of microvascular complications (MACRO and proliferative retinopathy). Coronary calcification was elevated in diabetes, however, not explained by albuminuria.
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Affiliation(s)
- Emilie H Zobel
- Complications Research, Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, Gentofte, Denmark
| | - Signe A Winther
- Complications Research, Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, Gentofte, Denmark
| | - Philip Hasbak
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, Copenhagen Ø, Denmark
| | - Bernt J von Scholten
- Complications Research, Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, Gentofte, Denmark
| | - Lene Holmvang
- Department of Cardiology, Rigshospitalet, Blegdamsvej 9, Copenhagen Ø, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, Copenhagen Ø, Denmark
| | - Peter Rossing
- Complications Research, Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, Gentofte, Denmark.,Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3, Copenhagen N, Denmark
| | - Tine W Hansen
- Complications Research, Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, Gentofte, Denmark
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Cardiovascular disease in type 1 diabetes: A review of epidemiological data and underlying mechanisms. DIABETES & METABOLISM 2020; 46:442-449. [PMID: 32998054 DOI: 10.1016/j.diabet.2020.09.001] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/27/2020] [Accepted: 09/05/2020] [Indexed: 12/15/2022]
Abstract
Cardiovascular disease (CVD) is highly prevalent in patients with type 1 diabetes (T1D) and a major cause of mortality. CVD arises earlier in life in T1D patients and is responsible for a significant reduction of at least 11 years' life expectancy. Also, the incidence of CVD is much more pronounced in patients with T1D onset at an earlier age. However, the factors responsible for increased atherosclerosis and CVD in T1D are not yet totally clarified. In addition to the usual cardiovascular (CV) risk factors, chronic hyperglycaemia plays an important role by promoting oxidative stress, vascular inflammation, monocyte adhesion, arterial wall thickening and endothelial dysfunction. Diabetic nephropathy and cardiac autonomic neuropathy are also associated with increased CVD in T1D. In fact, the CVD risk remains significantly increased even in well-controlled T1D patients who have no additional CV risk factors, indicating that other potential factors are likely to be involved. Hypoglycemia and glucose variability could enhance CV disease by promoting oxidative stress, vascular inflammation and endothelial dysfunction. Furthermore, even well-controlled T1D patients show significant qualitative and functional abnormalities of lipoproteins that are likely to be implicated in the development of atherosclerosis and premature CVD. In addition, recent data suggest that a dysfunctional immune system, which is typical of autoimmune T1D, might also promote CVD possibly through inflammatory pathways. Moreover, overweight and obese T1D patients can manifest additional CV risk through pathophysiological mechanisms resembling those observed in type 2 diabetes (T2D).
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Chen J, Cai J, Wei M, Zhang X, Zhong M, Liu M, Yu Y, Chen Q. Effects of Guizhi decoction for diabetic cardiac autonomic neuropathy: A protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e22317. [PMID: 32991439 PMCID: PMC7523786 DOI: 10.1097/md.0000000000022317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 08/20/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Diabetic cardiac autonomic neuropathy (DCAN) is one of the serious complications of diabetes. The pathogenesis of DCAN has not been fully elucidated. There is currently no effective treatment for such chronic disease. Traditional Chinese medicine has a long clinical history for the prevention and treatment of diabetes and chronic complications, and it also shows certain advantages in the treatment of DCAN. Many clinical studies have confirmed that Chinese medicine Guizhi decoction can reduce the clinical symptoms and improve neuronal function of patients with DCAN. So we intend to conduct a systematic review further clarified the effectiveness and safety of Guizhi decoction for DCAN. METHODS We will search each database from the built-in until July 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieval clinical registration tests and grey literatures. In this study, only the clinical randomized controlled trials (RCTs) were selected to evaluate the efficacy and safety of Guizhi decoction in the treatment of DCAN. The 2 researchers independently conducted literature selection, data extraction, and quality assessment. Statistical heterogeneity among studies will be evaluated using the Cochran Q test (x) and the I statistical value. We will utilize the Review Manage software V5.3.0 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014, Copenhagen, Denmark) to statistically analyze all data. ETHICS AND DISSEMINATION This study is a protocol for a systematic review of Guizhi decoction as a treatment of DCAN patients. RESULTS This study will provide high-quality synthesis of effectiveness and safety of Guizhi decoction for DCAN. CONCLUSION This systematic review aims to provide new options for Guizhi decoction treatment of DCAN in terms of its efficacy and safety. REGISTRATION NUMBER INPLASY202080018.
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Affiliation(s)
- Junmin Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Jiawei Cai
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Mengya Wei
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Xiaoran Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Min Zhong
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Min Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
| | - Yang Yu
- College of acupuncture and massage, Chengdu University of Traditional Chinese Medicine , No 37 Shi-er-qiao Road, Chengdu, Sichuan Province, PR China
| | - Qiu Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu
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Grotle AK, Macefield VG, Farquhar WB, O'Leary DS, Stone AJ. Recent advances in exercise pressor reflex function in health and disease. Auton Neurosci 2020; 228:102698. [PMID: 32861944 DOI: 10.1016/j.autneu.2020.102698] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/01/2020] [Accepted: 07/02/2020] [Indexed: 01/11/2023]
Abstract
Autonomic alterations at the onset of exercise are critical to redistribute cardiac output towards the contracting muscles while preventing a fall in arterial pressure due to excessive vasodilation within the contracting muscles. Neural mechanisms responsible for these adjustments include central command, the exercise pressor reflex, and arterial and cardiopulmonary baroreflexes. The exercise pressor reflex evokes reflex increases in sympathetic activity to the heart and systemic vessels and decreases in parasympathetic activity to the heart, which increases blood pressure (BP), heart rate, and total peripheral resistance through vasoconstriction of systemic vessels. In this review, we discuss recent advancements in our understanding of exercise pressor reflex function in health and disease. Specifically, we discuss emerging evidence suggesting that sympathetic vasoconstrictor drive to the contracting and non-contracting skeletal muscle is differentially controlled by central command and the metaboreflex in healthy conditions. Further, we discuss evidence from animal and human studies showing that cardiovascular diseases, including hypertension, diabetes, and heart failure, lead to an altered exercise pressor reflex function. We also provide an update on the mechanisms thought to underlie this altered exercise pressor reflex function in each of these diseases. Although these mechanisms are complex, multifactorial, and dependent on the etiology of the disease, there is a clear consensus that several mechanisms are involved. Ultimately, approaches targeting these mechanisms are clinically significant as they provide alternative therapeutic strategies to prevent adverse cardiovascular events while also reducing symptoms of exercise intolerance.
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Affiliation(s)
- Ann-Katrin Grotle
- Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, United States of America
| | | | - William B Farquhar
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States of America
| | - Donal S O'Leary
- Department of Physiology, Wayne State University School of Medicine, Detroit, MI, United States of America
| | - Audrey J Stone
- Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, United States of America.
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AlJaroudi W. Heart rate and 123I-MIBG in heart failure with preserved ejection fraction: More variability and slower washout-A secret recipe for better survival. J Nucl Cardiol 2020; 27:843-848. [PMID: 30414060 DOI: 10.1007/s12350-018-01514-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 10/30/2018] [Indexed: 10/27/2022]
Affiliation(s)
- Wael AlJaroudi
- Division of Cardiovascular Medicine, Clemenceau Medical Center, Beirut, Lebanon.
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Ang L, Dillon B, Mizokami-Stout K, Pop-Busui R. Cardiovascular autonomic neuropathy: A silent killer with long reach. Auton Neurosci 2020; 225:102646. [PMID: 32106052 DOI: 10.1016/j.autneu.2020.102646] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/30/2020] [Accepted: 02/11/2020] [Indexed: 02/07/2023]
Abstract
Cardiovascular autonomic neuropathy (CAN) is a common and deadly complication of diabetes mellitus, which is frequently overlooked in clinical practice due to its characteristic subtle presentation earlier in disease. Yet, timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including cardiovascular disease (CVD), cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure and all-cause mortality. This review highlights current CAN epidemiology trends, novel mechanisms linking CAN with other diabetes complications and current recommendations for diagnosis and management of the disease in the clinical setting.
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Affiliation(s)
- Lynn Ang
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Brendan Dillon
- University of Michigan Medical School, Ann Arbor, MI, United States of America
| | - Kara Mizokami-Stout
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America.
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25
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Pafili K, Trypsianis G, Papazoglou D, Maltezos E, Papanas N. Cardiovascular Autonomic Neuropathy and Distal Symmetric Sensorimotor Polyneuropathy: These Two Diabetic Microvascular Complications do not Invariably Co-Exist. Curr Vasc Pharmacol 2019; 18:50-56. [PMID: 30156161 DOI: 10.2174/1570161116666180829120101] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 08/02/2018] [Accepted: 08/07/2018] [Indexed: 11/22/2022]
Abstract
Background:
Cardiovascular autonomic neuropathy (CAN) and distal symmetrical sensorimotor
polyneuropathy (DSPN) are serious microvascular complications of diabetes mellitus (DM).
Their simultaneous development remains disputable. The aim of the present study was to examine the
correlation between CAN and the presence/severity of DSPN in DM.
Methods:
Subjects with type 1 (group A: n=51; mean age 40.4 years) and type 2 DM (group B: n=153;
mean age 64.6 years) were studied. Evaluation of DSPN was based on neuropathy disability score. Assessment
of CAN was based on the battery of 4 standardized cardiovascular autonomic function tests.
Results:
In group A, patients with moderate/severe DSPN exhibited a 12-fold higher likelihood of CAN
in univariate analysis (p=0.035). However, significance was lost after adjustment for gender, age, DM
duration, and haemoglobin A1c. In group A, likelihood for CAN did not correlate with the presence of
mild DSPN in univariate and multivariate analysis. In group B, likelihood of CAN was similar in patients
with mild and in those with moderate/severe DSPN compared with patients without DSPN in
univariate and multivariate analysis. In between group comparison CAN was similarly distributed in the
2 groups (p for interaction=0.367), in patients with no, mild and moderate/severe DSPN.
Conclusion:
CAN does not always co-exist with degrees of DSPN, ranging from mild to moderate/
severe and is similarly distributed in T1DM and T2DM patients with mild and moderate/severe
DSPN and in patients without DSPN.
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Affiliation(s)
- Kalliopi Pafili
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Grigoris Trypsianis
- Department of Medical Statistics, Medical Faculty, Democritus University of Thrace, Alexandroupolis, Alexandroupolis, Greece
| | - Dimitrios Papazoglou
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Efstratios Maltezos
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Nikolaos Papanas
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
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26
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Bassil G, Chang M, Pauza A, Diaz Vera J, Tsalatsanis A, Lindsey BG, Noujaim SF. Pulmonary Vein Ganglia Are Remodeled in the Diabetic Heart. J Am Heart Assoc 2019; 7:e008919. [PMID: 30511897 PMCID: PMC6405566 DOI: 10.1161/jaha.118.008919] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Background Cardiac autonomic neuropathy is thought to cause adverse cardiovascular effects in diabetes mellitus. Pulmonary vein ganglia ( PVG ), which have been implicated in normal and abnormal heart rhythm regulation, have not been fully investigated in type 1 diabetes mellitus (T1D). We examined the functional and anatomical effects of T1D on PVG and studied the details of T1D-induced remodeling on the PVG structure and function. Methods and Results We used a mouse model of T1D (Akita mouse), immunofluorescence, isolated Langendorff-perfused hearts, and mathematical simulations to explore the effects of T1D on PVG . Whole-mount atrial immunofluorescence of choline acetyltransferase and tyrosine hydroxylase labeling showed that sympathetic and parasympathetic somas of the PVG neurons were significantly hypotrophied in T1D hearts versus wild type. Stimulation of PVG in isolated Langendorff-perfused hearts caused more pronounced P-P interval prolongation in wild type compared with Akita hearts. Propranolol resulted in a comparable P-P prolongation in both phenotypes, and atropine led to more pronounced P-P interval shortening in wild type compared with Akita hearts. Numerical modeling using network simulations revealed that a decrease in the sympathetic and parasympathetic activities of PVG in T1D could explain the experimental results. Conclusions T1D leads to PVG remodeling with hypotrophy of sympathetic and parasympathetic cell bodies and a concomitant decrease in the PVG sympathetic and parasympathetic activities.
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Affiliation(s)
- Guillaume Bassil
- 1 Department of Internal Medicine Weill Cornell Medical College New York NY
| | - Mengmeng Chang
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| | - Audrys Pauza
- 3 Laboratories for Integrative Neuroscience and Endocrinology University of Bristol United Kingdom
| | - Jesus Diaz Vera
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| | - Athanasios Tsalatsanis
- 4 Research Methodology and Biostatistics Morsani College of Medicine University of South Florida Tampa FL
| | - Bruce G Lindsey
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| | - Sami F Noujaim
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
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27
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Yang Y, Zhao M, Yu XJ, Liu LZ, He X, Deng J, Zang WJ. Pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice. Am J Physiol Endocrinol Metab 2019; 317:E312-E326. [PMID: 31211620 DOI: 10.1152/ajpendo.00569.2018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Diabetic patients are more susceptible to myocardial ischemia damage than nondiabetic patients, with worse clinical outcomes and greater mortality. The mechanism may be related to glucose metabolism, mitochondrial homeostasis, and oxidative stress. Pyridostigmine may improve vagal activity to protect cardiac function in cardiovascular diseases. Researchers have not determined whether pyridostigmine regulates glucose metabolism and mitochondrial homeostasis to reduce myocardial vulnerability to injury in diabetic mice. In the present study, autonomic imbalance, myocardial damage, mitochondrial dysfunction, and oxidative stress were exacerbated in isoproterenol-stimulated diabetic mice, revealing the myocardial vulnerability of diabetic mice to injury compared with mice with diabetes or exposed to isoproterenol alone. Compared with normal mice, the expression of glucose transporters (GLUT)1/4 phosphofructokinase (PFK) FB3, and pyruvate kinase isoform (PKM) was decreased in diabetic mice, but increased in isoproterenol-stimulated normal mice. Following exposure to isoproterenol, the expression of (GLUT)1/4 phosphofructokinase (PFK) FB3, and PKM decreased in diabetic mice compared with normal mice. The downregulation of SIRT3/AMPK and IRS-1/Akt in isoproterenol-stimulated diabetic mice was exacerbated compared with that in diabetic mice or isoproterenol-stimulated normal mice. Pyridostigmine improved vagus activity, increased GLUT1/4, PFKFB3, and PKM expression, and ameliorated mitochondrial dysfunction and oxidative stress to reduce myocardial damage in isoproterenol-stimulated diabetic mice. Based on these results, it was found that pyridostigmine may reduce myocardial vulnerability to injury via the SIRT3/AMPK and IRS-1/Akt pathways in diabetic mice with isoproterenol-induced myocardial damage. This study may provide a potential therapeutic target for myocardial damage in diabetic patients.
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Affiliation(s)
- Yang Yang
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
| | - Ming Zhao
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
| | - Xiao-Jiang Yu
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
| | - Long-Zhu Liu
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
| | - Xi He
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
| | - Juan Deng
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
| | - Wei-Jin Zang
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shannxi, People's Republic of China
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29
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Zobel EH, Hasbak P, Winther SA, Hansen CS, Fleischer J, von Scholten BJ, Holmvang L, Kjaer A, Rossing P, Hansen TW. Cardiac Autonomic Function Is Associated With Myocardial Flow Reserve in Type 1 Diabetes. Diabetes 2019; 68:1277-1286. [PMID: 30862683 DOI: 10.2337/db18-1313] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 03/06/2019] [Indexed: 11/13/2022]
Abstract
The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods. This was a cross-sectional study in patients with type 1 diabetes, stratified by normoalbuminuria (n = 30) and macroalbuminuria (n = 30), and in healthy control subjects (n = 30). Cardiac autonomic function was evaluated using heart rate variability (HRV) indices, cardiovascular autonomic reflex tests (CARTs), and cardiac 123I-metaiodobenzylguanidine (MIBG) imaging. Cardiac vascular function was assessed as myocardial flow reserve (MFR) measured by cardiac 82Rb-positron emission tomography/computed tomography. The measures of cardiac autonomic function (except low frequency-to-high frequency ratio and the Valsalva test ratio) were positively correlated to MFR in unadjusted analysis. All the HRV indices lost significance after adjustment for age and heart rate. After further adjustment for relevant cardiovascular risk factors, the late heart-to-mediastinum ratio directly measuring the function of adrenergic receptors and sympathetic integrity (from the MIBG scintigraphy) and the 30-to-15 ratio (a CART), remained positively associated with MFR (P ≤ 0.04). Cardiac autonomic dysfunction, including loss of cardiac sympathetic integrity in type 1 diabetes, is associated with and may contribute to impaired myocardial blood flow regulation.
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Affiliation(s)
| | - Philip Hasbak
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Copenhagen, Denmark
| | | | | | | | | | - Lene Holmvang
- Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Copenhagen, Denmark
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- University of Copenhagen, Copenhagen, Denmark
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30
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Albu A, Para I. Left ventricular diastolic dysfunction in diabetes mellitus and the therapeutic role of exercise training. BALNEO RESEARCH JOURNAL 2019. [DOI: 10.12680/balneo.2019.254] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Abstract
Left ventricular diastolic dysfunction (LVDD) with normal ejection fraction is considered common among people with diabetes mellitus (DM). LVDD is a progressive condition and an independent predictor of mortality in diabetic patients. The etiopathogenesis of LVDD is multifactorial, including diabetes associated comorbidities, such as hypertension, coronary atherosclerosis and obesity, as well as myocardial vascular and metabolic disturbances which lead to diabetic cardiomyopathy. Early stages of LVDD may be detected using echocardiographic techniques. Treatment strategies evolve, based on a better understanding of pathogenic mechanisms, although it is still difficult to efficiently control LVDD evolution. This review synthesizes the main pathophysiological processes and clinical features that characterize DM associated LVDD. Among treatment options, the therapeutic relevance of exercise training programs is underlined.
Key words: diabetes mellitus, left ventricular diastolic dysfunction, physical training,
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Affiliation(s)
- Adriana Albu
- 2nd Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
| | - Ioana Para
- 4th Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania
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31
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Dhalla NS, Ganguly PK, Bhullar SK, Tappia PS. Role of catecholamines in the pathogenesis of diabetic cardiomyopathy 1. Can J Physiol Pharmacol 2019; 97:815-819. [PMID: 30913398 DOI: 10.1139/cjpp-2019-0044] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Although the sympathetic nervous system plays an important role in the regulation of cardiac function, the overactivation of the sympathetic nervous system under stressful conditions including diabetes has been shown to result in the excessive production of circulating catecholamines as well as an increase in the myocardial concentration of catecholamines. In this brief review, we provide some evidence to suggest that the oxidation products of catecholamines such as aminochrome and oxyradicals, lead to metabolic derangements, Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+, as well as activation of proteases and changes in myocardial gene expression. These alterations due to elevated levels of circulatory catecholamines are associated with oxidative stress, subcellular remodeling, and the development of cardiac dysfunction in chronic diabetes.
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Affiliation(s)
- Naranjan S Dhalla
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.,Department of Physiology and Pathophysiology, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
| | - Pallab K Ganguly
- College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
| | - Sukhwinder K Bhullar
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.,Department of Physiology and Pathophysiology, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
| | - Paramjit S Tappia
- Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada
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32
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Komici K, Femminella GD, de Lucia C, Cannavo A, Bencivenga L, Corbi G, Leosco D, Ferrara N, Rengo G. Predisposing factors to heart failure in diabetic nephropathy: a look at the sympathetic nervous system hyperactivity. Aging Clin Exp Res 2019; 31:321-330. [PMID: 29858985 DOI: 10.1007/s40520-018-0973-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Accepted: 05/17/2018] [Indexed: 12/30/2022]
Abstract
Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities among elderly patients. HF, a leading cause of mortality and morbidity worldwide, is characterized by sympathetic nervous system hyperactivity. The prevalence of diabetes mellitus (DM) is rapidly growing and the risk of developing HF is higher among DM patients. DM is responsible for several macro- and micro-angiopathies that contribute to the development of coronary artery disease (CAD), peripheral artery disease, retinopathy, neuropathy and diabetic nephropathy (DN) as well. Independently of CAD, chronic kidney disease (CKD) and DM increase the risk of HF. Individuals with diabetic nephropathy are likely to present a distinct pathological condition, defined as diabetic cardiomyopathy, even in the absence of hypertension or CAD, whose pathogenesis is only partially known. However, several hypotheses have been proposed to explain the mechanism of diabetic cardiomyopathy: increased oxidative stress, altered substrate metabolism, mitochondrial dysfunction, activation of renin-angiotensin-aldosterone system (RAAS), insulin resistance, and autonomic dysfunction. In this review, we will focus on the involvement of sympathetic system hyperactivity in the diabetic nephropathy.
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Affiliation(s)
- Klara Komici
- Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
| | - Grazia Daniela Femminella
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
| | - Claudio de Lucia
- Center for Translational Medicine and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
| | - Alessandro Cannavo
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
| | - Leonardo Bencivenga
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
| | - Graziamaria Corbi
- Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
| | - Dario Leosco
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
| | - Nicola Ferrara
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy
- Istituti Clinici Scientifici Maugeri SPA - Società Benefit, IRCCS - Istituto Scientifico di Telese, Terme, BN, Italy
| | - Giuseppe Rengo
- Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy.
- Istituti Clinici Scientifici Maugeri SPA - Società Benefit, IRCCS - Istituto Scientifico di Telese, Terme, BN, Italy.
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Aitchison RT, Ward L, Kennedy GJ, Shu X, Mansfield DC, Shahani U. Measuring visual cortical oxygenation in diabetes using functional near-infrared spectroscopy. Acta Diabetol 2018; 55:1181-1189. [PMID: 30083981 PMCID: PMC6182359 DOI: 10.1007/s00592-018-1200-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 07/25/2018] [Indexed: 02/01/2023]
Abstract
AIMS Diabetes mellitus affects about 6% of the world's population, and the chronic complications of the disease may result in macro- and micro-vascular changes. The purpose of the current study was to shed light on visual cortical oxygenation in diabetic individuals. We then aimed to compare the haemodynamic response (HDR) to visual stimulation with glycaemic control, given the likelihood of diabetic individuals suffering from such macro- and micro-vascular insult. METHODOLOGY Thirty participants took part in this explorative study, fifteen of whom had diabetes and fifteen of whom were non-diabetic controls. The HDR, measured as concentrations of oxyhaemoglobin [HbO] and deoxyhaemoglobin [HbR], to visual stimulation was recorded over the primary visual cortex (V1) using a dual-channel oximeter. The stimulus comprised a pattern-reversal checkerboard presented in a block design. Participants' mean glycated haemoglobin (HbA1c) level (± SD) was 7.2 ± 0.6% in the diabetic group and 5.5 ± 0.4% in the non-diabetic group. Raw haemodynamic data were normalised to baseline, and the last 15 s of data from each 'stimulus on' and 'stimulus off' condition were averaged over seven duty cycles for each participant. RESULTS There were statistically significant differences in ∆[HbO] and ∆[HbR] to visual stimulation between diabetic and non-diabetic groups (p < 0.05). In the diabetic group, individuals with type 1 diabetes displayed an increased [HbO] (p < 0.01) and decreased [HbR] (p < 0.05) compared to their type 2 counterparts. There was also a linear relationship between both ∆[HbO] and ∆[HbR] as a function of HbA1c level (p < 0.0005). CONCLUSIONS Our findings suggest that fNIRS can be used as a quantitative measure of cortical oxygenation in diabetes. Diabetic individuals have a larger HDR to visual stimulation compared to non-diabetic individuals. This increase in ∆[HbO] and decrease in ∆[HbR] appears to be correlated with HbA1c level.
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Affiliation(s)
- Ross T Aitchison
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.
| | - Laura Ward
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Graeme J Kennedy
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | - Xinhua Shu
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | - David C Mansfield
- Department of Ophthalmology, Inverclyde Royal Hospital, Greenock, UK
| | - Uma Shahani
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
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34
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Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ. Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms. Endocr Rev 2018; 39:629-663. [PMID: 30060120 DOI: 10.1210/er.2017-00191] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 06/21/2018] [Indexed: 02/07/2023]
Abstract
There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia, and cardiometabolic complications in type 1 diabetes. Unique therapeutic strategies may be required to address these comorbidities within the context of intensive insulin therapy, which promotes weight gain. There is an urgent need for clinical guidelines for the prevention and management of obesity in type 1 diabetes. The development of these recommendations will require a transdisciplinary research strategy addressing metabolism, molecular mechanisms, lifestyle, neuropsychology, and novel therapeutics. In this review, the prevalence, clinical impact, energy balance physiology, and potential mechanisms of obesity in type 1 diabetes are described, with a special focus on the substantial gaps in knowledge in this field. Our goal is to provide a framework for the evidence base needed to develop type 1 diabetes-specific weight management recommendations that account for the competing outcomes of glycemic control and weight management.
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Affiliation(s)
- Karen D Corbin
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida
| | - Kimberly A Driscoll
- Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, Colorado.,Barbara Davis Center for Diabetes, Aurora, Colorado
| | - Richard E Pratley
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida
| | - Steven R Smith
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida
| | - David M Maahs
- Division of Pediatric Endocrinology, Department of Pediatrics, Stanford University, Stanford, California
| | - Elizabeth J Mayer-Davis
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Oktay AA, Akturk HK, Esenboğa K, Javed F, Polin NM, Jahangir E. Pathophysiology and Prevention of Heart Disease in Diabetes Mellitus. Curr Probl Cardiol 2018; 43:68-110. [DOI: 10.1016/j.cpcardiol.2017.05.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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36
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Wilson LC, Peebles KC, Hoye NA, Manning P, Sheat C, Williams MJA, Wilkins GT, Wilson GA, Baldi JC. Resting heart rate variability and exercise capacity in Type 1 diabetes. Physiol Rep 2018; 5:5/8/e13248. [PMID: 28420762 PMCID: PMC5408283 DOI: 10.14814/phy2.13248] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 03/16/2017] [Accepted: 03/18/2017] [Indexed: 01/27/2023] Open
Abstract
People with type 1 diabetes (T1D) have lower exercise capacity (V̇O2max) than their age‐matched nondiabetic counterparts (CON), which might be related to cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV; indicator of cardiac autonomic modulation) was associated with exercise capacity in those with and without T1D. Twenty‐three participants with uncomplicated T1D and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP; finger photo‐plethysmography), and respiratory rate (respiratory belt) were measured during baseline, paced‐breathing and clinical autonomic reflex tests (CARTs); deep breathing, lying‐to‐stand, and Valsalva maneuver. Baseline and paced‐breathing ECG were analyzed for HRV (frequency‐domain). Exercise capacity was determined during an incremental cycle ergometer test while V̇O2, 12‐lead ECG, and BP were measured. In uncomplicated T1D, resting HR was elevated and resting HRV metrics were reduced, indicative of altered cardiac parasympathetic modulation; this was generally undetected by the CARTs. However, BP and plasma catecholamines were not different between groups. In T1D, V̇O2max tended to be lower (P = 0.07) and HR reserve was lower (P < 0.01). Resting Total Power (TP) had stronger positive associations with V̇O2max (R2 ≥ 0.3) than all other traditional indicators such as age, resting HR, and self‐reported exercise (R2 = 0.042–0.3) in both T1D and CON. Alterations in cardiac autonomic modulation are an early manifestation of uncomplicated T1D. Total Power was associated with reduced exercise capacity regardless of group, and these associations were generally stronger than traditional indicators.
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Affiliation(s)
- Luke C Wilson
- Department of Medicine, University of Otago, Dunedin, New Zealand .,HeartOtago, University of Otago, Dunedin, New Zealand
| | - Karen C Peebles
- Cardiovascular Systems Laboratory, University of Otago, Wellington, New Zealand.,Department of Physiology, University of Otago, Dunedin, New Zealand.,Department of Health Professions, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, Australia
| | - Neil A Hoye
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | - Patrick Manning
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | - Catherine Sheat
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | - Michael J A Williams
- Department of Medicine, University of Otago, Dunedin, New Zealand.,HeartOtago, University of Otago, Dunedin, New Zealand
| | - Gerard T Wilkins
- Department of Medicine, University of Otago, Dunedin, New Zealand.,HeartOtago, University of Otago, Dunedin, New Zealand
| | - Genevieve A Wilson
- Department of Medicine, University of Otago, Dunedin, New Zealand.,HeartOtago, University of Otago, Dunedin, New Zealand
| | - James C Baldi
- Department of Medicine, University of Otago, Dunedin, New Zealand.,HeartOtago, University of Otago, Dunedin, New Zealand
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Nakanishi K, Fukuda S, Tanaka A, Otsuka K, Taguchi H, Shimada K. Relationships Between Periventricular Epicardial Adipose Tissue Accumulation, Coronary Microcirculation, and Left Ventricular Diastolic Dysfunction. Can J Cardiol 2017; 33:1489-1497. [DOI: 10.1016/j.cjca.2017.08.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 08/02/2017] [Accepted: 08/02/2017] [Indexed: 01/23/2023] Open
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Pennathur S, Jaiswal M, Vivekanandan-Giri A, White EA, Ang L, Raffel DM, Rubenfire M, Pop-Busui R. Structured lifestyle intervention in patients with the metabolic syndrome mitigates oxidative stress but fails to improve measures of cardiovascular autonomic neuropathy. J Diabetes Complications 2017; 31:1437-1443. [PMID: 28709739 PMCID: PMC5580245 DOI: 10.1016/j.jdiacomp.2017.03.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/20/2017] [Accepted: 03/22/2017] [Indexed: 01/03/2023]
Abstract
AIMS To assess the role of oxidative stress in mediating adverse outcomes in metabolic syndrome (MetS) and resultant cardiovascular autonomic neuropathy (CAN), and to evaluate the effects of lifestyle interventions on measures of oxidative stress and CAN in subjects with MetS. METHODS Pilot study in 25 non-diabetic subjects with MetS (age 49±10years, 76% females) participating in a 24-week lifestyle intervention (supervised aerobic exercise/Mediterranean diet), and 25 age-matched healthy controls. CAN was assessed by cardiovascular reflex tests, heart rate variability (HRV) and PET imaging with sympathetic analog [11C] meta-hydroxyephedrine ([11C]HED). Specific oxidative fingerprints were measured by liquid-chromatography/mass-spectrometry (LC/MS). RESULTS At baseline, MetS subjects had significantly higher oxidative stress markers [3-nitrotyrosine (234±158 vs. 54±47μmol/mol tyrosine), ortho-tyrosine (59±38 vs. 18±10μmol/molphenylalanine, all P<0.0001], and impaired HRV at rest and during deep breathing (P=0.039 and P=0.021 respectively) compared to controls. Twenty-four-week lifestyle intervention significantly reduced all oxidative stress markers (all P<0.01) but did not change any of the CAN measures. CONCLUSIONS Subjects with MetS present with signs of CAN and increased oxidative stress in the absence of diabetes. The 24-week lifestyle intervention was effective in ameliorating oxidative stress, but did not improve measures of CAN. Larger clinical trials with longer duration are required to confirm these findings.
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Affiliation(s)
- Subramaniam Pennathur
- Department of Internal Medicine and Molecular and Integrative Physiology, Division of Nephrology, University of Michigan, Ann Arbor, MI, United States
| | - Mamta Jaiswal
- Department of Neurology, University of Michigan, Ann Arbor, MI, United States
| | | | - Elizabeth A White
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, United States
| | - David M Raffel
- Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Melvyn Rubenfire
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Rodica Pop-Busui
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, United States.
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Wang Q, Tan K, Xia H, Gao Y. Association of pulse pressure with left ventricular geometry and function in elderly nonhypertensive patients with diabetes: A 3D speckle tracking echocardiography study. JOURNAL OF CLINICAL ULTRASOUND : JCU 2017; 45:416-425. [PMID: 28543090 DOI: 10.1002/jcu.22484] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 01/31/2017] [Accepted: 03/05/2017] [Indexed: 06/07/2023]
Abstract
PURPOSE The aims of this study were to investigate and compare the left ventricular (LV) geometry and function in elderly nonhypertensive type 2 diabetic patients with normal (NPP, <60 mm Hg) and with high (HPP, ≥60 mmHg) 24-hour pulse pressure, and to explore the independent predictors of LV strain values in these patients. METHODS A total of 76 elderly nonhypertensive type 2 diabetic patients with normal (≥55%) LV ejection fraction (LVEF) were included, 36 of whom had HPP. The control group included 40 age- and sex-matched healthy volunteers with normal NPP. Conventional echocardiography and three-dimensional speckle-tracking echocardiography (3DSTE) were performed and LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were measured. RESULTS Significant differences in the two-dimensional LV geometry were found among the three groups (p = 0.015), and concentric geometry was most prevalent in the diabetic patients with HPP. The diabetic patients with NPP only showed significantly lower GLS than the controls (p < 0.05). However, the diabetic patients with HPP showed significantly lower LVEF and severely lower strain values in all directions than the controls and the diabetic patients with NPP (p < 0.01or p < 0.05 or p < 0.001). Fasting plasma glucose, HPP, and body mass index were independently associated with all strain parameters in diabetic patients. CONCLUSIONS The combination of conventional echocardiography and 3DSTE could detect LV subclinical abnormalities in nonhypertensive type 2 diabetic patients with NPP and HPP. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:416-425, 2017.
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Affiliation(s)
- Qingqing Wang
- Department of Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Kaibin Tan
- Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China
| | - Hongmei Xia
- Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China
| | - Yunhua Gao
- Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China
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Landes S, Dela Cruz S, Wei J, AlBadri A, Shufelt C, Mehta P, Thomson LE, Diniz MA, Zhang X, Petersen JW, Anderson RD, Pepine CJ, Berman DS, Bairey Merz CN. Cold Pressor Stress Cardiac Magnetic Resonance Myocardial Flow Reserve Is Not Useful for Detection of Coronary Endothelial Dysfunction in Women with Signs and Symptoms of Ischemia and No Obstructive CAD. PLoS One 2017; 12:e0169818. [PMID: 28081214 PMCID: PMC5231328 DOI: 10.1371/journal.pone.0169818] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Accepted: 12/22/2016] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Coronary endothelial function testing using acetylcholine is not routinely available, while non-pharmacological cold pressor testing (CPT) is considered an endothelial stressor. Noninvasive cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index (MPRI) can detect coronary microvascular dysfunction (CMD). We evaluated if CPT stress CMRI MPRI could detect invasive coronary endothelial dysfunction. METHODS Coronary reactivity testing was performed in 189 women with symptoms and signs of ischemic but no obstructive coronary artery disease as previously described plus CPT stress. Subjects also underwent pharmacologic and CPT stress during CMRI (1.5 T). Statistical analysis comparing CPT MPRI between groups was performed by Welch`s t-test and Mann-Whitney where appropriate. Anderson-Darling test and Levene test were considered to verify the normality and homogeneity of variances assumptions. Correlation analyses between CPT MPRI and both invasive and noninvasive measures of CMD were performed using Spearman correlation. RESULTS While CPT MPRI correlated with pharmacological stress MPRI, it did not correlate with invasive measures of CMD including invasively measured responses to intracoronary (IC) adenosine, IC acetylcholine, CPT, or IC nitroglycerin. Additionally CPT MPRI was not significantly different between subjects with normal compared to abnormal pharm stress MPRI or normal compared to abnormal invasive CMD parameters. CONCLUSION Despite correlation with pharmacological stress MPRI, non-invasive CPT MPRI does not appear to be useful for detecting CMD in symptomatic women.
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Affiliation(s)
- Sofy Landes
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Sherwin Dela Cruz
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Janet Wei
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Ahmed AlBadri
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Chrisandra Shufelt
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Puja Mehta
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Louise E. Thomson
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - Marcio A. Diniz
- Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, United States of America
| | - Xiao Zhang
- Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, United States of America
| | - John W. Petersen
- Univerity of Florida, Gainesville, Florida, United States of America
| | - R. David Anderson
- Univerity of Florida, Gainesville, Florida, United States of America
| | - Carl J. Pepine
- Univerity of Florida, Gainesville, Florida, United States of America
| | - Daniel S. Berman
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
| | - C. Noel Bairey Merz
- Barbra Streisand Women’s Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America
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Fang P, Dong J, Zeng F, Tang Z. Analysis of the association between glucose profiles and β-cell function for diabetic cardiovascular autonomic neuropathy in China. J Diabetes Investig 2016; 8:354-362. [PMID: 27736036 PMCID: PMC5415463 DOI: 10.1111/jdi.12584] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 09/07/2016] [Accepted: 09/25/2016] [Indexed: 12/18/2022] Open
Abstract
AIMS/INTRODUCTION The purpose of the present study was to investigate the severity of glucose profiles and β-cell function associated with diabetic cardiovascular autonomic neuropathy (DCAN) in a Chinese sample. MATERIALS AND METHODS A community-based, cross-sectional study to analyze the risk factors of DCAN was carried out with 455 individuals recruited from a Chinese population. The glucose profile risk score was calculated to identify the association between the severity of the glucose profiles and DCAN. The associations of the severity of the glucose profiles and β-cell function with DCAN were analyzed using multivariable logistic regression. RESULTS Univariate analysis showed that the glucose profiles and homeostatic model assessment of insulin resistance were significantly associated with the DCAN outcome, respectively. Multivariable logistic regression showed that significant associations exist between glucose profile indices and DCAN, after controlling for potential confounding factors (P < 0.01 for all) in both models. Multivariable logistic regression also showed that parameters of β-cell function were associated with the DCAN outcome in the category model (P < 0.1 for all). The glucose profile risk score was independently and significantly associated with the DCAN outcome after controlling for confounding factors (P < 0.001 and P for a trend <0.001). CONCLUSIONS Our observations suggest that parameters of glucose profile indices and β-cell function are significantly and independently associated with DCAN, respectively. There was a tendency toward increased glucose profile risk score with increasing prevalence of DCAN.
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Affiliation(s)
- Ping Fang
- Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.,Department of Endocrinology, Shanghai Tongji Hospital, Tongji University, Shanghai, China
| | - Jingcheng Dong
- Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Integrative Medicine, Fudan University, Shanghai, China
| | - Fangfang Zeng
- Department of Endocrinology and Metabolism, Fudan University Huashan Hospital, Shanghai, China
| | - Zihui Tang
- Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Integrative Medicine, Fudan University, Shanghai, China
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von Scholten BJ, Hansen CS, Hasbak P, Kjaer A, Rossing P, Hansen TW. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes. Diabetes 2016; 65:3129-38. [PMID: 27352886 DOI: 10.2337/db16-0437] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 06/22/2016] [Indexed: 11/13/2022]
Abstract
Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac (123)I-metaiodobenzylguanidine scintigraphy was conducted in a subgroup of 29 patients and 14 control subjects and evaluated as the late heart-to-mediastinum ratio and washout rate. Impaired function of all the cardiac autonomic measures (except the washout rate) was associated with reduced CFR. A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate. The late heart-to- mediastinum ratio remained correlated with CFR after further adjustment. In patients with T2DM without cardiovascular disease, we demonstrate an independent association between cardiac autonomic function and CFR. We suggest that a reduced cardiac autonomic function and damage to the adrenergic receptors may contribute to the development of cardiac microvascular dysfunction.
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Affiliation(s)
| | | | - Philip Hasbak
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Peter Rossing
- Steno Diabetes Center, Gentofte, Denmark University of Copenhagen, Copenhagen, Denmark Aarhus University, Aarhus, Denmark
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Duvernoy CS, Raffel DM, Swanson SD, Jaiswal M, Mueller G, Ibrahim ES, Pennathur S, Plunkett C, Stojanovska J, Brown MB, Pop-Busui R. Left ventricular metabolism, function, and sympathetic innervation in men and women with type 1 diabetes. J Nucl Cardiol 2016; 23:960-969. [PMID: 27146882 PMCID: PMC5103640 DOI: 10.1007/s12350-016-0434-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Revised: 01/29/2016] [Indexed: 01/09/2023]
Abstract
BACKGROUND In type I diabetes (T1DM), alterations in LV function may occur due to changes in innervation, metabolism, and efficiency. OBJECTIVES We evaluated the association between sympathetic nerve function, oxidative metabolism, resting blood flow, LV efficiency and function in healthy diabetics, and assessed gender differences. METHODS Cross-sectional study of 45 subjects with T1DM, 60% females, age 34 ± 13 years, and 10 age-matched controls. Positron emission tomography (PET) imaging with [(11)C]acetate and [(11)C]meta-hydroxyephedrine was performed, in addition to cardiac magnetic resonance imaging. RESULTS There were no significant differences in LV function, innervation, or oxidative metabolism between T1DM and controls. Cardiac oxidative metabolism was positively associated with higher levels of sympathetic activation, particularly in women. Diabetic women had significantly lower efficiency compared with diabetic men. Resting flow was significantly higher in diabetic women compared with diabetic men, and tended to be higher in female controls as well. CONCLUSIONS Measures of myocardial function, metabolism, blood flow, and sympathetic activation were preserved in young, otherwise healthy, T1DM patients. However, T1DM women presented with greater myocardial oxidative metabolism requirements than men. Ongoing studies are evaluating changes over time.
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Affiliation(s)
- Claire S Duvernoy
- Cardiology Section, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
- Division of Cardiology, University of Michigan, Ann Arbor, MI, USA
| | - David M Raffel
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Scott D Swanson
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Mamta Jaiswal
- Division of Metabolism, Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA
| | - Gisela Mueller
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - El-Sayed Ibrahim
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Subramaniam Pennathur
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Cynthia Plunkett
- Division of Metabolism, Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA
| | | | - Morton B Brown
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA.
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Mikhalkova D, McGill JB, Peterson LR. 'SeXX' matters: In the myocardium of patients with type 1 diabetes. J Nucl Cardiol 2016; 23:970-972. [PMID: 27301960 DOI: 10.1007/s12350-016-0507-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 03/10/2016] [Indexed: 11/27/2022]
Affiliation(s)
- Deana Mikhalkova
- The Cardiovascular Division of the Department of Medicine of Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, MO 63110, Saint Louis, MO, USA
| | - Janet B McGill
- The Endocrine Division of the Department of Medicine of Washington University School of Medicine, Saint Louis, MO, USA
| | - Linda R Peterson
- The Cardiovascular Division of the Department of Medicine of Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, MO 63110, Saint Louis, MO, USA.
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Activation of PPARβ/δ prevents hyperglycaemia-induced impairment of Kv7 channels and cAMP-mediated relaxation in rat coronary arteries. Clin Sci (Lond) 2016; 130:1823-36. [PMID: 27413020 DOI: 10.1042/cs20160141] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 07/13/2016] [Indexed: 01/09/2023]
Abstract
PPARβ/δ activation protects against endothelial dysfunction in diabetic models. Elevated glucose is known to impair cAMP-induced relaxation and Kv channel function in coronary arteries (CA). Herein, we aimed to analyse the possible protective effects of the PPARβ/δ agonist GW0742 on the hyperglycaemic-induced impairment of cAMP-induced relaxation and Kv channel function in rat CA. As compared with low glucose (LG), incubation under high glucose (HG) conditions attenuated the relaxation induced by the adenylate cyclase activator forskolin in CA and this was prevented by GW0742. The protective effect of GW0742 was supressed by a PPARβ/δ antagonist. In myocytes isolated from CA under LG, forskolin enhanced Kv currents and induced hyperpolarization. In contrast, when CA were incubated with HG, Kv currents were diminished and the electrophysiological effects of forskolin were abolished. These deleterious effects were prevented by GW0742. The protective effects of GW0742 on forskolin-induced relaxation and Kv channel function were confirmed in CA from type-1 diabetic rats. In addition, the differences in the relaxation induced by forskolin in CA incubated under LG, HG or HG + GW0742 were abolished by the Kv7 channel inhibitor XE991. Accordingly, GW0742 prevented the down-regulation of Kv7 channels induced by HG. Finally, the preventive effect of GW0742 on oxidative stress and cAMP-induced relaxation were overcome by the pyruvate dehydrogenase kinase 4 (PDK4) inhibitor dichloroacetate (DCA). Our results reveal that the PPARβ/δ agonist GW0742 prevents the impairment of the cAMP-mediated relaxation in CA under HG. This protective effect was associated with induction of PDK4, attenuation of oxidative stress and preservation of Kv7 channel function.
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Duvnjak L, Tomić M, Blaslov K, Vučković Rebrina S. Autonomic nervous system function assessed by conventional and spectral analysis might be useful in terms of predicting retinal deterioration in persons with type 1 diabetes mellitus. Diabetes Res Clin Pract 2016; 116:111-6. [PMID: 27321325 DOI: 10.1016/j.diabres.2016.04.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 04/01/2016] [Accepted: 04/21/2016] [Indexed: 01/29/2023]
Abstract
AIMS To determine whether cardiac autonomic dysfunction represents a risk factor for diabetic retinopathy (DR) development and progression in persons with type 1 diabetes mellitus (T1DM). METHODS The study comprised 154 normoalbuminuric persons with T1DM divided into two groups according to the DR presence: with and without DR. Cardiovascular autonomic functioning was measured at baseline using conventional and spectral analysis. Participants were re-examined for the DR presence 18months after. RESULTS The group with DR had longer disease duration compared to the group without DR (20 vrs 11.5years, p<0.001), heart rate coefficient of variation (HRV-CV) at rest and during deep breathing were lower in participants with DR (p=0.001 and 0.004), as well did spectral indices of HRV: low frequency (LF) band, high frequency (HF) band (p=0.003 and 0.022) while LF/HF ratio indicating sympathovagal balance was higher (p=0.037). No difference in glycaemic control or blood pressure value were observed. Twenty-one (13.36%) participants developed non proliferative DR or progressed to proliferative DR. Cox proportional regression showed that the 18months risk from retinal deterioration was reduced by 33.4% by each increase in the HRV-CV of 1%, 12.7% for the same HRV-CV increase during deep breathing while LF band of 1ms(2) results in 8.6% risk reduction. CONCLUSIONS This study provides evidence that DR should not be considered merely a metabolic control manifestation and that HRV-CV as well as spectral indices of HRV might serve as a practical tool to identify a subgroup of T1DM patients with higher risk of retinal deterioration.
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Affiliation(s)
- L Duvnjak
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia; School of Medicine Zagreb, Croatia
| | - M Tomić
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia
| | - K Blaslov
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia.
| | - S Vučković Rebrina
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia
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Abstract
Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase-2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs.
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Affiliation(s)
- Rodica Pop-Busui
- Department of Internal Medicine, Division of Metabolism, Metabolism Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA.
| | - Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Metabolism Endocrinology and Diabetes, University of Michigan, 5329 Brehm Tower, 1000 Wall Street, Ann Arbor, MI, 48105, USA.
| | - Crystal Holmes
- The Division of Metabolism, Endocrinology and Diabetes, Dominos Farms, Lobby C, Suite 1300 24 Frank Lloyd Wright Drive, PO Box 451, Ann Arbor, MI, 48106-0451, USA.
| | - Katherine Gallagher
- Department of Surgery, Section of Vascular Surgery, University of Michigan Health System, 1500 East Medical Center Dr, SPC 5867, Ann Arbor, MI, 48109, USA.
| | - Eva L Feldman
- Department of Neurology, University of Michigan, 5017 AATBSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.
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Xiang L, Mittwede PN, Clemmer JS. Glucose Homeostasis and Cardiovascular Alterations in Diabetes. Compr Physiol 2015; 5:1815-39. [PMID: 26426468 DOI: 10.1002/cphy.c150001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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11C-meta-hydroxyephedrine: a promising PET radiopharmaceutical for imaging the sympathetic nervous system. Clin Nucl Med 2015; 40:e96-e103. [PMID: 24999701 DOI: 10.1097/rlu.0000000000000512] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Dysfunction of the sympathetic nervous system underlies many cardiac diseases and can be assessed by molecular imaging using SPECT tracers as I-metaiodobenzylguanidine (I-MIBG). The norepinephrine analog C-meta-hydroxyephedrine (HED) has been used with PET to map the regional distribution of cardiac sympathetic neurons. Hydroxyephedrine is rapidly transported into sympathetic neurons by the norepinephrine transporter and stored in vesicles. This review describes the mechanism of action, radiosynthesis, and application of HED in the assessment of the cardiac sympathetic nervous system in heart failure, myocardial infarction, and arrhythmias. Noncardiac applications of HED in the clinical setting of sympathetic nervous system tumors and other emerging research applications are described.
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Dasanayake IS, Bevier WC, Castorino K, Pinsker JE, Seborg DE, Doyle FJ, Dassau E. Early Detection of Physical Activity for People With Type 1 Diabetes Mellitus. J Diabetes Sci Technol 2015; 9:1236-45. [PMID: 26134831 PMCID: PMC4667311 DOI: 10.1177/1932296815592409] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Early detection of exercise in individuals with type 1 diabetes mellitus (T1DM) may allow changes in therapy to prevent hypoglycemia. Currently there is limited experience with automated methods that detect the onset and end of exercise in this population. We sought to develop a novel method to quickly and reliably detect the onset and end of exercise in these individuals before significant changes in blood glucose (BG) occur. METHODS Sixteen adults with T1DM were studied as outpatients using a diary, accelerometer, heart rate monitor, and continuous glucose monitor for 2 days. These data were used to develop a principal component analysis based exercise detection method. Subjects also performed 60 and 30 minute exercise sessions at 30% and 50% predicted heart rate reserve (HRR), respectively. The detection method was applied to the exercise sessions to determine how quickly the detection of start and end of exercise occurred relative to change in BG. RESULTS Mild 30% HRR and moderate 50% HRR exercise onset was identified in 6 ± 3 and 5 ± 2 (mean ± SD) minutes, while completion was detected in 3 ± 8 and 6 ± 5 minutes, respectively. BG change from start of exercise to detection time was 1 ± 6 and -1 ± 3 mg/dL, and, from the end of exercise to detection time was 6 ± 4 and -17 ± 13 mg/dL, respectively, for the 2 exercise sessions. False positive and negative ratios were 4 ± 2% and 21 ± 22%. CONCLUSIONS The novel method for exercise detection identified the onset and end of exercise in approximately 5 minutes, with an average BG change of only -6 mg/dL.
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Affiliation(s)
- Isuru S Dasanayake
- Department of Chemical Engineering, University of California, Santa Barbara, CA, USA William Sansum Diabetes Center, Santa Barbara, CA, USA The first 2 authors contributed equally to this study
| | - Wendy C Bevier
- William Sansum Diabetes Center, Santa Barbara, CA, USA The first 2 authors contributed equally to this study
| | | | | | - Dale E Seborg
- Department of Chemical Engineering, University of California, Santa Barbara, CA, USA William Sansum Diabetes Center, Santa Barbara, CA, USA
| | - Francis J Doyle
- Department of Chemical Engineering, University of California, Santa Barbara, CA, USA William Sansum Diabetes Center, Santa Barbara, CA, USA
| | - Eyal Dassau
- Department of Chemical Engineering, University of California, Santa Barbara, CA, USA William Sansum Diabetes Center, Santa Barbara, CA, USA
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