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Draghici AE, Ely MR, Hamner JW, Taylor JA. Nitric oxide-mediated vasodilation in human bone. Microcirculation 2024; 31:e12842. [PMID: 38133925 PMCID: PMC10922487 DOI: 10.1111/micc.12842] [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: 08/10/2023] [Revised: 11/20/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
OBJECTIVE Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone. METHODS In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg. RESULTS LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 μM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 μM) at 10 min (p = .01). CONCLUSIONS In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.
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Affiliation(s)
- Adina E. Draghici
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA
- Cardiovascular Research Laboratory, Spaulding Hospital Cambridge, Cambridge, MA
- Schoen Adams Research Institute at Spaulding Rehabilitation, Boston, MA
| | - Matthew R. Ely
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA
- Cardiovascular Research Laboratory, Spaulding Hospital Cambridge, Cambridge, MA
- Schoen Adams Research Institute at Spaulding Rehabilitation, Boston, MA
| | - Jason W. Hamner
- Cardiovascular Research Laboratory, Spaulding Hospital Cambridge, Cambridge, MA
- Schoen Adams Research Institute at Spaulding Rehabilitation, Boston, MA
| | - J. Andrew Taylor
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA
- Cardiovascular Research Laboratory, Spaulding Hospital Cambridge, Cambridge, MA
- Schoen Adams Research Institute at Spaulding Rehabilitation, Boston, MA
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Draghici AE, Zahedi B, Taylor JA, Bouxsein ML, Yu EW. Vascular deficits contributing to skeletal fragility in type 1 diabetes. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2023; 4:1272804. [PMID: 37867730 PMCID: PMC10587602 DOI: 10.3389/fcdhc.2023.1272804] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/15/2023] [Indexed: 10/24/2023]
Abstract
Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.
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Affiliation(s)
- Adina E. Draghici
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States
- Cardiovascular Research Laboratory, Schoen Adams Research Institute at Spaulding Rehabilitation, Cambridge, MA, United States
| | - Bita Zahedi
- Endocrine Unit, Massachusetts General Hospital, Boston, MA, United States
| | - J. Andrew Taylor
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States
- Cardiovascular Research Laboratory, Schoen Adams Research Institute at Spaulding Rehabilitation, Cambridge, MA, United States
| | - Mary L. Bouxsein
- Endocrine Unit, Massachusetts General Hospital, Boston, MA, United States
- Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Boston, MA, United States
| | - Elaine W. Yu
- Endocrine Unit, Massachusetts General Hospital, Boston, MA, United States
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3
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Jahn LA, Hartline LM, Kleiner AJ, Horton WB, Hasan F, Wai Kit Tan A, Liu Z, Barrett EJ. Insulin-induced vasoconstriction is prevalent in muscle microvasculature of otherwise healthy persons with type 1 diabetes. Am J Physiol Endocrinol Metab 2023; 324:E402-E408. [PMID: 36920998 PMCID: PMC10125023 DOI: 10.1152/ajpendo.00242.2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 02/09/2023] [Accepted: 03/09/2023] [Indexed: 03/16/2023]
Abstract
Insulin's microvascular actions and their relationship to insulin's metabolic actions have not been well studied in adults with type 1 diabetes mellitus (T1DM). We compared the metabolic and selected micro- and macrovascular responses to insulin by healthy adult control (n = 16) and subjects with T1DM (n = 15) without clinical microvascular disease. We measured insulin's effect on 1) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU), 2) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA), and 3) metabolic insulin sensitivity by the glucose infusion rate (GIR) during a 2-h, 1 mU/min/kg euglycemic-insulin clamp. Subjects with T1DM were metabolically insulin resistant (GIR = 5.2 ± 0.7 vs. 6.6 ± 0.6 mg/min/kg, P < 0.001). Insulin increased muscle microvascular blood volume and flow in control (P < 0.001, for each) but not in subjects with T1DM. Metabolic insulin sensitivity correlated with increases of muscle microvascular perfused volume (P < 0.05). Baseline measures of vascular stiffness did not differ between groups. However, during hyperinsulinemia, cfPWV was greater (P < 0.02) in the T1DM group and the backward pulse wave pressure declined with insulin only in controls (P < 0.03), both indices indicating that insulin-induced vascular relaxation in controls only. Subjects with T1DM have muscle microvascular insulin resistance that may precede clinical microvascular disease.NEW & NOTEWORTHY Using contrast ultrasound and measures of vascular stiffness, we compared vascular and metabolic responses to insulin in patients with type 1 diabetes with age-matched controls. The patients with type 1 diabetes demonstrated both vascular and metabolic insulin resistance with more than half of the patients with diabetes having a paradoxical vasoconstrictive vascular response to insulin.
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Affiliation(s)
- Linda A Jahn
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Lee M Hartline
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Amanda J Kleiner
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - William B Horton
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Farhad Hasan
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Alvin Wai Kit Tan
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Zhenqi Liu
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
| | - Eugene J Barrett
- Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
- Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, Virginia, United States
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Gamal Y, Badawy A, Ali AM, Farghaly HS, Metwalley KA, Gaber N, Allam MT, Farouk Y. Endothelial dysfunction in children with newly diagnosed Graves' disease. Eur J Pediatr 2023:10.1007/s00431-023-04919-z. [PMID: 37022495 PMCID: PMC10257599 DOI: 10.1007/s00431-023-04919-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 02/22/2023] [Accepted: 03/02/2023] [Indexed: 04/07/2023]
Abstract
The most frequent cause of hyperthyroidism in children is Graves' disease (GD). Vascular endothelium is a specific target of thyroid hormone. The purpose of this study is to assess flow-mediated dilatation (FMD)% and serum von Willebrand factor (vWF) levels in children with newly diagnosed GD to reflect the extent of endothelial dysfunction in those children. In this study, 40 children with newly discovered GD and 40 children who were healthy served as the control group. Both patients and controls had anthropometric assessment, as well as measurements of fasting lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), TSH, and free thyroxine (FT4 and FT3), thyrotropin receptor antibodies TRAbs and vWF. Noninvasive ultrasound was utilized to quantify the carotid arteries' intima-media thickness and the brachial artery's FMD. Patients reported significantly reduced FMD response and greater vWF and hs-CRP levels compared to controls (P = 0.001 for each). In multivariate analysis, we reported that vWF was significantly correlated with TSH (OR 2.5, 95% CI 1.32-5.32, P = 0.001), FT3 (OR 3.4, 95% CI 1.45-3.55, P = 0.001), TRAb (OR 2.1, 95% CI 1.16-2.23, P = 0.01), and FMD% (OR 4.2, 95% CI 1.18-8.23, P = 0.001). Conclusions: Children with newly diagnosed GD have endothelial dysfunction, which is shown by impaired FMD and increased vWF. These findings support the idea that GD may need to be treated as soon as possible. What is Known: • Graves' disease is the most common cause of hyperthyroidism in children. • vWF is a reliable marker for detection of vascular endothelial dysfunction. What is New: • Children with newly diagnosed Graves' disease may have endothelial dysfunction as reflected by impairment of FMD and raised vWF level. • Measurement of vWF level in children with newly diagnosed Graves' disease can be used for early detection of endothelial dysfunction.
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Affiliation(s)
- Yasser Gamal
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt.
| | - Ahlam Badawy
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed M Ali
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Hekma Saad Farghaly
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
| | | | - Noha Gaber
- Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Momtaz Thabet Allam
- Department of Radiology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yasser Farouk
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
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Ahmad FA, Metwalley KA, Mohamad IL. Association of Epicardial Fat with Diastolic and Vascular Functions in Children with Type 1 Diabetes. Pediatr Cardiol 2022; 43:999-1010. [PMID: 35088126 DOI: 10.1007/s00246-021-02811-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 12/20/2021] [Indexed: 11/28/2022]
Abstract
We aimed to examine the relationship between epicardial fat thickness (EFT) measured by echocardiography and cardiovascular functional parameters in children with type 1 diabetes mellitus (T1DM). The study included 50 type 1 diabetic children and 50 healthy subjects matched by sex, age, and body mass index. In addition to laboratory tests, all participants underwent transthoracic echocardiography for EFT, cardiac dimensions and left ventricular functions, and ultrasonographic examination for brachial artery flow-mediated dilation (FMD) response and carotid intima-media thickness (CIMT). Multivariate linear regression was used to analyze the relationship between EFT and CIMT, FMD, lateral mitral E' velocity, and mitral E/E' ratio. EFT was significantly increased in diabetic children compared with controls (P < 0.001). In comparison with controls diabetic children had significantly increased mitral A, decreased lateral mitral E', decreased mitral E/A ratio, decreased lateral mitral E'/A' ratio, and increased mitral E/E' ratio (P < 0.001). FMD response was significantly lower in diabetic group versus controls (P < 0.001) and CIMT was significantly increased in diabetics versus controls (P = 0.03). EFT was negatively correlated with lateral mitral E' velocity (r = - 0.613, P < 0.001), positively correlated with mitral E/E' ratio (r = 0.60, P < 0.001), positively correlated with CIMT (r = 0.881, P < 0.001), and negatively correlated with FMD (r = - 0.533, P < 0.001). By multivariate regression analysis, the EFT was independently and positively associated with CIMT mean and E/E' mean and negatively associated with FMD mean and E' mean. The cut-off point for EFT as predictor of endothelial dysfunction was 6.95 mm. Our findings suggest that children with T1DM have subclinical LV diastolic and vascular endothelial dysfunctions associated with increased EFT.
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Drozd I, Weiskorn J, Lange K, Kordonouri O. Typ-1-Diabetes und kardiovaskuläre Risikofaktoren bei Kindern und Jugendlichen. DIABETOL STOFFWECHS 2022. [DOI: 10.1055/a-1713-2438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungDie langfristigen kardiovaskulären Folgen des Typ-1-Diabetes determinieren die Lebenserwartung betroffener Kinder und Jugendlicher. Risikofaktoren für deren Entwicklung sind eine längere Diabetesdauer bzw. Diabetesmanifestation im frühen Lebensalter, Hypertonie, Rauchen, hoher BMI sowie Fettstoffwechselstörungen. Das Management der kardiovaskulären Risikofaktoren bei Kindern und Jugendlichen mit Typ-1-Diabetes beinhaltet zum einen Screeningsmaßnahmen zur frühzeitigen Aufdeckung der pathologischen Veränderungen und zum anderen eine Lebensstilanpassung im Sinne einer ausgewogenen, normokalorischen Ernährung, regelmäßiger Bewegung sowie ggf. einer medikamentösen lipid- bzw. blutdrucksenkenden Therapie.Die Leitlinien und Empfehlungen zur standardisierten Erkennung und Behandlung kardiovaskulärer Risikofaktoren bei jungen Menschen mit Typ-1-Diabetes sind bisher uneinheitlich formuliert und werden deshalb nicht immer im klinischen Alltag angewendet bzw. umgesetzt. Dies führt zu einer relevanten Unterversorgung dieser Patientengruppe. Dem gilt es mit mehr Forschungsansätzen und der Entwicklung eines universellen Prozederes zur Diagnostik und Therapie der kardiovaskulären Risikofaktoren entgegenzuwirken.
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Affiliation(s)
- Irena Drozd
- Diabetes-Zentrum für Kinder und Jugendliche, AUF DER BULT, Kinder- und Jugendkrankenhaus, Hannover, Germany
- Medizinische Psychologie, MHH Hannover, Hannover, Germany
| | - Jantje Weiskorn
- Diabetes-Zentrum für Kinder und Jugendliche, AUF DER BULT, Kinder- und Jugendkrankenhaus, Hannover, Germany
| | - Karin Lange
- Medizinische Psychologie, MHH Hannover, Hannover, Germany
| | - Olga Kordonouri
- Diabetes-Zentrum für Kinder und Jugendliche, AUF DER BULT, Kinder- und Jugendkrankenhaus, Hannover, Germany
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Jahn LA, Logan B, Love KM, Horton WB, Eichner NZ, Hartline LM, Weltman AL, Barrett EJ. Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes. Am J Physiol Endocrinol Metab 2022; 322:E101-E108. [PMID: 34894721 PMCID: PMC8799398 DOI: 10.1152/ajpendo.00267.2021] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 11/16/2021] [Accepted: 12/05/2021] [Indexed: 11/22/2022]
Abstract
Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1. Here, we assessed macro- and microvascular function in DM1 adolescents and age-matched controls at baseline and during an oral glucose challenge (OGTT). DM1 adolescents (n = 16) and controls (n = 14) were studied before and during an OGTT. At baseline, we measured: 1) large artery stiffness using both aortic augmentation index (AI) and carotid-femoral pulse wave velocity (cfPWV); 2) brachial flow-mediated dilation (FMD) and forearm endothelial function using postischemic flow velocity (PIFV); and 3) forearm muscle microvascular blood volume (MBV) using contrast-enhanced ultrasound. Following OGTT, AI, cfPWV, and MBV were reassessed at 60 min and MBV again at 120 min. Within individual and between-group, comparisons were made by paired and unpaired t tests or repeated measures ANOVA. Baseline FMD was lower (P = 0.02) in DM1. PWV at 0 and 60 min did not differ between groups. Baseline AI did not differ between groups but declined with OGTT only in controls (P = 0.02) and was lower than DM1 at 60 min (P < 0.03). Baseline MBV was comparable in DM1 and control groups, but declined in DM1 at 120 min (P = 0.01) and was lower than the control group (P < 0.03). There was an inverse correlation between plasma glucose and MBV at 120 min (r = -0.523, P < 0.01). No differences were noted between groups for V̇O2max (mL/min/kg), body fat (%), or body mass index (BMI). NO-dependent macro- and microvascular function, including FMD and AI, and microvascular perfusion, respectively, are impaired early in the course of DM1, precede increases of arterial stiffness, and may provide an early indicator of vascular risk.NEW & NOTEWORTHY This is the first study to show that type 1 diabetes impairs multiple nitric oxide-dependent vascular functions.
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Affiliation(s)
- Linda A Jahn
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Brent Logan
- Department of Pediatrics, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Kaitlin M Love
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - William B Horton
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Natalie Z Eichner
- Department of Kinesiology, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Lee M Hartline
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Arthur L Weltman
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
- Department of Kinesiology, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
| | - Eugene J Barrett
- Department of Medicine, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
- Department of Pediatrics, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
- Department of Pharmacology, School of Medicine, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia
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Calderón-Hernández MF, Altamirano-Bustamante NF, Revilla-Monsalve C, Mosquera-Andrade MB, Altamirano-Bustamante MM. What can we learn from β-cell failure biomarker application in diabetes in childhood? A systematic review. World J Diabetes 2021; 12:1325-1362. [PMID: 34512897 PMCID: PMC8394223 DOI: 10.4239/wjd.v12.i8.1325] [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: 01/28/2021] [Revised: 04/12/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prevalence of diabetes as a catastrophic disease in childhood is growing in the world. The search for novel biomarkers of β-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic syndrome.
AIM To determine which biomarkers are currently used to identify β-cell failure among children and adolescents with high risk factors for diabetes mellitus.
METHODS This systematic review was carried out using a modified version of the PICO protocol (Participants/Intervention/Comparison/Outcome). Once our research question was established, terms were individually researched on three different databases (PubMed, BIREME and Web of Science). The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further analysis. They were assessed individually according to quality criteria.
RESULTS First, we made the classification of the β-cell-failure biomarkers by the target tissue and the evolution of the disease, separating the biomarkers in relation to the types of diabetes. Second, we demonstrated that most biomarkers currently used as early signs of β-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Third, we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid oligomers. Finally, we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in childhood.
CONCLUSION This review makes widely evident that most biomarkers currently used as early signs of β-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Landing in the clinical practice we propose that real human islet amyloid polypeptide amyloid oligomers is good for identifying patients with β-cell damage and potentially could substitute many biomarkers.
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Affiliation(s)
- María F Calderón-Hernández
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, IMSS, Mexico 06720, Mexico
| | | | - Cristina Revilla-Monsalve
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, IMSS, Mexico 06720, Mexico
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Aleman MN, Díaz EI, Luciardi MC, Mariani AC, Bazán MC, Abregu AV. Hemostatic state of children with type 1 diabetes. Ann Pediatr Endocrinol Metab 2021; 26:99-104. [PMID: 34218631 PMCID: PMC8255861 DOI: 10.6065/apem.2040142.071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Hyperglycemia is one of the factors responsible for the molecular alterations that modify hemostasis. The aim of this study was to determine the levels of circulating molecules that have a prothrombotic impact on the child and adolescent population with type 1 diabetes mellitus. METHODS There were 35 patients with type 1 diabetes mellitus (11.0±2.5 years of age and a median 3.7±2.0 years of the disease) with no vascular complications and 20 healthy controls with similar age, sex, and body mass index included in the study. The evaluated parameters were fibrinogen, plasminogen activator inhibitor-1 (PAI1), von Willebrand factor antigen, and standard coagulation tests (platelet count, prothrombin time, and activated partial thromboplastin time). Glycemic control was evaluated by hemoglobin A1c and fasting blood glucose tests, and the presence of retinopathy and nephropathy was ruled out. The data obtained were analyzed by IBM SPSS Statistics ver. 20.0 and expressed as mean±standard deviation. The Pearson correlation coefficient was applied to investigate correlations between variables. RESULTS Diabetic patients showed significantly higher levels of fibrinogen (308±66 mg/dL vs. 246±18 mg/dL, P=0.0001), PAI-1 (41.6±12 ng/mL vs. 11.7±1.0 ng/mL, P=0.0001), and von Willebrand factor antigen (284%±55% vs. 121%±19%, P=0.0001). However, standard coagulation tests did not show differences between the 2 groups. PAI-1 was correlated with glycemia, hemoglobin A1c, fibrinogen, and von Willebrand factor antigen. CONCLUSION Elevated levels of fibrinogen, PAI-1, and von Willebrand factor antigen were found in the pediatric and adolescent population with type 1 diabetes mellitus, which suggests a prothrombotic state.
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Affiliation(s)
- Mariano Nicolás Aleman
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina,Address for correspondence: Mariano Nicolás Áleman Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Balcarce 747, San Miguel de Tucumán, Tucumán 4000, Argentina
| | - Elba Irma Díaz
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Maria Constanza Luciardi
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Ana Carolina Mariani
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Maria Cristina Bazán
- Departamento de Endocrinología, Hospital del Niño Jesús de Tucumán, Tucumán, Argentina
| | - Adela Victoria Abregu
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
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Cao L, Hou M, Zhou W, Sun L, Shen J, Chen Y, Tang Y, Wang B, Li X, Lv H. Decreased Flow-Mediated Dilatation in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis. Angiology 2021; 72:908-915. [PMID: 33896228 DOI: 10.1177/00033197211010096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Type 1 diabetes (T1DM) is a strong risk factor for the development of cardiovascular disease. Flow-mediated dilatation (FMD) is an early noninvasive marker of endothelial function and it predicts future cardiovascular disease. However, the changes in FMD among T1DM children are still controversial. The present meta-analysis aimed to investigate whether FMD is impaired in children with T1DM. PubMed, EMBASE, Cochrane library, and Web of Science were searched for studies comparing FMD in children with T1DM and healthy controls. The Newcastle-Ottawa quality assessment scale for case-control studies was used to assess study quality. Data were pooled using a random effects models to obtain the weighted mean differences (WMD) in FMD and 95% CIs. Overall, 19 studies with 1245 patients and 872 healthy controls were included in this meta-analysis. Children with T1DM had significantly lower FMDs compared with healthy controls (WMD: -2.58; 95% CI: -3.36 to -1.81; P < .001). Meta-regression analysis revealed that low-density lipoprotein cholesterol levels impacted the observed difference in FMD between T1DM and healthy children. This meta-analysis showed that T1DM children have impaired endothelial function, which indicates they are at higher risk of developing cardiovascular disease in later life.
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Affiliation(s)
- Lei Cao
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Miao Hou
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wanping Zhou
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ling Sun
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jie Shen
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ye Chen
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yunjia Tang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Bo Wang
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xuan Li
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Haitao Lv
- Department of Cardiology, Children's Hospital of Soochow University, Suzhou, Jiangsu, China
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11
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Hofeld BC, Puppala VK, Tyagi S, Ahn KW, Anger A, Jia S, Salzman NH, Hessner MJ, Widlansky ME. Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation. Sci Rep 2021; 11:3972. [PMID: 33597583 PMCID: PMC7889883 DOI: 10.1038/s41598-021-83252-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 01/25/2021] [Indexed: 12/15/2022] Open
Abstract
Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1β, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.
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Affiliation(s)
- Benjamin C Hofeld
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Venkata K Puppala
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sudhi Tyagi
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kwang Woo Ahn
- Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Amberly Anger
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Shuang Jia
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Nita H Salzman
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Martin J Hessner
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Michael E Widlansky
- Department of Medicine, Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
- Division of Cardiovascular Medicine, Professor of Medicine and Pharmacology, Medical College of Wisconsin, Hub for Collaborative Medicine, 5th Floor A5743, 8701 W. Watertown Plank Road, Milwaukee, WI, 53226, USA.
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12
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Chiesa ST, Marcovecchio ML, Benitez-Aguirre P, Cameron FJ, Craig ME, Couper JJ, Davis EA, Dalton RN, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dunger DB, Deanfield JE. Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes. Hypertension 2020; 76:1734-1743. [PMID: 33100044 DOI: 10.1161/hypertensionaha.120.15721] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0-7.2] versus 5.3% [4.7-5.9]; P=0.005), whereas no effect was observed following statin use (6.2% [5.5-6.8] versus 5.8% [5.1-6.4]; P=0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8-5.9] versus 6.3% [5.8-6.7] for high-risk versus low-risk groups; P=0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment (P>0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03-0.12]; P=0.001 and 0.5 m/s [0.4-0.6]; P<0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration- URL: https://www.clinicaltrials.gov; Unique identifier NCT01581476.
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Affiliation(s)
- Scott T Chiesa
- From the Institute of Cardiovascular Science, University College London, United Kingdom (S.T.C., J.E.D.)
| | | | - Paul Benitez-Aguirre
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, University of Sydney, Camperdown, Australia (P.B.-A., K.C.D.)
| | - Fergus J Cameron
- Department of Paediatrics, University of Melbourne, Australia (F.J.C.)
| | - Maria E Craig
- School of Women's and Children's Health, University of New South Wales, Australia (M.E.C.)
| | - Jennifer J Couper
- Departments of Endocrinology and Diabetes, Women's and Children's Hospital, Robinson Research Institute, University of Adelaide, Australia (J.J.C.)
| | - Elizabeth A Davis
- Telethon Kids Institute, University of Western Australia, Perth (E.A.D., T.W.J.)
| | - R Neil Dalton
- Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom (R.N.D.)
| | - Denis Daneman
- Department of Paediatrics, The Hospital for Sick Children, University of Toronto, ON, Canada (D.D., F.H.M.)
| | - Kim C Donaghue
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, University of Sydney, Camperdown, Australia (P.B.-A., K.C.D.)
| | - Timothy W Jones
- Telethon Kids Institute, University of Western Australia, Perth (E.A.D., T.W.J.)
| | - Farid H Mahmud
- Department of Paediatrics, The Hospital for Sick Children, University of Toronto, ON, Canada (D.D., F.H.M.)
| | - Sally M Marshall
- Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (S.M.M.)
| | - H Andrew W Neil
- Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, United Kingdom (H.A.W.N.)
| | - David B Dunger
- Department of Paediatrics (M.L.M., D.B.D.), University of Cambridge, United Kingdom.,Wellcome Trust-MRC Institute of Metabolic Science (D.B.D.), University of Cambridge, United Kingdom
| | - John E Deanfield
- From the Institute of Cardiovascular Science, University College London, United Kingdom (S.T.C., J.E.D.)
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13
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Chiesa ST, Charakida M, McLoughlin E, Nguyen HC, Georgiopoulos G, Motran L, Elia Y, Marcovecchio ML, Dunger DB, Dalton RN, Daneman D, Sochett E, Mahmud FH, Deanfield JE. Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation. Eur Heart J 2020; 40:3559-3566. [PMID: 30863865 PMCID: PMC6855140 DOI: 10.1093/eurheartj/ehz114] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 08/26/2018] [Accepted: 02/18/2019] [Indexed: 12/16/2022] Open
Abstract
AIMS High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed. METHODS AND RESULTS Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05). CONCLUSION Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation.
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Affiliation(s)
- Scott T Chiesa
- Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, UK
| | - Marietta Charakida
- Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, UK
| | - Eve McLoughlin
- Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, UK
| | - Helen C Nguyen
- Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, UK
| | | | - Laura Motran
- Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Yesmino Elia
- Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | | | - David B Dunger
- Department of Paediatrics, University of Cambridge, Cambridge, UK.,Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - R Neil Dalton
- WellChild Laboratory, St. Thomas' Hospital, King's College London, London, UK
| | - Denis Daneman
- Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Etienne Sochett
- Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Farid H Mahmud
- Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - John E Deanfield
- Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, UK
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14
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Altamirano-Bustamante NF, Garrido-Magaña E, Morán E, Calderón A, Pasten-Hidalgo K, Castillo-Rodríguez RA, Rojas G, Lara-Martínez R, Leyva-García E, Larralde-Laborde M, Domíguez G, Murata C, Margarita-Vazquez Y, Payro R, Barbosa M, Valderrama A, Montesinos H, Domínguez-Camacho A, García-Olmos VH, Ferrer R, Medina-Bravo PG, Santoscoy F, Revilla-Monsalve C, Jiménez-García LF, Morán J, Villalobos-Alva J, Villalobos MJ, Calzada-León R, Altamirano P, Altamirano-Bustamante MM. Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes. PLoS One 2020; 15:e0237667. [PMID: 32833960 PMCID: PMC7446879 DOI: 10.1371/journal.pone.0237667] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/30/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIMS This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when β-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early β-cell damage. MATERIALS AND METHODS We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early β-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS RIAO level increases as the number of complications rises; RIAOs > 3.35 μg/ml is a predictor of changes in the current indicators of β-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.
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MESH Headings
- Adolescent
- Animals
- Cell Line
- Cell Survival
- Cells, Cultured
- Child
- Child, Preschool
- Cross-Sectional Studies
- Diabetes Mellitus, Type 1/blood
- Diabetes Mellitus, Type 1/pathology
- Diabetes Mellitus, Type 2/blood
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/pathology
- Humans
- Insulin-Secreting Cells/pathology
- Islet Amyloid Polypeptide/blood
- Islet Amyloid Polypeptide/metabolism
- Islet Amyloid Polypeptide/toxicity
- Islet Amyloid Polypeptide/ultrastructure
- Microscopy, Electron, Transmission
- Neurons/drug effects
- Obesity/blood
- Obesity/complications
- Obesity/pathology
- Pilot Projects
- Primary Cell Culture
- Protein Multimerization
- Protein Structure, Quaternary
- Rats
- Toxicity Tests, Acute
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Affiliation(s)
| | - Eulalia Garrido-Magaña
- UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Eugenia Morán
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Aurora Calderón
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Karina Pasten-Hidalgo
- Instituto Nacional de Pediatría, Mexico City, Mexico
- Cátedras Conacyt, Consejo Nacional de Ciencia y Tecnología, Mexico City, Mexico
| | - Rosa Angélica Castillo-Rodríguez
- Instituto Nacional de Pediatría, Mexico City, Mexico
- Cátedras Conacyt, Consejo Nacional de Ciencia y Tecnología, Mexico City, Mexico
| | - Gerardo Rojas
- UMAE Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | - Edgar Leyva-García
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Mateo Larralde-Laborde
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | | | | | - Rafael Payro
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Manuel Barbosa
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | | | | | | | - Regina Ferrer
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | - Fernanda Santoscoy
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Cristina Revilla-Monsalve
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | - Julio Morán
- Instituto de Fisiología Celular, UNAM, Mexico City, Mexico
| | - Jalil Villalobos-Alva
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Mario Javier Villalobos
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | - Perla Altamirano
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Myriam M. Altamirano-Bustamante
- Unidad de Investigación en Enfermedades Metabólicas, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
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15
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Anık A, Çelik E, Çevik Ö, Ünüvar T, Anık A. The relation of serum endocan and soluble endoglin levels with metabolic control in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2020; 33:/j/jpem.ahead-of-print/jpem-2020-0146/jpem-2020-0146.xml. [PMID: 32697760 DOI: 10.1515/jpem-2020-0146] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 05/06/2020] [Indexed: 02/06/2023]
Abstract
Objectives Endothelial dysfunction is an early marker of vascular disease in Type 1 diabetes mellitus (T1DM). In the present study, we aimed to investigate serum endocan and soluble endoglin (S-endoglin) levels, and their relation with metabolic control in children with T1DM, which was not previously assessed. Methods A total of 64 T1DM subjects and 64 healthy subjects were included in this study. Their anthropometric features, arterial blood pressures, pubertal status, insulin doses were recorded. Glycated hemoglobin, serum endocan and S-endoglin levels were measured and compared to each other. Results Serum endocan and S-endoglin levels were higher in children with T1DM than those of healthy group (p<0.01). Significant positive correlation was detected between both endocan and S-endoglin (r=0.579, p<0.001); and HbA1c and endocan (r=0.296, p=0.01). Compared to patients with good metabolic control, those with poorer metabolic control (HbA1c > 8%) had an older age, longer duration of diabetes, higher number of pubertal children. Also, patients with poorer metabolic control had higher endocan and S-endoglin levels than those of healthy group, but this finding did not reach statistical significance. There was no correlation between the endocan/S-endoglin levels and age, duration of diabetes and insulin dose. Conclusion Serum levels of endocan and S-endoglin which are novel biomarkers of endothelial dysfunction are high in children with T1DM. Elevated serum endocan and endoglin levels in children with T1DM without microvascular complications indicates endothelial damage in very early stages of the disease.
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Affiliation(s)
- Ayşe Anık
- Department of Pediatrics, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey
| | - Elif Çelik
- Department of Pediatrics, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey
| | - Özge Çevik
- Department of Biochemistry, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey
| | - Tolga Ünüvar
- Department of Pediatric Endocrinology, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey
| | - Ahmet Anık
- Department of Pediatric Endocrinology, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey
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16
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Pastore I, Bolla AM, Montefusco L, Lunati ME, Rossi A, Assi E, Zuccotti GV, Fiorina P. The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents. Int J Mol Sci 2020; 21:ijms21144928. [PMID: 32664699 PMCID: PMC7403998 DOI: 10.3390/ijms21144928] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/07/2020] [Accepted: 07/09/2020] [Indexed: 12/20/2022] Open
Abstract
The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later in life. Interestingly, it seems that hyperglycemia is not the only factor that establishes an increased cardiovascular risk in adolescence. Other factors have been recognized to play a role in triggering the onset of latent cardiovascular diseases in the pediatric population. Among these cardiovascular risk factors, some are modifiable: glucose variability, hypoglycemia, obesity, insulin resistance, waist circumference, hypertension, dyslipidemia, smoking alcohol, microalbuminuria and smoking. Others are unmodifiable, such as diabetes duration and family history. Among the etiological factors, subclinical endothelial dysfunction represents one of the earliest key players of atherosclerosis and it can be detected during early ages in patients with diabetes. A better assessment of cardiovascular risk in pediatric population still represents a challenge for clinicians, and thus further efforts are required to properly identify and treat pediatric patients who may suffer from cardiovascular disease later in early adulthood.
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Affiliation(s)
- Ida Pastore
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (I.P.); (A.M.B.); (L.M.); (M.E.L.); (A.R.)
| | - Andrea Mario Bolla
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (I.P.); (A.M.B.); (L.M.); (M.E.L.); (A.R.)
| | - Laura Montefusco
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (I.P.); (A.M.B.); (L.M.); (M.E.L.); (A.R.)
| | - Maria Elena Lunati
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (I.P.); (A.M.B.); (L.M.); (M.E.L.); (A.R.)
| | - Antonio Rossi
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (I.P.); (A.M.B.); (L.M.); (M.E.L.); (A.R.)
| | - Emma Assi
- International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, 20157 Milan, Italy;
| | - Gian Vincenzo Zuccotti
- Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Università di Milano and Department of Pediatrics, Buzzi Children’s Hospital, 20157 Milan, Italy;
| | - Paolo Fiorina
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157 Milan, Italy; (I.P.); (A.M.B.); (L.M.); (M.E.L.); (A.R.)
- International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, 20157 Milan, Italy;
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Correspondence: ; Tel.: +1-617-919-2624
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Hewgley RA, Moore BT, Willingham TB, Jenkins NT, McCully KK. MUSCLE MITOCHONDRIAL CAPACITY AND ENDURANCE IN ADULTS WITH TYPE 1 DIABETES. MEDICAL RESEARCH ARCHIVES 2020; 8. [PMID: 34222650 DOI: 10.18103/mra.v8i2.2049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The impact of type 1 diabetes (T1D) on muscle endurance and oxidative capacity is currently unknown. Purpose Measure muscle endurance and oxidative capacity of adults with T1D compared to controls. Methods A cross-sectional study design with a control group was used. Subjects (19-37 years old) with T1D (n=17) and controls (n=17) were assessed with hemoglobin A1c (HbA1c) and casual glucose. Muscle endurance was measured with an accelerometer at stimulation frequencies of 2, 4, and 6 Hz for a total of nine minutes. Mitochondrial capacity was measured using near-infrared spectroscopy after exercise as the rate constant of the rate of recovery of oxygen consumption. Results T1D and control groups were similar in age, sex, height, and race. The T1D group had slightly higher BMI values and adipose tissue thickness over the forearm muscles. Casual glucose was 150±70 mg/dL for T1D and 98±16 mg/dL for controls (P=0.006). HbA1c of T1D subjects was 7.1±0.9% and 5.0±0.4% for controls (P<0.01). Endurance indexes at 2, 4, and 6 Hz were 94.5±5.2%, 81.8±8.4%, and 68.6±13.5% for T1D and 94.6±4.1%, 85.9±6.3%, and 68.7±15.4% for controls (p = 0.97, 0.12, 0.99, respectively). There were no differences between groups in mitochondrial capacity (T1D= 1.9±0.5 min-1 and control=1.8±0.4 min-1, P=0.29) or reperfusion rate (T1D= 8.8±2.8s and control=10.3±3.0s, P=0.88). There were no significant correlations between HbA1c and either muscle endurance, mitochondrial capacity or reperfusion rate. Conclusions Adults with T1D did not have reduced oxidative capacity, muscle endurance or muscle reperfusion rates compared to controls. HbA1c also did not correlate with muscle endurance, mitochondrial capacity or reperfusion rates. Future studies should extend these measurements to older people or people with poorly-controlled T1D.
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Affiliation(s)
- Riley A Hewgley
- Dept. of Kinesiology, University of Georgia, Athens, GA 30602
| | - Bethany T Moore
- Dept. of Kinesiology, University of Georgia, Athens, GA 30602
| | | | | | - Kevin K McCully
- Dept. of Kinesiology, University of Georgia, Athens, GA 30602
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Lespagnol E, Dauchet L, Pawlak-Chaouch M, Balestra C, Berthoin S, Feelisch M, Roustit M, Boissière J, Fontaine P, Heyman E. Early Endothelial Dysfunction in Type 1 Diabetes Is Accompanied by an Impairment of Vascular Smooth Muscle Function: A Meta-Analysis. Front Endocrinol (Lausanne) 2020; 11:203. [PMID: 32362871 PMCID: PMC7180178 DOI: 10.3389/fendo.2020.00203] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 03/23/2020] [Indexed: 12/15/2022] Open
Abstract
Background: A large yet heterogeneous body of literature exists suggesting that endothelial dysfunction appears early in type 1 diabetes, due to hyperglycemia-induced oxidative stress. The latter may also affect vascular smooth muscles (VSM) function, a layer albeit less frequently considered in that pathology. This meta-analysis aims at evaluating the extent, and the contributing risk factors, of early endothelial dysfunction, and of the possible concomitant VSM dysfunction, in type 1 diabetes. Methods: PubMed, Web of Sciences, Cochrane Library databases were screened from their respective inceptions until October 2019. We included studies comparing vasodilatory capacity depending or not on endothelium (i.e., endothelial function or VSM function, respectively) in patients with uncomplicated type 1 diabetes and healthy controls. Results: Fifty-eight articles studying endothelium-dependent function, among which 21 studies also assessed VSM, were included. Global analyses revealed an impairment of standardized mean difference (SMD) (Cohen's d) of endothelial function: -0.61 (95% CI: -0.79, -0.44) but also of VSM SMD: -0.32 (95% CI: -0.57, -0.07). The type of stimuli used (i.e., exercise, occlusion-reperfusion, pharmacological substances, heat) did not influence the impairment of the vasodilatory capacity. Endothelial dysfunction appeared more pronounced within macrovascular than microvascular beds. The latter was particularly altered in cases of poor glycemic control [HbA1c > 67 mmol/mol (8.3%)]. Conclusions: This meta-analysis not only corroborates the presence of an early impairment of endothelial function, even in response to physiological stimuli like exercise, but also highlights a VSM dysfunction in children and adults with type 1 diabetes. Endothelial dysfunction seems to be more pronounced in large than small vessels, fostering the debate on their relative temporal appearance.
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Affiliation(s)
- Elodie Lespagnol
- Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
| | - Luc Dauchet
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France
| | - Mehdi Pawlak-Chaouch
- Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
| | - Costantino Balestra
- Environmental and Occupational (Integrative) Physiology Laboratory, Haute École Bruxelles-Brabant HE2B, Brussels, Belgium
| | - Serge Berthoin
- Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
| | - Martin Feelisch
- Clinical and Experimental Sciences, Faculty of Medicine, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom
| | - Matthieu Roustit
- Univ. Grenoble Alpes, HP2, Inserm, CHU Grenoble Alpes, Grenoble, France
| | - Julien Boissière
- Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
| | - Pierre Fontaine
- Département d'endocrinologie, Diabète et maladies métaboliques, Hôpital Huriez, Université de Lille, Lille, France
| | - Elsa Heyman
- Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
- *Correspondence: Elsa Heyman
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Reid RER, Thivel D, Mathieu ME. Understanding the potential contribution of a third "T" to FITT exercise prescription: the case of timing in exercise for obesity and cardiometabolic management in children. Appl Physiol Nutr Metab 2019; 44:911-914. [PMID: 30875478 DOI: 10.1139/apnm-2018-0462] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Currently, exercise prescription relies heavily on parameters included in the FITT principle: frequency, intensity, time (duration), and type of exercise. In this paper, the benefits of including timing (FITT+T), referring to when exercise is performed in relation to meal-time, is discussed. Current research indicates that timing is outcome-specific. Total energy and lipid intakes, and postprandial hypertriglyceridemia can be reduced when exercise is performed pre-meal, while glycemic control is improved with post-meal exercise. Although findings indicate that timing can aid in obesity management and cardiometabolic-risk reduction, most research involves adult subjects and acute investigations. Some research with children, concerning the effect of timing on appetite, indicates that pre-meal exercise helps regulate energy balance, but also identifies key differences in response compared with adults. Overall, current findings support the benefits of timing, but research is required to establish guidelines that are specific to the pediatric population and their health-related goals, while incorporating other FITT components.
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Affiliation(s)
- Ryan E R Reid
- a Department of Kinesiology, Université de Montréal, Montréal, QC H3C 3J7, Canada
| | - David Thivel
- b Metabolic Adaptation to Exercise Under PhyioPathological condition Laboratory (AME2P), Center for Human Nutrition Research (CRNH Auvergne), Clermont Auvergne University, Clermont-Ferrand, France
| | - Marie-Eve Mathieu
- a Department of Kinesiology, Université de Montréal, Montréal, QC H3C 3J7, Canada.,c Research Center, Sainte-Justine University Hospital Research Center, Montréal, QC H3T 1C5, Canada
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Colomo N, López-Siguero JP, Leiva I, Fuentes N, Rubio-Martín E, Omiste A, Guerrero M, Tapia MJ, Martín-Tejedor B, Ruiz de Adana MS, Olveira G. Relationship between glucose control, glycemic variability, and oxidative stress in children with type 1 diabetes. ACTA ACUST UNITED AC 2019; 66:540-549. [PMID: 30853269 DOI: 10.1016/j.endinu.2018.12.010] [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: 09/06/2018] [Revised: 12/14/2018] [Accepted: 12/20/2018] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Few studies assessing the relationship between oxidative stress and glycemic variability in children with type 1 diabetes mellitus (T1DM) are available, and most of them reported no significant results. OBJECTIVE To assess the relationship between glucose control, glycemic variability, and oxidative stress as measured by urinary excretion of 8-iso-prostanglandin F2-alpha (8-iso-PGF2α) in children with T1DM. MATERIALS AND METHODS A cross-sectional study including 25 children with T1DM. Participants were evaluated during five days in two different situations: 1st phase during a summer camp, and 2nd phase in their everyday life at home. The following data were collected in each study phase:. - Six capillary blood glucose measurements per day. Mean blood glucose (MBG) levels and glucose variability parameters, including standard deviation, coefficient of variation, and mean amplitude of glycemic excursions (MAGE), were calculated. - Capillary HbA1c level. - 24-h urine sample to measure 8-iso-PGF2α. RESULTS There were no statistically significant differences in urinary 8-iso-PGF2α levels (142±37 vs. 172±61pg/mg creatinine) and glucose control and glycemic variability parameters between both phases. In the 2nd phase, statistically significant correlations were found between urinary 8-iso-PGF2α and HbA1c levels (r=0.53), MBG (r=0.72), standard deviation (r=0.49), and MAGE (r=0.42). No significant correlations between glucose control, glycemic variability and urinary 8-iso-PGF2α excretion were found in the 1st phase. CONCLUSIONS A significant correlation was found between glycemic variability and HbA1c level and urinary 8-iso-PGF2α excretion in a group of children with T1DM during their daily lives. Additional studies are needed to confirm this finding and to explore its long-term impact on health.
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Affiliation(s)
- Natalia Colomo
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, C/Sinesio Delgado 4, 28029 Madrid, Spain.
| | - Juan Pedro López-Siguero
- Servicio de Endocrinología Pediátrica, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Avenida Arroyo de los Ángeles sn, 29011 Málaga, Spain
| | - Isabel Leiva
- Servicio de Endocrinología Pediátrica, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Avenida Arroyo de los Ángeles sn, 29011 Málaga, Spain
| | - Noemí Fuentes
- Servicio de Endocrinología Pediátrica, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Avenida Arroyo de los Ángeles sn, 29011 Málaga, Spain
| | - Elehazara Rubio-Martín
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, C/Sinesio Delgado 4, 28029 Madrid, Spain
| | - Antonio Omiste
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain
| | - Mercedes Guerrero
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain
| | - María José Tapia
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, C/Sinesio Delgado 4, 28029 Madrid, Spain
| | - Beatriz Martín-Tejedor
- Servicio de Endocrinología Pediátrica, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Avenida Arroyo de los Ángeles sn, 29011 Málaga, Spain
| | - María Soledad Ruiz de Adana
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, C/Sinesio Delgado 4, 28029 Madrid, Spain
| | - Gabriel Olveira
- Servicio de Endocrinología y Nutrición, Hospital Regional de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Plaza del Hospital Civil sn, 29009 Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, C/Sinesio Delgado 4, 28029 Madrid, Spain
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Babar G, Clements M, Dai H, Raghuveer G. Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus. J Pediatr Endocrinol Metab 2019; 32:109-113. [PMID: 30710485 DOI: 10.1515/jpem-2018-0192] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 10/15/2018] [Indexed: 12/24/2022]
Abstract
Background Type-1 diabetes mellitus (T1DM) causes endothelial dysfunction and early atherosclerosis, which can result in premature coronary artery disease. The aim of this study was to determine the impact of glycemic control, vascular oxidative stress and inflammation on vascular health in adolescents with T1DM. Methods This was a cross-sectional study in adolescents with age- and sex-matched T1DM who were ≥12 years and were at least 2 years post-diagnosis. Recruitment was balanced to include individuals with hemoglobin A1c (HbA1c) ≤8.5% (n=27) or with HbA1c ≥9.5% (n=25). Biomarkers of inflammation were measured in the blood including C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), E-selectin, fibrinogen and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and peripheral arterial tonometry (PAT) were assessed. Results Plasma E-selectin level was significantly different between the two groups with higher levels in the group with HbA1c ≥9.5% (65.0±27.7 ng/mL vs. 48.8±21.5 ng/mL, p=0.02). Though cIMT and PAT were not significantly different between the groups, Pearson correlation showed a significant direct relationship between rising HbA1c and mean right cIMT (p=0.02; r=0.37), PAT (p=0.03, r=0.31) and fibrinogen (p=0.03, r=0.03). Conclusions Elevated E-selectin level is an early marker of oxidative stress in T1DM patients with an elevated HbA1c level. Suboptimal glycemic control as evidenced by a rising HbA1c causes early atherosclerosis.
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Affiliation(s)
- Ghufran Babar
- Children's Mercy Hospitals and Clinics, Kansas City, MO, USA
| | - Mark Clements
- Children's Mercy Hospitals and Clinics, Kansas City, MO, USA
| | - Hongying Dai
- Children's Mercy Hospitals and Clinics, Kansas City, MO, USA
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22
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Widlansky ME, Jensen DM, Wang J, Liu Y, Geurts AM, Kriegel AJ, Liu P, Ying R, Zhang G, Casati M, Chu C, Malik M, Branum A, Tanner MJ, Tyagi S, Usa K, Liang M. miR-29 contributes to normal endothelial function and can restore it in cardiometabolic disorders. EMBO Mol Med 2019; 10:emmm.201708046. [PMID: 29374012 PMCID: PMC5840545 DOI: 10.15252/emmm.201708046] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR‐29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients. Intraluminal delivery of miR‐29a‐3p or miR‐29b‐3p mimics restored normal endothelium‐dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD. Intraluminal delivery of anti‐miR‐29b‐3p in arterioles from non‐DM human subjects or rats or targeted mutation of Mir29b‐1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR‐29b‐3p mimic increased, while anti‐miR‐29b‐3p or Mir29b‐1/a gene mutation decreased, nitric oxide levels in arterioles. The mutation of Mir29b‐1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1. Lypla1 was a direct target of miR‐29 and could abrogate the effect of miR‐29 in promoting nitric oxide production. Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b‐1/a mutant rats or treated with anti‐miR‐29b‐3p. These findings indicate miR‐29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders.
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Affiliation(s)
- Michael E Widlansky
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - David M Jensen
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Jingli Wang
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Yong Liu
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Aron M Geurts
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alison J Kriegel
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Pengyuan Liu
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Rong Ying
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Guangyuan Zhang
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Marc Casati
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Chen Chu
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mobin Malik
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Amberly Branum
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Michael J Tanner
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sudhi Tyagi
- Division of Cardiovascular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kristie Usa
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mingyu Liang
- Department of Physiology, Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
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Karavanaki K, Tsouvalas E, Vakaki M, Soldatou A, Tsentidis C, Kaparos G, Augoulea A, Alexandrou A, Lambrinoudaki Ι. Carotid intima media thickness and associations with serum osteoprotegerin and s-RANKL in children and adolescents with type 1 diabetes mellitus with increased risk for endothelial dysfunction. J Pediatr Endocrinol Metab 2018; 31:1169-1177. [PMID: 30352039 DOI: 10.1515/jpem-2018-0147] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 09/25/2018] [Indexed: 11/15/2022]
Abstract
Background Although carotid intima media thickness (CIMT) is an established marker of endothelial dysfunction, limited data exist on relative laboratory biomarkers in youngsters with type 1 diabetes mellitus (T1DM). Our aim was to study CIMT and the biomarkers of the osteoprotegerin (OPG)/RANKL system in young T1DM patients and controls, and also in subgroups of patients with increased risk for endothelial dysfunction, such as those with overweight/obesity, poor metabolic control or the presence of microalbuminuria. Methods CIMT and OPG/RANKL of 56 T1DM children and adolescents were compared to 28 healthy controls. Results Anthropometric, laboratory, CIMT and OPG/RANKL measurements were similar between patients and controls. Overweight/obese patients had greater CIMT than the normal weight ones (0.50 vs. 0.44 mm, p=0.001). Microalbuminuric patients had greater CIMT (0.49 vs. 0.44 mm, p=0.035) than the normoalbuminuric ones, with no difference in terms of OPG/RANKL. In the microalbuminuric group, OPG (r=-0.90, p=0.036) and RANKL (r=-0.92, p=0.024) were significantly negatively associated with CIMT. Following linear regression analysis, in the total patients group, microalbuminuria was the only factor significantly associated with CIMT (beta±SE: 0.050±0.021, p=0.035), body mass index (BMI)-z-scores were negatively associated with OPG (beta±SE: -0.25±0.12, p=0.05), while in the microalbuminuric group, CIMT was negatively associated with OPG (beta±SE: -0.070±0.019, p=0.036). During the forward stepwise procedure, microalbuminuria and age were the only variables negatively associated with RANKL (b=-0.334, p=0.034, b=-35.95, p=0.013, respectively). Conclusions In T1DM pediatric patients, overweight/obesity and microalbuminuria were associated with greater CIMT and with impaired OPG/RANKL levels, as biochemical indices of calcification of the atherosclerotic plaque.
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Affiliation(s)
- Kyriaki Karavanaki
- Diabetes and Metabolism Clinic, Second Department of Pediatrics, University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - Emmanouil Tsouvalas
- Diabetes and Metabolism Clinic, Second Department of Pediatrics, University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - Marina Vakaki
- Radiology Department, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - Alexandra Soldatou
- Diabetes and Metabolism Clinic, Second Department of Pediatrics, University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - Charalambos Tsentidis
- Diabetes and Metabolism Clinic, Second Department of Pediatrics, University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - George Kaparos
- Hormonal Laboratory, University of Athens, Aretaieio Hospital, Athens, Greece
| | - Areti Augoulea
- Second Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece
| | - Andreas Alexandrou
- Second Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece
| | - Ιrene Lambrinoudaki
- Second Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece
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24
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Alman AC, Talton JW, Wadwa RP, Urbina EM, Dolan LM, Hamman RF, D'Agostino RB, Marcovina SM, Dabelea DM. Inflammation, adiposity, and progression of arterial stiffness in adolescents with type 1 diabetes: The SEARCH CVD Study. J Diabetes Complications 2018; 32:995-999. [PMID: 30209019 PMCID: PMC6174105 DOI: 10.1016/j.jdiacomp.2018.08.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 12/28/2017] [Accepted: 08/06/2018] [Indexed: 11/30/2022]
Abstract
AIMS We examined the association between inflammation and progression of arterial stiffness in a population of youth with type 1 diabetes (T1D). METHODS A total of 287 youth with T1D (median age 13 years) from SEARCH CVD, an ancillary study to the SEARCH for Diabetes in Youth, were included. Markers of inflammation (CRP, IL-6, fibrinogen, leptin, and adiponectin) and measures of pulse wave velocity (PWV) of the arm (PWV-R), trunk (PWV-T), and lower extremity (PWV-LE) were measured at baseline. Measures of PWV were repeated approximately five years later. RESULTS PWV-R (0.50 m/s), PWV-T (0.65 m/s), and PWV-LE (1.0 m/s) significantly increased over the follow-up (p < 0.001 for each). A significant interaction was found between waist circumference and fibrinogen (p = 0.036) on the progression of PWV-T, suggesting that fibrinogen is more strongly associated with PWV progression in lean participants. CONCLUSIONS Improved understanding of adiposity, inflammation, and functional changes in the vascular system in patients with T1D is crucial.
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Affiliation(s)
- Amy C Alman
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, USA.
| | - Jennifer W Talton
- Department of Biostatistical Sciences, Wake Forest School of Medicine, USA
| | - R Paul Wadwa
- Barbara Davis Center, University of Colorado Denver, USA
| | - Elaine M Urbina
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, USA
| | - Lawrence M Dolan
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, USA
| | - Richard F Hamman
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, USA
| | - Ralph B D'Agostino
- Department of Biostatistical Sciences, Wake Forest School of Medicine, USA
| | - Santica M Marcovina
- Department of Metabolism, Endocrinology and Nutrition, University of Washington, USA
| | - Dana M Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, USA
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Heier M, Espeland CN, Brunborg C, Seljeflot I, Margeirsdottir HD, Hanssen KF, Fugelseth D, Dahl-Jørgensen K. Preserved endothelial function in young adults with type 1 diabetes. PLoS One 2018; 13:e0206523. [PMID: 30359432 PMCID: PMC6201945 DOI: 10.1371/journal.pone.0206523] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 10/15/2018] [Indexed: 01/02/2023] Open
Abstract
Background and aim Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and is typically present in older adults with type 1 diabetes (T1D). In young adults, we aimed to assess the impact of T1D on endothelial function as detected by digital peripheral arterial tonometry (PAT) and its relationship with cardiovascular risk factors and long term glycemic control. Materials and methods Reactive hyperemia index (RHI) as a measure of endothelial function was assessed by PAT in 46 T1D patients and 32 healthy controls. All were participants in the "Atherosclerosis and Childhood Diabetes" study, with baseline values registered five years previously. Annual measurements of HbA1c for assessment of glycemic burden were provided by the Norwegian Childhood Diabetes Registry. Results The diabetes patients had a mean age of 20.8 years, a median duration of diabetes of 10.0 years and a mean HbA1c of 8.7%. RHI was not significantly decreased in the diabetes group, mean 2.00 (SD = 0.59) vs. 2.21 (SD = 0.56), p = .116. There was no gender difference or any associations with traditional risk factors. Furthermore, there was no significant association between RHI and either HbA1c or long term glycemic burden. Conclusions RHI as a measure of endothelial function was preserved in young adults with T1D compared with healthy controls.
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Affiliation(s)
- Martin Heier
- Pediatric Department, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Oslo Diabetes Research Centre, Oslo, Norway
- * E-mail:
| | | | - Cathrine Brunborg
- Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway
| | - Ingebjørg Seljeflot
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Center for Clinical Heart Research and Department of Cardiology, Oslo University Hospital, Oslo, Norway
| | - Hanna Dis Margeirsdottir
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Oslo Diabetes Research Centre, Oslo, Norway
- Pediatric Department, Akershus University Hospital, Lørenskog, Norway
| | - Kristian F. Hanssen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Oslo Diabetes Research Centre, Oslo, Norway
- Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Drude Fugelseth
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Neonatal Intensive Care, Oslo University Hospital, Oslo, Norway
| | - Knut Dahl-Jørgensen
- Pediatric Department, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Oslo Diabetes Research Centre, Oslo, Norway
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26
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Malik M, Suboc TM, Tyagi S, Salzman N, Wang J, Ying R, Tanner MJ, Kakarla M, Baker JE, Widlansky ME. Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease. Circ Res 2018; 123:1091-1102. [PMID: 30355158 PMCID: PMC6205737 DOI: 10.1161/circresaha.118.313565] [Citation(s) in RCA: 142] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 07/26/2018] [Indexed: 01/16/2023]
Abstract
RATIONALE A strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest Lactobacillus plantarum 299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature. OBJECTIVE To determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD). METHODS AND RESULTS Twenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation ( P=0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 ( P=0.01), IL-12 ( P=0.02), and leptin ( P=0.0007) but did not significantly change plasma trimethylamine oxide concentrations ( P=0.27). Plasma propionate ( P=0.004) increased, whereas acetate levels decreased ( P=0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD ( P=0.02).16S rRNA analysis showed the Lactobacillus genus was enriched in postprobiotic stool samples without other changes. CONCLUSIONS Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov . Unique identifier: NCT01952834.
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Affiliation(s)
- Mobin Malik
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - Tisha M. Suboc
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - Sudhi Tyagi
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - Nita Salzman
- Departments of Pediatrics and Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Jingli Wang
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - Rong Ying
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - Michael J. Tanner
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - Mamatha Kakarla
- Department of Medicine, Division of Cardiovascular Medicine, Milwaukee, WI, USA
| | - John E. Baker
- Department of Surgery, Division of Congenital Cardiac Surgery and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Michael E. Widlansky
- Department of Medicine, Division of Cardiovascular Medicine and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA
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27
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Donaghue KC, Marcovecchio ML, Wadwa RP, Chew EY, Wong TY, Calliari LE, Zabeen B, Salem MA, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2018; 19 Suppl 27:262-274. [PMID: 30079595 PMCID: PMC8559793 DOI: 10.1111/pedi.12742] [Citation(s) in RCA: 192] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 07/27/2018] [Indexed: 12/25/2022] Open
Affiliation(s)
- Kim C Donaghue
- The Children's Hospital at Westmead, Westmead, NSW, Australia
- Discipline of Child and Adolescent Health, University of Sydney, Camperdown, Australia
| | | | - R P Wadwa
- University of Colorado School of Medicine, Denver, Colorado
| | - Emily Y Chew
- Division of Epidemiology and Clinical Applications, the National Eye Institute, National Institutes of Health, Bethesda, Maryland
| | - Tien Y Wong
- Singapore Eye Research Institute, Singapore National Eye Center, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | | | - Bedowra Zabeen
- Department of Paediatrics and Changing Diabetes in Children Program, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Dhaka, Bangladesh
| | - Mona A Salem
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maria E Craig
- The Children's Hospital at Westmead, Westmead, NSW, Australia
- Discipline of Child and Adolescent Health, University of Sydney, Camperdown, Australia
- School of Women's and Children's Health, University of New South Wales, Sydney, Australia
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28
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Anderson J, Couper JJ, Toome S, Mpundu-Kaambwa C, Giles LC, Gent R, Coppin B, Peña AS. Dietary sodium intake relates to vascular health in children with type 1 diabetes. Pediatr Diabetes 2018; 19:138-142. [PMID: 28488397 DOI: 10.1111/pedi.12537] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Revised: 03/14/2017] [Accepted: 04/11/2017] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Children with type 1 diabetes (T1D) have vascular dysfunction and frequently struggle to adhere to dietary recommendations. Limited data exist for the vascular consequences of poor diet quality in children. We aimed to evaluate the association between dietary components and vascular function in children with T1D. METHODS Cross-sectional study including 90 children (13.6 [3.5] years, 41 boys) with T1D. They had evaluation of dietary micro and macronutrients (Australian Child and Adolescent Eating Survey), vascular endothelial and smooth muscle function (flow-mediated dilatation and glyceryl trinitrate mediated dilatation [GTN], respectively), clinical and biochemical variables. RESULTS Children had a sodium intake of 3.013 (0.76) (mean [SD]) g/day. Vascular smooth muscle dysfunction, as measured by GTN, related to higher daily sodium intake (r = -0.31, P = .003), independent of the inverse relationships between GTN and total energy (r = -0.30, P = .005) and fat intake (r = -0.28, P = .007). Multiregression model showed that an increase in 1 g of daily sodium intake was independently associated with a deterioration of 3 percentage units in GTN (95% CI -4.3, -0.9; P = .003). There was an association between sodium intake and systolic blood pressure after adjustment for age and gender (regression coefficient 2.4; 95% CI 0.5, 4.3; P = .01). CONCLUSIONS High dietary sodium intake in children with T1D is common and relates to vascular dysfunction, independently of other dietary intake, blood pressure, and glycemic control.
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Affiliation(s)
- Jemma Anderson
- Discipline of Paediatrics, The University of Adelaide and Robinson Research Institute, North Adelaide, SA, Australia.,Endocrinology and Diabetes Department, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Jennifer J Couper
- Discipline of Paediatrics, The University of Adelaide and Robinson Research Institute, North Adelaide, SA, Australia.,Endocrinology and Diabetes Department, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Sarah Toome
- Dietetics Department, Women's and Children's Hospital, North Adelaide, SA, Australia
| | | | - Lynne C Giles
- Epidemiology and Biostatistics Unit, The University of Adelaide, Adelaide, SA, Australia
| | - Roger Gent
- Medical Imaging, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Brian Coppin
- Department of Paediatrics, Flinders Medical Centre and Flinders University, North Adelaide, SA, Australia
| | - Alexia S Peña
- Discipline of Paediatrics, The University of Adelaide and Robinson Research Institute, North Adelaide, SA, Australia.,Endocrinology and Diabetes Department, Women's and Children's Hospital, North Adelaide, SA, Australia
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29
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Moniotte S, Owen M, Barrea T, Robert A, Lysy PA. Outcomes of algorithm-based modifications of insulinotherapy during exercise in MDI vs insulin pump-treated children with type 1 diabetes: Results from the TREAD-DIAB study. Pediatr Diabetes 2017; 18:925-933. [PMID: 28251726 DOI: 10.1111/pedi.12509] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 01/10/2017] [Accepted: 01/11/2017] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES To evaluate the evolution of subcutaneous glucose (SG) after a standardized aerobic exercise in children and adolescents treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) regimen before and after adaptation of insulin doses. RESEARCH DESIGN AND METHODS Eleven CSII- and 13 MDI-treated patients performed 2 30-minute sessions of moderate to vigorous (70% of age-based maximal heart rate) exercise on a treadmill under continuous glucose monitoring (CGM). First sessions were scheduled without insulin modification (TT#1) while patients performed second sessions (TT#2) after preemptive algorithm-based insulin dose modifications. RESULTS While insulin adaptations did not modify immediate postexercise drops in blood glucose during TT#2 in either group, CSII-treated patients had their glucose control improved during TT#2 (mean of 141 ± 56 mg/dL vs 144 ± 80 mg/dL in TT#1; P < .05) with up to 86% of SG levels within targets during 16 hours postexercise. Contrarily, SG levels did not normalize during TT#2 in MDI-treated patients who experienced higher rates of hyperglycemia during the afternoon snack. As compared with TT#1, CSII-treated patients had reduced rates of hypoglycemia during 4 hours post-TT#2 (from 19.5% to 2.1%; P < .01) and had shorter duration of nocturnal hypoglycemia (35.5 ± 12.8 vs 204.7 ± 165 minutes; P = .04) whereas in the MDI group no changes in percentages of hypoglycemia were observed during TT#2. CONCLUSION In our pediatric cohort, algorithmic adaptations of insulin doses were associated with better outcomes in terms of postexercise glucose control in patients with CSII therapy but not with MDI treatment.
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Affiliation(s)
- S Moniotte
- Pediatric Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.,Pôle de Pédiatrie (PEDI), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Leuven, Belgium
| | - M Owen
- Pediatric Endocrinology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - T Barrea
- Pediatric Endocrinology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - A Robert
- Pôle Epidémiologie et Biostatistique, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - P A Lysy
- Pôle de Pédiatrie (PEDI), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Leuven, Belgium.,Pediatric Endocrinology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
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30
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Gourgari E, Dabelea D, Rother K. Modifiable Risk Factors for Cardiovascular Disease in Children with Type 1 Diabetes: Can Early Intervention Prevent Future Cardiovascular Events? Curr Diab Rep 2017; 17:134. [PMID: 29101482 PMCID: PMC5670186 DOI: 10.1007/s11892-017-0968-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE OF REVIEW Patients with type 1 diabetes have increased risk for cardiovascular disease. The purpose of this review is to examine the following: i) current evidence for subclinical cardiovascular disease (CVD) in children with type 1 diabetes (T1DM) ii) known modifiable risk factors for CVD and their relationship to subclinical CVD in this population iii) studies that have addressed these risk factors in order to improve CVD outcomes in children with T1DM RECENT FINDINGS: Subclinical CVD presents in children as increased carotid intima-media thickness, increased arterial stiffness, and endothelial and myocardial dysfunction. Modifiable risk factors for CVD include hyperglycemia, hyperlipidemia, obesity, hypertension, depression, and autonomic dysfunction. Very few randomized controlled studies have been done in children with T1DM to examine how modification of these risk factors can affect their CVD. Children with T1DM have subclinical CVD and multiple modifiable risk factors for CVD. More research is needed to define how modification of these factors affects the progression of CVD.
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Affiliation(s)
- Evgenia Gourgari
- Department of Pediatrics, Georgetown University, Washington DC, USA
- Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics (PDEGEN) and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD USA
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO USA
| | - Kristina Rother
- Section on Pediatric Diabetes and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD USA
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31
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Marcovecchio ML, de Giorgis T, Di Giovanni I, Chiavaroli V, Chiarelli F, Mohn A. Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes. Pediatr Diabetes 2017; 18:283-289. [PMID: 27246625 DOI: 10.1111/pedi.12391] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 02/11/2016] [Accepted: 03/23/2016] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. METHODS A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). RESULTS Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI. CONCLUSIONS Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction.
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Affiliation(s)
- M L Marcovecchio
- Department of Paediatrics, "G. d'Annunzio" University, Chieti, Italy.,Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy
| | - T de Giorgis
- Department of Paediatrics, "G. d'Annunzio" University, Chieti, Italy.,Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy
| | - I Di Giovanni
- Department of Paediatrics, "G. d'Annunzio" University, Chieti, Italy.,Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy
| | - V Chiavaroli
- Department of Paediatrics, "G. d'Annunzio" University, Chieti, Italy.,Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy
| | - F Chiarelli
- Department of Paediatrics, "G. d'Annunzio" University, Chieti, Italy.,Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy
| | - A Mohn
- Department of Paediatrics, "G. d'Annunzio" University, Chieti, Italy.,Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Chieti, Italy
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Hoffman RP, Dye AS, Huang H, Bauer JA. Glycemic variability predicts inflammation in adolescents with type 1 diabetes. J Pediatr Endocrinol Metab 2016; 29:1129-1133. [PMID: 27658133 PMCID: PMC5546213 DOI: 10.1515/jpem-2016-0139] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 08/01/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities. METHODS This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A1c (HbA1c), and HbA1c×duration area under the curve (A1cDur). RESULTS Seventeen adolescents (8 F/9M; age, 13.1±1.6 years (mean±SD); duration, 4.8±3.8 years, BMI, 20.3±3.1 kg/m2; A1c, 8.3±1.2%) were studied. Log CRP but was not related to age, duration, body mass index (BMI), HbA1c, or A1cDUR. TAOC increased as logA1cDUR increased (n=13, r=0.61, p=0.028). CRP and sICAM were not related to CGM average glucose but log CRP increased as 3 day glucose standard deviation increased (r=0.66, p=0.006). TAOC increased as glucose standard deviation increased (r=0.63, p=0.028). CONCLUSIONS Increased glucose variability is associated with increased inflammation in adolescents withT1D. Increased TAOC with increasing variability may be an effort to compensate for the ongoing oxidative stress.
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Affiliation(s)
| | - Amanda S. Dye
- Department of Pediatrics, West Virginia University, Charleston, WV, USA
| | - Hong Huang
- Department of Pediatrics, University of Kentucky, UK Medical Center MN, Lexington, KY, USA
| | - John A. Bauer
- Department of Pediatrics, University of Kentucky, UK Medical Center MN, Lexington, KY, USA
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33
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Vascular Aging: Lessons From Pediatric Hypertension. Can J Cardiol 2016; 32:642-9. [PMID: 27040097 DOI: 10.1016/j.cjca.2016.02.064] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 02/05/2016] [Accepted: 02/23/2016] [Indexed: 12/31/2022] Open
Abstract
Hypertension (HTN) in children is associated with early vascular aging (EVA) and underlying immunologic-metabolic abnormalities and accelerated biological maturation. Morphologic and functional vascular changes underlying EVA and HTN in children resemble those seen in the elderly including but not limited to an increase in intima-media thickness (IMT) and arterial stiffness and endothelial dysfunction. Although progeria syndrome leading to EVA and the development of clinically manifested cardiovascular (CV) disease in the second decade of life is a rare hereditary disorder, primary HTN, which is also associated with EVA, is much more common (reported in up to 10% in adolescents). EVA associated with HTN in children leads to the premature development of target organ injury in childhood and CV events in early adulthood. Limited evidence from prospective observational studies in children and adolescents indicates that early lifestyle measures (low salt/low sugar intake and exercise) or pharmacologic treatment of HTN, or both, partially reverses morphologic and functional changes underlying EVA such as an increase in carotid IMT and pulse wave velocity, a decrease in flow-mediated dilation of the brachial artery, and an increase in oxidative stress and visceral fat. Future mechanistic and therapeutic clinical trials are desirable to assess the mechanisms and treatment strategies of EVA in the context of HTN in children and their effect on CV events in early adulthood.
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34
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Giacchi V, Timpanaro T, Lo Presti D, Passanisi S, Mattia C, Betta P, Grasso C, Caruso M, Sciacca P. Prehypertension in adolescents with cardiovascular risk: a comparison between type 1 diabetic patients and overweight subjects. BMC Res Notes 2016; 9:122. [PMID: 26911143 PMCID: PMC4766686 DOI: 10.1186/s13104-016-1839-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 01/06/2016] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Adolescents with type 1 diabetes and obesity present higher cardiovascular risk and ambulatory blood pressure measurements (ABPM) has been shown to predict vascular events, especially by identifying the nondipper status. The aim of our observational cross-sectional study conducted in adolescents with type 1 diabetes, overweight subjects and healthy controls was to assess mean blood pressure parameters to identify subclinical cardiovascular risk. METHODS The study included adolescents patients with type 1 diabetes followed in our Pediatric Department in University of Catania between January 2011 and 2013. A total of 60 patients were enrolled, and 48 (32 male and 16 female) completed the study. For each subject we performed systolic and diastolic Ambulatory Blood Pressure Measurements (ABPM) during wakefulness and sleep recording blood pressure every 30 min for 24 h with the Tonoport V/2 GE CardioSoft V6.51 device. We compared the data of patients with those of overweight subjects and healthy controls. RESULTS ABPM revealed no significant difference between type 1 diabetic patients and overweight subjects in 24 h Systolic, 24 h Diastolic, Day-time Systolic, Night-time systolic and Day-time Diastolic blood pressure values but significantly different values in Night-time Diastolic blood pressure values (p < 0.001). We found significant differences between type 1 diabetic patients and healthy controls in all 24 h Systolic (p < 0.001), 24 h Diastolic (p < 0.01), Day-time Systolic (p < 0.01), Night-time Systolic (p < 0.001), Day-time Diastolic (p < 0.05) and Night-time Diastolic (p < 0.001) blood pressure values. We detected hypertension in 12/48 (25%) type 1 diabetic patients and in 10/48 overweight subjects (p = 0.62; OR 1.2; CI 0.48-3.29), whereas no-one of healthy controls presented hypertension (p < 0.001). We observed nondipper pattern in 40/48 (83.3%) type 1 diabetic patients, in 33/48 (68.8%) overweight subjects (p = 0.094; OR 2.27; CI 0.85-6.01), and in 16/48 (33.3%) of healthy controls (p < 0.001; OR 10; CI 3.79-26.3). CONCLUSIONS ABPM studies might help to define a subset of patients at increased risk for the development of hypertension. In evaluating blood pressure in type 1 diabetes and overweight subjects, ABPM should be used since a reduced dipping can indicate incipient hypertension.
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Affiliation(s)
- Valentina Giacchi
- Department of Pediatrics, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Tiziana Timpanaro
- Department of Pediatrics, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Donatella Lo Presti
- Pediatric Endocrinology, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Stefano Passanisi
- Department of Pediatrics, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Carmine Mattia
- Department of Pediatrics, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Pasqua Betta
- Department of Pediatrics, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Chiara Grasso
- Department of Pediatrics, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Manuela Caruso
- Pediatric Endocrinology, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
| | - Pietro Sciacca
- Pediatric Cardiology, AOU Policlinico-Vittorio Emanuele, via Santa Sofia 78, 95123, Catania, Italy.
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Bradley TJ, Slorach C, Mahmud FH, Dunger DB, Deanfield J, Deda L, Elia Y, Har RLH, Hui W, Moineddin R, Reich HN, Scholey JW, Mertens L, Sochett E, Cherney DZI. Early changes in cardiovascular structure and function in adolescents with type 1 diabetes. Cardiovasc Diabetol 2016; 15:31. [PMID: 26879273 PMCID: PMC4754808 DOI: 10.1186/s12933-016-0351-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 02/05/2016] [Indexed: 01/24/2023] Open
Abstract
Background Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters. Methods and results 199 T1D [14.4 ± 1.6 years, diabetes duration 6.2 (2.0–12.8) years] and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 ± 10 vs. 110 ± 9 mmHg; p = 0.0005) and diastolic (62 ± 7 vs. 58 ± 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e’ (17.6 ± 2.6 vs. 18.6 ± 2.6 cm/s; p < 0.001) and a’ (5.4 ± 1.1 vs. 5.9 ± 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e’ (7.3 ± 1.2 vs. 6.7 ± 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (−20.4 ± 2.3 vs. −19.5 ± 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (−19.0 ± 1.9 vs. −19.8 ± 1.5 % p < 0.001) in T1D. Conclusions Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions.
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Affiliation(s)
- Timothy J Bradley
- Department of Paediatrics, Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Cameron Slorach
- Department of Paediatrics, Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Farid H Mahmud
- Department of Paediatrics, Division of Endocrinology, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) Sick Kids Multicenter Clinical Trial Center, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - David B Dunger
- Department of Pediatrics, University of Cambridge, Cambridge, UK.
| | - John Deanfield
- University College Hospital, London, UK. .,Heart Hospital and Great Ormond Street Hospital, London, UK.
| | - Livia Deda
- Department of Paediatrics, Division of Endocrinology, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) Sick Kids Multicenter Clinical Trial Center, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Yesmino Elia
- Department of Paediatrics, Division of Endocrinology, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) Sick Kids Multicenter Clinical Trial Center, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Ronnie L H Har
- Department of Paediatrics, Division of Endocrinology, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) Sick Kids Multicenter Clinical Trial Center, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Wei Hui
- Department of Paediatrics, Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Rahim Moineddin
- Department of Family and Community Medicine, University of Toronto, Toronto, Canada.
| | - Heather N Reich
- Department of Medicine, Division of Nephrology, University Health Network, Toronto General Hospital, University of Toronto, 585 University Avenue, 8 N-845, Toronto, ON, M5G 2N2, Canada.
| | - James W Scholey
- Department of Medicine, Division of Nephrology, University Health Network, Toronto General Hospital, University of Toronto, 585 University Avenue, 8 N-845, Toronto, ON, M5G 2N2, Canada.
| | - Luc Mertens
- Department of Paediatrics, Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Etienne Sochett
- Department of Paediatrics, Division of Endocrinology, JDRF-Canadian Clinical Trial Network (JDRF-CCTN) Sick Kids Multicenter Clinical Trial Center, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - David Z I Cherney
- Department of Medicine, Division of Nephrology, University Health Network, Toronto General Hospital, University of Toronto, 585 University Avenue, 8 N-845, Toronto, ON, M5G 2N2, Canada.
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Association between metabolic control and lipid parameters in Indian children with type 1 diabetes. Indian Pediatr 2016; 53:39-41. [DOI: 10.1007/s13312-016-0787-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Ostrem JD, Evanoff N, Kelly AS, Dengel DR. Presence of a high-flow-mediated constriction phenomenon prior to flow-mediated dilation in normal weight, overweight, and obese children and adolescents. JOURNAL OF CLINICAL ULTRASOUND : JCU 2015; 43:495-501. [PMID: 25801746 PMCID: PMC4565738 DOI: 10.1002/jcu.22267] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Accepted: 01/13/2015] [Indexed: 05/24/2023]
Abstract
PURPOSE When assessing vasomotor endothelial function by reactive hyperemia, the brachial artery, in some individuals, constricts immediately before beginning to dilate following cuff release. We call this response high-flow-mediated constriction (H-FMC). The aim of this study was to describe the rate of the H-FMC during reactive hyperemia in children and adolescents throughout a range of body mass index (BMI) values, and to investigate differences in flow-mediated dilation (FMD), cardiovascular, and anthropometric measures between subjects with and without H-FMC. METHODS FMD was assessed in 136 children and adolescents (61 male, 75 female; 13 ± 3 years) by sonographic imaging of the brachial artery. H-FMC was characterized as the lowest point from the baseline brachial artery diameter immediately following reactive cuff release. Independent t tests were used to compare subjects with and without H-FMC. RESULTS H-FMC was observed in 91 of the 136 participants (66.9%). No significant difference was found between H-FMC and non-H-FMC subjects for age (p = 0.602), gender (p = 0.767), height (p = 0.227), or weight (p = 0.171). BMI percentile was nonsignificantly higher (91.8 ± 4.9th versus 84.6 ± 22.8th percentile, p = 0.057) and FMD was significantly lower (5.43 ± 3.41% versus 8.05 ± 3.97%, p < 0.001) in H-FMC than in non-H-FMC subjects. Adding H-FMC to FMD produced no significant difference between H-FMC and non-H-FMC individuals (8.03 ± 3.27% versus 8.05 ± 3.97%, p = 0.977). CONCLUSIONS Approximately 67% of participants demonstrated an H-FMC during reactive hyperemia. BMI percentile was nonsignificantly higher and FMD was significantly lower in children and adolescents who displayed this phenomenon.
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Affiliation(s)
- Joseph D Ostrem
- Laboratory of Integrative Human Physiology, School of Kinesiology, University of Minnesota, Minneapolis, MN 55455
| | - Nicholas Evanoff
- Laboratory of Integrative Human Physiology, School of Kinesiology, University of Minnesota, Minneapolis, MN 55455
| | - Aaron S Kelly
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455
| | - Donald R Dengel
- Laboratory of Integrative Human Physiology, School of Kinesiology, University of Minnesota, Minneapolis, MN 55455
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455
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Takeuchi D, Furutani M, Harada Y, Furutani Y, Inai K, Nakanishi T, Matsuoka R. High prevalence of cardiovascular risk factors in children and adolescents with Williams-Beuren syndrome. BMC Pediatr 2015; 15:126. [PMID: 26384008 PMCID: PMC4574554 DOI: 10.1186/s12887-015-0445-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Accepted: 09/09/2015] [Indexed: 12/19/2022] Open
Abstract
Background A high incidence of cardiovascular (CV) risk factors has been reported in adults with Williams-Beuren syndrome (WS). However, the prevalence of these factors in children and adolescents with WS is unknown. Therefore, the purpose of this study was to evaluate the prevalence of CV risk factors in these patients. Methods Thirty-two WS patients aged <18 years were enrolled in the study. Oxidized low-density lipoprotein levels (n = 32), oral glucose tolerance test results (n = 20), plasma renin and aldosterone levels (n = 31), 24-h ambulatory blood pressure (ABP; n = 24), carotid artery intima-media thickness (IMT; n = 15), and brachial artery flow-mediated dilatation (FMD; n = 15) were measured and analyzed. Results The lipid profile revealed hypercholesterolemia in 22 % and elevated oxidized low-density lipoprotein levels in 94 % of the patients. Glucose metabolism abnormalities were found in 70 % of the patients. Insulin resistance was observed in 40 % of the patients. High plasma renin and aldosterone levels were detected in 45 and 39 % of the patients, respectively. A mean systolic blood pressure above the 90th percentile was noted in 29 % of patients. High IMT (>0.65 mm) and low FMD (<9 %) were detected in 80 and 73 % of patients, respectively. Conclusion In patients with WS, CV risk factors are frequently present from childhood. In children with WS, screening tests for the early detection of CV risk factors and long-term follow-up are required to determine whether long-term exposure to these factors increases the risk for CV events in adulthood.
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Affiliation(s)
- Daiji Takeuchi
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Michiko Furutani
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. .,The International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Yuriko Harada
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. .,The International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Yoshiyuki Furutani
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. .,The International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Kei Inai
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Toshio Nakanishi
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. .,The International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Rumiko Matsuoka
- Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. .,The International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. .,International Center for Molecular, Cellular, and Immunological Research (IMCIR), Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
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Feng Y, Shan MQ, Bo L, Zhang XY, Hu J. Association of homocysteine with type 1 diabetes mellitus: a meta-analysis. Int J Clin Exp Med 2015; 8:12529-12538. [PMID: 26550163 PMCID: PMC4612848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 08/11/2015] [Indexed: 06/05/2023]
Abstract
PURPOSE To figure out the association between plasma Hcy status and type 1 diabetes mellitus (T1DM). METHODS We searched the PubMed Web of Science, and The Cochrane Library to identify eligible studies. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of selected studies. All analyses were performed using the STATA, version 12 software. RESULTS 15 studies were included in this investigation. Our meta-analysis indicated that plasma Hcy concentrations in T1DM patients without any complications were normal compared with healthy people [13 studies, SMD: -0.08, 95% confidence interval (CI): -0.44 to 0.28, P=0.67]. However, a significant elevation of plasma Hcy concentrations was observed in T1DM patients with only diabetic retinopathy (DR) (5 studies, SMD: 0.34, 95% CI: 0.13 to 0.55, P=0.002), only diabetic nephropathy (DN) (4 studies, SMD: 0.76, 95% CI: 0.18 to 1.33, P=0.01) and both the two complications (3 studies, SMD: 1.05, 95% CI: 0.03 to 2.07, P=0.043) compared with T1DM patients without any complications. CONCLUSIONS Homocysteine levels elevate in T1DM patients with DR and DN, but don't elevate in T1DM without any complications.
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Affiliation(s)
- Yu Feng
- Department of Endocrinology, The Second Affiliated Hospital of Soochow UniversitySuzhou 215004, China
| | - Mei-Qin Shan
- Department of Endocrinology, The Second Affiliated Hospital of Soochow UniversitySuzhou 215004, China
| | - Lin Bo
- Department of Rheumatology, The Second Affiliated Hospital of Soochow UniversitySuzhou 215004, China
| | - Xiao-Yan Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow UniversitySuzhou 215004, China
| | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow UniversitySuzhou 215004, China
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40
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Abstract
In this article, the author reviews the long-term outcomes and their precursors of type 1 diabetes starting in youth. The author also contrasts the changing incidence of these long-term complications as we have moved from the pre-Diabetes Control and Complications Trial (DCCT) to the post-DCCT standard of care and reviews the emerging data related to complications in youths with type 2 diabetes. Finally, the author reviews the recent understanding related to the effects of diabetes on the brain and cognition.
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Affiliation(s)
- Neil H White
- Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Box 8116, St Louis, MO 63110, USA.
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41
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Joy NG, Tate DB, Younk LM, Davis SN. Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans. Diabetes 2015; 64:2571-80. [PMID: 25695946 PMCID: PMC4477350 DOI: 10.2337/db14-1729] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 02/09/2015] [Indexed: 12/21/2022]
Abstract
The aim of this study was to determine the effects of single and repeated episodes of clamped hypoglycemia on fibrinolytic balance, proinflammatory biomarkers, proatherothrombotic mechanisms, and endothelial function. Twenty healthy individuals (12 male and 8 female) were studied during separate 2-day randomized protocols. Day 1 consisted of either two 2-h hyperinsulinemic (812 ± 50 pmol/L)-euglycemic (5 ± 0.1 mmol/L) or hyperinsulinemic (812 ± 50 pmol/L)-hypoglycemic (2.9 ± 0.1 mmol/L) clamps. Day 2 consisted of a single 2-h hyperinsulinemic-hypoglycemic clamp. Two-dimensional Doppler ultrasound was used to determine brachial arterial endothelial function. Plasminogen activator inhibitor 1, vascular cell adhesion molecule-1, intracellular adhesion molecule-1, E-selectin, P-selectin, TAT (thrombin/antithrombin complex), tumor necrosis factor-α, and interleukin-6 responses were increased (P < 0.05) during single or repeated hypoglycemia compared with euglycemia. Endogenous and exogenous nitric oxide (NO)-mediated vasodilation were both impaired by repeated hypoglycemia. Neuroendocrine and autonomic nervous system (ANS) responses were also blunted by repeated hypoglycemia (P < 0.05). In summary, acute moderate hypoglycemia impairs fibrinolytic balance; increases proinflammatory responses, platelet activation, and coagulation biomarkers; and reduces NO-mediated endothelial function in healthy individuals. Repeated episodes of hypoglycemia further impair vascular function by additionally reducing exogenously NO-mediated endothelial function and increasing coagulation biomarkers. We conclude that despite reduced neuroendocrine and ANS responses, antecedent hypoglycemia results in greater endothelial dysfunction and an increased proatherothrombotic state compared with a single acute episode of hypoglycemia.
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Affiliation(s)
- Nino G Joy
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Donna B Tate
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Lisa M Younk
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
| | - Stephen N Davis
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
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Sun YP, Cai YY, Li HM, Deng SM, Leng RX, Pan HF. Increased carotid intima-media thickness (CIMT) levels in patients with type 1 diabetes mellitus (T1DM): A meta-analysis. J Diabetes Complications 2015; 29:724-30. [PMID: 25890843 DOI: 10.1016/j.jdiacomp.2015.03.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 03/18/2015] [Accepted: 03/23/2015] [Indexed: 01/28/2023]
Abstract
AIM To derive a more precise estimation of carotid intima-media thickness (CIMT) levels in patients with type 1 diabetes mellitus (T1DM) by meta-analysis. METHODS PubMed and Embase databases were searched to identify all available studies comparing CIMT levels between T1DM group and control group. Meta-analysis was performed to compare the difference of overall mean CIMT levels between the two groups. Publication bias was evaluated by funnel plot, Begg' test and Egger' test. Meta-regression analysis was conducted to investigate the influential factors on CIMT difference. The meta-analysis was conducted by STATA 12.0 software. RESULTS A total of 1840 articles were obtained after searching databases; 47 studies were finally included in the meta-analysis. Significant heterogeneity was observed among these studies (Q = 768.75, P < 0.001, I(2) = 94.0%). Compared with the control group, the T1DM group had significantly higher CIMT levels (standardized mean difference: 1.01, 95% CI: 0.75-1.28; P < 0.001). A likely source of heterogeneity was Newcastle-Ottawa Scale (NOS) scores and sample size ratio of patents and controls. The funnel plot did not show a skewed or asymmetrical shape, and the result of Begg' test and Egger' test was P = 0.178 and P = 0.145 respectively. Accordingly, it could be assumed that publication bias was not present. CONCLUSION T1DM patients have significantly increased CIMT levels compared to control subjects.
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Affiliation(s)
- Yi-Peng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Faculty of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Yuan-Yuan Cai
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China; Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Hong-Miao Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
| | - Sen-Miao Deng
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
| | - Rui-Xue Leng
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China
| | - Hai-Feng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, China.
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Joshi MS, Williams D, Horlock D, Samarasinghe T, Andrews KL, Jefferis AM, Berger PJ, Chin-Dusting JP, Kaye DM. Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol. Diab Vasc Dis Res 2015; 12:208-16. [PMID: 25767181 DOI: 10.1177/1479164114565629] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Microvascular complications are now recognized to play a major role in diabetic complications, and understanding the mechanisms is critical. Endothelial dysfunction occurs early in the course of the development of complications; the precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur in a diabetic rat heart and may act as a source of the oxidative stress. However, the role of endothelial cell-specific mitochondrial dysfunction in diabetic vascular complications is poorly studied. Here, we studied the role of diabetes-induced abnormal endothelial mitochondrial function and the resultant endothelial dysfunction. Understanding the role of endothelial mitochondrial dysfunction in diabetic vasculature is critical in order to develop new therapies. We demonstrate that hyperglycaemia leads to mitochondrial dysfunction in microvascular endothelial cells, and that mitochondrial inhibition induces endothelial dysfunction. Additionally, we show that resveratrol acts as a protective agent; resveratrol-mediated mitochondrial protection may be used to prevent long-term diabetic cardiovascular complications.
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Affiliation(s)
- Mandar S Joshi
- Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia The Ritchie Centre, Monash University, Melbourne, VIC, Australia Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, USA
| | - David Williams
- Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Duncan Horlock
- Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
| | | | - Karen L Andrews
- Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Ann-Maree Jefferis
- Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Philip J Berger
- The Ritchie Centre, Monash University, Melbourne, VIC, Australia
| | - Jaye P Chin-Dusting
- Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - David M Kaye
- Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia Heart Failure Unit, Alfred Hospital, Melbourne, VIC, Australia
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Cardiovascular magnetic resonance imaging-based computational fluid dynamics/fluid-structure interaction pilot study to detect early vascular changes in pediatric patients with type 1 diabetes. Pediatr Cardiol 2015; 36:851-61. [PMID: 25577225 DOI: 10.1007/s00246-014-1071-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 11/27/2014] [Indexed: 12/19/2022]
Abstract
We hypothesized that pediatric patients with type 1 diabetes have cardiac magnetic resonance (CMR) detectable differences in thoracic aortic wall properties and hemodynamics leading to significant local differences in indices of wall shear stress, when compared with age-matched control subjects without diabetes. Pediatric patients with type 1 diabetes were recruited from Children's Hospital of Wisconsin and compared with controls. All underwent morning CMR scanning, 4-limb blood pressure, brachial artery reactivity testing, and venipuncture. Patient-specific computational fluid dynamics modeling with fluid-structure interaction, based on CMR data, determined regional time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI). Twenty type 1 diabetic subjects, median age 15.8 years (11.6-18.4) and 8 controls 15.4 years (10.3-18.2) were similar except for higher glucose, hemoglobin A1c, and triglycerides for type 1 diabetic subjects. Lower flow-mediated dilation was seen for those with type 1 diabetes (6.5) versus controls (7.8), p = 0.036. For type 1 diabetic subjects, the aorta had more regions with high TAWSS when compared to controls. OSI maps appeared similar. Flow-mediated dilation positively correlated with age at diabetes diagnosis (r = 0.468, p = 0.038) and hemoglobin A1c (r = 0.472, p = 0.036), but did not correlate with aortic distensibility, TAWSS, or OSI. TAWSS did not correlate with any clinical parameter for either group. CMR shows regional differences in aortic wall properties for young diabetic patients. Some local differences in wall shear stress indices were also observed, but a longitudinal study is now warranted.
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45
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Scaramuzza AE, Redaelli F, Giani E, Macedoni M, Giudici V, Gazzarri A, Bosetti A, De Angelis L, Zuccotti GV. Adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction. Acta Paediatr 2015; 104:192-7. [PMID: 25424745 DOI: 10.1111/apa.12877] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/14/2014] [Accepted: 11/20/2014] [Indexed: 12/21/2022]
Abstract
AIM Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH-PAT). METHODS This prospective, observational, 1-year study focused on 73 adolescents with type 1 diabetes, using multiple daily injections or continuous subcutaneous insulin infusion. The subjects were assessed using RH-PAT, body mass index, blood pressure, fasting lipid profile, glycated haemoglobin, insulin requirements and hours of physical exercise per week. RESULTS Endothelial dysfunction was observed in 56 patients (76.7%), with lower mean RH-PAT scores (1.26 ± 0.22 versus 2.24 ± 0.48, p < 0.0001) and higher glycated haemoglobin values at baseline (8.27 ± 1.24% versus 7.37 ± 0.54%, p = 0.006) and as a mean of the whole period since diagnosis (8.25 ± 1.22% versus 7.72 ± 0.82%, p = 0.034). A higher percentage of patients with endothelial dysfunction showed abnormal cardiac autonomic tests (p = 0.02) and were more sedentary, exercising <4 hours a week, than patients with normal endothelial function. After follow-up in 64/73 patients, we observed endothelial dysfunction in 81.8% of patients, despite a modest improvement in glycated haemoglobin. CONCLUSION Adolescents with type 1 diabetes displayed evidence of endothelial dysfunction. Good metabolic control (glycated haemoglobin ≤7.5%, 58 mmol/mol) and regular physical activity of at least 4 h a week might be protective.
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Affiliation(s)
- A E Scaramuzza
- Department of Pediatrics; Azienda Ospedaliera; University of Milano; “Ospedale Luigi Sacco”; Milano Italy
| | - F Redaelli
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
| | - E Giani
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
| | - M Macedoni
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
| | - V Giudici
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
| | - A Gazzarri
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
| | - A Bosetti
- Department of Pediatrics; Azienda Ospedaliera; University of Milano; “Ospedale Luigi Sacco”; Milano Italy
| | - L De Angelis
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
| | - G V Zuccotti
- Department of Pediatrics; University of Milano; Ospedale dei Bambini V. Buzzi; Milano Italy
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46
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Giurgea GA, Nagl K, Gschwandtner M, Höbaus C, Hörtenhuber T, Koppensteiner R, Margeta C, Fritsch M, Rami-Merhar B, Schernthaner GH, Schlager O, Schober E, Steiner S, Willfort-Ehringer A. Gender, metabolic control and carotid intima-media-thickness in children and adolescents with type 1 diabetes mellitus. Wien Klin Wochenschr 2014; 127:116-23. [DOI: 10.1007/s00508-014-0640-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 10/07/2014] [Indexed: 12/20/2022]
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Quirk H, Blake H, Tennyson R, Randell TL, Glazebrook C. Physical activity interventions in children and young people with Type 1 diabetes mellitus: a systematic review with meta-analysis. Diabet Med 2014; 31:1163-73. [PMID: 24965376 PMCID: PMC4232875 DOI: 10.1111/dme.12531] [Citation(s) in RCA: 149] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 03/19/2014] [Accepted: 06/20/2014] [Indexed: 12/27/2022]
Abstract
AIMS To synthesize evidence from randomized and non-randomized studies of physical activity interventions in children and young people with Type 1 diabetes so as to explore clinically relevant health outcomes and inform the promotion of physical activity. METHOD We conducted a search of CINAHL Plus, the Cochrane Library, EMBASE, MEDLINE, PsycINFO, SCOPUS, SportDiscus and Web of Science between October and December 2012. Eligible articles included subjects aged ≤18 years with Type 1 diabetes and a physical activity intervention that was more than a one-off activity session. Physiological, psychological, behavioural or social outcomes were those of interest. RESULTS A total of 26 articles (10 randomized and 16 non-randomized studies), published in the period 1964-2012, were reviewed. Although there was heterogeneity in study design, methods and reporting, 23 articles reported at least one significant beneficial health outcome at follow-up. Meta-analyses of these studies showed potential benefits of physical activity on HbA1c (11 studies, 345 participants, standardized mean difference -0.52, 95% CI -0.97 to -0.07; P = 0.02), BMI (four studies, 195 participants, standardized mean difference -0.41, 95% CI -0.70 to -0.12; P = 0.006) and triglycerides (five studies, 206 participants, standardized mean difference -0.70, 95% CI -1.25 to -0.14; P = 0.01).The largest effect size was for total cholesterol (five studies, 206 participants, standardized mean difference -0.91, 95% CI -1.66 to -0.17; P = 0.02). CONCLUSIONS Physical activity is important for diabetes management and has the potential to delay cardiovascular disease, but there is a lack of studies that are underpinned by psychological behaviour change theory, promoting sustained physical activity and exploring psychological outcomes. There remains a lack of knowledge of how to promote physical activity in people with Type 1 diabetes.
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Affiliation(s)
- H Quirk
- School of Health Sciences, University of Nottingham
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48
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Donaghue KC, Wadwa RP, Dimeglio LA, Wong TY, Chiarelli F, Marcovecchio ML, Salem M, Raza J, Hofman PL, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2014. Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2014; 15 Suppl 20:257-69. [PMID: 25182318 DOI: 10.1111/pedi.12180] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Accepted: 06/13/2014] [Indexed: 01/21/2023] Open
Affiliation(s)
- Kim C Donaghue
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia
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Basu A, Jenkins AJ, Stoner JA, Thorpe SR, Klein RL, Lopes-Virella MF, Garvey WT, Lyons TJ. Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: a prospective study. Atherosclerosis 2014; 236:188-195. [PMID: 25063949 PMCID: PMC4134979 DOI: 10.1016/j.atherosclerosis.2014.07.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 06/15/2014] [Accepted: 07/02/2014] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Plasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. RESEARCH DESIGN AND METHODS tHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC "Year 6" (1998-2000) and "Year 12" (2004-2006), using B-mode ultra-sonography. RESULTS After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. CONCLUSIONS In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997-1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.
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Affiliation(s)
- Arpita Basu
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, Oklahoma
| | - Alicia J Jenkins
- University of Sydney, NHMRC Clinical Trials Centre, Camperdown, Sydney, NSW, Australia
- Centre for Experimental Medicine, Queen's University of Belfast, N. Ireland, UK
| | - Julie A Stoner
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Suzanne R Thorpe
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina
| | - Richard L Klein
- Division of Endocrinology, Medical University of South Carolina, Charleston, South Carolina
- The Ralph H Johnson Veterans Affairs Medical Center, Charleston, South Carolina
| | - Maria F Lopes-Virella
- Division of Endocrinology, Medical University of South Carolina, Charleston, South Carolina
- The Ralph H Johnson Veterans Affairs Medical Center, Charleston, South Carolina
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
| | - Timothy J Lyons
- Centre for Experimental Medicine, Queen's University of Belfast, N. Ireland, UK
- Section of Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
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Maahs DM, Daniels SR, de Ferranti SD, Dichek HL, Flynn J, Goldstein BI, Kelly AS, Nadeau KJ, Martyn-Nemeth P, Osganian SK, Quinn L, Shah AS, Urbina E. Cardiovascular disease risk factors in youth with diabetes mellitus: a scientific statement from the American Heart Association. Circulation 2014; 130:1532-58. [PMID: 25170098 DOI: 10.1161/cir.0000000000000094] [Citation(s) in RCA: 128] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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