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Starr L, Dutta S, Danne T, Karpen SR, Hutton C, Kowalski A. The Urgent Need for Breakthrough Therapies and a World Without Type 1 Diabetes. Diabetes Ther 2025; 16:1063-1076. [PMID: 40214899 PMCID: PMC12085400 DOI: 10.1007/s13300-025-01735-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Accepted: 03/24/2025] [Indexed: 05/18/2025] Open
Abstract
Despite significant progress, type 1 diabetes (T1D) still results in premature death, significant complications, and a substantial daily burden for those affected. T1D remains a lifelong condition that demands constant vigilance and resilience and has a significant social and economic impact. Individuals with T1D must walk a tightrope to minimize disease-related complications that result from insufficient insulin while also avoiding adverse effects from too much insulin. Achieving this balance is challenging, as diet, activity, medications, physiology, the environment, stress, and many other aspects of daily living all affect glucose levels, often differently from day to day. Persistent challenges of T1D go beyond maintaining glycemic control and include managing long-term complications and preventing potentially life-threating adverse reactions from insulin therapy, and the emotional and cognitive burdens that often lead to diabetes distress and burnout. The T1D community-researchers, sponsors, clinicians, those living with T1D, and advocates-must look beyond managing symptoms of T1D and aim for better treatments and to bring cures. Emerging therapies need clear and efficient regulatory pathways, and new solutions are needed to address ongoing regulatory challenges. The perspectives of people with T1D must be front and center in research and regulatory decision-making. Through the collective efforts of the T1D community, the urgent needs of those with T1D can be met, and T1D can be made a thing of the past.
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Affiliation(s)
- Lynn Starr
- Breakthrough T1D, 1400 K St. NW Suite 1200, Washington, DC, 20005, USA
| | - Sanjoy Dutta
- Breakthrough T1D, 200 Vesey Street, 28th Floor, New York, NY, 10281, USA
| | - Thomas Danne
- Breakthrough T1D, 200 Vesey Street, 28th Floor, New York, NY, 10281, USA
| | - Stephen R Karpen
- Breakthrough T1D, 1400 K St. NW Suite 1200, Washington, DC, 20005, USA.
| | - Campbell Hutton
- Breakthrough T1D, 1400 K St. NW Suite 1200, Washington, DC, 20005, USA
| | - Aaron Kowalski
- Breakthrough T1D, 200 Vesey Street, 28th Floor, New York, NY, 10281, USA
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Yang D, Zhou J, Garstka MA, Xu Q, Li Q, Wang L, Ren L, Ji Q, Liu T. Association of obesity- and insulin resistance-related indices with subclinical carotid atherosclerosis in type 1 diabetes: a cross-sectional study. Cardiovasc Diabetol 2025; 24:193. [PMID: 40319311 PMCID: PMC12049799 DOI: 10.1186/s12933-025-02736-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 04/09/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Obesity and insulin resistance are well-established risk factors for atherosclerosis and cardiovascular disease (CVD). Although some obesity- and insulin resistance-related indices (OIRIs) have been linked to CVD, their associations with subclinical carotid atherosclerosis (SCA) in individuals with type 1 diabetes (T1D) remain unclear. This study aims to systematically explore and compare the associations of various common OIRIs with SCA in T1D population. METHODS A total of 418 adult inpatients with classic T1D admitted from October 2008 to June 2021 to the First Affiliated Hospital of Air Force Medical University in Xi'an, China were included in this study. Demographic, anthropometric, and laboratory data were collected. Studied OIRIs comprised body mass index, waist-to-height ratio, waist-to-hip ratio (WHR), a body shape index, abdominal volume index, body adiposity index, body roundness index, conicity index, triglyceride-glucose index, visceral adiposity index, Chinese visceral adiposity index (CVAI), lipid accumulation product, estimated glucose disposal rate (eGDR), triglyceride-to-HDL ratio, and cardiometabolic index. Binary logistic regression, restricted cubic spline (RCS), and receiver operating characteristic curves were used to examine the associations of these indices with SCA. RESULTS In multivariable logistic regression analyses, after adjusting for potential confounders, per 1.0-standard deviation (SD) increase in CVAI (OR, 95% CI: 1.68, 1.16-2.47), eGDRWHR (eGDR calculated with WHR; OR, 95% CI: 0.44, 0.22-0.82), and eGDRWC (eGDR calculated with waist circumference; OR, 95% CI: 0.49, 0.24-0.93) were significantly associated with SCA. CVAI exhibited the highest area under the curve (AUC) in diagnosing SCA, with a value of 0.73 (95% CI: 0.69-0.77). RCS analyses indicated a linear and positive association between CVAI and SCA in the overall population and the females. Subgroup analyses and sensitivity analyses further supported the association between CVAI and SCA. Additionally, adding CVAI to the Steno Type 1 Risk Engine (ST1RE) improved the reclassification, but did not enhance the overall discriminative ability of ST1RE to identify SCA. CONCLUSION Among various OIRIs, CVAI shows the strongest association with SCA in adults with T1D. These findings suggest that CVAI may merit further longitudinal investigation as a potential marker for SCA assessment in this population.
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Affiliation(s)
- Dongli Yang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Air Force Medical University, Xi'an, 710032, Shaanxi, China
- Department of Endocrinology and Metabolism, Xi'an International Medical Center Hospital of Northwest University, Xi'an, 710100, Shaanxi, China
| | - Jie Zhou
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Malgorzata A Garstka
- Department of Endocrinology, Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Qian Xu
- Department of Endocrinology and Metabolism, Xi'an International Medical Center Hospital of Northwest University, Xi'an, 710100, Shaanxi, China
| | - Qiaoyue Li
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Li Wang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Air Force Medical University, Xi'an, 710032, Shaanxi, China
| | - Lijun Ren
- Department of Endocrinology and Metabolism, Xi'an International Medical Center Hospital of Northwest University, Xi'an, 710100, Shaanxi, China
| | - Qiuhe Ji
- Department of Endocrinology and Metabolism, Xi'an International Medical Center Hospital of Northwest University, Xi'an, 710100, Shaanxi, China.
| | - Tao Liu
- Department of Endocrinology and Metabolism, Xi'an International Medical Center Hospital of Northwest University, Xi'an, 710100, Shaanxi, China.
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Moro O, Gram IT, Løchen ML, Veierød MB, Wägner AM, Sebastiani G. A Bayesian Belief Network model for the estimation of risk of cardiovascular events in subjects with type 1 diabetes. Comput Biol Med 2025; 190:109967. [PMID: 40117794 DOI: 10.1016/j.compbiomed.2025.109967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 01/08/2025] [Accepted: 03/01/2025] [Indexed: 03/23/2025]
Abstract
OBJECTIVES Cardiovascular diseases (CVDs) represent a major risk for people with type 1 diabetes (T1D). Our aim here is to develop a new methodology that overcomes some of the problems and limitations of existing risk calculators. First, they are rarely tailored to people with T1D and, in general, they do not deal with missing values for any risk factor. Moreover, they do not take into account information on risk factors dependencies, which is often available from medical experts. METHOD This study introduces a Bayesian Belief Network (BBN) model to quantify CVD risk in individuals with T1D. The developed methodology is applied to a large T1D dataset and its performances are assessed. A simulation study is also carried out to quantify the parameter estimation properties. RESULTS The performances of individual risk estimation, as measured by the area under the ROC curve and by the C-index, are about 0.75 for both real and simulated data with comparable sample sizes. CONCLUSIONS We observe a good predictive ability of the proposed methodology with accurate parameter estimation. The BBN approach takes into account causal relationships between variables, providing a comprehensive description of the system. This makes it possible to derive useful tools for optimising intervention.
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Affiliation(s)
- Ornella Moro
- Istituto per le Applicazioni del Calcolo "Mauro Picone", Consiglio Nazionale delle Ricerche, Rome, Italy.
| | - Inger Torhild Gram
- Norwegian Centre for E-health Research, University Hospital of North Norway, Tromsø, Norway; Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Maja-Lisa Løchen
- Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Marit B Veierød
- Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Ana Maria Wägner
- Endocrinology and Nutrition Department. Complejo Hospitalario Universitario Insular Materno-Infantil. Instituto de Investigaciones Biomédicas y Sanitarias (IUIBS). Universidad de Las Palmas de Gran Canaria (ULPGC). Las Palmas de Gran Canaria, Spain
| | - Giovanni Sebastiani
- Istituto per le Applicazioni del Calcolo "Mauro Picone", Consiglio Nazionale delle Ricerche, Rome, Italy; Dipartimento di Matematica Guido Castelnuovo, Sapienza Università di Roma, Rome, Italy; Department of Mathematics and Statistics, UiT The Arctic University of Norway, Tromsø, Norway
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Nwosu BU. The partial clinical remission phase of type 1 diabetes: early-onset dyslipidemia, long-term complications, and disease-modifying therapies. Front Endocrinol (Lausanne) 2025; 16:1462249. [PMID: 40309446 PMCID: PMC12042277 DOI: 10.3389/fendo.2025.1462249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 03/03/2025] [Indexed: 05/02/2025] Open
Abstract
No therapy confers complete β-cell protection at any of the 3 stages of type 1 diabetes (T1D). Disease-modifying therapies in type 1 diabetes aim to prolong the preclinical (stages I and II) and the post-diagnostic partial clinical remission (PR) phases of T1D to reduce its short- and long-term complications. These therapies are focused on mitigating β-cell apoptosis by reducing autoimmune attacks on surviving β-cells through several pathways; as well as improving β-cell function to enable the production of functional endogenous insulin and C-peptide through the reduction of proinsulin to C-peptide ratios and other measures. These therapies target the 3 stages of T1D as monotherapy or combination therapy. Stage I of T1D is marked by the presence of at least one diabetes-associated autoantibody in an individual with normoglycemia; stage II is marked by the presence of diabetes-associated autoantibodies and dysglycemia; stage III is marked by the clinical diagnosis of T1D in an individual with antibodies, hyperglycemia, and symptoms. Conventional thinking suggests that the long-term complications of diabetes are principally rooted in early-stage hyperglycemia at the time of diagnosis of the disease, i.e., stage III of T1D. However, this theory of hyperglycemic memory is limited as it does not address the dichotomy in lipid-based atherosclerotic cardiovascular disease (ASCVD) risk in those with T1D. Given the current limitations to developing disease-modifying therapies in T1D because of the limited impact of current agents on β-cell preservation, we introduce the theory of hyperlipidemic memory of type 1 diabetes. This theory was developed by the author in 2022 using the same population as in this article to address the shortcomings of the theory of hyperglycemic memory and explain that the dichotomy in ASCVD risk is based on PR history. In this Review, the theory presents new pathways for disease-modifying therapies in T1D that focus on preventing early-phase dyslipidemia. It is hoped that including this theoretical framework in designing disease-modifying therapies in T1D will help move the field forward. This new theory supports the hypothesis that PR is an imprimatur rather than a process. It hypothesizes that pre-diagnostic interventions, at stages I or II of T1D, to ensure the occurrence of PR may be more effective in the long term than post-diagnostic interventions, at stage III, to prolong PR. This paradigm shift in approach to disease-modifying therapy in T1D is discussed in this review.
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Affiliation(s)
- Benjamin Udoka Nwosu
- Division of Endocrinology, Department of Pediatrics, Zucker School of Medicine at Hofstra/Northwell, New York, NY, United States
- Division of Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, United States
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McCrea DL. Managing Heart Disease in Persons with Diabetes. Crit Care Nurs Clin North Am 2025; 37:53-66. [PMID: 39890350 DOI: 10.1016/j.cnc.2024.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2025]
Abstract
There are an estimated 38 million people in the United States who have diabetes mellitus, both diagnosed and undiagnosed. Chronic complications are generally due to insulin deficiency or insulin resistance, with persistent hyperglycemia, dyslipidemia, and other metabolic pathways disorders. They have 2 to 8 times greater risk of cardiovascular (CV) disease including complications from ischemic heart disease, peripheral artery disease, heart failure, and stroke, which can result in death for more than 50% of persons with type 2 diabetes. This article will discuss the latest CV risk reduction guideline recommended for persons with diabetes.
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Affiliation(s)
- Deborah L McCrea
- Department of Graduate Studies, UTHealth Houston, Cizik School of Nursing, 6901 Bertner, Suite 695, Houston, TX 77030, USA.
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Tomic D, Harding JL, Jenkins AJ, Shaw JE, Magliano DJ. The epidemiology of type 1 diabetes mellitus in older adults. Nat Rev Endocrinol 2025; 21:92-104. [PMID: 39448829 DOI: 10.1038/s41574-024-01046-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/26/2024] [Indexed: 10/26/2024]
Abstract
Although type 1 diabetes mellitus (T1DM) is traditionally viewed as a youth-onset disorder, the number of older adults being diagnosed with this disease is growing. Improvements in the average life expectancy of people with T1DM have also contributed to the growing number of older people living with this disease. We summarize the evidence regarding the epidemiology (incidence, prevalence and excess mortality) of T1DM in older adults (ages ≥60 years) as well as the genetics, immunology and diagnostic challenges. Several studies report an incidence peak of T1DM in older adults of a similar size to or exceeding that in children, and population prevalence generally increases with increasing age. Glutamic acid decarboxylase antibody positivity is frequently observed in adult-onset T1DM. Guidelines for differentiating T1DM from type 2 diabetes mellitus in older adults recommend measuring levels of C-peptide and autoantibodies, including glutamic acid decarboxylase antibodies. However, there is no gold standard for differentiating T1DM from type 2 diabetes mellitus in people aged 60 years and over. As such, the global variation observed in T1DM epidemiology might be in part explained by misclassification, which increases with increasing age of diabetes mellitus onset. With a growing global population of older adults with T1DM, improved genetic and immunological evidence is needed to differentiate diabetes mellitus type at older ages so that a clear epidemiological picture can emerge.
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Affiliation(s)
- Dunya Tomic
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
| | - Jessica L Harding
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Alicia J Jenkins
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Faculty of Medicine, Monash University, Melbourne, Victoria, Australia
- Baker Department of Cardiometabolic Health, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
| | - Jonathan E Shaw
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | - Dianna J Magliano
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
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Shao B, Snell-Bergeon JK, de Boer IH, Davidson WS, Bornfeldt KE, Heinecke JW. Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes. J Lipid Res 2025; 66:100741. [PMID: 39761918 PMCID: PMC11841089 DOI: 10.1016/j.jlr.2025.100741] [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: 08/15/2024] [Revised: 12/19/2024] [Accepted: 12/31/2024] [Indexed: 02/01/2025] Open
Abstract
Atherosclerotic CVD is a major cause of death in individuals with type 1 diabetes mellitus (T1DM). However, conventional risk factors do not fully account for the increased risk. This study aimed to investigate whether serum proteins associate with diabetes status and the occurrence of CVD in T1DM. We used isotope dilution-MS/MS to quantify 28 serum proteins in 228 subjects participating in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used linear regression to analyze the association between serum protein levels and T1DM status using 47 healthy controls and 134 T1DM patients without CVD and Cox proportional hazards regression to assess their prediction for incident CVD by a case-cohort study using a subcohort of 145 T1DM subjects and a total of 47 CVD events. Of the 28 serum proteins studied, five of them-alpha-2-macroglobulin (A2M), apolipoprotein A-IV, apolipoprotein L1, insulin-like growth factor 2, and phospholipid transfer protein-were significantly associated with T1DM status, with A2M being 1.6-fold higher in T1DM. After adjusting for potential confounders, A2M independently predicted incident CVD, with a mean hazard ratio of 3.3 and 95% CI of 1.8-6.1. In our study, A2M showed the largest increase in serum levels when comparing patients with T1DM to control subjects. A2M also predicted incident CVD, suggesting that it could serve as both a marker and possibly a mediator of atherosclerosis in T1DM. These findings emphasize the importance of specific serum proteins in assessing and managing CVD risk in T1DM.
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Affiliation(s)
- Baohai Shao
- Department of Medicine, University of Washington, Seattle, WA.
| | - Janet K Snell-Bergeon
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Ian H de Boer
- Department of Medicine, University of Washington, Seattle, WA
| | - W Sean Davidson
- Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH
| | | | - Jay W Heinecke
- Department of Medicine, University of Washington, Seattle, WA
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Huang X, Hu L, Li J, Wang X. U-shaped association of uric acid to HDL cholesterol ratio (UHR) with ALL-cause and cardiovascular mortality in diabetic patients: NHANES 1999-2018. BMC Cardiovasc Disord 2024; 24:744. [PMID: 39725874 DOI: 10.1186/s12872-024-04436-3] [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: 08/07/2024] [Accepted: 12/18/2024] [Indexed: 12/28/2024] Open
Abstract
OBJECTIVE To investigate the relationship between the uric acid to high-density lipoprotein cholesterol ratio (UHR) and ALL-cause and cardiovascular mortality among diabetic patients. METHODS This study utilized health data from diabetic patients included in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The Kaplan-Meier curves was employed to preliminarily explore the association between UHR, its components, and all-cause and cardiovascular mortality in diabetic patients, as well as to analyze UHR levels and mortality across different genders. Subsequently, the Cox proportional hazards model was used to further investigate the relationship between UHR, its components, and mortality in diabetic patients. Restricted cubic spline (RCS) curves were applied to examine the nonlinear relationship between UHR, its components, and mortality, with a particular focus on the association between UHR and mortality across different genders. RESULTS This longitudinal cohort study included a total of 6,370 participants, comprising 3,268 males and 3,102 females. Kaplan-Meier analysis revealed a positive correlation between UHR, UA, and mortality in diabetic patients, while the association between HDL and mortality was negligible. The Cox proportional hazards model demonstrated a positive association between UHR and mortality in the diabetic population, while the statistical effects of UA and HDL on mortality were less pronounced compared to UHR. When analyzed by gender, no significant linear relationship was observed between UHR and mortality in either males or females. Subsequently, RCS analysis indicated a U-shaped nonlinear relationship between UHR and mortality in the overall diabetic population and among female patients, with a similar trend observed in males. Furthermore, stratified RCS analysis confirmed the persistence of the U-shaped relationship between UHR and prognosis across most subgroups. CONCLUSION This study found a U-shaped relationship between UHR and both ALL-cause and cardiovascular mortality in diabetic population. This suggests that clinicians should control UHR around 9-10 to improve the long-term prognosis of diabetic patients.
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Affiliation(s)
- Xuanchun Huang
- Guang'anmen Hospital, China Academy of Traditional Chinese Medicine, Beijing, China
| | - Lanshuo Hu
- Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing, China
| | - Jun Li
- Guang'anmen Hospital, China Academy of Traditional Chinese Medicine, Beijing, China.
| | - Xuejiao Wang
- Guang'anmen Hospital, China Academy of Traditional Chinese Medicine, Beijing, China.
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Lai X, Luo J, Luo Y, Zheng Y, Yang H, Zou F. Targeting the autoreactive CD8 + T-cell receptor in type 1 diabetes: Insights from scRNA-seq for immunotherapy. Pharmacol Res 2024; 209:107433. [PMID: 39343113 DOI: 10.1016/j.phrs.2024.107433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 10/01/2024]
Abstract
Type 1 Diabetes (T1D) is an autoimmune disease characterized by the attack and destruction of Pancreatic islet beta cells by T cells. Understanding the role of T-cell receptor (TCR) in the development of T1D is of paramount importance. This study employs single-cell RNA sequencing (scRNA-seq) to delve into the mechanistic actions and potential therapeutic applications of autoreactive stem cell-like CD8 TCR in T1D. By retrieving T-cell data from non-obese diabetic (NOD) mice via the GEO database, it was revealed that CD8+ T cells are the predominant T-cell subset in the pancreatic tissue of T1D mice, along with the identification of T-cell marker genes closely associated with T1D. Moreover, the gene TRAJ23 exhibits a preference for T1D, and its knockout alleviates T1D symptoms and adverse reactions in NOD mice. Additionally, engineered TCR-T cells demonstrate significant cytotoxicity towards β cells in T1D.
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Affiliation(s)
- Xiaoyang Lai
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China
| | - Junming Luo
- Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China
| | - Yue Luo
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China
| | - Yijing Zheng
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China
| | - Huan Yang
- Department of Endocrinology, Jiujiang University Affiliated Hospital, Jiujiang, PR China
| | - Fang Zou
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
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Escobar Vasco MA, Fantaye SH, Raghunathan S, Solis-Herrera C. The potential role of finerenone in patients with type 1 diabetes and chronic kidney disease. Diabetes Obes Metab 2024; 26:4135-4146. [PMID: 39021345 DOI: 10.1111/dom.15773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/20/2024] [Accepted: 06/22/2024] [Indexed: 07/20/2024]
Abstract
Chronic kidney disease (CKD) represents a global health concern, associated with an increased risk of cardiovascular morbidity and mortality and decreased quality of life. Many patients with type 1 diabetes (T1D) will develop CKD over their lifetime. Uncontrolled glucose levels, which occur in patients with T1D as well as type 2 diabetes (T2D), are associated with substantial mortality and cardiovascular disease burden. T2D and T1D share common pathological features of CKD, which is thought to be driven by haemodynamic dysfunction, metabolic disturbances, and subsequently an influx of inflammatory and profibrotic mediators, both of which are major interrelated contributors to CKD progression. The mineralocorticoid receptor is also involved, and, under conditions of oxidative stress, salt loading and hyperglycaemia, it switches from homeostatic regulator to pathophysiological mediator by promoting oxidative stress, inflammation and fibrosis. Progressive glomerular and tubular injury leads to macroalbuminuria a progressive reduction in the glomerular filtration rate and eventually end-stage renal disease. Finerenone, a non-steroidal, selective mineralocorticoid receptor antagonist, is approved for treatment of patients with CKD associated with T2D; however, the benefit of finerenone in patients with T1D has yet to be determined. This narrative review will discuss treatment of CKD in T1D and the potential future role of finerenone in this setting.
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Affiliation(s)
| | - Samuel H Fantaye
- Division of Endocrinology, University of Texas Health, San Antonio, Texas, USA
| | - Sapna Raghunathan
- Division of Endocrinology, University of Texas Health, San Antonio, Texas, USA
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11
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Li Y, Li Z, Ren Y, Lei Y, Yang S, Shi Y, Peng H, Yang W, Guo T, Yu Y, Xiong Y. Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities. J Adv Res 2024; 64:99-115. [PMID: 38008175 PMCID: PMC11464474 DOI: 10.1016/j.jare.2023.11.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/14/2023] [Accepted: 11/17/2023] [Indexed: 11/28/2023] Open
Abstract
BACKGROUND Mitochondria-derived peptides (MDPs) represent a recently discovered family of peptides encoded by short open reading frames (ORFs) found within mitochondrial genes. This group includes notable members including humanin (HN), mitochondrial ORF of the 12S rDNA type-c (MOTS-c), and small humanin-like peptides 1-6 (SHLP1-6). MDPs assume pivotal roles in the regulation of diverse cellular processes, encompassing apoptosis, inflammation, and oxidative stress, which are all essential for sustaining cellular viability and normal physiological functions. Their emerging significance extends beyond this, prompting a deeper exploration into their multifaceted roles and potential applications. AIM OF REVIEW This review aims to comprehensively explore the biogenesis, various types, and diverse functions of MDPs. It seeks to elucidate the central roles and underlying mechanisms by which MDPs participate in the onset and development of cardiovascular diseases (CVDs), bridging the connections between cell apoptosis, inflammation, and oxidative stress. Furthermore, the review highlights recent advancements in clinical research related to the utilization of MDPs in CVD diagnosis and treatment. KEY SCIENTIFIC CONCEPTS OF REVIEW MDPs levels are diminished with aging and in the presence of CVDs, rendering them potential new indicators for the diagnosis of CVDs. Also, MDPs may represent a novel and promising strategy for CVD therapy. In this review, we delve into the biogenesis, various types, and diverse functions of MDPs. We aim to shed light on the pivotal roles and the underlying mechanisms through which MDPs contribute to the onset and advancement of CVDs connecting cell apoptosis, inflammation, and oxidative stress. We also provide insights into the current advancements in clinical research related to the utilization of MDPs in the treatment of CVDs. This review may provide valuable information with MDPs for CVD diagnosis and treatment.
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Affiliation(s)
- Yang Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Zhuozhuo Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Yuanyuan Ren
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Ying Lei
- School of Medicine, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Silong Yang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Yuqi Shi
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Han Peng
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Weijie Yang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Tiantian Guo
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China
| | - Yi Yu
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China; School of Medicine, Northwest University, Xi'an 710069, Shaanxi, PR China.
| | - Yuyan Xiong
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, PR China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, 710018 Xi'an, Shaanxi, PR China.
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12
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Syragakis KM, Henderson M, Harnois-Leblanc S, Barnett TA, Mathieu ME, Drapeau V, Benedetti A, Van Hulst A. Neighbourhood Environments and Lifestyle Behaviours in Adolescents With Type 1 Diabetes. Can J Diabetes 2024; 48:471-479.e1. [PMID: 39098660 DOI: 10.1016/j.jcjd.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 06/28/2024] [Accepted: 07/26/2024] [Indexed: 08/06/2024]
Abstract
OBJECTIVES Early prevention strategies are needed to mitigate the high risk of cardiovascular disease in adolescents with type 1 diabetes (T1D). Residential neighbourhood features can promote healthy lifestyle behaviours and reduce cardiovascular risk, but less is known about their role in lifestyle behaviours in adolescents with T1D, and no studies used comparisons to healthy controls. METHODS We examined associations between residential neighbourhood features and lifestyle behaviours in adolescents with T1D and healthy controls. Data were analyzed from the CARdiovascular Disease risk factors in pEdiatric type 1 diAbetes (CARDEA) study, a cross-sectional investigation of 100 adolescents with T1D (14 to 18 years) from a pediatric diabetes clinic in Montréal, Canada, and 97 healthy controls. Outcomes included physical activity and sedentary behaviour (accelerometry), screen time and sleep duration (questionnaires), and dietary habits (24-hour recalls). Cluster analysis of selected neighbourhood indicators computed for participants' postal codes resulted in 2 neighbourhood types: central urban and peri-urban. Central urban neighbourhoods were characterized by very high population density, high active living index, numerous points of interest, higher social deprivation, higher residential mobility, and lower median household income compared with peri-urban neighbourhoods. Associations of neighbourhood type with lifestyle behaviours were estimated with multiple linear regressions and interactions by T1D status were tested. RESULTS Living in central urban neighbourhoods was associated with greater daily minutes of moderate-to-vigorous physical activity (beta = 8.61, 95% confidence interval 1.79 to 15.44) compared with living in peri-urban neighbourhoods. No associations were observed for other lifestyle behaviours, and no statistically significant interactions were found between neighbourhood type and T1D status. CONCLUSION Features that characterize central urban built environments appear to promote physical activity in adolescents, regardless of T1D status.
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Affiliation(s)
| | - Mélanie Henderson
- Azrieli Research Centre of Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; School of Public Health, Department of Social and Preventive Medicine, Université de Montréal, Montréal, Québec, Canada
| | - Soren Harnois-Leblanc
- Azrieli Research Centre of Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; Harvard Pilgrim Health Care Institute, Department of Population Medicine, Harvard University, Boston, Massachusetts, United States
| | - Tracie A Barnett
- Azrieli Research Centre of Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; Department of Family Medicine, Faculty of Medicine and Health Sciences, McGill University, Montréal, Québec, Canada
| | - Marie-Eve Mathieu
- Azrieli Research Centre of Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec, Canada; School of Kinesiology and Physical Activity Sciences, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada
| | - Vicky Drapeau
- Department of Kinesiology, Faculty of Medicine, Université Laval, Québec City, Québec, Canada
| | - Andrea Benedetti
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada
| | - Andraea Van Hulst
- Ingram School of Nursing, McGill University, Montréal, Québec, Canada.
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13
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Kerns S, Owen KA, Daamen A, Kain J, Grammer AC, Lipsky PE. Genetic association with autoimmune diseases identifies molecular mechanisms of coronary artery disease. iScience 2024; 27:110715. [PMID: 39262791 PMCID: PMC11387803 DOI: 10.1016/j.isci.2024.110715] [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: 06/04/2024] [Revised: 06/28/2024] [Accepted: 08/08/2024] [Indexed: 09/13/2024] Open
Abstract
Autoimmune patients have a significantly increased risk of developing coronary artery disease (CAD) compared to the general population. However, autoimmune patients often lack traditional risk factors for CAD and there is increasing recognition of inflammation in CAD development. In this study, we leveraged genome-wide association study (GWAS) data to understand whether there is a genetic relationship between CAD and autoimmunity. Statistical genetic comparison methods were used to identify correlated and causal SNPs between various autoimmune diseases and CAD. Pleiotropic SNPs were identified by cross-phenotype association analysis (CPASSOC) and overlap between GWAS. Causal SNPs were identified using Mendelian Randomization (MR) and Colocalization (COLOC). Using SNP-to-gene mapping, we additionally identified pleiotropic and causal genes and pathways associated between autoimmunity and CAD, which were contextualized by documentation of enrichment in individual cell types identified from coronary atherosclerotic plaques by single-cell RNA sequencing. These results provide insight into potential inflammatory therapeutic targets for CAD.
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Affiliation(s)
- Sophia Kerns
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Katherine A Owen
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Andrea Daamen
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Jessica Kain
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
- Stanford University Department of Genetics, Stanford, CA 94305, USA
| | - Amrie C Grammer
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Peter E Lipsky
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
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14
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Shenker MN, Shalitin S. Use of GLP-1 Receptor Agonists for the Management of Type 1 Diabetes: A Pediatric Perspective. Horm Res Paediatr 2024:1-20. [PMID: 39222618 DOI: 10.1159/000541228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 08/28/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Despite all the technological advances in treatment of patients with type 1 diabetes (T1D), glucose control remains suboptimal in most patients. In addition, a relatively high percentage of patients with T1D, including children, have obesity. Therefore, new interventions are required that focus their effects on weight loss, in order to help with associated insulin resistance and improve glycemic control. SUMMARY GLP-1 receptor agonists (GLP-1 RAs) have proven to be effective and safe in adults with T1D, showing improvement in glycemic control, body weight and cardiorenal protection. GLP-1 RAs are also approved for children with obesity (above the age of 12 years) or type 2 diabetes (above the age of 10 years). However, currently these medications are not approved for use in children with T1D. Only a few published studies have evaluated their efficacy and safety for this indication. KEY MESSAGE This review presents the rationale and experience of add-on GLP-1 RA therapy to pediatric and adolescent patients with T1D, otherwise treated, from RCTs and real-world data. Results of studies of GLP-1 RA in children with T1D are still pending, while large multicenter randomized controlled trials (RCTs) in this population are lacking.
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Affiliation(s)
- Michal Nevo Shenker
- Jesse Z. and Lea Shafer Institute of Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Shlomit Shalitin
- Jesse Z. and Lea Shafer Institute of Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
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15
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Bakhashab S, Barber R, O’Neill J, Arden C, Weaver JU. Overexpression of miR-199b-5p in Colony Forming Unit-Hill's Colonies Positively Mediates the Inflammatory Response in Subclinical Cardiovascular Disease Model: Metformin Therapy Attenuates Its Expression. Int J Mol Sci 2024; 25:8087. [PMID: 39125657 PMCID: PMC11311364 DOI: 10.3390/ijms25158087] [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: 06/25/2024] [Revised: 07/20/2024] [Accepted: 07/21/2024] [Indexed: 08/12/2024] Open
Abstract
Well-controlled type 1 diabetes (T1DM) is characterized by inflammation and endothelial dysfunction, thus constituting a suitable model of subclinical cardiovascular disease (CVD). miR-199b-5p overexpression in murine CVD has shown proatherosclerotic effects. We hypothesized that miR-199b-5p would be overexpressed in subclinical CVD yet downregulated following metformin therapy. Inflammatory and vascular markers were measured in 29 individuals with T1DM and 20 matched healthy controls (HCs). miR-199b-5p expression in CFU-Hill's colonies was analyzed from each study group, and correlations with inflammatory/vascular health indices were evaluated. Significant upregulation of miR-199b-5p was observed in T1DM, which was significantly downregulated by metformin. miR-199b-5p correlated positively with vascular endothelial growth factor-D and c-reactive protein (CRP: nonsignificant). ROC analysis determined miR-199b-5p to define subclinical CVD by discriminating between HCs and T1DM individuals. ROC analyses of HbA1c and CRP showed that the upregulation of miR-199b-5p in T1DM individuals defined subclinical CVD at HbA1c > 44.25 mmol and CRP > 4.35 × 106 pg/mL. Ingenuity pathway analysis predicted miR-199b-5p to inhibit the target genes SIRT1, ETS1, and JAG1. Metformin was predicted to downregulate miR-199b-5p via NFATC2 and STAT3 and reverse its downstream effects. This study validated the antiangiogenic properties of miR-199b-5p and substantiated miR-199b-5p overexpression as a biomarker of subclinical CVD. The downregulation of miR-199b-5p by metformin confirmed its cardio-protective effect.
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Affiliation(s)
- Sherin Bakhashab
- Biochemistry Department, King Abdulaziz University, P.O. Box 80218, Jeddah 21589, Saudi Arabia;
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK (J.O.)
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah 21589, Saudi Arabia
| | - Rosie Barber
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK (J.O.)
- Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK;
| | - Josie O’Neill
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK (J.O.)
- Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK;
| | - Catherine Arden
- Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK;
| | - Jolanta U. Weaver
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK (J.O.)
- Department of Diabetes, Queen Elizabeth Hospital, Gateshead, Newcastle upon Tyne NE9 6SH, UK
- Vascular Biology and Medicine Theme, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
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Kaddour N, Benyettou F, Moulai K, Mebarki A, Allal-Taouli K, Ghemrawi R, Whelan J, Merzouk H, Trabolsi A, Mokhtari-Soulimane NA. Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study. Heliyon 2024; 10:e30450. [PMID: 38711655 PMCID: PMC11070859 DOI: 10.1016/j.heliyon.2024.e30450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 04/06/2024] [Accepted: 04/26/2024] [Indexed: 05/08/2024] Open
Abstract
Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.
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Affiliation(s)
- Nawel Kaddour
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | - Farah Benyettou
- New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
| | - Kawtar Moulai
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | - Abdelouahab Mebarki
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | | | - Rose Ghemrawi
- College of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates
| | - Jamie Whelan
- New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
| | - Hafida Merzouk
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | - Ali Trabolsi
- New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
| | - Nassima Amel Mokhtari-Soulimane
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
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17
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Maqusood S, Chakole V, Dash S. Navigating Cardiovascular Risk in Type 1 Diabetes: A Comprehensive Review of Strategies for Prevention and Management. Cureus 2024; 16:e60426. [PMID: 38882982 PMCID: PMC11179738 DOI: 10.7759/cureus.60426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 05/02/2024] [Indexed: 06/18/2024] Open
Abstract
Type 1 diabetes mellitus (T1DM) poses a significant cardiovascular risk, necessitating comprehensive prevention and management strategies. This review provides insights into the cardiovascular risk landscape in T1DM, emphasizing the importance of glycemic control, lipid management, blood pressure regulation, and lifestyle modifications. Pharmacological interventions, including insulin therapy and lipid-lowering medications, are discussed alongside lifestyle interventions such as diet, exercise, and smoking cessation. Early detection and management of cardiovascular complications are essential, highlighting the need for regular screening and multidisciplinary care. Patient-centered approaches, including shared decision-making and psychosocial support, are vital to effective care delivery. The review concludes with a call to action for healthcare providers and policymakers to prioritize cardiovascular risk management in T1DM. It explores future directions, including emerging therapies and technological innovations. By implementing evidence-based strategies and fostering collaboration across disciplines, we can mitigate cardiovascular risk and improve outcomes for individuals with T1DM.
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Affiliation(s)
- Shafaque Maqusood
- Anaesthesiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Vivek Chakole
- Anaesthesiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sambit Dash
- Anesthesiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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18
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Salah NY, Madkour SS, Ahmed KS, Abdelhakam DA, Abdullah FA, Mahmoud RAEH. Adiponectin rs1501299 and chemerin rs17173608 gene polymorphism in children with type 1 diabetes mellitus: relation with macroangiopathy and peripheral artery disease. J Endocrinol Invest 2024; 47:983-994. [PMID: 37831337 PMCID: PMC10965736 DOI: 10.1007/s40618-023-02215-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/27/2023] [Indexed: 10/14/2023]
Abstract
AIM Although macrovascular complications represent the leading cause of mortality in type 1 diabetes mellitus (T1DM), the prevalence of subtle macrovascular affection including peripheral artery disease (PAD) among children with T1DM and its genetic predictors remains to be unraveled. Increasing evidence suggests a link between adiponectin rs1501299 and chemerin rs17173608 gene polymorphism and atherogenesis, and insulin resistance. Hence, this study assess the prevalence of these variants among children with T1DM in comparison to healthy controls and their association with macrovascular complications, namely PAD and hyperlipidemia. METHODS Fifty children with T1DM and 50 matched controls underwent a thorough assessment including adiponectin rs1501299 and chemerin rs17173608 gene polymorphisms, fasting lipids, glycated hemoglobin (HbA1c), and ankle-brachial index (ABI). Cochran-Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and PAD using a case-control design. RESULTS Children with T1DM were found to have significantly higher ABI (p = 0.011) than controls. Chemerin gene polymorphism was detected in 41 children with T1DM (82.0%), while adiponectin gene polymorphism was detected in 19 children (38.0%). Children with T1DM having GG chemerin variant and those having TT adiponectin variant had significantly higher cholesterol with significantly lower HDL-C and ABI than those having the other two variants (p < 0.005). Children with T1DM having abnormal ABI had significantly higher chemerin G (p = 0.017) and adiponectin T (p = 0.022) alleles than those with normal ABI. Cholesterol and ABI were independently associated with chemerin and adiponectin gene polymorphism by multivariable regression analysis. CONCLUSION Children with T1DM having chemerin and adiponectin gene polymorphisms have significantly higher cholesterol and ABI than those without these polymorphisms and controls. TRIAL REGISTRATION The Research Ethics Committee of Ain Shams University, approval number R 31/2021.
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Affiliation(s)
- N Y Salah
- Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - S S Madkour
- Radiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Diagnostic and Interventional Radiology and Molecular Imaging, Ain Shams University, Cairo, Egypt
| | - K S Ahmed
- Radiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Diagnostic and Interventional Radiology and Molecular Imaging, Ain Shams University, Cairo, Egypt
| | - D A Abdelhakam
- Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - F A Abdullah
- Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - R A E H Mahmoud
- Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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19
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Sardà H, Colom C, Benitez S, Carreras G, Amigó J, Miñambres I, Viladés D, Blanco-Vaca F, Sanchez-Quesada JL, Pérez A. PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes. Sci Rep 2024; 14:7195. [PMID: 38532033 DOI: 10.1038/s41598-024-57708-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 03/21/2024] [Indexed: 03/28/2024] Open
Abstract
Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.
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Affiliation(s)
- Helena Sardà
- Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau - Hospital Dos de Maig, Antoni Maria Claret, 167, 08025, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Cristina Colom
- Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau - Hospital Dos de Maig, Antoni Maria Claret, 167, 08025, Barcelona, Spain
| | - Sonia Benitez
- Cardiovascular Biochemistry Group, Institut de Recerca Sant Pau (IR Sant Pau), Sant Quintí, 77-79, 08041, Barcelona, Spain
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain
| | - Gemma Carreras
- Department of Pediatrics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Department of Pediatrics, Obstetrics and Gynecology, and Preventive Medicine and Public Health, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Judit Amigó
- Department of Endocrinology and Nutrition, Hospital Universitari Vall d'Hebrón, Barcelona, Spain
| | - Inka Miñambres
- Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau - Hospital Dos de Maig, Antoni Maria Claret, 167, 08025, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain
| | - David Viladés
- Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Centro de Investigación en red de enfermedades cardiovasculares (CIBERCV), Madrid, Spain
| | - Francisco Blanco-Vaca
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain
- Department of Clinical Biochemistry, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
- Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Jose Luís Sanchez-Quesada
- Cardiovascular Biochemistry Group, Institut de Recerca Sant Pau (IR Sant Pau), Sant Quintí, 77-79, 08041, Barcelona, Spain.
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain.
| | - Antonio Pérez
- Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau - Hospital Dos de Maig, Antoni Maria Claret, 167, 08025, Barcelona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
- CIBER en Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain.
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20
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Grassi BA, Teresa Onetto M, Sánchez C, Tapia N, Mena F. Effect of low dose Semaglutide in people with Type 1 Diabetes and excess weight. Diabetes Res Clin Pract 2024; 209:111593. [PMID: 38403174 DOI: 10.1016/j.diabres.2024.111593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/12/2023] [Accepted: 02/22/2024] [Indexed: 02/27/2024]
Abstract
Obesity is a prevalent problem in people living with T1D (PwT1D), and it has been linked to cardiovascular disease in this population. The use of low dose weekly Semaglutide (0,5 mg) was evaluated in a cohort of PwT1D and excess weight.
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Affiliation(s)
- Bruno A Grassi
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile.
| | - María Teresa Onetto
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile
| | - Camila Sánchez
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile
| | - Nicole Tapia
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile
| | - Francisca Mena
- Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile
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21
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Shillah WB, Yahaya JJ, Morgan ED, Bintabara D. Predictors of microvascular complications in patients with type 2 diabetes mellitus at regional referral hospitals in the central zone, Tanzania: a cross-sectional study. Sci Rep 2024; 14:5035. [PMID: 38424145 PMCID: PMC10904798 DOI: 10.1038/s41598-024-55556-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 02/25/2024] [Indexed: 03/02/2024] Open
Abstract
Microvascular complications encompass a group of diseases which result from long-standing chronic effect of diabetes mellitus (DM). We aimed to determine the prevalence of microvascular complications and associated risk factors among patients with type 2 diabetes mellitus (T2DM). A cross-sectional analytical hospital-based study was conducted at Singida and Dodoma regional referral hospitals in Tanzania from December 2021 to September 2022. A total of 422 patients with T2DM were included in the analysis by determining the prevalence of microvascular complications and their predictors using multivariable logistic regression analysis. A two-tailed p value less than 0.05 was considered statistically significant. The prevalence of microvascular complications was 57.6% (n = 243) and diabetic retinopathy was the most common microvascular complication which accounted for 21.1% (n = 89). Having irregular physical activity (AOR = 7.27, 95% CI = 2.98-17.71, p < 0.001), never having physical activity (AOR = 2.38, 95% CI = 1.4-4.01, p = 0.013), being hypertensive (AOR = 5.0, 95% CI = 2.14-11.68, p = 0.030), having T2DM for more than 5 years (AOR = 2.74, 95% CI = 1.42-5.26, p = 0.025), being obese (AOR = 2.63, 95% CI = 1.22-5.68, p = 0.010), and taking anti-diabetic drugs irregularly (AOR = 1.94, 95% CI = 0.15-0.77, p < 0.001) were the predictors of microvascular complications. This study has revealed a significant proportion of microvascular complications in a cohort of patients with T2DM. Lack of regular physical activity, being obese, taking anti-diabetic drugs irregularly, presence of hypertension, and long-standing duration of the disease, were significantly associated with microvascular complications.
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Affiliation(s)
- Wilfred B Shillah
- Department of Community Medicine, School of Medicine and Dentistry, University of Dodoma, Dodoma, Tanzania
| | - James J Yahaya
- Department of Pathology, School of Health Sciences, Soroti University, P. O. Box 211, Soroti, Uganda.
| | - Emmanuel D Morgan
- Department of Pathology, School of Health Sciences, Soroti University, P. O. Box 211, Soroti, Uganda
| | - Deogratius Bintabara
- Department of Community Medicine, School of Medicine and Dentistry, University of Dodoma, Dodoma, Tanzania
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22
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Yoo J, Jeon J, Baek M, Song SO, Kim J. Impact of statin treatment on cardiovascular risk in patients with type 1 diabetes: a population-based cohort study. J Transl Med 2023; 21:806. [PMID: 37951886 PMCID: PMC10640735 DOI: 10.1186/s12967-023-04691-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 11/02/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. METHODS We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin-angiotensin-aldosterone system inhibitors. RESULTS During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66-0.88; p < 0.001). Statin use led to decreased risks of ischemic stroke and myocardial infarction, but was not related to hemorrhagic stroke. We also found that the risk of cardiovascular events decreased as the cumulative exposure duration of statins increased. CONCLUSIONS Statin use was associated with a lower risk of cardiovascular events in T1D patients. Further prospective studies are needed to confirm the potential role of statins in prevention of CVD in patients with T1D.
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Affiliation(s)
- Joonsang Yoo
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Jimin Jeon
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Minyoul Baek
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea
| | - Sun Ok Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, 100 Ilsan-ro, Ilsandong-gu, Goyang, 10444, Republic of Korea.
| | - Jinkwon Kim
- Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea.
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23
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Navodnik MP, Janež A, Žuran I. The Effect of Additional Treatment with Empagliflozin or Semaglutide on Endothelial Function and Arterial Stiffness in Subjects with Type 1 Diabetes Mellitus-ENDIS Study. Pharmaceutics 2023; 15:1945. [PMID: 37514131 PMCID: PMC10385568 DOI: 10.3390/pharmaceutics15071945] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/05/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
We investigated the effect of additional treatment with newer antidiabetic drugs on endothelium function and arterial stiffness in subjects with type 1 diabetes mellitus (T1DM) without cardiovascular diseases. A total of 89 participants, all users of CGMS (continuous monitoring glucose system), were randomized into three comparable groups, receiving empagliflozin (E; n = 30), receiving semaglutide (S; n = 30), and a control group (C; n = 29). At baseline and 12 weeks post treatment, we measured FMD (brachial artery flow-mediated dilation) and FBF (forearm blood flow as reactive hyperemia assessed with strain gauge plethysmography) as parameters of endothelial function, as well as pulse wave velocity (PWV) and peripheral resistance as parameters of arterial stiffness. Improvement in FMD was significant in both intervention groups compared to controls (E group 2.0-fold, p = 0.000 and S group 1.9-fold, p = 0.000), with no changes between those two groups (p = 0.745). During the evaluation of FBF, there were statistically insignificant improvements in both therapeutic groups compared to controls (E group 1.39-fold, p = 0.074 and S group 1.22-fold, p = 0.701). In arterial stiffness parameters, improvements were seen only in the semaglutide group, with a decline in peripheral resistance by 5.1% (p = 0.046). We can conclude that, for arterial stiffness, semaglutide seems better, but both drugs positively impact endothelial function and, thus, could also have a protective role in T1DM.
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Affiliation(s)
- Maja Preložnik Navodnik
- Department of Angiology, Endocrinology and Rheumatology, General Hospital Celje, Oblakova ul. 5, 3000 Celje, Slovenia
| | - Andrej Janež
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška Cesta 7, 1000 Ljubljana, Slovenia
| | - Ivan Žuran
- Department of Angiology, Endocrinology and Rheumatology, General Hospital Celje, Oblakova ul. 5, 3000 Celje, Slovenia
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24
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Goh YA, Lan NSR, Linn K, Wood C, Gupta A, Yeap BB, Fegan PG. Comparison of coronary artery calcium score and cardiovascular risk-stratification by European Society of Cardiology Guidelines and Steno Type 1 Risk Engine in statin-naïve adults with type 1 diabetes. J Diabetes Complications 2023; 37:108557. [PMID: 37473636 DOI: 10.1016/j.jdiacomp.2023.108557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 06/30/2023] [Accepted: 07/08/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND Coronary artery calcium (CAC) is a marker of atherosclerotic cardiovascular disease (CVD). However, for patients with type 1 diabetes (T1D), its relationship with T1D-specific cardiovascular (CV) risk-stratification tools is unknown. AIMS Assess prevalence of CAC and evaluate relationship between CAC and T1D-specific CV risk-stratification methods in T1D. METHODS Cross-sectional study of adults with T1D age 20-60 years, statin-naïve and no history of CVD. Data was obtained from electronic medical records and by interview. Presence of CAC was assessed using non-contrast cardiac computed tomography and quantified by Agatston Units (AU). CV risk-stratification was assessed using the 2019 European Society of Cardiology (ESC) Guidelines and the Steno T1 Risk Engine (ST1RE). RESULTS 85 patients were included with mean age 35.4 ± 10.3 years, HbA1c 8.3 ± 1.5 % and T1D duration 17.0 ± 10.1 years. 67 patients (78.9 %) had a CAC score of 0 AU, 17 (20.0 %) >0-100 AU, and one (1.2 %) >100 AU. Duration of T1D (p = 0.009), body mass index (p = 0.029), neuropathy (p = 0.016) and low-density lipoprotein cholesterol levels (p = 0.016) were independently associated with a positive CAC score on multivariate analysis. Positive predictive value for a positive CAC score was 85.7 % for the ST1RE high risk category and 31.3 % for the 2019 ESC Guidelines very high risk category. CONCLUSIONS One-fifth of this T1D cohort had a positive CAC score. The ST1RE was superior in identifying positive CAC compared to the 2019 ESC Guidelines. Further studies are required to elucidate the role of CAC in personalising CV risk-stratification and statin initiation in T1D.
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Affiliation(s)
- Yuhan A Goh
- Department of Endocrinology and Diabetes, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia.
| | - Nick S R Lan
- Department of Cardiology, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia; Medical School, The University of Western Australia, Crawley, Australia
| | - Kathryn Linn
- Department of Nuclear Medicine, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia
| | - Chris Wood
- Department of Radiology, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia
| | - Ashu Gupta
- Department of Radiology, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia
| | - Bu B Yeap
- Department of Endocrinology and Diabetes, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia; Medical School, The University of Western Australia, Crawley, Australia
| | - P Gerry Fegan
- Department of Endocrinology and Diabetes, Fiona Stanley Fremantle Hospitals Group, Murdoch, Australia; Medical School, Curtin University, Bentley, Australia
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25
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Mertens J, Weyler J, Dirinck E, Vonghia L, Kwanten WJ, Mortelmans L, Peleman C, Chotkoe S, Spinhoven M, Vanhevel F, Van Gaal LF, De Winter BY, De Block CE, Francque SM. Prevalence, risk factors and diagnostic accuracy of non-invasive tests for NAFLD in people with type 1 diabetes. JHEP Rep 2023; 5:100753. [PMID: 37274774 PMCID: PMC10232726 DOI: 10.1016/j.jhepr.2023.100753] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 03/16/2023] [Accepted: 03/30/2023] [Indexed: 06/07/2023] Open
Abstract
BACKGROUND & AIMS The epidemiology of non-alcoholic fatty liver disease (NAFLD) in people with type 1 diabetes (T1D) is not yet elucidated. This study aimed to assess the diagnostic accuracy of non-invasive tests for NAFLD, to investigate the prevalence and severity of NAFLD, and to search for factors contributing to NAFLD in people with T1D. METHODS In this prospective cohort study, we consecutively screened 530 adults with T1D from a tertiary care hospital, using ultrasound (US), vibration-controlled transient elastography equipped with liver stiffness measurement (LSM) and controlled attenuation parameter, and the fatty liver index. Magnetic resonance spectroscopy (MRS) was performed in a representative subgroup of 132 individuals to validate the diagnostic accuracy of the non-invasive tests. RESULTS Based on MRS as reference standard, US identified individuals with NAFLD with an AUROC of 0.98 (95% CI 0.95-1.00, sensitivity: 1.00, specificity: 0.96). The controlled attenuation parameter was also accurate with an AUROC of 0.85 (95% CI 0.77-0.93). Youden cut-off was ≥270 dB/m (sensitivity: 0.90, specificity: 0.74). The fatty liver index yielded a similar AUROC of 0.83 (95% CI 0.74-0.91), but the conventional cut-off used to rule in (≥60) had low sensitivity and specificity (0.62, 0.78). The prevalence of NAFLD in the overall cohort was 16.2% based on US. Metabolic syndrome was associated with NAFLD (OR: 2.35 [1.08-5.12], p = 0.031). The overall prevalence of LSM ≥8.0 kPa indicating significant fibrosis was 3.8%, but reached 13.2% in people with NAFLD. CONCLUSIONS NAFLD prevalence in individuals with T1D is 16.2%, with approximately one in 10 featuring elevated LSM. US-based screening could be considered in people with T1D and metabolic syndrome. IMPACT AND IMPLICATIONS We aimed to report on the prevalence, disease severity, and risk factors of NAFLD in type 1 diabetes (T1D), while also tackling which non-invasive test for NAFLD is the most accurate. We found that ultrasound is the best test to diagnose NAFLD. NAFLD prevalence is 16.2%, and is associated with metabolic syndrome and BMI. Elevated liver stiffness indicating fibrosis is overall not prevalent in people with T1D (3.8%), but it reaches 13.2% in those with T1D and NAFLD.
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Affiliation(s)
- Jonathan Mertens
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Jonas Weyler
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Eveline Dirinck
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Luisa Vonghia
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Wilhelmus J. Kwanten
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Laura Mortelmans
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Cedric Peleman
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
| | - Shivani Chotkoe
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Maarten Spinhoven
- Department of Radiology, Antwerp University Hospital, Antwerp, Belgium
| | - Floris Vanhevel
- Department of Radiology, Antwerp University Hospital, Antwerp, Belgium
| | - Luc F. Van Gaal
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
| | - Benedicte Y. De Winter
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Christophe E.M. De Block
- Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
| | - Sven M. Francque
- Laboratory of Experimental Medicine and Paediatrics and Member of the Infla-Med Centre of Excellence, University of Antwerp, Faculty of Medicine & Health Sciences, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Antwerp, Belgium
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26
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Brady RP, Jensen ET, Rigdon J, Crimmins NA, Mallon D, Dolan LM, Imperatore G, Kahkoska AR, Mottl AK, Honor A, Pettitt DJ, Merjaneh L, Dabelea D, Shah AS. The Frequency of Undiagnosed Celiac Disease in Youth with Type 1 Diabetes and Its Association with Diabetic Retinopathy: The SEARCH for Diabetes in Youth Study. Pediatr Diabetes 2023; 2023:9038795. [PMID: 39845332 PMCID: PMC11753297 DOI: 10.1155/2023/9038795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 02/07/2023] [Accepted: 05/08/2023] [Indexed: 01/24/2025] Open
Abstract
Aims Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study, we aimed to assess the frequency of CD and the potential for undiagnosed CD among youth with childhood onset type 1 diabetes. In addition, we assessed the burden of cardiovascular risk factors and diabetes-associated complications in youth with type 1 diabetes by CD status and IgA tissue transglutaminase autoantibody (tTGA) levels. Methods 2,444 youths with type 1 diabetes completed a CD questionnaire and underwent tTGA testing. Integrating the celiac disease questionnaire and tTGA results for this cross-sectional analysis, participants were categorized as follows: (1) reported CD; (2) seropositive for CD (no reported CD and seropositive tTGA); and (3) type 1 diabetes only (comparison group: no reported CD and seronegative tTGA). Subanalyses were performed on those with no reported CD and tTGA ≥10x ULN, designated potentially undiagnosed CD. Cardiovascular risk factors and diabetes-associated complications were evaluated by CD status and tTGA levels utilizing a Poisson model to estimate relative risk. Results Reported CD in youths with type 1 diabetes was 7%. Seropositivity for tTGA with no reported CD was present in 4%, and 1.2% had potentially undiagnosed CD. Youths with potentially undiagnosed CD had a 2.69x higher risk of diabetic retinopathy than comparison group. In addition, CD with tTGA <0.05 (controlled CD) was associated with lower HbA1c. Conclusions Undiagnosed CD is likely present in youths with type 1 diabetes and potentially undiagnosed CD is associated with a higher risk of diabetic retinopathy. These findings indicate the importance of routine screening for CD in type 1 diabetes in youths.
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Affiliation(s)
- Ryan P. Brady
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Elizabeth T. Jensen
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Joseph Rigdon
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Nancy A. Crimmins
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Daniel Mallon
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Lawrence M. Dolan
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
| | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA
| | - Anna R. Kahkoska
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Amy K. Mottl
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Ann Honor
- Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | | | - Lina Merjaneh
- Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
| | - Dana Dabelea
- Lifeourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Departments of Epidemiology and Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Amy S. Shah
- Department of Pediatrics, Cincinnati Children's Hospital & University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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27
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Taatjes DJ, Roth J. In focus in HCB. Histochem Cell Biol 2023; 159:309-311. [PMID: 36977938 DOI: 10.1007/s00418-023-02190-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
Affiliation(s)
- Douglas J Taatjes
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, 05405, USA.
| | - Jürgen Roth
- University of Zurich, CH-8091, Zurich, Switzerland
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28
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Rennie C, Huang Y, Siwakoti P, Du Z, Padula M, Bao G, Tuch BE, Xu X, McClements L. In vitro evaluation of a hybrid drug delivery nanosystem for fibrosis prevention in cell therapy for Type 1 diabetes. Nanomedicine (Lond) 2023; 18:53-66. [PMID: 36938861 DOI: 10.2217/nnm-2022-0231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2023] Open
Abstract
Background: Implantation of insulin-secreting cells has been trialed as a treatment for Type 1 diabetes mellitus; however, the host immunogenic response limits their effectiveness. Methodology: The authors developed a core-shell nanostructure of upconversion nanoparticle-mesoporous silica for controlled local delivery of an immunomodulatory agent, MCC950, using near-infrared light and validated it in in vitro models of fibrosis. Results: The individual components of the nanosystem did not affect the proliferation of insulin-secreting cells, unlike fibroblast proliferation (p < 0.01). The nanosystem is effective at releasing MCC950 and preventing fibroblast differentiation (p < 0.01), inflammation (IL-6 expression; p < 0.05) and monocyte adhesion (p < 0.01). Conclusion: This MCC950-loaded nanomedicine system could be used in the future together with insulin-secreting cell implants to increase their longevity as a curative treatment for Type 1 diabetes mellitus.
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Affiliation(s)
- Claire Rennie
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Yanan Huang
- School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Prakriti Siwakoti
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Ziqing Du
- School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Matthew Padula
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Guochen Bao
- Institute for Biomedical Materials & Devices, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Bernard E Tuch
- Department of Diabetes, Central Clinical School, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, 3004, Australia.,Australian Foundation for Diabetes Research, 2000, NSW, Australia
| | - Xiaoxue Xu
- School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia.,School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Lana McClements
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia.,Institute for Biomedical Materials & Devices, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
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29
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Varkevisser RDM, Birnie E, Mul D, van Dijk PR, Aanstoot H, Wolffenbuttel BHR, van der Klauw MM. Type 1 diabetes management: Room for improvement. J Diabetes 2023; 15:255-263. [PMID: 36808864 PMCID: PMC10036258 DOI: 10.1111/1753-0407.13368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 01/03/2023] [Accepted: 01/27/2023] [Indexed: 02/20/2023] Open
Abstract
AIMS/HYPOTHESIS Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. METHODS Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. RESULTS Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. CONCLUSION Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.
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Affiliation(s)
- Rita D. M. Varkevisser
- Department of EndocrinologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Erwin Birnie
- Diabeter Nederland, Center for Focussed Diabetes Care and ResearchRotterdamThe Netherlands
- Department of GeneticsUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Dick Mul
- Diabeter Nederland, Center for Focussed Diabetes Care and ResearchRotterdamThe Netherlands
| | - Peter R. van Dijk
- Department of EndocrinologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Henk‐Jan Aanstoot
- Diabeter Nederland, Center for Focussed Diabetes Care and ResearchRotterdamThe Netherlands
| | - Bruce H. R. Wolffenbuttel
- Department of EndocrinologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
| | - Melanie M. van der Klauw
- Department of EndocrinologyUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands
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Gammon JM, Carey ST, Saxena V, Eppler HB, Tsai SJ, Paluskievicz C, Xiong Y, Li L, Ackun-Farmmer M, Tostanoski LH, Gosselin EA, Yanes AA, Zeng X, Oakes RS, Bromberg JS, Jewell CM. Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation. Nat Commun 2023; 14:681. [PMID: 36755035 PMCID: PMC9908900 DOI: 10.1038/s41467-023-36225-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 01/18/2023] [Indexed: 02/10/2023] Open
Abstract
Antigen-specific tolerance is a key goal of experimental immunotherapies for autoimmune disease and allograft rejection. This outcome could selectively inhibit detrimental inflammatory immune responses without compromising functional protective immunity. A major challenge facing antigen-specific immunotherapies is ineffective control over immune signal targeting and integration, limiting efficacy and causing systemic non-specific suppression. Here we use intra-lymph node injection of diffusion-limited degradable microparticles that encapsulate self-antigens with the immunomodulatory small molecule, rapamycin. We show this strategy potently inhibits disease during pre-clinical type 1 diabetes and allogenic islet transplantation. Antigen and rapamycin are required for maximal efficacy, and tolerance is accompanied by expansion of antigen-specific regulatory T cells in treated and untreated lymph nodes. The antigen-specific tolerance in type 1 diabetes is systemic but avoids non-specific immune suppression. Further, microparticle treatment results in the development of tolerogenic structural microdomains in lymph nodes. Finally, these local structural and functional changes in lymph nodes promote memory markers among antigen-specific regulatory T cells, and tolerance that is durable. This work supports intra-lymph node injection of tolerogenic microparticles as a powerful platform to promote antigen-dependent efficacy in type 1 diabetes and allogenic islet transplantation.
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Affiliation(s)
- Joshua M Gammon
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Sean T Carey
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Vikas Saxena
- Department of Surgery, University of Maryland Medical School, 22 S. Greene Street, S8B06, Baltimore, MD, 21201, USA
| | - Haleigh B Eppler
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Shannon J Tsai
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Christina Paluskievicz
- Department of Surgery, University of Maryland Medical School, 22 S. Greene Street, S8B06, Baltimore, MD, 21201, USA
| | - Yanbao Xiong
- Department of Surgery, University of Maryland Medical School, 22 S. Greene Street, S8B06, Baltimore, MD, 21201, USA
| | - Lushen Li
- Department of Surgery, University of Maryland Medical School, 22 S. Greene Street, S8B06, Baltimore, MD, 21201, USA
| | - Marian Ackun-Farmmer
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Lisa H Tostanoski
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Emily A Gosselin
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Alexis A Yanes
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Xiangbin Zeng
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
| | - Robert S Oakes
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA
- Department of Veterans Affairs, VA Maryland Health Care System, 10. N Green Street, Baltimore, MD, 21201, USA
| | - Jonathan S Bromberg
- Department of Surgery, University of Maryland Medical School, 22 S. Greene Street, S8B06, Baltimore, MD, 21201, USA.
- Department of Microbiology and Immunology, University of Maryland Medical School, 685 West 30 Baltimore Street, HSF-I Suite 380, Baltimore, MD, 21201, USA.
| | - Christopher M Jewell
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, USA.
- Department of Surgery, University of Maryland Medical School, 22 S. Greene Street, S8B06, Baltimore, MD, 21201, USA.
- Department of Veterans Affairs, VA Maryland Health Care System, 10. N Green Street, Baltimore, MD, 21201, USA.
- Department of Microbiology and Immunology, University of Maryland Medical School, 685 West 30 Baltimore Street, HSF-I Suite 380, Baltimore, MD, 21201, USA.
- Robert E. Fischell Institute for Biomedical Devices, 8278 Paint Branch Drive, College Park, MD, 20742, USA.
- Marlene and Stewart Greenebaum Cancer Center, 22 S. Greene Street, Suite N9E17, Baltimore, 32 MD 21201, USA.
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31
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Fernández-González JF, García-Pedraza JÁ, Ordóñez JL, Terol-Úbeda AC, Martín ML, Morán A, García-Domingo M. Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT 1D Receptor Activation via NO Pathway. Int J Mol Sci 2023; 24:ijms24021378. [PMID: 36674892 PMCID: PMC9865738 DOI: 10.3390/ijms24021378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/24/2022] [Accepted: 12/28/2022] [Indexed: 01/13/2023] Open
Abstract
Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.
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Affiliation(s)
- Juan Francisco Fernández-González
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - José Ángel García-Pedraza
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - José Luis Ordóñez
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Anaïs Clara Terol-Úbeda
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
| | - María Luisa Martín
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Asunción Morán
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
- Correspondence: ; Tel.: +34-663-18-24-55; Fax: +34-923-29-45-15
| | - Mónica García-Domingo
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
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Hagelqvist PG, Andersen A, Maytham KB, Andreasen CR, Engberg S, Lindhardt TB, Faber J, Holst JJ, Forman JL, Pedersen-Bjergaard U, Knop FK, Vilsbøll T. Exercise-related hypoglycaemia induces QTc-interval prolongation in individuals with type 1 diabetes. Diabetes Obes Metab 2023; 25:1186-1195. [PMID: 36593718 DOI: 10.1111/dom.14964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/20/2022] [Accepted: 12/30/2022] [Indexed: 01/04/2023]
Abstract
AIMS To investigate changes in cardiac repolarisation during exercise-related hypoglycaemia compared to hypoglycaemia induced at rest in people with type 1 diabetes. MATERIAL AND METHODS In a randomised crossover study, 15 men with type 1 diabetes underwent two separate hyperinsulinaemic euglycaemic-hypoglycaemic clamp experiments during Holter-ECG monitoring. One experiment included a bout of moderate-intensity cycling exercise (60 min) along with declining plasma glucose (PG; Clamp-exercise). In the other experiment, hypoglycaemia was induced with the participants at rest (Clamp-rest). We studied QTc interval, T-peak to T-end (Tpe) interval and hormonal responses during three steady-state phases: (i) baseline (PG 4.0-8.0 mmol/L); (ii) hypoglycaemic phase (PG <3.0 mmol/L); and (iii) recovery phase (PG 4.0-8.0 mmol/L). RESULTS Both QTc interval and Tpe interval increased significantly from baseline during the hypoglycaemic phase but with no significant difference between test days. These changes were accompanied by an increase in plasma adrenaline and a decrease in plasma potassium on both days. During the recovery phase, ΔQTc interval was longer during Clamp-rest compared to Clamp-exercise, whereas ΔTpe interval remained similar on the two test days. CONCLUSIONS We found that both exercise-related hypoglycaemia and hypoglycaemia induced at rest can cause QTc-interval prolongation and Tpe-interval prolongation in people with type 1 diabetes. Thus, both scenarios may increase susceptibility to ventricular arrhythmias.
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Affiliation(s)
- Per G Hagelqvist
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Andreas Andersen
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Kaisar B Maytham
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Christine R Andreasen
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Susanne Engberg
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Tommi B Lindhardt
- Department of Cardiology, Nordsjaellands Hospital Hillerød, University of Copenhagen, Hillerød, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Faber
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Endocrinology, Herlev Hospital, Herlev, Denmark
| | - Jens J Holst
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Julie L Forman
- Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ulrik Pedersen-Bjergaard
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital Hillerød, University of Copenhagen, Hillerød, Denmark
| | - Filip K Knop
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Clinical Research, Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Griggs S, Al-Kindi S, Hardin H, Irani E, Rajagopalan S, Crawford SL, Hickman RL. Socioeconomic deprivation and cardiometabolic risk factors in individuals with type 1 diabetes: T1D exchange clinic registry. Diabetes Res Clin Pract 2023; 195:110198. [PMID: 36513270 PMCID: PMC9908846 DOI: 10.1016/j.diabres.2022.110198] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 09/05/2022] [Accepted: 11/29/2022] [Indexed: 12/14/2022]
Abstract
AIMS Social determinants of health (SDOH) influence cardiovascular health in the general population; however, the degree to which this occurs in individuals with type 1 diabetes (T1D) is not well understood. We evaluated associations among socioeconomic deprivation and cardiometabolic risk factors (hemoglobin A1c, low-density lipoprotein, blood pressure, body mass index, physical activity) in individuals with T1D from the T1D Clinic Exchange Registry. METHODS We evaluated the association between the social deprivation index (SDI) and cardiometabolic risk factors using multivariable and logistic regression among 18,754 participants ages 13 - 90 years (mean 29.2 ± 17) in the T1D Exchange clinic registry from 6,320 zip code tabulation areas (2007-2017). RESULTS SDI was associated with multiple cardiometabolic risk factors even after adjusting for covariates (age, biological sex, T1D duration, and race/ethnicity) in the multivariable linear regression models. Those in the highest socially deprived areas had 1.69 (unadjusted) and 1.78 (adjusted) times odds of a triple concomitant risk burden of poor glycemia, dyslipidemia, and hypertension. CONCLUSIONS Persistent SDOH differences could account for a substantial degree of poor achievement of cardiometabolic targets in individuals with T1D. Our results suggest the need for a broader framework to understand the association between T1D and adverse cardiometabolic outcomes.
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Affiliation(s)
- Stephanie Griggs
- Case Western Reserve University, Frances Payne Bolton School of Nursing, Cleveland, OH 44106, United States.
| | - Sadeer Al-Kindi
- Center for Vascular Metabolic Disease, School of Medicine, Cleveland, OH, 44106, United States; Cardiovascular Research Institute, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, United States.
| | - Heather Hardin
- Case Western Reserve University, Frances Payne Bolton School of Nursing, Cleveland, OH 44106, United States
| | - Elliane Irani
- Case Western Reserve University, Frances Payne Bolton School of Nursing, Cleveland, OH 44106, United States.
| | - Sanjay Rajagopalan
- Cardiovascular Research Institute, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, United States.
| | - Sybil L Crawford
- University of Massachusetts Chan Medical School, Tan Chingfen Graduate School of Nursing, Worcester, MA 01655, United States.
| | - Ronald L Hickman
- Case Western Reserve University, Frances Payne Bolton School of Nursing, Cleveland, OH 44106, United States.
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Challenges with Cell-based Therapies for Type 1 Diabetes Mellitus. Stem Cell Rev Rep 2022; 19:601-624. [PMID: 36434300 DOI: 10.1007/s12015-022-10482-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2022] [Indexed: 11/27/2022]
Abstract
Type 1 diabetes (T1D) is a chronic, lifelong metabolic disease. It is characterised by the autoimmune-mediated loss of insulin-producing pancreatic β cells in the islets of Langerhans (β-islets), resulting in disrupted glucose homeostasis. Administration of exogenous insulin is the most common management method for T1D, but this requires lifelong reliance on insulin injections and invasive blood glucose monitoring. Replacement therapies with beta cells are being developed as an advanced curative treatment for T1D. Unfortunately, this approach is limited by the lack of donated pancreatic tissue, the difficulties in beta cell isolation and viability maintenance, the longevity of the transplanted cells in vivo, and consequently high costs. Emerging approaches to address these limitations are under intensive investigations, including the production of insulin-producing beta cells from various stem cells, and the development of bioengineered devices including nanotechnologies for improving islet transplantation efficacy without the need for recipients taking toxic anti-rejection drugs. These emerging approaches present promising prospects, while the challenges with the new techniques need to be tackled for ultimately clinical treatment of T1D. This review discussed the benefits and limitations of the cell-based therapies for beta cell replacement as potential curative treatment for T1D, and the applications of bioengineered devices including nanotechnology to overcome the challenges associated with beta cell transplantation.
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Itzkovitz A, Maggio V, Roy-Fleming A, Legault L, Brazeau AS. Nutrition and food literacy among young Canadian adults living with type 1 diabetes. Diabet Med 2022; 39:e14921. [PMID: 35870142 DOI: 10.1111/dme.14921] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 06/23/2022] [Accepted: 07/21/2022] [Indexed: 11/29/2022]
Abstract
AIM Nutrition and food literacy encompasses knowledge, skills and confidence to prepare healthy meals. This project aimed to assess and compare the proportion of young Canadian adults (18-29 years old) living with type 1 diabetes and without diabetes (controls) who demonstrated adequate nutritional health literacy. METHODS This cross-sectional study involved participants completing an online survey that included questions on socio-economic status, nutrition knowledge, confidence and skills in meal preparation and the Short Food Literacy Questionnaire (SFLQ). Proportion of participants with adequate SFLQ score (i.e. ≥34/52) was compared between the groups (two-sample t-test). RESULTS Among the 236 people living with type 1 diabetes and 191 controls (81.5% women), mean age was 24 ± 3 years for people living with type 1 diabetes and 22 ± 3 years for controls (p < 0.001). More people living with type 1 diabetes reported adequate SFLQ score (people living with type 1 diabetes 88.0% vs. Controls 68.0%; p < 0.001). Similarly, majority of people living with type 1 diabetes prepared their own meals compared to the controls (74.5% vs. 47.6%; p < 0.001). Enhanced SFLQ score was associated with higher cooking skills (p = 0.02) and confidence (p < 0.01) in preparing healthy meals. CONCLUSIONS Living with type 1 diabetes was associated with greater SFLQ scores among young Canadian adults. Having the independence, the confidence and skills in meal preparation were contributing factors.
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Affiliation(s)
| | - Vanessa Maggio
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
| | | | - Laurent Legault
- Department of Pediatrics, McGill University, Montreal, Quebec, Canada
| | - Anne-Sophie Brazeau
- School of Human Nutrition, McGill University, Montreal, Quebec, Canada
- Montreal Diabetes Research Center, Montreal, Quebec, Canada
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Chen M, Hu R, Cavinato C, Zhuang ZW, Zhang J, Yun S, Fernandez Tussy P, Singh A, Murtada SI, Tanaka K, Liu M, Fernández-Hernando C, Humphrey JD, Schwartz MA. Fibronectin-Integrin α5 Signaling in Vascular Complications of Type 1 Diabetes. Diabetes 2022; 71:2020-2033. [PMID: 35771994 PMCID: PMC9450851 DOI: 10.2337/db21-0958] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 06/20/2022] [Indexed: 11/13/2022]
Abstract
Vascular complications are a major cause of illness and death in patients with type 1 diabetes (T1D). Diabetic vascular basement membranes are enriched in fibronectin (FN), an extracellular matrix protein that amplifies inflammatory signaling in endothelial cells through its main receptor, integrin α5β1. Binding of the integrin α5 cytoplasmic domain to phosphodiesterase 4D5 (PDE4D5), which increases phosphodiesterase catalytic activity and inhibits antiinflammatory cAMP signaling, was found to mediate these effects. Here, we examined mice in which the integrin α5 cytoplasmic domain is replaced by that of α2 (integrin α5/2) or the integrin α5 binding site in PDE4D is mutated (PDE4Dmut). T1D was induced via injection of streptozotocin and hyperlipidemia induced via injection of PCSK9 virus and provision of a high-fat diet. We found that in T1D and hyperlipidemia, the integrin α5/2 mutation reduced atherosclerosis plaque size by ∼50%, with reduced inflammatory cell invasion and metalloproteinase expression. Integrin α5/2 T1D mice also had improved blood-flow recovery from hindlimb ischemia and improved biomechanical properties of the carotid artery. By contrast, the PDE4Dmut had no beneficial effects in T1D. FN signaling through integrin α5 is thus a major contributor to diabetic vascular disease but not through its interaction with PDE4D.
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Affiliation(s)
- Minghao Chen
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Rui Hu
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Cristina Cavinato
- Department of Biomedical Engineering, Yale University, New Haven, CT
| | - Zhenwu W. Zhuang
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Jiasheng Zhang
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Sanguk Yun
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Pablo Fernandez Tussy
- Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT
- Departments of Comparative Medicine and Pathology, Yale Center for Molecular and Systems Metabolism, Yale School of Medicine, New Haven, CT
| | - Abhishek Singh
- Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT
- Departments of Comparative Medicine and Pathology, Yale Center for Molecular and Systems Metabolism, Yale School of Medicine, New Haven, CT
| | - Sae-Il Murtada
- Department of Biomedical Engineering, Yale University, New Haven, CT
| | - Keiichiro Tanaka
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
| | - Min Liu
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
- Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Carlos Fernández-Hernando
- Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT
- Departments of Comparative Medicine and Pathology, Yale Center for Molecular and Systems Metabolism, Yale School of Medicine, New Haven, CT
| | - Jay D. Humphrey
- Department of Biomedical Engineering, Yale University, New Haven, CT
- Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT
| | - Martin A. Schwartz
- Yale Cardiovascular Research Center, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT
- Department of Biomedical Engineering, Yale University, New Haven, CT
- Departments of Cell Biology and Biomedical Engineering, Yale University, New Haven, CT
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Benedict Á, Hankosky ER, Marczell K, Chen J, Klein DJ, Caro JJ, Bae JP, Benneyworth BD. A Framework for Integrating Continuous Glucose Monitor-Derived Metrics into Economic Evaluations in Type 1 Diabetes. PHARMACOECONOMICS 2022; 40:743-750. [PMID: 35668248 DOI: 10.1007/s40273-022-01148-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/18/2022] [Indexed: 06/15/2023]
Abstract
Economic models in type 1 diabetes have relied on a change in haemoglobin A1c as the link between the blood glucose trajectory and long-term clinical outcomes, including microvascular and macrovascular disease. The landscape has changed in the past decade with the availability of regulatory approved, accurate and convenient continuous glucose monitoring devices and their ability to track patients' glucose levels over time. The data emerging from continuous glucose monitoring have enriched the clinical understanding of the disease and indirectly of patients' behaviour. This has triggered the development of new measures proposed to better define the quality of glycaemic control, beyond haemoglobin A1c. The objective of this paper is to review recent developments in clinical knowledge brought into focus with the application of continuous glucose monitoring devices, and to discuss potential approaches to incorporate the concepts into economic models in type 1 diabetes. Based on a targeted review and a series of multidisciplinary workshops, an influence diagram was developed that captures newer concepts (e.g. continuous glucose monitoring metrics) that can be integrated into economic models and illustrates their association with more established concepts. How the additional continuous glucose monitoring-based indicators of glycaemic control may contribute to economic modelling beyond haemoglobin A1c, and more accurately reflect the economic value of novel type 1 diabetes treatments, is discussed.
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Affiliation(s)
- Ágnes Benedict
- Evidera, Bocskai út 134-146. E/2, 1113, Budapest, Hungary.
| | | | - Kinga Marczell
- Evidera, Bocskai út 134-146. E/2, 1113, Budapest, Hungary
| | | | | | | | - Jay P Bae
- Eli Lilly and Company, Indianapolis, IN, USA
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Fernández-González JF, García-Pedraza JÁ, Marín-Quílez A, Bastida JM, Martín ML, Morán A, García-Domingo M. Effect of sarpogrelate treatment on 5-HT modulation of vascular sympathetic innervation and platelet activity in diabetic rats. Biomed Pharmacother 2022; 153:113276. [PMID: 35717784 DOI: 10.1016/j.biopha.2022.113276] [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: 04/19/2022] [Revised: 05/26/2022] [Accepted: 06/08/2022] [Indexed: 11/16/2022] Open
Abstract
This study aimed to investigate whether the 5-HT2 receptor blockade alters the 5-HT effect on vascular sympathetic neurotransmission and platelet activation in type 1 diabetes. 28-day diabetes was obtained by alloxan (150 mg/kg; s.c.) in male Wistar rats, administering sarpogrelate (5-HT2 blocker; 30 mg/kg/day; p.o.) for 14 days. Blood glucose and body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet 5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous noradrenaline administration, examining the induced vasoconstrictor responses. Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain, hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma 5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in sarpogrelate-treated diabetic rats. 5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT1D or 5-HT7 antagonists (LY310762 or SB-258719, respectively), and totally annulled by the mixture of LY310762+SB-258719. Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day sarpogrelate treatment improves polydipsia and polyuria, reduces platelet hyperactivation, plasma 5-HT and the vascular sympathetic tone, and changes 5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT1D/7 are involved in the sympatho-inhibition.
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Affiliation(s)
- Juan Francisco Fernández-González
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - José Ángel García-Pedraza
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Ana Marín-Quílez
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain; Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), 37007 Salamanca, Spain
| | - José María Bastida
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain; Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), 37007 Salamanca, Spain
| | - María Luisa Martín
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Asunción Morán
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Mónica García-Domingo
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain.
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Helleputte S, Van Bortel L, Verbeke F, Op 't Roodt J, Calders P, Lapauw B, De Backer T. Arterial stiffness in patients with type 1 diabetes and its comparison to cardiovascular risk evaluation tools. Cardiovasc Diabetol 2022; 21:97. [PMID: 35681143 PMCID: PMC9185867 DOI: 10.1186/s12933-022-01537-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 05/28/2022] [Indexed: 11/15/2022] Open
Abstract
Background Arterial stiffness is a potential biomarker for cardiovascular disease (CVD) risk in patients with type 1 diabetes (T1D). However, its relation with other CV risk evaluation tools in T1D has not been elucidated yet. This study aimed to evaluate arterial stiffness in T1D patients free from known CVD, and compare it to other CV risk evaluation tools used in T1D. Methods Cross-sectional study in adults with a T1D duration of at least 10 years and without established CVD. Patients were categorized in CVD risk groups based on 2019 European Society of Cardiology (ESC) guidelines, and the STENO T1D risk engine was used to estimate 10-year risk for CV events. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV). Coronary artery calcium (CAC) score was assessed and carotid ultrasound was performed. Ambulatory 24-h blood pressure and central hemodynamic parameters were evaluated. Data on renal function and diabetic kidney disease was retrieved. Results 54 patients (age: 46 ± 9.5 years; T1D duration: 27 ± 8.8 years) were included. One-fourth of patients showed prematurely increased aortic stiffness based on cf-PWV (24%). Cf-PWV was significantly associated with CAC score, carotid intima-media thickness, central hemodynamic parameters and diabetic kidney disease. Based on STENO, 20 patients (37%) were at low, 20 patients (37%) at moderate, and 14 patients (26%) at high 10-year risk for CV event. Cf-PWV was strongly associated with the STENO score (rs = + 0.81; R2 = 0.566, p < 0.001), increasing with each higher STENO group (p < 0.01). However, cf-PWV was not significantly different between the two CV risk groups (high versus very high) based on ESC criteria, and ESC criteria compared to STENO classified 10 patients more as having > 10% 10-year risk for CV events (n = 44/54; 81.5% versus n = 34/54; 63%). Conclusions This study demonstrated that a substantial proportion of long-standing T1D patients free from known CVD show premature arterial stiffening. Cf-PWV strongly associates with the STENO risk score for future CV events and with cardiovascular imaging and function outcomes, thereby illustrating the clinical importance of arterial stiffness. The data, however, also show considerable heterogeneity in CV risk and differences in risk categorisation between the STENO tool and ESC criteria.There is a need for refinement of CV risk classification in T1D, and future studies should investigate if evaluation of arterial stiffness should be implemented in T1D clinical practice and which patients benefit the most from its assessment.
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Affiliation(s)
- Simon Helleputte
- Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium. .,Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen, Ghent, Belgium.
| | - Luc Van Bortel
- Unit of Clinical Pharmacology, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
| | - Francis Verbeke
- Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium.,Department of Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Jos Op 't Roodt
- Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands
| | - Patrick Calders
- Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium
| | - Bruno Lapauw
- Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium.,Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Tine De Backer
- Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000, Ghent, Belgium.,Unit of Clinical Pharmacology, Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.,Department of Cardiology, Ghent University Hospital, Ghent, Belgium
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Praveen PA, Anandakumar A, Singh K, Prabhakaran D, Narayan KMV, Mohan V, Tandon N. Cardiovascular disease risk profile of Indian young adults with type 1 diabetes compared to general population - A sub-study from the Young Diabetes Registry (YDR), India. Diabetes Res Clin Pract 2022; 187:109863. [PMID: 35381291 DOI: 10.1016/j.diabres.2022.109863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 03/06/2022] [Accepted: 03/30/2022] [Indexed: 11/21/2022]
Abstract
OBJECTIVE We estimated the prevalence of traditional CVD risk factors among young adults with type 1 diabetes and compared them with the general population without diabetes. METHODS Participants were young adults (aged 20 years and above) with type 1 diabetes, from the Delhi and Chennai sites of the ICMR -Young Diabetes Registry (YDR) and their age, gender and location matched controls, without diabetes from the CARRS (Cardio metabolic Risk Reduction in South Asia) cohort. YDR and CARRS used similar standard methodologies to quantify the CVD risk factors. Linear and logistic regression models were used to compare the adjusted means and proportions of risk factors. RESULTS Individuals with type 1 diabetes had lower levels of mean BMI (21.9 kg/m2 vs 24.3 kg/m2), waist circumference (76.8 cm vs 82.1 cm), favourable lipid profile (lower LDL and higher HDL), higher mean systolic blood pressure (122.1 mmHg vs 118.7 mmHg) and hypertension (29.2% vs 21.0%), compared to controls. The extent of clustering of two or more traditional CVD risk factors was higher among general population compared to people with type 1 diabetes. CONCLUSION We found that young adults with type 1 diabetes have relatively low prevalence and clustering of traditional CVD risk factors compared to general population.
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Affiliation(s)
- Pradeep A Praveen
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Amutha Anandakumar
- Dr. Mohan's Diabetes Specialties Centre and Madras Diabetes Research Foundation, Chennai, India
| | | | - Dorairaj Prabhakaran
- Centre for Control of Chronic Conditions, Public Health Foundation of India, Gurgaon, Haryana, India.
| | - K M Venkat Narayan
- Ruth and O.C. Hubert Professor of Global Health and Epidemiology, Rollins School of Public Health, Emory University, USA.
| | - Viswanathan Mohan
- Dr. Mohan's Diabetes Specialties Centre and Madras Diabetes Research Foundation, Chennai, India.
| | - Nikhil Tandon
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
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Garavelli S, Prattichizzo F, Ceriello A, Galgani M, de Candia P. Type 1 Diabetes and Associated Cardiovascular Damage: Contribution of Extracellular Vesicles in Tissue Crosstalk. Antioxid Redox Signal 2022; 36:631-651. [PMID: 34407376 DOI: 10.1089/ars.2021.0053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Significance: Type 1 diabetes (T1D) is characterized by the autoimmune destruction of the insulin secreting β-cells, with consequent aberrant blood glucose levels. Hyperglycemia is the common denominator for most of the chronic diabetic vascular complications, which represent the main cause of life reduction in T1D patients. For this disease, three interlaced medical needs remain: understanding the underlying mechanisms involved in pancreatic β-cell loss; identifying biomarkers able to predict T1D progression and its related complications; recognizing novel therapeutic targets. Recent Advances: Extracellular vesicles (EVs), released by most cell types, were discovered to contain a plethora of different molecules (including microRNAs) with regulatory properties, which are emerging as mediators of cell-to-cell communication at the paracrine and endocrine level. Recent knowledge suggests that EVs may act as pathogenic factors, and be developed into disease biomarkers and therapeutic targets in the context of several human diseases. Critical Issues: EVs have been recently shown to sustain a dysregulated cellular crosstalk able to exacerbate the autoimmune response in the pancreatic islets of T1D; moreover, EVs were shown to be able to monitor and/or predict the progression of T1D and the insurgence of vasculopathies. Future Directions: More mechanistic studies are needed to investigate whether the dysregulation of EVs in T1D patients is solely reflecting the progression of diabetes and related complications, or EVs also directly participate in the disease process, thus pointing to a potential use of EVs as therapeutic targets/tools in T1D. Antioxid. Redox Signal. 36, 631-651.
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Affiliation(s)
- Silvia Garavelli
- Institute for Endocrinology and Experimental Oncology "G. Salvatore," Consiglio Nazionale delle Ricerche (C.N.R.), Naples, Italy
| | | | | | - Mario Galgani
- Institute for Endocrinology and Experimental Oncology "G. Salvatore," Consiglio Nazionale delle Ricerche (C.N.R.), Naples, Italy.,Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II," Italy
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Inkeri J, Adeshara K, Harjutsalo V, Forsblom C, Liebkind R, Tatlisumak T, Thorn LM, Groop PH, Shams S, Martola J, Putaala J, Gordin D. Glycemic control is not related to cerebral small vessel disease in neurologically asymptomatic individuals with type 1 diabetes. Acta Diabetol 2022; 59:481-490. [PMID: 34778921 PMCID: PMC8917104 DOI: 10.1007/s00592-021-01821-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/22/2021] [Indexed: 11/30/2022]
Abstract
AIMS To determine if medium- and long-term blood glucose control as well as glycemic variability, which are known to be strong predictors of vascular complications, are associated with underlying cerebral small vessel disease (cSVD) in neurologically asymptomatic individuals with type 1 diabetes. METHODS A total of 189 individuals (47.1% men; median age 40.0, IQR 33.0-45.2 years) with type 1 diabetes (median diabetes duration of 21.7, IQR 18.3-30.7 years) were enrolled in a cross-sectional retrospective study, as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Glycated hemoglobin (HbA1c) values were collected over the course of ten years before the visit including a clinical examination, biochemical sampling, and brain magnetic resonance imaging. Markers of glycemic control, measured during the visit, included HbA1c, fructosamine, and glycated albumin. RESULTS Signs of cSVD were present in 66 (34.9%) individuals. Medium- and long-term glucose control and glycemic variability did not differ in individuals with signs of cSVD compared to those without. Further, no difference in any of the blood glucose variables and cSVD stratified for cerebral microbleeds (CMBs) or white matter hyperintensities were detected. Neither were numbers of CMBs associated with the studied glucose variables. Additionally, after dividing the studied variables into quartiles, no association with cSVD was observed. CONCLUSIONS We observed no association between glycemic control and cSVD in neurologically asymptomatic individuals with type 1 diabetes. This finding was unexpected considering the large number of signs of cerebrovascular pathology in these people after two decades of chronic hyperglycemia and warrants further studies searching for underlying factors of cSVD.
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Affiliation(s)
- Jussi Inkeri
- HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
| | - Krishna Adeshara
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland
| | - Carol Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland
| | - Ron Liebkind
- Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Turgut Tatlisumak
- Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Clinical Neuroscience/Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Lena M Thorn
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland
- Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia.
| | - Sara Shams
- Department of Radiology, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
- Department of Radiology, Stanford University, Stanford, CA, USA
| | - Juha Martola
- HUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Jukka Putaala
- Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Daniel Gordin
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Minerva Foundation Institute for Medical Research, Helsinki, Finland
- Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
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Abstract
PURPOSE OF REVIEW To critically appraise new insights into HDL structure and function in type 1 diabetes (T1DM) and type 2 diabetes (T2DM). RECENT FINDINGS In young T1DM patients with early renal impairment and a high inflammatory score, both HDL antioxidative activity and endothelial vasodilatory function were impaired, revealing a critical link between HDL dysfunction, subclinical vascular damage, systemic inflammation and end organ damage. HDL may inhibit development of T2DM by attenuating endoplasmic reticulum (ER) stress and apoptotic loss of pancreatic β-cells, an effect due in part to ABC transporter-mediated efflux of specific oxysterols with downstream activation of the hedghehog signalling receptor, Smoothened. The apoM-sphingosine-1-phosphate complex is critical to HDL antidiabetic activity, encompassing protection against insulin resistance, promotion of insulin secretion, enhanced β-cell survival and inhibition of hepatic glucose production. Structure-function studies of HDL in hyperglycemic, dyslipidemic T2DM patients revealed both gain and loss of lipidomic and proteomic components. Such changes attenuated both the optimal protective effects of HDL on mitochondrial function and its capacity to inhibit endothelial cell apoptosis. Distinct structural components associated with individual HDL functions. SUMMARY Extensive evidence indicates that both the proteome and lipidome of HDL are altered in T1DM and T2DM, with impairment of multiple functions.
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Affiliation(s)
- M. John Chapman
- Faculty of Medicine, Sorbonne University
- Endocrinology and Cardiovascular Disease Prevention, Pitie-Salpetriere University Hospital
- National Institute for Health and Medical Research (INSERM), Paris, France
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Shao B, Snell-Bergeon JK, Pyle LL, Thomas KE, de Boer IH, Kothari V, Segrest J, Davidson WS, Bornfeldt KE, Heinecke JW. Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes. J Lipid Res 2022; 63:100196. [PMID: 35300983 PMCID: PMC9010748 DOI: 10.1016/j.jlr.2022.100196] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 12/22/2022] Open
Abstract
Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein-SFTPB (pulmonary surfactant protein B)-predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker-and perhaps mediator-of CVD risk in patients with T1DM.
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Affiliation(s)
- Baohai Shao
- Department of Medicine, University of Washington, Seattle, WA, USA.
| | | | - Laura L Pyle
- Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Katie E Thomas
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Ian H de Boer
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Vishal Kothari
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Jere Segrest
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - William S Davidson
- Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA
| | | | - Jay W Heinecke
- Department of Medicine, University of Washington, Seattle, WA, USA
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Abstract
A literature search was conducted to identify publications addressing the early phases of lipid phenotypes in children and adults with either type 1 diabetes or type 2 diabetes. Medline, EMBASE, and Ovid were searched using the following search terms: clinical remission, partial remission, partial clinical remission, honeymoon phase, C-peptide, type 1 or 2 diabetes, children, pediatric type 1 or 2 diabetes, and paediatrics type 1 or 2 diabetes, adults, adult type 1 or type 2 diabetes. Partial clinical remission (PR) of type 1 diabetes (T1D) is characterized by continued endogenous production of insulin and C-peptide following the diagnosis and the introduction of exogenous insulin therapy. PR is associated with improved glycemic control and reduced prevalence of diabetes complications. The theory of hyperglycemic memory was proposed to explain this concept of improved glycemic outcomes in remitters (those who experienced PR) versus non-remitters (those who did not experience PR). However, this theory is incomplete as it does not explain the dichotomy in early lipid phenotypes in T1D based on PR status, which is an understudied area in diabetology and lipidology. To fill this knowledge gap, we propose the Theory of Hyperlipidemic Memory of T1D. This theory is premised on our 5-year research on early post-diagnostic dichotomy in lipid phenotypes between remitters and non-remitters across the lifespan. It provides a more rigorous explanation for the differences in lifelong atherosclerotic cardiovascular disease (ASCVD) risk between remitters and non-remitters. We conducted 4 clinical studies in pediatric and adult subjects with diabetes mellitus to characterize the particulars of the hyperlipidemic memory. In the first investigation, we explored the impact of the presence or absence of PR on lipid parameters in children and adolescents with T1D. In the second, we investigated whether pubertal maturation influenced our findings in T1D; and whether these findings could be replicated in healthy, non-diabetic children and adolescents. In the third, we leveraged our findings from T1D and controls to investigate the mechanisms of early lipid changes in T2D by comparing the earliest lipid phenotype of subjects with type 2 diabetes (T2D) to those of remitters, non-remitters, and controls. In the fourth, we investigated the impact of PR on the earliest lipid phenotypes in adults with T1D and compared these early lipid data to those of T2D subjects and controls. This body of work across the lifespan in children, adolescents, and adults supports the Theory of Hyperlipidemic Memory. This new theory clarifies why PR largely determines the risks for early-phase dyslipidemia, mid-term microvascular disease risk, and long-term ASCVD risk in subjects with T1D.
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Affiliation(s)
- Benjamin Udoka Nwosu
- Division of Endocrinology, Department of Pediatrics, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, United States
- Division of Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, United States
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Wake AD. Protective effects of physical activity against health risks associated with type 1 diabetes: "Health benefits outweigh the risks". World J Diabetes 2022; 13:161-184. [PMID: 35432757 PMCID: PMC8984568 DOI: 10.4239/wjd.v13.i3.161] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 12/08/2021] [Accepted: 02/20/2022] [Indexed: 02/06/2023] Open
Abstract
The magnitude of diabetes mellitus (DM) has increased in recent decades, where the number of cases and the proportion of the disease have been gradually increasing over the past few decades. The chronic complications of DM affect many organ systems and account for the majority of morbidity and mortality associated with the disease. The prevalence of type 1 DM (T1DM) is increasing globally, and it has a very significant burden on countries and at an individual level. T1DM is a chronic illness that requires ongoing medical care and patient self-management to prevent complications. This study aims to discuss the health benefits of physical activity (PA) in T1DM patients. The present review article was performed following a comprehensive literature search. The search was conducted using the following electronic databases: "Cochrane Library", Web of Science, PubMed, HINARI, EMBASE, Google for grey literature, Scopus, African journals Online, and Google Scholar for articles published up to June 21, 2021. The present review focused on the effects of PA on many outcomes such as blood glucose (BG) control, physical fitness, endothelial function, insulin sensitivity, well-being, the body defense system, blood lipid profile, insulin resistance, cardiovascular diseases (CVDs), insulin requirements, blood pressure (BP), and mortality. It was found that many studies recommended the use of PA for the effective management of T1DM. PA is a component of comprehensive lifestyle modifications, which is a significant approach for the management of T1DM. It provides several health benefits, such as improving BG control, physical fitness, endothelial function, insulin sensitivity, well-being, and the body defense system. Besides this, it reduces the blood lipid profile, insulin resistance, CVDs, insulin requirements, BP, and mortality. Overall, PA has significant and essential protective effects against the health risks associated with T1DM. Even though PA has several health benefits for patients with T1DM, these patients are not well engaged in PA due to barriers such as a fear of exercise-induced hypoglycemia in particular. However, several effective strategies have been identified to control exercise-induced hypoglycemia in these patients. Finally, the present review concludes that PA should be recommended for the management of patients with T1DM due to its significant health benefits and protective effects against associated health risks. It also provides suggestions for the future direction of research in this field.
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Affiliation(s)
- Addisu Dabi Wake
- Department of Nursing, College of Health Sciences, Arsi University, Asella 193/4, Ethiopia
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Lithovius R, Antikainen AA, Mutter S, Valo E, Forsblom C, Harjutsalo V, Sandholm N, Groop PH. Genetic Risk Score Enhances Coronary Artery Disease Risk Prediction in Individuals With Type 1 Diabetes. Diabetes Care 2022; 45:734-741. [PMID: 35019974 DOI: 10.2337/dc21-0974] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 12/05/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Individuals with type 1 diabetes are at a high lifetime risk of coronary artery disease (CAD), calling for early interventions. This study explores the use of a genetic risk score (GRS) for CAD risk prediction, compares it to established clinical markers, and investigates its performance according to the age and pharmacological treatment. RESEARCH DESIGN AND METHODS This study in 3,295 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) used three risk scores: a GRS, a validated clinical score, and their combined score. Hazard ratios (HR) were calculated with Cox regression, and model performances were compared with the Harrell C-index (C-index). RESULTS A HR of 6.7 for CAD was observed between the highest and the lowest 5th percentile of the GRS (P = 1.8 × 10-6). The performance of GRS (C-index = 0.562) was similar to HbA1c (C-index = 0.563, P = 0.96 for difference), HDL (C-index = 0.571, P = 0.6), and total cholesterol (C-index = 0.594, P = 0.1). The GRS was not correlated with the clinical score (r = -0.013, P = 0.5). The combined score outperformed the clinical score (C-index = 0.813 vs. C-index = 0.820, P = 0.003). The GRS performed better in individuals below the median age (38.6 years) compared with those above (C-index = 0.637 vs. C-index = 0.546). CONCLUSIONS A GRS identified individuals at high risk of CAD and worked better in younger individuals. GRS was also an independent risk factor for CAD, with a predictive power comparable to that of HbA1c and HDL and total cholesterol, and when incorporated into a clinical model, modestly improved the predictions. The GRS promises early risk stratification in clinical practice by enhancing the prediction of CAD.
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Affiliation(s)
- Raija Lithovius
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Anni A Antikainen
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Stefan Mutter
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Erkka Valo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Carol Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,National Institute for Health and Welfare, Chronic Disease Prevention Unit, Helsinki, Finland
| | - Niina Sandholm
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
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Reis RMDF, Azulay RSDS, Tavares MDG, Nascimento GC, Damianse SDSP, Rocha VCDC, Almeida AG, Lago DCF, Rodrigues V, Magalhães M, Sobral CS, Parente C, França J, Ribeiro J, Ferraz PCD, Junior CAA, Silva DA, Gomes MB, Faria MDS. Early Markers of Cardiovascular Disease Associated with Clinical Data and Autosomal Ancestry in Patients with Type 1 Diabetes: A Cross-Sectional Study in an Admixed Brazilian Population. Genes (Basel) 2022; 13:genes13020389. [PMID: 35205433 PMCID: PMC8872303 DOI: 10.3390/genes13020389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/13/2022] [Accepted: 02/14/2022] [Indexed: 11/16/2022] Open
Abstract
Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from an admixed Brazilian population. A cross-sectional study was conducted with 99 T1D patients. The mean age of the study sample was 27.6 years and the mean duration of T1D was 14.4 years. The frequencies of abnormalities of the early markers of CVD were 19.6% in the ankle-brachial index (ABI), 4.1% in the coronary artery calcium score (CACS), and 5% in the carotid Doppler. A significant percentage of agreement was observed for the comparison of the frequency of abnormalities between CACS and carotid Doppler (92.2%, p = 0.041). There was no significant association between the level of autosomal ancestry proportions and early markers of CVD. The ABI was useful in the early identification of CVD in asymptomatic young patients with T1D and with a short duration of disease. Although CACS and carotid Doppler are non-invasive tests, carotid Doppler is more cost-effective, and both have limitations in screening for CVD in young patients with a short duration of T1D. We did not find a statistically significant relationship between autosomal ancestry proportions and early CVD markers in an admixed Brazilian population.
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Affiliation(s)
- Roberta Maria Duailibe Ferreira Reis
- Graduate Program in Adult Health (PPGSAD), Federal University of Maranhão-UFMA, Av. dos Portugueses, São Luís 65085-580, Brazil; (M.M.); (M.d.S.F.)
- Correspondence:
| | - Rossana Santiago de Sousa Azulay
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Maria da Glória Tavares
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Gilvan Cortês Nascimento
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Sabrina da Silva Pereira Damianse
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Viviane Chaves de Carvalho Rocha
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Ana Gregória Almeida
- Research Group in Clinical and Molecular Endocrinology and Metabology (ENDOCLIM), São Luís 65020-070, Brazil; (A.G.A.); (V.R.); (J.R.); (P.C.D.F.); (C.A.A.J.)
| | - Débora Cristina Ferreira Lago
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Vandilson Rodrigues
- Research Group in Clinical and Molecular Endocrinology and Metabology (ENDOCLIM), São Luís 65020-070, Brazil; (A.G.A.); (V.R.); (J.R.); (P.C.D.F.); (C.A.A.J.)
| | - Marcelo Magalhães
- Graduate Program in Adult Health (PPGSAD), Federal University of Maranhão-UFMA, Av. dos Portugueses, São Luís 65085-580, Brazil; (M.M.); (M.d.S.F.)
| | - Carla Souza Sobral
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Conceição Parente
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Joana França
- Service of Endocrinology, University Hospital of the Federal University of Maranhão (HUUFMA/EBSERH), Rua Barão de Itapary, 227-Centro, São Luís 65020-070, Brazil; (R.S.d.S.A.); (M.d.G.T.); (G.C.N.); (S.d.S.P.D.); (V.C.d.C.R.); (D.C.F.L.); (C.S.S.); (C.P.); (J.F.)
| | - Jacqueline Ribeiro
- Research Group in Clinical and Molecular Endocrinology and Metabology (ENDOCLIM), São Luís 65020-070, Brazil; (A.G.A.); (V.R.); (J.R.); (P.C.D.F.); (C.A.A.J.)
| | - Paulo Cézar Dias Ferraz
- Research Group in Clinical and Molecular Endocrinology and Metabology (ENDOCLIM), São Luís 65020-070, Brazil; (A.G.A.); (V.R.); (J.R.); (P.C.D.F.); (C.A.A.J.)
| | - Carlos Alberto Azulay Junior
- Research Group in Clinical and Molecular Endocrinology and Metabology (ENDOCLIM), São Luís 65020-070, Brazil; (A.G.A.); (V.R.); (J.R.); (P.C.D.F.); (C.A.A.J.)
| | - Dayse Aparecida Silva
- DNA Diagnostic Laboratory (LDD), Rio de Janeiro State University (UERJ), R. São Francisco Xavier, Rio de Janeiro 20550-013, Brazil;
| | - Marília Brito Gomes
- Diabetes Unit, State University of Rio de Janeiro (UERJ), R. São Francisco Xavier, Rio de Janeiro 20550-013, Brazil;
| | - Manuel dos Santos Faria
- Graduate Program in Adult Health (PPGSAD), Federal University of Maranhão-UFMA, Av. dos Portugueses, São Luís 65085-580, Brazil; (M.M.); (M.d.S.F.)
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49
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SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes. PLoS One 2022; 17:e0263285. [PMID: 35176041 PMCID: PMC8853531 DOI: 10.1371/journal.pone.0263285] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 01/17/2022] [Indexed: 02/07/2023] Open
Abstract
Introduction Cardiovascular disease (CVD) is two to five times more prevalent in diabetic patients and is the leading cause of death. Therefore, identification of novel therapeutic strategies that reduce the risk of CVD is a research priority. Clinical trials showed that reduction in the relative risk of heart failure by sodium-glucose cotransporter 2 inhibitors (SGLT2i) are partly beyond their glucose lowering effects, however, the molecular mechanisms are still elusive. Here we investigated the role of SGLT2i dapagliflozin (DAPA) in the prevention of diabetes-induced cardiovascular complications. Methods Type 1 diabetes was induced with streptozotocin (65 mg/bwkg, ip.) in adult, male Wistar rats. Following the onset of diabetes rats were treated for six weeks with DAPA (1 mg/bwkg/day, po.). Results DAPA decreased blood glucose levels (D: 37±2.7 vs. D+DAPA: 18±5.6 mmol/L; p<0.05) and prevented metabolic decline. Aortic intima-media thickening was mitigated by DAPA. DAPA abolished cardiac hypertrophy, and myocardial damage. Cardiac inflammation and fibrosis were also moderated after DAPA treatment. Conclusions These data support the preventive and protective role of SGLT2i in diabetes-associated cardiovascular disease. SGLT2i may provide novel therapeutic strategy to hinder the development of cardiovascular diseases in type 1 diabetes, thereby improve the outcomes.
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50
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Maragkoudakis S, Katsi V, Melidonis A, Soulaidopoulos S, Kolovou GD, Papazafeiropoulou AK, Trikkalinou A, Toutouzas K, Tsioufis K. Antiplatelet and Antithrombotic Therapy in Type I Diabetes Mellitus: Update on Current Data. Curr Diabetes Rev 2022; 18:e030122199792. [PMID: 34979890 DOI: 10.2174/1573399818666220103091236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/07/2021] [Accepted: 10/21/2021] [Indexed: 11/22/2022]
Abstract
Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by a markedly elevated cardiovascular (CV) risk due to premature atherosclerosis. Previous studies have shown that intense glycemic control reduces the incidence of CV disease. Antiplatelet therapy is considered to be a very important therapy for secondary prevention of recurrent atherothrombotic events in patients with DM, while it may be considered for primary prevention in individuals with T1DM with additional CV risk factors. The aim of the present review is to summarize existing literature data regarding the thrombotic risk in T1DM patients and discuss current treatment strategies.
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Affiliation(s)
| | - Vasiliki Katsi
- First Department of Cardiology, National and Kapodistrian University of Athens,School of Medicine, Hippokration General Hospital, Athens, Greece
| | | | - Stergios Soulaidopoulos
- Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Genovefa D Kolovou
- Cardiometabolic Center, Lipid Center, Metropolitan Hospital, Athens, Greece
| | | | | | - Konstantinos Toutouzas
- Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Konstantinos Tsioufis
- Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
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