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Mesa A, Franch-Nadal J, Navas E, Mauricio D. Cardiovascular disease in women with type 1 diabetes: a narrative review and insights from a population-based cohort analysis. Cardiovasc Diabetol 2025; 24:217. [PMID: 40399939 PMCID: PMC12093901 DOI: 10.1186/s12933-025-02791-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2025] [Accepted: 05/14/2025] [Indexed: 05/23/2025] Open
Abstract
Cardiovascular disease (CVD) remains the leading cause of mortality among people with type 1 diabetes (T1D), with cardiovascular mortality rates 2-5 times higher than in the general population. A concerning sex disparity exists within this high-risk population, as the cardioprotective advantage typically observed in women without diabetes appears attenuated or eliminated in individuals with T1D. This disparity is evident across the CVD spectrum, including coronary artery disease, stroke, heart failure, and cardiovascular mortality, with women consistently experiencing an excess burden of disease. These differences are particularly pronounced in women with early-onset T1D, leading to a substantial loss of life-years-approximately 18 years for women compared to 14 for men. Several factors may contribute to this sex disparity. First, the effect of hyperglycemia on CVD appears to have a sex-based differential impact and women with T1D often demonstrate more difficulties to achieve optimal glycemic control. Second, although women with T1D generally exhibit a more favorable CVD risk factor profile than men with T1D, the presence of hypertension, smoking or diabetic kidney disease seem to have a strong impact on CVD in women. Diabetes also appears to diminish sex-based differences in lipid metabolism, and a trend towards increased obesity rates among women with T1D has been observed. Lastly, female-specific factors, which are more prevalent in T1D, exacerbate cardiovascular risk. These include premature menopause, pregnancy-related disorders (such as preeclampsia), polycystic ovary syndrome, and autoimmune diseases, which disproportionately affect women. This narrative review examines the epidemiological evidence highlighting the aspects regarding the excess risk of CVD in women with T1D and evaluates sex disparities in both traditional and female-specific risk factors. Finally, we include a sex-based analysis from the Catalan Registry, which highlights the critical need for greater awareness and enhanced early detection and management of CVD risk factors in this population.
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Affiliation(s)
- Alex Mesa
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Carrer de Sant Quintí 89, 08041, Barcelona, Spain.
- Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
| | - Josep Franch-Nadal
- Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
- Diabetis en Atenció Primaria (DAP-Cat) Group, Unitat de Suport a la Recerca Barcelona, Fundació IDIAP Jordi Gol I Gurina, Barcelona, Spain
- Primary Health Care Center Raval Sud, Gerència d'Atenció Primaria, Institut Català de la Salut, Barcelona, Spain
| | - Elena Navas
- Diabetis en Atenció Primaria (DAP-Cat) Group, Unitat de Suport a la Recerca Barcelona, Fundació IDIAP Jordi Gol I Gurina, Barcelona, Spain
| | - Dídac Mauricio
- Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Carrer de Sant Quintí 89, 08041, Barcelona, Spain.
- Centro de Investigación Biomédica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
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Erwin AP, Patrie JT, Horton WB. Heart failure phenotypes in people with type 1 diabetes. Diabetes Obes Metab 2025; 27:1588-1590. [PMID: 39690327 PMCID: PMC11802393 DOI: 10.1111/dom.16133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 11/22/2024] [Accepted: 12/02/2024] [Indexed: 12/19/2024]
Affiliation(s)
- Abigail P. Erwin
- Division of Endocrinology and Metabolism, Department of MedicineUniversity of Virginia School of MedicineCharlottesvilleVirginiaUSA
| | - James T. Patrie
- Division of Biostatistics, Department of Public Health SciencesUniversity of Virginia School of MedicineCharlottesvilleVirginiaUSA
| | - William B. Horton
- Division of Endocrinology and Metabolism, Department of MedicineUniversity of Virginia School of MedicineCharlottesvilleVirginiaUSA
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Khalafi M, Dinizadeh F, Rosenkranz SK, Symonds ME, Fatolahi S. The Effects of Exercise Training on Body Composition and Cardiometabolic Risk Factors in Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Healthcare (Basel) 2025; 13:246. [PMID: 39942435 PMCID: PMC11816365 DOI: 10.3390/healthcare13030246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/31/2024] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
INTRODUCTION AND AIM We performed a systematic review and meta-analysis to investigate the effects of exercise training on body composition and cardiometabolic health in patients with Type 1 diabetes (T1D). METHOD A search in three main databases including PubMed, Web of Science, and Scopus was conducted from the inception of this review until June 2024 to identify randomized control trials investigating the effects of exercise training compared to a control on body composition and cardiometabolic risk factors in patients with T1D. The data were pooled using random effects models to calculate weighted mean differences (WMDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs). RESULTS Overall, 25 studies involving 1120 patients with T1D were included in the meta-analysis. Exercise training decreased body mass index (BMI) [WMD: -0.18 kg.m2, p = 0.02], fasting glucose [WMD: -14.97 mg/dl, p = 0.01], and HbA1c [WMD: -0.49%, p = 0.003], and increased VO2max/peak [WMD: 2.76 mL/kg/min, p = 0.001] as compared with controls. Exercise training had no effect on body fat percentage or lean body mass, lipid profiles, or blood pressure. Subgroup analysis indicated that age, exercise mode, and intervention duration were the main moderators for the beneficial effects of exercise training. CONCLUSIONS In patients with T1D, exercise training is effective for decreasing body weight and cardiometabolic risk factors.
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Affiliation(s)
- Mousa Khalafi
- Department of Sport Sciences, Faculty of Humanities, University of Kashan, Kashan 87317-53153, Iran
| | - Farnaz Dinizadeh
- Department of Sport Sciences, Tabriz Branch, Azad University, Tabriz 51579-44533, Iran;
| | - Sara K. Rosenkranz
- Department of Kinesiology and Nutrition Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USA;
| | - Michael E. Symonds
- Centre for Perinatal Research, Academic Unit of Population and Lifespan Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK;
| | - Saeid Fatolahi
- Department of Physical Education and Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran 14117-13116, Iran
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Li J, Liu J, Shi W, Guo J. Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review. Medicine (Baltimore) 2024; 103:e37844. [PMID: 38640337 PMCID: PMC11029945 DOI: 10.1097/md.0000000000037844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/08/2024] [Accepted: 03/19/2024] [Indexed: 04/21/2024] Open
Abstract
Diabetes mellitus (DM) is one of the most prevalent diseases worldwide, greatly impacting patients' quality of life. This article reviews the progress in Salvia miltiorrhiza, an ancient Chinese plant, for the treatment of DM and its associated complications. Extensive studies have been conducted on the chemical composition and pharmacological effects of S miltiorrhiza, including its anti-inflammatory and antioxidant activities. It has demonstrated potential in preventing and treating diabetes and its consequences by improving peripheral nerve function and increasing retinal thickness in diabetic individuals. Moreover, S miltiorrhiza has shown effectiveness when used in conjunction with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and statins. The safety and tolerability of S miltiorrhiza have also been thoroughly investigated. Despite the established benefits of managing DM and its complications, further research is needed to determine appropriate usage, dosage, long-term health benefits, and safety.
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Affiliation(s)
- Jiajie Li
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, PR China
| | - Jinxing Liu
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, PR China
| | - Weibing Shi
- The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, PR China
| | - Jinchen Guo
- School of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui, PR China
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Fridolfsson C, Thegerström J, Åkesson K, Engvall J, Blomstrand P. Lower left atrial function in young individuals with type 1 diabetes mellitus compared to healthy controls: an echocardiographic study. Sci Rep 2024; 14:3982. [PMID: 38368449 PMCID: PMC10874446 DOI: 10.1038/s41598-024-54597-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 02/14/2024] [Indexed: 02/19/2024] Open
Abstract
In adulthood, individuals with type 1 diabetes mellitus may develop a condition of heart failure with preserved ejection fraction. However, subclinical changes to the heart in diabetes are likely to occur prior to the clinical presentation. This cross-sectional study aimed to compare left atrial function by echocardiography between 43 individuals with type 1 diabetes and 43 healthy controls, aged 10-30 years. All participants underwent echocardiography and 2D speckle tracking measurements for left atrial phase function parameters. Physical capacity was assessed by exercise test on a bicycle. Results showed that participants with type 1 diabetes had significantly lower left atrial function parameters than healthy controls (p < 0.05). There was a significant negative correlation between HbA1c means and reservoir and conduit strain (p < 0.05) and individuals with BMI < 30 showed a lower left atrial stiffness (p < 0.05). Individuals with type 1 diabetes and a higher physical capacity did not differ from their healthy peers. Results indicate that lower HbA1c levels, BMI < 30 and a higher physical capacity are favourable in terms of left atrial function in children and young adults with type 1 diabetes mellitus. Left atrial strain by echocardiography might become a new important tool in assessing heart function in T1DM.
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Affiliation(s)
- Cecilia Fridolfsson
- Department of Clinical Physiology in Kalmar, Region Kalmar County, Kalmar, Sweden.
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
| | - Johanna Thegerström
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Paediatrics in Kalmar, Region Kalmar County, Kalmar, Sweden
- Faculty of Health and Life Sciences (FHL), Linnaeus University, Kalmar, Sweden
| | - Karin Åkesson
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Pediatrics, Ryhov County Hospital, Jönköping, Sweden
| | - Jan Engvall
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Clinical Physiology in Linköping, Linköping University Hospital, Linköping, Sweden
| | - Peter Blomstrand
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Natural Sciences and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden
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Lassen MCH, Biering-Sørensen T, Jørgensen PG, Bahrami HSZ, Andersen HU, Rossing P, Jensen MT. Ratio of transmitral early filling velocity to diastolic strain rate and prognosis in type-1 diabetes. Int J Cardiol 2024; 397:131653. [PMID: 38101702 DOI: 10.1016/j.ijcard.2023.131653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 11/13/2023] [Accepted: 12/10/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND Impaired diastolic function is a hallmark of diabetic cardiomyopathy and a common feature in type 1 diabetes mellitus (T1DM). The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to have strong prognostic value. This study aimed to investigate the prognostic value of E/e'sr compared to E/e' in T1DM without known heart disease. METHODS In this prospective cohort of T1DM patients, echocardiography was performed including two-dimensional speckle tracking. Follow-up was performed using nationwide registries. Outcomes were all-cause mortality and major cardiovascular events (MACE). RESULTS In total 1079 patients (age: 49.6 ± 14.5 years, 52.5% male, duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, IQR:5.7-6.9) 13.2% experienced MACE and 5.8% died. Following multivariable adjustment, both E/e'sr and E/e' was significantly associated with both MACE (E/e'sr: HR 1.16 CI95%:[1.05-1.29], p = 0.005, per 10 cm increase) vs. (E/e': HR 1.09 CI95%:[1.03-1.15], p = 0.001, per 1 unit increase) and all-cause mortality (E/e'sr: HR 1.20 [1.03-1.40], p = 0.016) vs. (E/e': HR: 1.11 [1.02-1.20], p = 0.016). Sex modified the association between E/e'sr and MACE (p for interaction = 0.008) such that E/e'sr after multivariable adjustment only remained significantly associated with MACE in females (HR: 1.41 [1.19-1.67], p < 0.001) but not in males (HR: 1.06 [0.93-1.20], p = 0.42). In females, E/e'sr provided incremental information beyond the Steno T1 Risk Engine (Harrell's C-statistic: 0.78 (0.72-0.83) vs. 0.81 (0.75-0.86), p = 0.007). CONCLUSION In patients with T1DM, both E/e'sr and E/e' provides independent prognostic information regarding prognosis. E/e'sr seems to have stronger prognostic value in females with T1DM.
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Affiliation(s)
- Mats Christian Højbjerg Lassen
- Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark.
| | - Tor Biering-Sørensen
- Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 København, Denmark; Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, 2730 Herlev, Denmark
| | - Peter Godsk Jørgensen
- Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Hashmat S Z Bahrami
- Department of Cardiology, Amager & Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, 2650 Hvidovre, Denmark
| | | | - Peter Rossing
- Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, 2730 Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
| | - Magnus T Jensen
- Steno Diabetes Center Copenhagen, Borgmester Ib Juuls Vej 83, 2730 Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
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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: 7] [Impact Index Per Article: 7.0] [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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8
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American Diabetes Association Professional Practice Committee, ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Das SR, Ekhlaspour L, Hilliard ME, Johnson EL, Khunti K, Kosiborod MN, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Gabbay RA. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S179-S218. [PMID: 38078592 PMCID: PMC10725811 DOI: 10.2337/dc24-s010] [Citation(s) in RCA: 168] [Impact Index Per Article: 168.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Nyström T, Schwarz E, Dahlqvist S, Wijkman M, Ekelund M, Holmer H, Bolinder J, Hellman J, Imberg H, Hirsch IB, Lind M. Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With Multiple Daily Insulin Injections: An Analysis Based on the GOLD Randomized Trial (GOLD 8). J Diabetes Sci Technol 2024; 18:89-98. [PMID: 35677967 PMCID: PMC10899843 DOI: 10.1177/19322968221101916] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. METHOD The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. RESULTS There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 (P = .16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment (P < .001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. CONCLUSION Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.
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Affiliation(s)
- Thomas Nyström
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Erik Schwarz
- Department of Internal Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Sofia Dahlqvist
- Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Wijkman
- Department of Internal Medicine and Department of Medical and Health Sciences, Linköping University, Norrköping, Sweden
| | - Magnus Ekelund
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Helen Holmer
- Department of Internal Medicine, Centralsjukhuset, Kristianstad, Sweden
| | - Jan Bolinder
- Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Jarl Hellman
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | - Henrik Imberg
- Statistiska Konsultgruppen, Gothenburg, Sweden
- Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden
| | - Irl B. Hirsch
- School of Medicine, University of Washington, Seattle, WA, USA
| | - Marcus Lind
- Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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10
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Movahed MR, Bahrami A, Manrique C, Hashemzadeh M. Strong independent association between third-degree AV-block and diabetes mellitus using a large database. Diabetes Res Clin Pract 2023; 205:110948. [PMID: 37832726 DOI: 10.1016/j.diabres.2023.110948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/27/2023] [Accepted: 10/10/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND Recent data suggests an association between DM and third-degree AV- Block. The goal of this study was to evaluate the independent association between diabetes and third-degree AV-Block using a very large database. METHOD We used ICD-9 Codes for DM and third-degree AV-block from the Nationwide Inpatient Sample (NIS) database. We randomly selected the 1992 and 2002 databases which are 10 years apart as two independent samples. We used uni- and multi-variate analysis to evaluate this association. RESULTS 1992 database contained a total of 6,195,744 patients. Diabetes occurred in (0.5 %) of patients with third-degree AV-block vs. (0.2 %) of the control (OR: 2.15, CI 2.06-2.25, p < 0.0001). 2002 database contained a total of 7,853,982 patients. Diabetes occurred in (0.4 %) of patients with third-degree AV-block vs. (0.2 %) of the control (OR: 1.86, CI: 1.80-1.93, p < 0.0001). Using Multivariate analysis adjusting for age, congestive heart failure, and coronary artery disease, DM remained independently associated with third-degree AV block in both databases. (for 1999: OR: 2.54, CI 2.51-2.57, p < 0.0001 and for 2002 OR: 1.56, CI 1.55-1.57, p < 0.0001). CONCLUSION DM is independently associated with third-degree AV-block with persistent association over a period of 10 years. The cause of this association warrants further investigation.
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Affiliation(s)
- Mohammad Reza Movahed
- University of Arizona College of Medicine, Tucson, AZ, United States; University of Arizona, College of Medicine, Phoenix, AZ, United States.
| | - Ashkan Bahrami
- University of Arizona College of Medicine, Tucson, AZ, United States
| | - Coraly Manrique
- University of Arizona College of Medicine, Tucson, AZ, United States
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11
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Cristelo C, Nunes R, Pinto S, Marques JM, Gama FM, Sarmento B. Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats. ACS Pharmacol Transl Sci 2023; 6:1544-1560. [PMID: 37854630 PMCID: PMC10580391 DOI: 10.1021/acsptsci.3c00218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Indexed: 10/20/2023]
Abstract
Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing β cells. Cathelicidin-based peptides have been shown to improve β cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the β cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ζ-potential (-10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with β cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the β cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment.
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Affiliation(s)
- Cecília Cristelo
- i3S
− Instituto de Investigação e Inovação
em Saúde, Universidade do Porto, Porto 4200-135, Portugal
- Centro
de Engenharia Biológica, Universidade
do Minho, Campus de Gualtar, Braga 4710-057, Portugal
- ICBAS
− Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto 4050-313, Portugal
| | - Rute Nunes
- i3S
− Instituto de Investigação e Inovação
em Saúde, Universidade do Porto, Porto 4200-135, Portugal
- IUCS-CESPU, Instituto
Universitário de Ciências
da Saúde, Gandra 4585-116, Portugal
| | - Soraia Pinto
- i3S
− Instituto de Investigação e Inovação
em Saúde, Universidade do Porto, Porto 4200-135, Portugal
- ICBAS
− Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto 4050-313, Portugal
| | - Joana Moreira Marques
- i3S
− Instituto de Investigação e Inovação
em Saúde, Universidade do Porto, Porto 4200-135, Portugal
- Faculdade
de Farmácia, Universidade do Porto, Porto 4099-002, Portugal
| | - Francisco Miguel Gama
- Centro
de Engenharia Biológica, Universidade
do Minho, Campus de Gualtar, Braga 4710-057, Portugal
| | - Bruno Sarmento
- i3S
− Instituto de Investigação e Inovação
em Saúde, Universidade do Porto, Porto 4200-135, Portugal
- IUCS-CESPU, Instituto
Universitário de Ciências
da Saúde, Gandra 4585-116, Portugal
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12
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Haji M, Erqou S, Fonarow GC, Echouffo-Tcheugui JB. Type 1 diabetes and risk of heart failure: A systematic review and meta-analysis. Diabetes Res Clin Pract 2023; 202:110805. [PMID: 37356724 PMCID: PMC10530158 DOI: 10.1016/j.diabres.2023.110805] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 06/14/2023] [Accepted: 06/22/2023] [Indexed: 06/27/2023]
Abstract
AIM Robust data on type 1 diabetes (T1DM) and the risk of heart failure (HF) is scarce. METHODS We searched PubMed and EMBASE for relevant studies, abstracted data on HF incidence rate and adjusted relative risk (aRR) for T1DM, type 2 diabetes (T2DM) and controls, and pooled incidence rates and aRRs for HF across studies. RESULTS Four studies including 61,885 T1DM patients, 4,599,213 non-diabetic controls, and 248,021 T2DM patients (three studies) were included. The pooled average proportions of men were 56%, 54%, and 55%, for T1DM, T2DM, and controls, respectively. The corresponding pooled average participants' ages were 40, 65 and 57 years, respectively. Over a 1 to 12 years follow-up, 1378, 3993, 18,945 HF events occurred among individuals with T1DM, T2DM, and controls, yielding pooled HF incidence rates of 5.8 (95%CI: 4.1-7.6), 10.0 (95% CI: 6.1-13.9), 2.3 (95% CI: 1.5-3.2) per 1000 person-years, respectively. Compared to controls, T1DM patients had a 3-fold higher HF risk (aRR 3.4, 95% CI 2.71-4.26). The RR of HF was ∼ 5-fold higher in women (aRR: 4.9, 95% CI: 4.1-5.9) vs. 3-fold higher in men (aRR: 3.0, 95% CI: 2.2-4.0). CONCLUSIONS Individuals with T1DM had a substantially higher risk of HF compared to those without diabetes.
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Affiliation(s)
- Mohammed Haji
- Department of Medicine, Brown University, Providence, RI, USA
| | - Sebhat Erqou
- Department of Medicine, Brown University, Providence, RI, USA; Department of Medicine, Providence VA Medical Center, Providence, RI, USA
| | - Gregg C Fonarow
- Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA
| | - Justin B Echouffo-Tcheugui
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, John Hopkins University School of Medicine, Baltimore, MD, USA.
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13
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Yeung AM, Huang J, Pandey A, Hashim IA, Kerr D, Pop-Busui R, Rhee CM, Shah VN, Bally L, Bayes-Genis A, Bee YM, Bergenstal R, Butler J, Fleming GA, Gilbert G, Greene SJ, Kosiborod MN, Leiter LA, Mankovsky B, Martens TW, Mathieu C, Mohan V, Patel KV, Peters A, Rhee EJ, Rosano GMC, Sacks DB, Sandoval Y, Seley JJ, Schnell O, Umpierrez G, Waki K, Wright EE, Wu AHB, Klonoff DC. Biomarkers for the Diagnosis of Heart Failure in People with Diabetes: A Consensus Report from Diabetes Technology Society. Prog Cardiovasc Dis 2023; 79:65-79. [PMID: 37178991 DOI: 10.1016/j.pcad.2023.05.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 05/08/2023] [Indexed: 05/15/2023]
Abstract
Diabetes Technology Society assembled a panel of clinician experts in diabetology, cardiology, clinical chemistry, nephrology, and primary care to review the current evidence on biomarker screening of people with diabetes (PWD) for heart failure (HF), who are, by definition, at risk for HF (Stage A HF). This consensus report reviews features of HF in PWD from the perspectives of 1) epidemiology, 2) classification of stages, 3) pathophysiology, 4) biomarkers for diagnosing, 5) biomarker assays, 6) diagnostic accuracy of biomarkers, 7) benefits of biomarker screening, 8) consensus recommendations for biomarker screening, 9) stratification of Stage B HF, 10) echocardiographic screening, 11) management of Stage A and Stage B HF, and 12) future directions. The Diabetes Technology Society panel recommends 1) biomarker screening with one of two circulating natriuretic peptides (B-type natriuretic peptide or N-terminal prohormone of B-type natriuretic peptide), 2) beginning screening five years following diagnosis of type 1 diabetes (T1D) and at the diagnosis of type 2 diabetes (T2D), 3) beginning routine screening no earlier than at age 30 years for T1D (irrespective of age of diagnosis) and at any age for T2D, 4) screening annually, and 5) testing any time of day. The panel also recommends that an abnormal biomarker test defines asymptomatic preclinical HF (Stage B HF). This diagnosis requires follow-up using transthoracic echocardiography for classification into one of four subcategories of Stage B HF, corresponding to risk of progression to symptomatic clinical HF (Stage C HF). These recommendations will allow identification and management of Stage A and Stage B HF in PWD to prevent progression to Stage C HF or advanced HF (Stage D HF).
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Affiliation(s)
- Andrea M Yeung
- Diabetes Technology Society, Burlingame, CA, United States of America
| | - Jingtong Huang
- Diabetes Technology Society, Burlingame, CA, United States of America
| | - Ambarish Pandey
- UT Southwestern Medical Center, Dallas, TX, United States of America
| | - Ibrahim A Hashim
- UT Southwestern Medical Center, Dallas, TX, United States of America
| | - David Kerr
- Diabetes Technology Society, Burlingame, CA, United States of America
| | | | - Connie M Rhee
- Division of Nephrology, Hypertension, and Kidney Transplantation, University of California Irvine, Orange, CA, United States of America
| | - Viral N Shah
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Lia Bally
- Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Antoni Bayes-Genis
- Hospital Universitari Germans Trias I Pujol, CIBERCV, Universitat Autonoma Barcelona, Spain
| | | | - Richard Bergenstal
- International Diabetes Center, HealthPartners Institute, Minneapolis, MN, United States of America
| | - Javed Butler
- Baylor Scott and White Research Institute, Dallas, TX and University of Mississippi, Jackson, MS, United States of America
| | | | - Gregory Gilbert
- Mills-Peninsula Medical Center, Burlingame, CA, United States of America
| | - Stephen J Greene
- Division of Cardiology, Duke University School of Medicine, Durham, NC, United States of America
| | - Mikhail N Kosiborod
- Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States of America
| | - Lawrence A Leiter
- Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | | | - Thomas W Martens
- International Diabetes Center and Park Nicollet Clinic, Minneapolis, MN, United States of America
| | | | - Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Chennai, India
| | - Kershaw V Patel
- Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, United States of America
| | - Anne Peters
- University of Southern California Keck School of Medicine, Los Angeles, CA, United States of America
| | - Eun-Jung Rhee
- Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | | | - David B Sacks
- National Institutes of Health, Bethesda, MD, United States of America
| | - Yader Sandoval
- Minneapolis Heart Institute, Abbott Northwestern Hospital and Minneapolis Heart Institute Foundation, Minneapolis, MN, United States of America
| | | | - Oliver Schnell
- Forschergruppe Diabetes e.V., Munich-, Neuherberg, Germany
| | | | - Kayo Waki
- The University of Tokyo, Tokyo, Japan
| | - Eugene E Wright
- Charlotte Area Health Education Center, Charlotte, NC, United States of America
| | - Alan H B Wu
- University of California, San Francisco, San Francisco, CA, United States of America
| | - David C Klonoff
- Mills-Peninsula Medical Center, San Mateo, CA, United States of America.
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14
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Haxha S, Halili A, Malmborg M, Pedersen-Bjergaard U, Philbert BT, Lindhardt TB, Hoejberg S, Schjerning AM, Ruwald MH, Gislason GH, Torp-Pedersen C, Bang CN. Type 2 diabetes mellitus and higher rate of complete atrioventricular block: a Danish Nationwide Registry. Eur Heart J 2023; 44:752-761. [PMID: 36433808 DOI: 10.1093/eurheartj/ehac662] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 10/10/2022] [Accepted: 11/02/2022] [Indexed: 11/27/2022] Open
Abstract
AIMS The present study aimed to determine the association between Type 2 diabetes mellitus (T2DM) and third-degree (complete) atrioventricular block. METHODS AND RESULTS This nationwide nested case-control study included patients older than 18 years, diagnosed with third-degree atrioventricular block between 1 July 1995 and 31 December 2018. Data on medication, comorbidity, and outcomes were collected from Danish registries. Five controls, from the risk set of each case of third-degree atrioventricular block, were matched on age and sex to fit a Cox regression model with time-dependent exposure and time-dependent covariates. Subgroup analysis was conducted with Cox regression models for each subgroup. We located 25 995 cases with third-degree atrioventricular block that were matched with 130 004 controls. The mean age was 76 years and 62% were male. Cases had more T2DM (21% vs. 11%), hypertension (69% vs. 50%), atrial fibrillation (25% vs. 10%), heart failure (20% vs. 6.3%), and myocardial infarction (19% vs. 9.2%), compared with the control group. In Cox regression analysis, adjusting for comorbidities and atrioventricular nodal blocking agents, T2DM was significantly associated with third-degree atrioventricular block (hazard ratio: 1.63, 95% confidence interval: 1.57-1.69). The association remained in several subgroup analyses of diseases also suspected to be associated with third-degree atrioventricular block. There was a significant interaction with comorbidities of interest including hypertension, atrial fibrillation, heart failure, and myocardial infarction. CONCLUSION In this nationwide study, T2DM was associated with a higher rate of third-degree atrioventricular block compared with matched controls. The association remained independent of atrioventricular nodal blocking agents and other comorbidities known to be associated with third-degree atrioventricular block.
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Affiliation(s)
- Saranda Haxha
- Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.,Department of Cardiology, North Zealand Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark
| | - Andrim Halili
- Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.,Department of Cardiology, North Zealand Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark
| | - Morten Malmborg
- Danish Heart Foundation, Randersgade 60, 2100 Copenhagen, Denmark
| | - Ulrik Pedersen-Bjergaard
- Department of Endocrinology and Nephrology, North Zealand Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark.,Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3b 33.5, 2200 Copenhagen, Denmark
| | - Berit T Philbert
- Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark
| | - Tommi B Lindhardt
- Department of Cardiology, Herlev-Gentofte University Hospital, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Soeren Hoejberg
- Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark
| | - Anne-Marie Schjerning
- Department of Cardiology, Zealand University Hospital, Sygehusvej 10, 4000 Roskilde, Denmark
| | - Martin H Ruwald
- Department of Cardiology, Herlev-Gentofte University Hospital, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Gunnar H Gislason
- Department of Cardiology, Herlev-Gentofte University Hospital, Gentofte Hospitalsvej 1, 2900 Hellerup, Denmark
| | - Christian Torp-Pedersen
- Department of Cardiology, North Zealand Hospital, Dyrehavevej 29, 3400 Hillerød, Denmark.,Faculty of Health and Medical Sciences, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, build. 24 Q, 1st floor 1353 Copenhagen, Denmark
| | - Casper N Bang
- Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark
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15
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Abstract
Diabetes is one of the most prevalent cardiometabolic disorders on the planet. Type 1 diabetes accounts for only a minority of all cases (recently estimated to be ~2% globally); however, since this is a disorder with an early onset, many people live with type 1 diabetes for a long time. CVD and premature death are the main long-term outcomes for both types of diabetes; however, the type of diabetes that carries the highest risk of these outcomes is a controversial topic and has not been widely studied. Because of the association between diabetes and CVD, the rise in type 2 diabetes prevalence over the past decades has huge effects on global health. The excess risk in people with diabetes compared with those without depends, to a large extent, on the presence of other factors, such as general cardiovascular risk factors (e.g. elevated LDL-cholesterol, hypertension and smoking) and also factors that are more specific to diabetes (e.g. HbA1c, and micro- and macroalbuminuria). Some contributory factors are modifiable, while others are not, such as age, sex and type of diabetes. Older people with type 2 diabetes who have risk factors that are under control can achieve levels of CVD risk that are similar to that of the general population, while younger individuals with type 1 diabetes are mostly unable to achieve similar levels of risk, probably because of long and cumulative exposure to raised blood glucose levels. Despite reports of declining rates of CVD among people with type 1 and type 2 diabetes, rising rates of both types of diabetes lead to a continuing rise in the number of people with cardiometabolic disorders worldwide, offsetting the progress made in many countries. Comparison between individuals with type 1 and type 2 diabetes with respect to risk of CVD is fraught with difficulties and highly dependent on other, concomitant factors, some of which are modifiable and others not. Nonetheless, as a whole, what matters most in determining the management of diabetes is absolute risk and lifetime risk. Life-long efforts to achieve glycaemic control, control of lipids and hypertension, and not smoking are key to prevention, with a healthy lifestyle and pharmacological therapy to be implemented as needed.
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Affiliation(s)
- Annika Rosengren
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Region Västra Götaland, Department of Medicine, Geriatrics and Emergency Medicine, Sahlgrenska University Hospital, Östra Hospital, Gothenburg, Sweden.
| | - Pigi Dikaiou
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
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16
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Puig-Jové C, Julve J, Castelblanco E, Julián MT, Amigó N, Andersen HU, Ahluwalia TS, Rossing P, Mauricio D, Jensen MT, Alonso N. The novel inflammatory biomarker GlycA and triglyceride-rich lipoproteins are associated with the presence of subclinical myocardial dysfunction in subjects with type 1 diabetes mellitus. Cardiovasc Diabetol 2022; 21:257. [PMID: 36434633 PMCID: PMC9700974 DOI: 10.1186/s12933-022-01652-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 09/23/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Subjects with Type 1 diabetes mellitus (T1DM) have an increased incidence of heart failure (HF). Several pathophysiological mechanisms have been involved in its development. The aim of this study was to analyze the potential contribution of the advanced lipoprotein profile and plasma glycosylation (GlycA) to the presence of subclinical myocardial dysfunction in subjects with T1DM. METHODS We included subjects from a Danish cohort of T1DM subjects (Thousand & 1 study) with either diastolic and/or systolic subclinical myocardial dysfunction, and a control group without myocardial dysfunction, matched by age, sex and HbA1c. All underwent a transthoracic echocardiogram and an advanced lipoprotein profile obtained by using the NMR-based Liposcale® test. GlycA NMR signal was also analyzed. Systolic dysfunction was defined as left ventricular ejection fraction ≤ 45% and diastolic dysfunction was considered as E/e'≥12 or E/e' 8-12 + volume of the left atrium > 34 ml/m2. To identify a metabolic profile associated with the presence of subclinical myocardial dysfunction, a multivariate supervised model of classification based on least squares regression (PLS-DA regression) was performed. RESULTS One-hundred forty-six subjects had diastolic dysfunction and 18 systolic dysfunction. Compared to the control group, patients with myocardial dysfunction had longer duration of diabetes (p = 0.005), and higher BMI (p = 0.013), serum NTproBNP concentration (p = 0.001), systolic blood pressure (p < 0.001), albuminuria (p < 0.001), and incidence of advanced retinopathy (p < 0.001). The supervised classification model identified a specific pattern associated with myocardial dysfunction, with a capacity to discriminate patients with myocardial dysfunction from controls. PLS-DA showed that triglyceride-rich lipoproteins (TGRLs), such as VLDL (total VLDL particles, large VLDL subclass and VLDL-TG content) and IDL (IDL cholesterol content), as well as the plasma concentration of GlycA, were associated with the presence of subclinical myocardial dysfunction. CONCLUSION Proatherogenic TGRLs and the proinflammatory biomarker Glyc A are strongly associated to myocardial dysfunction in T1DM. These findings suggest a pivotal role of TGRLs and systemic inflammation in the development of subclinical myocardial dysfunction in T1DM.
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Affiliation(s)
- Carlos Puig-Jové
- grid.414875.b0000 0004 1794 4956Department of Endocrinology & Nutrition, University Hospital Mútua de Terrassa, Terrassa, Spain ,grid.7080.f0000 0001 2296 0625Department of Medicine, Autonomous University of Barcelona (UAB), Barcelona, Spain
| | - Josep Julve
- grid.413448.e0000 0000 9314 1427Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain ,grid.413396.a0000 0004 1768 8905Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
| | - Esmeralda Castelblanco
- grid.4367.60000 0001 2355 7002Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine in St. Louis, St Louis, MO USA
| | - M Teresa Julián
- grid.413448.e0000 0000 9314 1427Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain ,Department of Endocrinology & Nutrition, University Hospital and Health Sciences Research Institute Germans Trias i Pujol, Badalona, Spain
| | - Núria Amigó
- grid.413448.e0000 0000 9314 1427Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain ,Biosfer Teslab SL, Reus, Spain ,grid.410367.70000 0001 2284 9230Department of Basic Medical Sciences, Universitat Rovira i Virgili (URV), Reus, Spain
| | - Henrik U Andersen
- grid.419658.70000 0004 0646 7285Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Tarunveer S Ahluwalia
- grid.419658.70000 0004 0646 7285Steno Diabetes Center Copenhagen, Herlev, Denmark ,grid.5254.60000 0001 0674 042XDepartment of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Peter Rossing
- grid.419658.70000 0004 0646 7285Steno Diabetes Center Copenhagen, Herlev, Denmark ,grid.5254.60000 0001 0674 042XDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Dídac Mauricio
- grid.413448.e0000 0000 9314 1427Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain ,grid.440820.aFaculty of Medicine, University of Vic - Central University of Catalonia (UVic/UCC), Vic, Spain ,grid.413396.a0000 0004 1768 8905Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau & Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
| | - Magnus T Jensen
- grid.413660.60000 0004 0646 7437Department of Cardiology, Copenhagen University Hospital Amager Hvidovre, Copenhagen, Denmark
| | - Núria Alonso
- grid.7080.f0000 0001 2296 0625Department of Medicine, Autonomous University of Barcelona (UAB), Barcelona, Spain ,grid.413448.e0000 0000 9314 1427Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain ,Department of Endocrinology & Nutrition, University Hospital and Health Sciences Research Institute Germans Trias i Pujol, Badalona, Spain
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17
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Guo J, Costacou T, Orchard TJ. Long term risk of heart failure in individuals with childhood-onset type 1 diabetes. J Diabetes Complications 2022; 36:108233. [PMID: 35753927 DOI: 10.1016/j.jdiacomp.2022.108233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 06/12/2022] [Accepted: 06/15/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND We aimed to evaluate the risk of heart failure in young adults with childhood-onset type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. We also examined risk factors and microvascular disease burden associated with the incidence of heart failure. METHODS Participants in the EDC study without known baseline heart failure (n = 655) were enrolled and then followed for 25 years. "Any" heart failure comprised the underlying cause of death, primary reason for hospitalization, EDC clinic examination findings or self-report of a physician diagnosis. "Hard" heart failure was determined only by the underlying cause of death or primary reason for hospitalization. Incidence rates for heart failure were estimated using Poisson models. Cox models were constructed to examine the associations between risk factors and microvascular disease burden with incident heart failure. RESULTS The mean baseline age and diabetes duration were 27(8) years and 19 (8) years. Incidence for any and hard heart failure were 3.4 and 1.8/1000 person-years. Diabetes duration, ever smoking and triglycerides were significant risk factors of any heart failure; longer diabetes duration, lower estimated glomerular filtration rate and higher white blood cell count significantly predicted hard heart failure. A gradient association was observed between the number of microvascular disease (from 0 to 3) and "hard" heart failure endpoint but not "any" clinically defined heart failure. CONCLUSION Young adults with long-duration type 1 diabetes had a high risk of heart failure. As microvascular disease burden increases so does the risk of heart failure independently of diabetes duration, A1c and coronary artery disease.
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Affiliation(s)
- Jingchuan Guo
- Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, United States of America.
| | - Tina Costacou
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States of America
| | - Trevor J Orchard
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States of America
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18
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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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19
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Seyed Ahmadi S, Pivodic A, Svensson AM, Wedel H, Rathsman B, Nyström T, Ludvigsson J, Lind M. Risk factors for nephropathy in persons with type 1 diabetes: a population-based study. Acta Diabetol 2022; 59:761-772. [PMID: 35201418 PMCID: PMC9085666 DOI: 10.1007/s00592-022-01863-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/19/2021] [Indexed: 12/22/2022]
Abstract
AIMS Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. METHODS A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. RESULTS During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure ≥ 140/80 mmHg was associated with increased risk of albuminuria (p ≤ 0.0001), as were triglycerides ≥ 1.0 mmol/L (p = 0.039), total cholesterol ≥ 5.0 mmol/L (p = 0.0003), HDL < 1.0 mmol/L (p = 0.013), LDL 3.5- < 4.0 mmol/L (p = 0.020), and BMI ≥ 30 kg/m2 (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c > 65 mmol/mol (> 8.1%), blood pressure > 140/70 mmHg was associated with increased risk of albuminuria. CONCLUSIONS Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.
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Affiliation(s)
- Shilan Seyed Ahmadi
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
- Department of Medicine, Uddevalla Hospital, 45180, Uddevalla, Sweden.
| | - Aldina Pivodic
- Statistiska Konsultgruppen, Gothenburg, Sweden
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | | | - Hans Wedel
- Department of Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Björn Rathsman
- Department of Clinical Science and Education, Sachs' Children and Youth Hospital, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Nyström
- Department of Clinical Science and Education, Internal Medicine, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Johnny Ludvigsson
- Department of Biomedical and Clinical Sciences, Crown Princess Victoria Children's Hospital, and Division of Paediatrics, Linköping University, Linköping, Sweden
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden
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20
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Kruik-Kollöffel WJ, Vallejo-Yagüe E, Movig KLL, Linssen GCM, Heintjes EM, van der Palen J. Non-cardiovascular medication and readmission for heart failure: an observational cohort study. Int J Clin Pharm 2022; 44:762-768. [PMID: 35633434 DOI: 10.1007/s11096-022-01418-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 04/20/2022] [Indexed: 11/29/2022]
Abstract
Background Among heart failure (HF) patients, hospital readmissions are a major concern. The medication taken by a patient may provide information on comorbidities and conditions and may be used as an indicator to identify populations at an increased risk of HF readmission. Aim This study explored the use of non-cardiovascular medication at hospital discharge from the first HF admission in search of indicators of high risk of readmission for HF. Method The study included 22,476 HF patients from the Dutch PHARMO Database Network at their first HF hospitalization. The data was divided into training and validation sets. A Cox regression model with demographics, date of first HF hospital admission and non-cardiovascular medication present at discharge, adjusted for cardiovascular medication, was developed in the training set and subsequently implemented in the validation set. Results The study included 22,476 patients, mean age 76.7 years (range 18-104) and median follow-up time 2.5 years (range 0-15.7 years). During the study period 6,725 (29.9%) patients were readmitted for HF, with a median time-to-readmission of 7 months (range 0-14.3 years). Non-cardiovascular medication associated with a high risk of readmission for HF were identified as indicators of high risk, with no implied causal relationship. Patients prescribed antigout medications presented a 25% increased risk of readmission (HR 1.25, 95%CI 1.09-1.45, P = 0.002). Patients using insulin had an 18% higher risk of readmission versus patients not using insulin (HR 1.18, 95%CI 1.06-1.32, P = 0.002), but not versus patients treated with other blood-glucose-lowering drugs. No association between the risk of readmission and NSAIDs use was observed. Conclusion The results suggest that diabetes is responsible for the higher HF-readmission risk observed in patients prescribed insulin. The observed risk in users of antigout medication should be further investigated. The absence of an association with the use of NSAIDs should be interpreted with caution.
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Affiliation(s)
| | | | - Kris L L Movig
- Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Gerard C M Linssen
- Department of Cardiology, Hospital Group Twente, Almelo and Hengelo, The Netherlands
| | - Edith M Heintjes
- PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands
| | - Job van der Palen
- Medical School Twente, Medisch Spectrum Twente, Enschede, The Netherlands.,Section Cognition, Data and Education, University of Twente, Enschede, The Netherlands
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21
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Assiri SA, El Meligy OAES, Alzain IO, Bamashmous NO. Assessment of dental caries and salivary characteristics among type 1 diabetic Saudi children. J Dent Sci 2022; 17:1634-1639. [DOI: 10.1016/j.jds.2022.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 03/22/2022] [Indexed: 11/17/2022] Open
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22
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Kardiovaskuläre Risiken in der 4.–6. Lebensdekade mit Diabetes mellitus Typ 1. DIABETOLOGE 2022. [DOI: 10.1007/s11428-021-00854-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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23
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Kambis TN, Tofilau HMN, Gawargi FI, Chandra S, Mishra PK. Regulating Polyamine Metabolism by miRNAs in Diabetic Cardiomyopathy. Curr Diab Rep 2021; 21:52. [PMID: 34902085 PMCID: PMC8668854 DOI: 10.1007/s11892-021-01429-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/22/2021] [Indexed: 11/08/2022]
Abstract
PURPOSE OF REVIEW Insulin is at the heart of diabetes mellitus (DM). DM alters cardiac metabolism causing cardiomyopathy, ultimately leading to heart failure. Polyamines, organic compounds synthesized by cardiomyocytes, have an insulin-like activity and effect on glucose metabolism, making them metabolites of interest in the DM heart. This review sheds light on the disrupted microRNA network in the DM heart in relation to developing novel therapeutics targeting polyamine biosynthesis to prevent/mitigate diabetic cardiomyopathy. RECENT FINDINGS Polyamines prevent DM-induced upregulation of glucose and ketone body levels similar to insulin. Polyamines also enhance mitochondrial respiration and thereby regulate all major metabolic pathways. Non-coding microRNAs regulate a majority of the biological pathways in our body by modulating gene expression via mRNA degradation or translational repression. However, the role of miRNA in polyamine biosynthesis in the DM heart remains unclear. This review discusses the regulation of polyamine synthesis and metabolism, and its impact on cardiac metabolism and circulating levels of glucose, insulin, and ketone bodies. We provide insights on potential roles of polyamines in diabetic cardiomyopathy and putative miRNAs that could regulate polyamine biosynthesis in the DM heart. Future studies will unravel the regulatory roles these miRNAs play in polyamine biosynthesis and will open new doors in the prevention/treatment of adverse cardiac remodeling in diabetic cardiomyopathy.
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Affiliation(s)
- Tyler N Kambis
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | | | - Flobater I Gawargi
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Surabhi Chandra
- Department of Biology, University of Nebraska-Kearney, Kearney, NE, 68845, USA
| | - Paras K Mishra
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
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24
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El Hayek MS, Ernande L, Benitah JP, Gomez AM, Pereira L. The role of hyperglycaemia in the development of diabetic cardiomyopathy. Arch Cardiovasc Dis 2021; 114:748-760. [PMID: 34627704 DOI: 10.1016/j.acvd.2021.08.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 01/08/2023]
Abstract
Diabetes mellitus is a metabolic disorder with a chronic hyperglycaemic state. Cardiovascular diseases are the primary cause of mortality in patients with diabetes. Increasing evidence supports the existence of diabetic cardiomyopathy, a cardiac dysfunction with impaired cardiac contraction and relaxation, independent of coronary and/or valvular complications. Diabetic cardiomyopathy can lead to heart failure. Several preclinical and clinical studies have aimed to decipher the underlying mechanisms of diabetic cardiomyopathy. Among all the co-factors, hyperglycaemia seems to play an important role in this pathology. Hyperglycaemia has been shown to alter cardiac metabolism and function through several deleterious mechanisms, such as oxidative stress, inflammation, accumulation of advanced glycated end-products and upregulation of the hexosamine biosynthesis pathway. These mechanisms are responsible for the activation of hypertrophic pathways, epigenetic modifications, mitochondrial dysfunction, cell apoptosis, fibrosis and calcium mishandling, leading to cardiac stiffness, as well as contractile and relaxation dysfunction. This review aims to describe the hyperglycaemic-induced alterations that participate in diabetic cardiomyopathy, and their correlation with the severity of the disease and patient mortality, and to provide an overview of cardiac outcomes of glucose-lowering therapy.
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Affiliation(s)
| | - Laura Ernande
- INSERM U955, Université Paris-Est Créteil (UPEC), 94010 Créteil, France; Department of Cardiology, Institut Mondor de Recherche Biomédicale, INSERM U955-Équipe 8, Faculté de Médecine de Créteil, 94010 Créteil, France
| | | | - Ana-Maria Gomez
- Université Paris-Saclay, INSERM, UMR-S 1180, 92296 Châtenay-Malabry, France
| | - Laetitia Pereira
- Université Paris-Saclay, INSERM, UMR-S 1180, 92296 Châtenay-Malabry, France.
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25
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Harjutsalo V, Pongrac Barlovic D, Groop PH. Long-term population-based trends in the incidence of cardiovascular disease in individuals with type 1 diabetes from Finland: a retrospective, nationwide, cohort study. Lancet Diabetes Endocrinol 2021; 9:575-585. [PMID: 34303414 DOI: 10.1016/s2213-8587(21)00172-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 05/31/2021] [Accepted: 06/10/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Cardiovascular disease is the main determinant of premature mortality in patients with type 1 diabetes. However, time trends regarding different types of cardiovascular disease in childhood-onset type 1 diabetes with a long timespan from the diagnosis of diabetes are not well established. This study aimed to investigate the cumulative incidence of cardiovascular disease in individuals with type 1 diabetes in a population-based cohort in Finland, the country with the world's highest incidence of type 1 diabetes. METHODS In this retrospective, nationwide registry-based, cohort study, all patients who were diagnosed between Jan 1, 1965, and Dec 31, 1999 with type 1 diabetes when they were younger than 15 years old in Finland were followed up and monitored for the occurrence of cardiovascular disease (including coronary artery disease, stroke, peripheral artery disease, and heart failure) until the end of 2016 and for cardiovascular disease mortality until 2017. Cumulative incidences of cardiovascular disease were calculated by the Fine and Gray method according to the year of diabetes diagnosis using six diagnosis cohorts: 1965-69, 1970-74, 1975-1979, 1980-84, 1985-89, 1990-94, and 1990-95. Trends in cardiovascular disease event rates were analysed by Fine and Gray competing risks regression models using year of diabetes diagnosis as continuous variable. In addition, non-linearity in trends was assessed with restricted cubic splines. The excess risk of coronary artery disease and stroke was estimated by comparison with the risk in the Finnish general population by calculating standardised incidence ratios (SIRs) and their time trends. The data for Finnish general population were drawn from the Cardiovascular Disease Register of the National Institute of Health and Welfare. The SIRs were calculated as ratios of observed and expected number of events in individuals with type 1 diabetes during 1991-2014. FINDINGS 11 766 individuals were included in this study. During 361 033 person-years of follow-up and a median of 29·6 years (IQR 22·3-37·9) follow-up, a total of 1761 individuals had single or multiple types of cardiovascular disease events. 2686 events (864 [32·2%] coronary artery disease events, of which 663 were acute myocardial infarctions; 497 [18·5%] strokes; 854 [31·8%] peripheral artery diseases, of which 498 were lower extremity amputations; and 471 [17·5%] heart failure events) were reported until Dec 31, 2016, and 1467 deaths until Dec 31, 2017. Cardiovascular disease risk decreased linearly by 3·8% (hazard ratio [HR] 0·96 [95% CI 0·96-0·97]; p<0·0001) by later calendar year of diabetes diagnosis (p<0·0001). There was a decrease in the SIRs for both coronary artery disease and stroke within all 10-year age groups under 65 years, except for stroke in the oldest age group. However, the SIR was still 8·9 (95% CI 3·9-17·5) for coronary artery disease and 2·9 (1·3-5·7) for stroke in those diagnosed with type 1 diabetes in the 1990s. Finally, the cardiovascular disease death rate decreased constantly by diagnosis year. INTERPRETATION The risk of cardiovascular disease has decreased over time in Finland in individuals with childhood-onset type 1 diabetes. However, there is still considerable excess cardiovascular disease risk in individuals with type 1 diabetes compared with the general population. These results highlight the need for studies on the mechanisms of atherosclerosis from the time of diagnosis of type 1 diabetes to facilitate early and effective prevention of cardiovascular disease in these individuals. FUNDING Folkhälsan Research Foundation, Academy of Finland, Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation, and Helsinki University Hospital Research Funds.
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Affiliation(s)
- Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Finnish Institute for Health and Welfare, Department of Public Health and Welfare, Helsinki, Finland.
| | - Drazenka Pongrac Barlovic
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
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26
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Parente EB, Harjutsalo V, Forsblom C, Groop PH. The impact of central obesity on the risk of hospitalization or death due to heart failure in type 1 diabetes: a 16-year cohort study. Cardiovasc Diabetol 2021; 20:153. [PMID: 34315479 PMCID: PMC8314504 DOI: 10.1186/s12933-021-01340-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/09/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Obesity and type 2 diabetes are well-known risk factors for heart failure (HF). Although obesity has increased in type 1 diabetes, studies regarding HF in this population are scarce. Therefore, we investigated the impact of body fat distribution on the risk of HF hospitalization or death in adults with type 1 diabetes at different stages of diabetic nephropathy (DN). METHODS From 5401 adults with type 1 diabetes in the Finnish Diabetic Nephropathy Study, 4668 were included in this analysis. The outcome was HF hospitalization or death identified from the Finnish Care Register for Health Care or the Causes of Death Register until the end of 2017. DN was based on urinary albumin excretion rate. A body mass index (BMI) ≥ 30 kg/m2 defined general obesity, whilst WHtR ≥ 0.5 central obesity. Multivariable Cox regression was used to explore the associations between central obesity, general obesity and the outcome. Then, subgroup analyses were performed by DN stages. Z statistic was used for ranking the association. RESULTS During a median follow-up of 16.4 (IQR 12.4-18.5) years, 323 incident cases occurred. From 308 hospitalizations due to HF, 35 resulted in death. Further 15 deaths occurred without previous hospitalization. The WHtR showed a stronger association with the outcome [HR 1.51, 95% CI (1.26-1.81), z = 4.40] than BMI [HR 1.05, 95% CI (1.01-1.08), z = 2.71]. HbA1c [HR 1.35, 95% CI (1.24-1.46), z = 7.19] was the most relevant modifiable risk factor for the outcome whereas WHtR was the third. Individuals with microalbuminuria but no central obesity had a similar risk of the outcome as those with normoalbuminuria. General obesity was associated with the outcome only at the macroalbuminuria stage. CONCLUSIONS Central obesity associates with an increased risk of heart failure hospitalization or death in adults with type 1 diabetes, and WHtR may be a clinically useful screening tool.
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Affiliation(s)
- Erika B Parente
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,National Institute for Health and Welfare, Helsinki, Finland
| | - Carol Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. .,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. .,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. .,Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
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27
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Kapelios CJ, Bonou M, Barmpagianni A, Tentolouris A, Tsilingiris D, Eleftheriadou I, Skouloudi M, Kanellopoulos PN, Lambadiari V, Masoura C, Makrilakis K, Katsilambros N, Barbetseas J, Liatis S. Early left ventricular systolic dysfunction in asymptomatic patients with type 1 diabetes: a single-center, pilot study. J Diabetes Complications 2021; 35:107913. [PMID: 33867245 DOI: 10.1016/j.jdiacomp.2021.107913] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 02/26/2021] [Accepted: 03/14/2021] [Indexed: 01/18/2023]
Abstract
AIMS Prevalence and risk factors of pre-symptomatic left ventricular systolic dysfunction (LVSD) in individuals with type 1 diabetes (T1D) have not been adequately studied. The present cross-sectional study assessed the prevalence of early LVSD in asymptomatic patients with type 1 diabetes and investigated potential risk factors. METHODS Consecutive patients with T1D, free of cardiovascular disease and significant evident microvascular complications were examined. LVSD was assessed by speckle-tracking echocardiography and calculation of global longitudinal strain (GLS). Abnormal GLS was defined as a value>-18.7%. We looked for possible associations between the presence of LVSD and patient demographic, clinical and laboratory characteristics, as well as with autonomic nervous system (ANS) function and arterial stiffness. RESULTS We enrolled 155 T1D patients (29.7% men, age 36.7 ± 13.1 years, diabetes duration 19.1 ± 10.0 years, HbA1c 7.5 ± 1.4% [58 ± 15 mmol/mol]). Early LVSD was prevalent in 53 (34.2%) patients. Multivariable analysis identified male gender (OR:4.14; 95% CI:1.39-12.31, p = 0.011), HbA1c (OR:1.59 per 1% increase; 95% CI:1.11-2.28, p = 0.011), glomerular filtration rate (GFR, OR:0.97; 95% CI:0.95-0.99, p = 0.010) and BMI (OR:1.19; 95% CI:1.06-1.34, p = 0.003) as independent predictors of LVSD presence. CONCLUSIONS Early subclinical LVSD is a common finding in asymptomatic patients with T1D, free of macrovascular and significant microvascular complications. Apart from chronic hyperglycemia, increased adiposity may be implicated in its etiology. Further investigation is warranted to identify patients at high risk for whom early screening is required and to determine possible associations between risk markers identified in the present analysis and long-term outcomes.
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Affiliation(s)
- Chris J Kapelios
- Department of Cardiology, Laiko General Hospital, Athens, Greece.
| | - Maria Bonou
- Department of Cardiology, Laiko General Hospital, Athens, Greece
| | - Aikaterini Barmpagianni
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasios Tentolouris
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Tsilingiris
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioanna Eleftheriadou
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Marina Skouloudi
- Department of Cardiology, Laiko General Hospital, Athens, Greece
| | | | - Vaia Lambadiari
- Second Department of Internal Medicine, Attikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Konstantinos Makrilakis
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Katsilambros
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - John Barbetseas
- Department of Cardiology, Laiko General Hospital, Athens, Greece
| | - Stavros Liatis
- First Department of Propaedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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28
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Cai X, Li J, Cai W, Chen C, Ma J, Xie Z, Dong Y, Liu C, Xue R, Zhao J. Meta-analysis of type 1 diabetes mellitus and risk of cardiovascular disease. J Diabetes Complications 2021; 35:107833. [PMID: 33514477 DOI: 10.1016/j.jdiacomp.2020.107833] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Individuals with diabetes have a high risk of cardiovascular disease (CVD). However, the association between type 1 diabetes mellitus (T1DM) and the risk of CVD has not been well addressed. This meta-analysis aimed to investigate the association between T1DM and CVD. METHODS We searched the PubMed and EMBASE for studies that examined the association between T1DM and CVD until October 2020. We calculated the pooled risk ratios (RRs) with confidence intervals (CIs) from individual studies based on a random-effects model. RESULTS We included 10 observational studies involving 166,027 patients with T1DM, and individuals were matched controls from the general population. Among T1DM patients, the RR of CVD was 5.09 (95% CI, 3.72-6.96), of coronary heart disease (CHD) was 9.38 (95% CI, 5.56-15.82), and of myocardial infarction was 6.37 (95% CI, 3.81-10.66). The RR of heart failure was 4.29 (95% CI, 3.54-5.19), of atrial fibrillation was 1.36 (95% CI, 1.17-1.59), and of stroke was 4.08 (95% CI, 3.42-4.86). Moreover, there was an increased RR among females for CHD, CVD, myocardial infarction, and stroke associated with T1DM. CONCLUSIONS This study suggests that T1DM is associated with an increased risk of several types of CVD. However, the possible mechanisms for the increased risk of CVD remain unclear.
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Affiliation(s)
- Xingming Cai
- Department of Geriatric, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China
| | - Jiayong Li
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China
| | - Wenting Cai
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China
| | - Chen Chen
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China
| | - Jianyong Ma
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Zengshuo Xie
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China
| | - Yugang Dong
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China
| | - Chen Liu
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China
| | - Ruicong Xue
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China.
| | - Jingjing Zhao
- Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, PR China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou 510080, PR China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular, Diseases, Guangzhou, PR China.
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Avogaro A, Azzolina D, Fadini GP, Baldi I. Incidence of heart failure in patients with type 1 diabetes: a systematic review of observational studies. J Endocrinol Invest 2021; 44:745-753. [PMID: 32734319 DOI: 10.1007/s40618-020-01368-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 07/18/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Heart failure (HF) is considered an important contributor to cardiovascular morbidity and mortality in diabetes mellitus. However, a precise identification of hyperglycemia as contributor for HF is missing. OBJECTIVES We performed a review and a meta-regression of the available observational studies on the incidence of HF in type 1 diabetes (T1D). DATA SOURCE AND ANALYSIS We conducted a systematic search of the literature on the incidence of HF in patients with T1D identifying suitable studies published between January 1970 and June 2018 using the following search string: "type 1 diabetes" AND, "heart failure" OR "cardiac failure" OR "congestive heart failure" AND "incidence" NOT "type 2 diabetes" OR "diabetes type 2". Six observational studies were included. A random effect meta-regression model has been estimated to evaluate the incidence rate ratio (IRR) of HF in T1D compared to healthy controls. RESULTS The mean ± SD age of patients with T1D was 42 ± 11 years, the mean HbA1c was 8.4 ± 0.3%, and average follow-up was 11 ± 3 years. The age-adjusted model shows an incidence rate ratio (IRR) effect of 3.18 (p < 0.001), in correspondence of the mean age at enrollment of studies involved in the analysis. A negative correlation was observed between IRR and average age. CONCLUSIONS This review shows that the incidence rate of HF is three times higher in patients with T1D than in controls. A careful surveillance of the risk factors for this condition should be included, since the onset of T1D may be important to reduce HF risk in these patients.
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Affiliation(s)
- A Avogaro
- Unit of Metabolic Diseases, Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.
| | - D Azzolina
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, 35128, Padua, Italy
| | - G P Fadini
- Unit of Metabolic Diseases, Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy
| | - I Baldi
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, 35128, Padua, Italy
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30
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Ammar HI, Shamseldeen AM, Shoukry HS, Ashour H, Kamar SS, Rashed LA, Fadel M, Srivastava A, Dhingra S. Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol Heart Circ Physiol 2021; 320:H1290-H1302. [PMID: 33513084 DOI: 10.1152/ajpheart.00317.2020] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 01/21/2021] [Indexed: 12/15/2022]
Abstract
Bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated potential in treating diabetic cardiomyopathy. However, patients with diabetes are on multiple drugs and there is a lack of understanding of how transplanted stem cells would respond in presence of such drugs. Metformin is an AMP kinase (AMPK) activator, the widest used antidiabetic drug. In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSC-mediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually improved cardiac function with no synergistic effect of metformin supplementation along with BM-MSCs. Investigating the mechanisms of loss of efficacy of BM-MSCs in the presence of metformin, we found that metformin treatment impairs homing of implanted BM-MSCs in the heart and leads to poor survival of transplanted cells. Furthermore, our data demonstrate that metformin-mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart. Hence, the current study confirms that a conflict arises between metformin and BM-MSCs for treating diabetic cardiomyopathy. Approximately 10% of the world population is diabetic to which metformin is prescribed very commonly. Hence, future cell replacement therapies in combination with AMPK inhibitors may be more effective for patients with diabetes.NEW & NOTEWORTHY Metformin treatment reduces the efficacy of mesenchymal stem cell therapy for cardiac repair during diabetic cardiomyopathy. Stem cell therapy in diabetics may be more effective in combination with AMPK inhibitors.
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Affiliation(s)
- Hania Ibrahim Ammar
- Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt
| | | | - Heba Samy Shoukry
- Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Hend Ashour
- Department of Physiology, Faculty of Medicine, Cairo University, Giza, Egypt
- Department of Physiology, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Samaa Samir Kamar
- Department of Medical Histology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Laila Ahmed Rashed
- Department of Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Mostafa Fadel
- Diagnostic Imaging and Endoscopy Unit, Animal Reproduction Research Institute, Cairo, Egypt
| | - Abhay Srivastava
- Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, St. Boniface Hospital, Albrechtsen Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Sanjiv Dhingra
- Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, St. Boniface Hospital, Albrechtsen Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
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31
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Carnicer R, Duglan D, Ziberna K, Recalde A, Reilly S, Simon JN, Mafrici S, Arya R, Rosello-Lleti E, Chuaiphichai S, Tyler D, Lygate CA, Channon KM, Casadei B. BH4 Increases nNOS Activity and Preserves Left Ventricular Function in Diabetes. Circ Res 2021; 128:585-601. [PMID: 33494625 PMCID: PMC7612785 DOI: 10.1161/circresaha.120.316656] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 01/25/2021] [Indexed: 12/20/2022]
Abstract
RATIONALE In diabetic patients, heart failure with predominant left ventricular (LV) diastolic dysfunction is a common complication for which there is no effective treatment. Oxidation of the NOS (nitric oxide synthase) cofactor tetrahydrobiopterin (BH4) and dysfunctional NOS activity have been implicated in the pathogenesis of the diabetic vascular and cardiomyopathic phenotype. OBJECTIVE Using mice models and human myocardial samples, we evaluated whether and by which mechanism increasing myocardial BH4 availability prevented or reversed LV dysfunction induced by diabetes. METHODS AND RESULTS In contrast to the vascular endothelium, BH4 levels, superoxide production, and NOS activity (by liquid chromatography) did not differ in the LV myocardium of diabetic mice or in atrial tissue from diabetic patients. Nevertheless, the impairment in both cardiomyocyte relaxation and [Ca2+]i (intracellular calcium) decay and in vivo LV function (echocardiography and tissue Doppler) that developed in wild-type mice 12 weeks post-diabetes induction (streptozotocin, 42-45 mg/kg) was prevented in mGCH1-Tg (mice with elevated myocardial BH4 content secondary to trangenic overexpression of GTP-cyclohydrolase 1) and reversed in wild-type mice receiving oral BH4 supplementation from the 12th to the 18th week after diabetes induction. The protective effect of BH4 was abolished by CRISPR/Cas9-mediated knockout of nNOS (the neuronal NOS isoform) in mGCH1-Tg. In HEK (human embryonic kidney) cells, S-nitrosoglutathione led to a PKG (protein kinase G)-dependent increase in plasmalemmal density of the insulin-independent glucose transporter GLUT-1 (glucose transporter-1). In cardiomyocytes, mGCH1 overexpression induced a NO/sGC (soluble guanylate cyclase)/PKG-dependent increase in glucose uptake via GLUT-1, which was instrumental in preserving mitochondrial creatine kinase activity, oxygen consumption rate, LV energetics (by 31phosphorous magnetic resonance spectroscopy), and myocardial function. CONCLUSIONS We uncovered a novel mechanism whereby myocardial BH4 prevents and reverses LV diastolic and systolic dysfunction associated with diabetes via an nNOS-mediated increase in insulin-independent myocardial glucose uptake and utilization. These findings highlight the potential of GCH1/BH4-based therapeutics in human diabetic cardiomyopathy. Graphic Abstract: A graphic abstract is available for this article.
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Affiliation(s)
| | - Drew Duglan
- Cardiovascular Medicine, University of Oxford
| | | | | | | | | | | | - Ritu Arya
- Cardiovascular Medicine, University of Oxford
| | | | | | - Damian Tyler
- Physiology, Anatomy and Genetics, University of Oxford
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32
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Cristelo C, Machado A, Sarmento B, Gama FM. The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility. Endocr Connect 2021; 10:R1-R12. [PMID: 33263562 PMCID: PMC7923048 DOI: 10.1530/ec-20-0484] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 11/25/2020] [Indexed: 12/20/2022]
Abstract
Type 1 diabetes has an increasingly greater incidence and prevalence with no cure available. Vitamin D supplementation is well documented to reduce the risk of developing type 1 diabetes. Being involved in the modulation of cathelicidin expression, the question whether cathelicidin may be one of the underlying cause arises. Cathelicidin has been implicated in both the development and the protection against type 1 diabetes by mediating the interplay between the gut microbiome, the immune system and β cell function. While its potential on type 1 diabetes treatment seems high, the understanding of its effects is still limited. This review aims to contribute to a more comprehensive understanding of the potential of vitamin D and cathelicidin as adjuvants in type 1 diabetes therapy.
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Affiliation(s)
- Cecília Cristelo
- i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- CEB – Centro de Engenharia Biológica, Universidade do Minho, Braga, Portugal
| | - Alexandra Machado
- CEB – Centro de Engenharia Biológica, Universidade do Minho, Braga, Portugal
| | - Bruno Sarmento
- i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal
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33
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Battault S, Renguet E, Van Steenbergen A, Horman S, Beauloye C, Bertrand L. Myocardial glucotoxicity: Mechanisms and potential therapeutic targets. Arch Cardiovasc Dis 2020; 113:736-748. [PMID: 33189592 DOI: 10.1016/j.acvd.2020.06.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/01/2020] [Accepted: 06/03/2020] [Indexed: 12/19/2022]
Abstract
Besides coronary artery disease, which remains the main cause of heart failure in patients with diabetes, factors independent of coronary artery disease are involved in the development of heart failure in the onset of what is called diabetic cardiomyopathy. Among them, hyperglycaemia - a hallmark of type 2 diabetes - has both acute and chronic deleterious effects on myocardial function, and clearly participates in the establishment of diabetic cardiomyopathy. In the present review, we summarize the cellular and tissular events that occur in a heart exposed to hyperglycaemia, and depict the complex molecular mechanisms proposed to be involved in glucotoxicity. Finally, from a more translational perspective, different therapeutic strategies targeting hyperglycaemia-mediated molecular mechanisms will be detailed.
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Affiliation(s)
- Sylvain Battault
- Pole of cardiovascular research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, B-1200 Brussels, Belgium
| | - Edith Renguet
- Pole of cardiovascular research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, B-1200 Brussels, Belgium
| | - Anne Van Steenbergen
- Pole of cardiovascular research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, B-1200 Brussels, Belgium
| | - Sandrine Horman
- Pole of cardiovascular research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, B-1200 Brussels, Belgium
| | - Christophe Beauloye
- Pole of cardiovascular research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, B-1200 Brussels, Belgium; Division of cardiology, Cliniques Universitaires Saint-Luc, B-1200 Brussels, Belgium.
| | - Luc Bertrand
- Pole of cardiovascular research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, B-1200 Brussels, Belgium; WELBIO, B-1300 Wavre, Belgium.
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Cavallari I, Maddaloni E, Pieralice S, Mulè MT, Buzzetti R, Ussia GP, Pozzilli P, Grigioni F. The Vicious Circle of Left Ventricular Dysfunction and Diabetes: From Pathophysiology to Emerging Treatments. J Clin Endocrinol Metab 2020; 105:5866664. [PMID: 32615596 DOI: 10.1210/clinem/dgaa427] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/27/2020] [Indexed: 12/25/2022]
Abstract
CONTEXT Diabetes and heart failure (HF) are 2 deadly and strictly related epidemic disorders. The aim of this review is to present an updated discussion of the epidemiology, pathophysiology, clinical presentation and treatment options for HF in diabetes. EVIDENCE ACQUISITION Relevant references published up to February 2020 were identified through searches in PubMed. Quality was graded using the Newcastle-Ottawa score in observational studies and the Cochrane Collaboration tool in randomized studies. EVIDENCE SYNTHESIS Metabolic and neurohumoral derangements, oxidative stress, inflammation, micro- and macroangiopathy all contribute through complex molecular and cellular mechanisms to cardiac dysfunction in diabetes, which in turn, results as one the most frequent underlying conditions affecting up to 42% of patients with HF and causing a 34% increased risk of cardiovascular death. On top of traditional guideline-based HF medical and device therapies, equally effective in patients with and without diabetes, a new class of glucose-lowering agents acting through the sodium-glucose cotransporter 2 (SGLT2) inhibition showed impressive results in reducing HF outcomes in individuals with diabetes and represents an active area of investigation. CONCLUSIONS Diabetes and HF are strictly linked in a bidirectional and deadly vicious circle difficult to break. Therefore, preventive strategies and a timely diagnosis are crucial to improve outcomes in such patients. SGLT2 inhibitors represent a major breakthrough with remarkably consistent findings. However, it is still not clear whether their benefits may be definitely extended to patients with HF with preserved ejection fraction, to those without diabetes and in the acute setting.
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Affiliation(s)
- Ilaria Cavallari
- Department of Medicine, Unit of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Italy
| | - Ernesto Maddaloni
- Department of Experimental Medicine, Sapienza University of Rome, Italy
| | - Silvia Pieralice
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Italy
| | - Maria Tea Mulè
- Department of Medicine, Unit of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Italy
| | | | - Gian Paolo Ussia
- Department of Medicine, Unit of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Italy
| | - Paolo Pozzilli
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Italy
| | - Francesco Grigioni
- Department of Medicine, Unit of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Italy
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35
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Alkagiet S, Tziomalos K. Role of sodium-glucose co-transporter-2 inhibitors in the management of heart failure in patients with diabetes mellitus. World J Diabetes 2020; 11:150-154. [PMID: 32477451 PMCID: PMC7243487 DOI: 10.4239/wjd.v11.i5.150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 02/29/2020] [Accepted: 04/04/2020] [Indexed: 02/06/2023] Open
Abstract
Heart failure (HF) is a major complication of diabetes mellitus (DM). Patients with DM have considerably higher risk for HF than non-diabetic subjects and HF is also more severe in the former. Given the rising prevalence of DM, the management of HF in diabetic patients has become the focus of increased attention. In this context, the findings of several randomized, placebo-controlled trials that evaluated the effects of sodium-glucose co-transporter-2 inhibitors on the risk of hospitalization for HF in patients with type 2 DM represent a paradigm shift in the management of HF. These agents consistently reduced the risk of hospitalization for HF both in patients with and in those without HF. These benefits appear to be partly independent from glucose-lowering and have also been reported in patients without DM. However, there are more limited data regarding the benefit of sodium-glucose co-transporter-2 inhibitors in patients with HF and preserved left ventricular ejection fraction, which is the commonest type of HF in diabetic patients.
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Affiliation(s)
- Stelina Alkagiet
- Department of Cardiology, Georgios Papanikolaou Hospital, Thessaloniki 57010, Greece
| | - Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece
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36
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Vestberg D, Johansson MC, Letho A, Pivodic A, Hallström S, Ólafsdóttir AF, Rosengren A, Lind M. Investigation of early signs of systolic and diastolic dysfunction among persons with type 1 diabetes. Open Heart 2020; 6:e001020. [PMID: 31908811 PMCID: PMC6927507 DOI: 10.1136/openhrt-2019-001020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 10/20/2019] [Accepted: 11/04/2019] [Indexed: 11/17/2022] Open
Abstract
Background Persons with type 1 diabetes have a higher risk to develop heart failure than the general population, and the mechanism behind the increased risk is unclear. In epidemiological studies with hospitalisation for heart failure as endpoint HbA1c, body mass index and decreased kidney function are significant risk factors, but it is unclear how these risk factors influence the development of heart failure. Methods In this study, we investigated early signs of systolic and diastolic dysfunction with transthoracic echocardiography. Statistical analysis on correlation of risk factors and early signs of diastolic and systolic dysfunction was made. Results In this study population of 287 persons with type 1 diabetes, 160 were men and 127 were women with a mean age of 53.8 (SD 11.6) years and a mean diabetes duration of 36.2 (SD 13.5) years. There were 23 (8.2%) persons who fulfilled the definition of systolic dysfunction (ejection fraction <50% or regional wall motion abnormalities) and 24 persons (9%) the definition for diastolic dysfunction. When comparing the groups with either systolic or diastolic dysfunction to the rest of the population, the only significant risk factor was age in both groups and previous myocardial infarction in the systolic group. Conclusion In our study population with type 1 diabetes, we found signs of diastolic dysfunction in 9% and systolic dysfunction in 8.2%. Compared with published data from the general population, this rate is somewhat higher in a younger population. Only age was a significant risk factor in the study.
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Affiliation(s)
- Daniel Vestberg
- Department of Medicine, NU-hospital Group, Trollhattan/Uddevalla, Sweden.,Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Goteborg, Sweden
| | - Magnus Carl Johansson
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Goteborg, Sweden.,Department of Clinical Physiology, Sahlgrenska University Hospital, Region Västra Götaland, Goteborg, Sweden
| | - Anette Letho
- Department of Medicine, NU-hospital Group, Trollhattan/Uddevalla, Sweden
| | | | - Sara Hallström
- Department of Medicine, Sahlgrenska University Hospital, Goteborg, Sweden
| | - Arndís Finna Ólafsdóttir
- Department of Medicine, NU-hospital Group, Trollhattan/Uddevalla, Sweden.,Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Goteborg, Sweden
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Goteborg, Sweden.,Department of Medicine, Sahlgrenska University Hospital, Goteborg, Sweden
| | - Marcus Lind
- Department of Medicine, NU-hospital Group, Trollhattan/Uddevalla, Sweden.,Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Goteborg, Sweden
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van Dijk PR, Pasch A, van Ockenburg-Brunet SL, Waanders F, Eman Abdulle A, Muis MJ, Hillebrands JL, Bilo HJG, van Goor H. Thiols as markers of redox status in type 1 diabetes mellitus. Ther Adv Endocrinol Metab 2020; 11:2042018820903641. [PMID: 32095228 PMCID: PMC7011336 DOI: 10.1177/2042018820903641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 12/17/2019] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION Type 1 diabetes mellitus (T1DM) is associated with inflammation and the production of reactive oxygen species (ROS). Systemically, free thiols (R-SH) can be oxidized by ROS and circulating R-SH concentrations may directly reflect the systemic redox status. In this study the association between R-SH and clinical parameters of T1DM, including glycated haemoglobin A1c (HbA1c), was investigated. This is of particular interest since thiols are amendable to therapeutic intervention. METHODS As part of a prospective cohort study, data from 216 patients with a mean age of 45 (12) years, 57% male, diabetes duration 22 (16, 30) years and HbA1c of 60 (11) mmol/mol were examined. Baseline data were collected in 2002 and follow-up data in 2018. Cox proportional hazards regression analysis, with age, sex, HbA1c and R-SH, was used to assess prognostic factors for the development of complications. RESULTS At baseline, the plasma concentration of R-SH was 281.8 ± 34.0 μM. In addition to a lower concentration of NT-proBNP in the highest R-SH quartile (305-379 µM) there were no differences in baseline characteristics between the quartiles of R-SH. The Pearson correlation coefficient for R-SH and NT-proBNP was -0.290 (p < 0.001). No significant correlation between R-SH and baseline HbA1c (r = -0.024, p = 0.726) was present. During follow-up, 42 macrovascular and 92 microvascular complications occurred. In Cox regression, R-SH was not a prognostic factor for the development of microvascular [hazard ratio (HR) 0.999 (95% confidence interval (CI) 0.993, 1.005)] and macrovascular [HR 0.993 (95% CI 0.984, 1.002)] complications. CONCLUSIONS In addition to a negative association with NT-proBNP, no relevant relationships between R-SH and parameters of T1DM, including HbA1c, were present in this study.
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Affiliation(s)
| | | | | | - Femke Waanders
- Isala, Department of Internal Medicine, Zwolle,
the Netherlands
| | - A. Eman Abdulle
- Division of Vascular Medicine, University of
Groningen, University Medical Center, Groningen, the Netherlands
| | - Marian J. Muis
- Isala, Diabetes Centre, Zwolle, the
Netherlands
- Isala, Department of Internal Medicine, Zwolle,
the Netherlands
| | - J. L. Hillebrands
- Department of Pathology and Medical Biology,
University of Groningen, University Medical Center, Groningen, the
Netherlands
| | - Henk J. G. Bilo
- Department of Internal Medicine, University of
Groningen, University Medical Center, Groningen, the Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology,
University of Groningen, University Medical Center, Groningen, the
Netherlands
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McAllister DA, Read SH, Kerssens J, Livingstone S, McGurnaghan S, Jhund P, Petrie J, Sattar N, Fischbacher C, Kristensen SL, McMurray J, Colhoun HM, Wild SH. Incidence of Hospitalization for Heart Failure and Case-Fatality Among 3.25 Million People With and Without Diabetes Mellitus. Circulation 2019; 138:2774-2786. [PMID: 29950404 PMCID: PMC6287897 DOI: 10.1161/circulationaha.118.034986] [Citation(s) in RCA: 158] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Supplemental Digital Content is available in the text. Background: Recent clinical trials of new glucose-lowering treatments have drawn attention to the importance of hospitalization for heart failure as a complication of diabetes mellitus. However, the epidemiology is not well described, particularly for type 1 diabetes mellitus. We examined the incidence and case-fatality of heart failure hospitalizations in the entire population aged ≥30 years resident in Scotland during 2004 to 2013. Methods: Date and type of diabetes mellitus diagnosis were linked to heart failure hospitalizations and deaths using the national Scottish registers. Incidence rates and case-fatality were estimated in regression models (quasi-Poisson and logistic regression respectively). All estimates are adjusted for age, sex, socioeconomic status, and calendar-year. Results: Over the 10-year period of the study, among 3.25 million people there were 91, 429, 22 959, and 1313 incident heart failure events among those without diabetes mellitus, with type 2, and type 1 diabetes mellitus, respectively. The crude incidence rates of heart failure hospitalization were therefore 2.4, 12.4, and 5.6 per 1000 person-years for these 3 groups. Heart failure hospitalization incidence was higher in people with diabetes mellitus, regardless of type, than in people without. Relative differences were smallest for older men, in whom the difference was nonetheless large (men aged 80, rate ratio 1.78; 95% CI, 1.45–2.19). Rates declined similarly, by 0.2% per calendar-year, in people with type 2 diabetes mellitus and without diabetes mellitus. Rates fell faster, however, in those with type 1 diabetes mellitus (2.2% per calendar-year, rate ratio for type 1/calendar-year interaction 0.978; 95% CI, 0.959–0.998). Thirty-day case-fatality was similar among people with type 2 diabetes mellitus and without diabetes mellitus, but was higher in type 1 diabetes mellitus for men (odds ratio, 0.96; 95% CI, 0.95–0.96) and women (odds ratio, 0.98; 95% CI, 0.97–0.98). Case-fatality declined over time for all groups (3.3% per calendar-year, odds ratio per calendar-year 0.967; 95% CI, 0.961–0.973). Conclusions: Despite falling incidence, particularly in type 1 diabetes mellitus, heart failure remains ≈2-fold higher than in people without diabetes mellitus, with higher case-fatality in those with type 1 diabetes mellitus. These findings support the view that heart failure is an under-recognized and important complication in diabetes mellitus, particularly for type 1 disease.
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Affiliation(s)
- David A McAllister
- Institute of Health and Wellbeing (D.A.M.), University of Glasgow, United Kingdom.,NHS National Services Scotland, Edinburgh, United Kingdom (D.A.M., J.K., C.F.)
| | - Stephanie H Read
- Usher Institute of Population Health Sciences and Informatics (S.H.R, S.H.W)
| | - Jan Kerssens
- NHS National Services Scotland, Edinburgh, United Kingdom (D.A.M., J.K., C.F.)
| | | | | | - Pardeep Jhund
- Institute of Cardiovascular and Medical Sciences (P.J., J.P., N.S., J.M.), University of Glasgow, United Kingdom
| | - John Petrie
- Institute of Cardiovascular and Medical Sciences (P.J., J.P., N.S., J.M.), University of Glasgow, United Kingdom
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences (P.J., J.P., N.S., J.M.), University of Glasgow, United Kingdom
| | - Colin Fischbacher
- NHS National Services Scotland, Edinburgh, United Kingdom (D.A.M., J.K., C.F.)
| | | | - John McMurray
- Institute of Cardiovascular and Medical Sciences (P.J., J.P., N.S., J.M.), University of Glasgow, United Kingdom
| | - Helen M Colhoun
- MRC Institute of Genetics and Molecular Medicine (S.M., H.M.C)
| | - Sarah H Wild
- Usher Institute of Population Health Sciences and Informatics (S.H.R, S.H.W)
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39
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Ohkuma T, Komorita Y, Peters SAE, Woodward M. Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals. Diabetologia 2019; 62:1550-1560. [PMID: 31317230 PMCID: PMC6677875 DOI: 10.1007/s00125-019-4926-x] [Citation(s) in RCA: 177] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 05/10/2019] [Indexed: 12/13/2022]
Abstract
AIMS/HYPOTHESIS The prevalence of diabetes and heart failure is increasing, and diabetes has been associated with an increased risk of heart failure. However, whether diabetes confers the same excess risk of heart failure in women and men is unknown. The aim of this study was to conduct a comprehensive systematic review with meta-analysis of possible sex differences in the excess risk of heart failure consequent to diabetes. Our null hypothesis was that there is no such sex difference. METHODS A systematic search was conducted in PubMed for population-based cohort studies published between January 1966 and November 2018. Studies were selected if they reported sex-specific estimates of RRs for heart failure associated with diabetes, and its associated variability, which were adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratio of RRs (RRRs) for heart failure associated with diabetes. RESULTS Data from 47 cohorts, involving 12,142,998 individuals and 253,260 heart failure events, were included. The pooled multiple-adjusted RR for heart failure associated with type 1 diabetes was 5.15 (95% CI 3.43, 7.74) in women and 3.47 (2.57, 4.69) in men, leading to an RRR of 1.47 (1.44, 1.90). Corresponding pooled RRs for heart failure associated with type 2 diabetes were 1.95 (1.70, 2.22) in women and 1.74 (1.55, 1.95) in men, with a pooled RRR of 1.09 (1.05, 1.13). CONCLUSIONS/INTERPRETATION The excess risk of heart failure associated with diabetes is significantly greater in women with diabetes than in men with diabetes. PROSPERO registration: CRD42019135246.
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Affiliation(s)
- Toshiaki Ohkuma
- The George Institute for Global Health, University of New South Wales, Level 10, King George V Building, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia.
| | - Yuji Komorita
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Division of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan
| | - Sanne A E Peters
- The George Institute for Global Health, University of Oxford, Hayes House, 75 George Street, Oxford, OX1 2BQ, UK.
| | - Mark Woodward
- The George Institute for Global Health, University of New South Wales, Level 10, King George V Building, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia
- The George Institute for Global Health, University of Oxford, Hayes House, 75 George Street, Oxford, OX1 2BQ, UK
- Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA
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40
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Hallström S, Pivodic A, Rosengren A, Ólafsdóttir AF, Svensson AM, Lind M. Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry. Diabetes Care 2019; 42:1530-1538. [PMID: 31171564 DOI: 10.2337/dc18-2457] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 05/08/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. RESEARCH DESIGN AND METHODS We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. RESULTS In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA1c, coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m2), and elevated levels of HbA1c (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. CONCLUSIONS The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.
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Affiliation(s)
- Sara Hallström
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden .,Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Aldina Pivodic
- Department of Ophthalmology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Statistiska Konsultgruppen, Gothenburg, Sweden
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Arndís F Ólafsdóttir
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
| | - Ann-Marie Svensson
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Center of Registers in Region Västra Götaland, Gothenburg, Sweden
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Department of Medicine, NU-Hospital Group, Uddevalla, Sweden
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41
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Edqvist J, Rawshani A, Adiels M, Björck L, Lind M, Svensson AM, Gudbjörnsdottir S, Sattar N, Rosengren A. BMI, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes: Findings Against an Obesity Paradox. Diabetes Care 2019; 42:1297-1304. [PMID: 31048408 DOI: 10.2337/dc18-1446] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 04/08/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Low weight has been associated with increased mortality risks in type 1 diabetes. We aimed to investigate the importance of weight and weight gain/loss in the Swedish population diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (n = 26,125; mean age 33.3 years; 45% women) registered in the Swedish National Diabetes Registry from 1998 to 2012 were followed from the first day of study entry. Cox regression was used to calculate risk of death from cardiovascular disease (CVD), major CVD events, hospitalizations for heart failure (HF), and total deaths. RESULTS Population mean BMI in patients with type 1 diabetes increased from 24.7 to 25.7 kg/m2 from 1998 to 2012. Over a median follow-up of 10.9 years, there were 1,031 deaths (33.2% from CVD), 1,460 major CVD events, and 580 hospitalizations for HF. After exclusion of smokers, patients with poor metabolic control, and patients with a short follow-up time, there was no increased risk for mortality in those with BMI <25 kg/m2, while BMI >25 kg/m2 was associated with a minor increase in risk of mortality, major CVD, and HF. In women, associations with BMI were largely absent. Weight gain implied an increased risk of mortality and HF, while weight loss was not associated with higher risk. CONCLUSIONS Risk of major CVD, HF, CVD death, and mortality increased with increasing BMI, with associations more apparent in men than in women. After exclusion of factors associated with reverse causality, there was no evidence of an obesity paradox.
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Affiliation(s)
- Jon Edqvist
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
| | - Araz Rawshani
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Martin Adiels
- Health Metrics Unit, Sahlgrenska Academy, Gothenburg, Sweden
| | - Lena Björck
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,NU-Hospital Organisation, Uddevalla, Sweden
| | - Ann-Marie Svensson
- Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden
| | | | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, U.K
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden .,Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
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42
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Šuran D, Kanič V, Naji F, Krajnc I, Čokolič M, Zemljič E, Sinkovič A. Predictors of early cardiac changes in patients with type 1 diabetes mellitus: An echocardiography-based study. Bosn J Basic Med Sci 2019; 19:384-391. [PMID: 31215855 DOI: 10.17305/bjbms.2019.4250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 06/12/2019] [Indexed: 11/16/2022] Open
Abstract
In patients with type 1 diabetes mellitus (T1DM) imaging studies have demonstrated an increased prevalence of left ventricular diastolic dysfunction and increased left ventricular mass (LVM) unrelated to arterial hypertension and ischemic heart disease. The aim of our study was to identify potential predictors of early subclinical changes in cardiac chamber size and function in such patients. Sixty-one middle-aged asymptomatic normotensive patients with T1DM were included in the study. Conventional and tissue Doppler echocardiography was performed and fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, and creatinine were measured. We found moderate bivariate correlations of body mass index (BMI) with left atrial volume (r = 0.47, p < 0.01), LVM (r = 0.42, p < 0.01), left ventricular relative wall thickness (r = 0.32, p = 0.01), and all observed parameters of diastolic function of both ventricles. The five-year average value of HbA1c weakly correlated with the Doppler index of left ventricular filling pressure E/e´sept (r = 0.27, p = 0.04). We found no significant association of diabetes duration, five-year trend of HbA1c, serum lipids, and glomerular filtration rate with cardiac structure and function. After adjusting for other parameters, BMI remained significantly associated with left atrial volume, LVM as well as with the transmitral Doppler ratio E/A. In our study, BMI was the only observed parameter significantly associated with subclinical structural and functional cardiac changes in the asymptomatic middle-aged patients with T1DM.
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Affiliation(s)
- David Šuran
- Department of Cardiology and Angiology, University Medical Centre Maribor, Maribor, Slovenia.
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43
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Bell DSH, Goncalves E. Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose-lowering medications. Diabetes Obes Metab 2019; 21:1277-1290. [PMID: 30724013 DOI: 10.1111/dom.13652] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Revised: 01/29/2019] [Accepted: 02/03/2019] [Indexed: 12/24/2022]
Abstract
In people with type 2 diabetes the frequency of heart failure (HF) is increased and mortality from HF is higher than with non-diabetic HF. The increased frequency of HF is attributable to the cardiotoxic tetrad of ischaemic heart disease, left ventricular hypertrophy, diabetic cardiomyopathy and an extracellular volume expansion resistant to atrial natriuretic peptides. Activation of the renin-angiotensin-aldosterone system and sympathetic nervous systems results in cardiac remodelling, which worsens cardiac function. Reversal of remodelling can be achieved, and cardiac function improved in people with HF with reduced ejection fraction (HFrEF) by treatment with angiotensin-converting enzyme inhibitors and β-blockers. However, with HF with preserved ejection fraction (HFpEF), only therapy for the underlying risk factors helps. Blockers of mineralocorticoid receptors may be beneficial in both HFrEF and HFpEF. Glucose-lowering drugs can have a negative effect (insulin, sulphonylureas, dipeptidyl peptidase-4 inhibitors and thiazolidinediones), a neutral effect (α-glucosidase inhibitors and glucagon-like peptide-1 receptor agonists) or a positive effect (sodium-glucose co-transporter-2 inhibitors and metformin).
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44
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Ólafsdóttir AF, Svensson AM, Pivodic A, Gudbjörnsdottir S, Nyström T, Wedel H, Rosengren A, Lind M. Excess risk of lower extremity amputations in people with type 1 diabetes compared with the general population: amputations and type 1 diabetes. BMJ Open Diabetes Res Care 2019; 7:e000602. [PMID: 31114696 PMCID: PMC6501853 DOI: 10.1136/bmjdrc-2018-000602] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 01/04/2019] [Accepted: 01/29/2019] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE This study investigates how the excess risk of lower extremity amputations (amputations) in people with type 1 diabetes mellitus (DM) differs from the general population by diabetes duration, glycemic control, and renal complications. RESEARCH DESIGN AND METHODS We analyzed data from people with type 1 DM from the Swedish National Diabetes Register without prior amputation from January 1998 to December 2013. Each person (n=36 872) was randomly matched with five controls by sex, age, and county (n=184 360) from the population without diabetes. All were followed until first amputation, death or end of follow-up. RESULTS The overall adjusted HR for all amputation was 40.1 (95% CI 32.8 to 49.1) for type 1 DM versus controls. HR increased with longer diabetes duration. The incidence of amputation/1000 patient-years was 3.18 (95% CI 2.99 to 3.38) for type 1 DM and 0.07 (95% CI 0.05 to 0.08) for controls. The incidence decreased from 1998-2001 (3.09, 95% CI 2.56 to 3.62) to 2011-2013 (2.64, 95% CI 2.31 to 2.98). The HR for major amputations was lower than for minor amputations and decreased over the time period (p=0.0045). Worsening in glycemic control among patients with diabetes led to increased risk for amputation with an HR of 1.80 (95% CI 1.72 to 1.88) per 10 mmol/mol (1%) increase in hemoglobin A1c. CONCLUSIONS Although the absolute risk of amputation is relatively low, the overall excess risk was 40 times that of controls. Excess risk was substantially lower for those with good glycemic control and without renal complications, but excess risk still existed and is greatest for minor amputations.
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Affiliation(s)
- Arndís Finna Ólafsdóttir
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Ann-Marie Svensson
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
| | | | - Soffia Gudbjörnsdottir
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
| | - Thomas Nyström
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Hans Wedel
- Department of Health Metrics, Health Metrics Sahlgrenska Academy, Gothenburg, Sweden
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Marcus Lind
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
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45
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Aune D, Schlesinger S, Neuenschwander M, Feng T, Janszky I, Norat T, Riboli E. Diabetes mellitus, blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies. Nutr Metab Cardiovasc Dis 2018; 28:1081-1091. [PMID: 30318112 DOI: 10.1016/j.numecd.2018.07.005] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/17/2018] [Accepted: 07/17/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis. METHODS AND RESULTS PubMed and Embase databases were searched up to May 3rd 2018. Prospective studies on diabetes mellitus or blood glucose and heart failure risk were included. A random effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). Seventy seven studies were included. Among the population-based prospective studies, the summary RR for individuals with diabetes vs. no diabetes was 2.06 (95% CIs: 1.73-2.46, I2 = 99.8%, n = 30 studies, 401495 cases, 21416780 participants). The summary RR was 1.23 (95% CI: 1.15-1.32, I2 = 78.2%, n = 10, 5344 cases, 91758 participants) per 20 mg/dl increase in blood glucose and there was evidence of a J-shaped association with nadir around 90 mg/dl and increased risk even within the pre-diabetic blood glucose range. Among the patient-based studies the summary RR was 1.69 (95% CI: 1.57-1.81, I2 = 85.5%, pheterogeneity<0.0001) for diabetes vs. no diabetes (n = 41, 100284 cases and >613925 participants) and 1.25 (95% CI: 0.89-1.75, I2 = 95.6%, pheterogeneity<0.0001) per 20 mg/dl increase in blood glucose (1016 cases, 34309 participants, n = 2). In the analyses of diabetes and heart failure there was low or no heterogeneity among the population-based studies that adjusted for alcohol intake and physical activity and among the patient-based studies there was no heterogeneity among studies with ≥10 years follow-up. CONCLUSIONS These results suggest that individuals with diabetes are at an increased risk of developing heart failure and there is evidence of increased risk even within the pre-diabetic range of blood glucose.
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Affiliation(s)
- D Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Nutrition, Bjørknes University College, Oslo, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
| | - S Schlesinger
- Institute for Biometry and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - M Neuenschwander
- Institute for Biometry and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - T Feng
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - I Janszky
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Regional Center for Health Care Improvement, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - T Norat
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - E Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
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46
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Rosengren A, Edqvist J, Rawshani A, Sattar N, Franzén S, Adiels M, Svensson AM, Lind M, Gudbjörnsdottir S. Excess risk of hospitalisation for heart failure among people with type 2 diabetes. Diabetologia 2018; 61:2300-2309. [PMID: 30094466 PMCID: PMC6182656 DOI: 10.1007/s00125-018-4700-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 06/21/2018] [Indexed: 01/09/2023]
Abstract
AIMS/HYPOTHESIS Type 2 diabetes is an established risk factor for heart failure, but age-specific data are sparse. We aimed to determine excess risk of heart failure, based on age, glycaemic control and kidney function in comparison with age- and sex-matched control individuals from the general population. METHODS Individuals with type 2 diabetes registered in the Swedish National Diabetes Registry 1998-2012 (n = 266,305) were compared with age-, sex- and county-matched control individuals without diabetes (n = 1,323,504), and followed over a median of 5.6 years until 31 December 2013. RESULTS We identified 266,305 individuals with type 2 diabetes (mean age 62.0 years, 45.3% women) and 1,323,504 control individuals. Of the individuals with type 2 diabetes and control individuals, 18,715 (7.0%) and 50,157 (3.8%) were hospitalised with a diagnosis of heart failure, respectively. Comparing individuals with diabetes with those in the control group, men and women with type 2 diabetes who were younger than 55 years of age had HRs for hospitalisation for heart failure of 2.07 (95% CI 1.73, 2.48) and 4.59 (95% CI 3.50, 6.02), respectively, using analyses adjusted for socioeconomic variables and associated conditions. Younger age, poorer glycaemic control and deteriorating renal function were all associated with increased excess risk of heart failure in those with type 2 diabetes compared with the control group. However, people with diabetes who were ≥75 years and without albuminuria or with good glycaemic control (HbA1c ≤52 mmol/mol [≤6.9%]) had a similar risk of hospitalisation for heart failure as control individuals in the same age group. CONCLUSIONS/INTERPRETATION Men and women aged <55 years with type 2 diabetes are at markedly elevated excess risk of heart failure. The excess risk declined with age, but persisted even with good glycaemic control. However, among those who were 75 years and older, diabetic individuals with well controlled glucose levels or without albuminuria had a risk of heart failure that was on a par with individuals without diabetes.
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Affiliation(s)
- Annika Rosengren
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden.
- Sahlgrenska University Hospital, Östra Hospital, Gothenburg, Sweden.
| | - Jon Edqvist
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden
- Sahlgrenska University Hospital, Östra Hospital, Gothenburg, Sweden
| | - Araz Rawshani
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Stefan Franzén
- Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden
| | - Martin Adiels
- Health Metrics Unit, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ann-Marie Svensson
- Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden
| | - Soffia Gudbjörnsdottir
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden
- Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden
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47
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Winther JF, Bhatia S, Cederkvist L, Gudmundsdottir T, Madanat-Harjuoja L, Tryggvadottir L, Wesenberg F, Hasle H, Sällfors Holmqvist A. Risk of cardiovascular disease among Nordic childhood cancer survivors with diabetes mellitus: A report from adult life after childhood cancer in Scandinavia. Cancer 2018; 124:4393-4400. [PMID: 30307617 DOI: 10.1002/cncr.31696] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/14/2018] [Accepted: 06/25/2018] [Indexed: 11/11/2022]
Abstract
BACKGROUND Childhood cancer survivors have an increased risk of cardiovascular disease (CVD) and diabetes mellitus. Because diabetes is a potentially modifiable risk factor for CVD in the general population, it is important to understand how diabetes affects the risk of CVD among childhood cancer survivors. METHODS This study examined the risk of CVD among survivors with diabetes and 142,742 population comparison subjects. From the national cancer registries of the 5 Nordic countries, 29,324 one-year survivors of cancer diagnosed before the age of 20 years between 1968 and 2008 were identified. Study subjects were linked to the national hospital registers. The cumulative incidence of CVD was determined with competing risk methods. A Cox proportional hazards model was used to estimate the effects of diabetes and cancer on the hazard of CVD. The interaction between diabetes and cancer was analyzed. RESULTS Diabetes was diagnosed in 324 of the 29,324 one-year survivors, and CVD was diagnosed in 2108. The hazard of diabetes was 1.7 times higher among survivors than comparison subjects (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-1.9), whereas the HR of CVD was 3.6 (95% CI, 3.3-3.8) 1 to 15 years after the cancer diagnosis and 1.9 (95% CI, 1.8-2.0) after more than 15 years. Individuals with diabetes had a 2.4 times higher hazard of CVD (95% CI, 2.1-2.8) among both survivors and comparison subjects in comparison with individuals without diabetes. CONCLUSIONS Childhood cancer survivors with diabetes have a markedly increased risk of CVD in comparison with survivors without diabetes. However, diabetes does not increase the risk of CVD more in survivors than the general population.
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Affiliation(s)
- Jeanette F Winther
- Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
| | - Smita Bhatia
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama, , USA
| | | | | | | | - Laufey Tryggvadottir
- Icelandic Cancer Registry, Reykjavik, Iceland.,Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Finn Wesenberg
- Norwegian Cancer Registry, Oslo, Norway.,Department of Pediatric Medicine, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Henrik Hasle
- Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
| | - Anna Sällfors Holmqvist
- Pediatric Oncology and Hematology, Skane University Hospital, Lund, Sweden.,Department of Clinical Sciences, Lund University, Lund, Sweden
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48
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Yerra VG, Advani A. Histones and heart failure in diabetes. Cell Mol Life Sci 2018; 75:3193-3213. [PMID: 29934664 PMCID: PMC6063320 DOI: 10.1007/s00018-018-2857-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 06/12/2018] [Accepted: 06/15/2018] [Indexed: 12/22/2022]
Abstract
Although heart failure is now accepted as being a major long-term complication of diabetes, many of the recent advances in our understanding of the pathobiology of diabetes complications have come about through the study of more traditional microvascular or macrovascular diseases. This has been the case, for example, in the evolving field of the epigenetics of diabetes complications and, in particular, the post-translational modification of histone proteins. However, histone modifications also occur in human heart failure and their perturbation also occurs in diabetic hearts. Here, we review the principal histone modifications and their enzymatic writers and erasers that have been studied to date; we discuss what is currently known about their roles in heart failure and in the diabetic heart; we draw on lessons learned from the studies of microvascular and macrovascular complications; and we speculate that therapeutically manipulating histone modifications may alter the natural history of heart failure in diabetes.
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Affiliation(s)
- Veera Ganesh Yerra
- Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 6-151, 61 Queen Street East, Toronto, ON, M5C 2T2, Canada
| | - Andrew Advani
- Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, 6-151, 61 Queen Street East, Toronto, ON, M5C 2T2, Canada.
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Joubert M, Manrique A, Cariou B, Prieur X. Diabetes-related cardiomyopathy: The sweet story of glucose overload from epidemiology to cellular pathways. DIABETES & METABOLISM 2018; 45:238-247. [PMID: 30078623 DOI: 10.1016/j.diabet.2018.07.003] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 06/28/2018] [Accepted: 07/12/2018] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes (T2D) is a major risk factor for heart failure (HF). Although the number of cases of myocardial infarction in the T2D population has been reduced by 25% over the last 10 years, the incidence of HF is continuously increasing, making it the most worrying diabetes complication. This strongly reinforces the urgent need for innovative therapeutic interventions to prevent cardiac dysfunction in T2D patients. To this end, epidemiological, imaging and animal studies have aimed to highlight the mechanisms involved in the development of diabetic cardiomyopathy. Epidemiological observations clearly show that hyperglycaemia correlates with severity of cardiac dysfunction and mortality in T2D patients. Both animal and cellular studies have demonstrated that, in the context of diabetes, the heart loses its ability to utilize glucose, therefore leading to glucose overload in cardiomyocytes that, in turn, promotes oxidative stress, accumulation of advanced glycation end-products (AGEs) and chronic activation of the hexosamine pathway. These have all been found to activate apoptosis and to alter heart contractility, calcium signalling and mitochondrial function. Although, in the past, tight glycaemic control has failed to improve cardiac function in T2D patients, recent clinical trials have reported cardiovascular benefit with hypoglycaemic antidiabetic drugs of the SGLT2-inhibitor family. This review, based on clinical evidence from mechanistic studies as well as several large clinical trials, covers 15 years of research, and strongly supports the idea that hyperglycaemia and glucose overload play a central role in the pathophysiology of diabetic cardiomyopathy.
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Affiliation(s)
- M Joubert
- Diabetes care unit, Caen university hospital, 14033 Caen cedex, France; EA4650, UNICAEN, 14000 Caen, France
| | - A Manrique
- Nuclear medicine unit, Caen university hospital, 14033 Caen cedex, France; EA4650, UNICAEN, 14000 Caen, France
| | - B Cariou
- Institut du thorax, Inserm, CNRS, University of Nantes, CHU Nantes, 44000 Nantes, France
| | - X Prieur
- Institut du thorax, Inserm, CNRS, University of Nantes, 44000 Nantes, France.
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Diabetes mellitus and heart failure: insights from a toxic relationship. PRACTICAL DIABETES 2018. [DOI: 10.1002/pdi.2176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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