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Karipidou M, Liatis S, Kyrkili A, Skoufi A, Lambadiari V, Tigas S, Liberopoulos E, Kontogianni MD. Exploring the effect of adhering to a healthy lifestyle pattern on glycemic control in adults with type 1 diabetes mellitus. Nutr Metab Cardiovasc Dis 2025; 35:103868. [PMID: 39986932 DOI: 10.1016/j.numecd.2025.103868] [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: 09/22/2024] [Revised: 01/11/2025] [Accepted: 01/17/2025] [Indexed: 02/24/2025]
Abstract
BACKGROUND AND AIMS Diet, physical activity, sleep and smoking have been individually associated with glycemic control (GC) in adults with type 1 diabetes mellitus (T1D). However, the combined effect of these factors has not been investigated. The aim of the present study was to examine the single and combined effects of lifestyle parameters on GC of people with T1D (PwT1D). METHODS AND RESULTS Dietary, physical activity and sleep habits were evaluated using validated questionnaires. Diet quality was assessed with two scores (MedDietScore and PURE Diet Score) and two healthy lifestyle indices (HLI) were constructed (MLI based on MedDietScore and PLI based on PURE score). The score of both HLI ranged from 0 to 12 with higher scores indicating greater adherence to the healthy lifestyle pattern. One hundred ninety-two adults [61 % female, median age 42 (34, 51) years] with T1D were included in the analysis. Good GC (defined as HbA1c<7 %) was observed in 31 % of study participants. Examining lifestyle components separately, only smoking was marginally inversely associated with good GC [odds ratio (OR): 0.48, (95 % confidence interval, CI:0.23-1.00; p = 0.050)]. Individuals with better GC had significantly higher HLI scores (both p < 0.05). After adjusting for age, sex, body mass index, wearing an insulin pump and using continuous glucose monitoring, one-unit increase in the PLI was associated with 16 % higher likelihood of good GC (OR:1.16, 95 % CI:1.01-1.35, p = 0.04) and a similar trend was recorded for MLI (p = 0.05). CONCLUSION Our results suggest that adherence to a healthy lifestyle, more so than single lifestyle parameters, is associated with better GC in PwT1D.
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Affiliation(s)
- Melina Karipidou
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University of Athens, Athens, Greece
| | - Stavros Liatis
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, Athens, Greece
| | - Athanasia Kyrkili
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University of Athens, Athens, Greece
| | - Alexandra Skoufi
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University of Athens, Athens, Greece
| | - Vaia Lambadiari
- Second Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Stelios Tigas
- Department of Endocrinology, University of Ioannina, Ioannina, Greece
| | - Evangelos Liberopoulos
- First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens Medical School, Laiko General Hospital, Athens, Greece
| | - Meropi D Kontogianni
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University of Athens, Athens, Greece.
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Glynn L, Lind M, Andersson T, Eliasson B, Hofmann R, Nyström T. Trends in Survival After First Myocardial Infarction in People With Diabetes. J Am Heart Assoc 2024; 13:e034741. [PMID: 38761078 PMCID: PMC11179798 DOI: 10.1161/jaha.123.034741] [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: 02/02/2024] [Accepted: 04/16/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. METHODS AND RESULTS Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all-cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo-observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change -0.48% [95% CI, -0.52% to -0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, -0.33% [95% CI, -0.43% to -0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, -0.18% [95% CI, -0.53% to 0.17%]). Similar trends were observed with regard to 1-year death, cardiovascular death, and major adverse cardiovascular events. CONCLUSIONS During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.
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Affiliation(s)
- Linn Glynn
- Department of Clinical Science and Education, Södersjukhuset Karolinska Institutet Stockholm Sweden
| | - Marcus Lind
- Department of Medicine Sahlgrenska University Hospital Gothenburg Sweden
- Department of Medicine, NU-Hospital Group Uddevalla Sweden
- Department of Molecular and Clinical Medicine Institute of Medicine, University of Gothenburg Gothenburg Sweden
| | - Tomas Andersson
- Institute of Environmental Medicine, Karolinska Institutet Stockholm Sweden
- Center for Occupational and Environmental Medicine, Region Stockholm Stockholm Sweden
| | - Björn Eliasson
- Department of Medicine Sahlgrenska University Hospital Gothenburg Sweden
| | - Robin Hofmann
- Department of Clinical Science and Education, Södersjukhuset Karolinska Institutet Stockholm Sweden
| | - Thomas Nyström
- Department of Clinical Science and Education, Södersjukhuset Karolinska Institutet Stockholm Sweden
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Denimal D, Monier S, Simoneau I, Duvillard L, Vergès B, Bouillet B. HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control. Cardiovasc Diabetol 2022; 21:154. [PMID: 35962339 PMCID: PMC9375300 DOI: 10.1186/s12933-022-01591-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 08/04/2022] [Indexed: 11/21/2022] Open
Abstract
Background Reduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs. Methods In this open-label trial, 27 uncontrolled T1D patients were given a three-month standard medical intervention to improve glycemic control. HDL fraction was isolated from plasma, and CEC was measured on THP-1 macrophages. Carbamylation of HDLs was evaluated by an immunoassay. Control HDLs from healthy subjects were carbamylated in vitro with potassium cyanate. Results HbA1c decreased from 11.4% [10.2–12.9] (median [1st–3rd quartiles]) at baseline to 8.1% [6.6–9.0] after the three-month intervention (P < 0.00001). The CEC of HDLs increased after intervention in 19 (70%) patients (P = 0.038). At the same time, the carbamylation of HDLs decreased in 22 (82%) patients after intervention (P = 0.014). The increase in CEC significantly correlated with the decrease in carbamylated HDLs (r = −0.411, P = 0.034), even after adjustment for the change in HbA1c (β = −0.527, P = 0.003). In vitro carbamylation of control HDLs decreased CEC by 13% (P = 0.041) and 23% (P = 0.021) using 1 and 10 mmol/L of potassium cyanate, respectively. Conclusions The improvement of CEC in relation to a decrease in the carbamylation of HDLs may likely contribute to the beneficial cardiovascular effect of glycemic control in T1D patients. Trial registration: NCT02816099 ClinicalTrials.gov.
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Affiliation(s)
- Damien Denimal
- INSERM LNC UMR1231, University of Burgundy, Dijon, France. .,Department of Biochemistry - Plateforme de Biologie Hospitalo-Universitaire, CHU Dijon, Dijon, France.
| | - Serge Monier
- INSERM LNC UMR1231, University of Burgundy, Dijon, France
| | - Isabelle Simoneau
- INSERM LNC UMR1231, University of Burgundy, Dijon, France.,Department of Endocrinology-Diabetology, CHU Dijon, Dijon, France
| | - Laurence Duvillard
- INSERM LNC UMR1231, University of Burgundy, Dijon, France.,Department of Biochemistry - Plateforme de Biologie Hospitalo-Universitaire, CHU Dijon, Dijon, France
| | - Bruno Vergès
- INSERM LNC UMR1231, University of Burgundy, Dijon, France.,Department of Endocrinology-Diabetology, CHU Dijon, Dijon, France
| | - Benjamin Bouillet
- INSERM LNC UMR1231, University of Burgundy, Dijon, France.,Department of Endocrinology-Diabetology, CHU Dijon, Dijon, France
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Yang L, Hu ZM, Jiang FX, Wang W. Stem cell therapy for insulin-dependent diabetes: Are we still on the road? World J Stem Cells 2022; 14:503-512. [PMID: 36157527 PMCID: PMC9350623 DOI: 10.4252/wjsc.v14.i7.503] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/26/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
In insulin-dependent diabetes, the islet β cells do not produce enough insulin and the patients must receive exogenous insulin to control blood sugar. However, there are still many deficiencies in exogenous insulin supplementation. Therefore, the replacement of destroyed functional β cells with insulin-secreting cells derived from functional stem cells is a good idea as a new therapeutic idea. This review introduces the development schedule of mouse and human embryonic islets. The differences between mouse and human pancreas embryo development were also listed. Accordingly to the different sources of stem cells, the important research achievements on the differentiation of insulin-secreting β cells of stem cells and the current research status of stem cell therapy for diabetes were reviewed. Stem cell replacement therapy is a promising treatment for diabetes, caused by defective insulin secretion, but there are still many problems to be solved, such as the biosafety and reliability of treatment, the emergence of tumors during treatment, untargeted differentiation and autoimmunity, etc. Therefore, further understanding of stem cell therapy for insulin is needed.
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Affiliation(s)
- Lu Yang
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China
| | - Zhu-Meng Hu
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China
| | - Fang-Xu Jiang
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China
- School of Biomedical Science, University of Western Australia, Nedlands 6009, Australia
- School of Health and Medical Sciences, Edith Cowan University, Perth 6000, Australia
| | - Wei Wang
- Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, Fujian Province, China.
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Yang L, Hu ZM, Jiang FX, Wang W. Stem cell therapy for insulin-dependent diabetes: Are we still on the road? World J Stem Cells 2022. [DOI: 10.4252/wjsc.v14.i7.503 yang l] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Prandi FR, Lecis D, Illuminato F, Milite M, Celotto R, Lerakis S, Romeo F, Barillà F. Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers. Int J Mol Sci 2022; 23:4589. [PMID: 35562979 PMCID: PMC9105558 DOI: 10.3390/ijms23094589] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/18/2022] [Accepted: 04/20/2022] [Indexed: 12/21/2022] Open
Abstract
Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments ("epidrugs") with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.
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Affiliation(s)
- Francesca Romana Prandi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (D.L.); (F.I.); (M.M.); (R.C.); (F.B.)
- Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Dalgisio Lecis
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (D.L.); (F.I.); (M.M.); (R.C.); (F.B.)
| | - Federica Illuminato
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (D.L.); (F.I.); (M.M.); (R.C.); (F.B.)
| | - Marialucia Milite
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (D.L.); (F.I.); (M.M.); (R.C.); (F.B.)
| | - Roberto Celotto
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (D.L.); (F.I.); (M.M.); (R.C.); (F.B.)
| | - Stamatios Lerakis
- Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Francesco Romeo
- Department of Departmental Faculty of Medicine, Unicamillus-Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy;
| | - Francesco Barillà
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy; (D.L.); (F.I.); (M.M.); (R.C.); (F.B.)
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7
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Prandi FR, Evangelista I, Sergi D, Palazzuoli A, Romeo F. Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants. Heart Fail Rev 2022; 28:597-606. [PMID: 35001338 DOI: 10.1007/s10741-021-10200-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/01/2021] [Indexed: 12/14/2022]
Abstract
Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition characterized by cardiac structural, functional, and metabolic changes that can result in heart failure (HF), in the absence of coronary artery disease, hypertension, and valvular heart disease. Metabolic alterations such as hyperglycemia, insulin resistance, hyperinsulinemia, and increased metabolism of free fatty acids result in oxidative stress, inflammation, advanced glycation end products formation, abnormalities in calcium homeostasis, and apoptosis that are responsible for structural remodeling. Cardiac stiffness, hypertrophy, and fibrosis eventually lead to dysfunction and HF with preserved ejection fraction and/or HF with reduced ejection fraction. In this review, we analyzed in detail the cellular and molecular mechanisms and the metabolic pathways involved in the pathophysiology of DCM. Different phenotypes are observed in DCM, and it is not clear yet if the restrictive and the dilated phenotypes are distinct or represent an evolution of the same disease. Phenotypic differences can be observed between T1DM and T2DM DCM, possibly explained by the different myocardial insulin action. Further studies are needed in order to better understand the underlying mechanisms of DCM and to identify appropriate therapeutic targets and novel strategies to prevent and reverse the progression toward heart failure in diabetic patients.
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Affiliation(s)
| | - Isabella Evangelista
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria Alle Scotte Hospital, University of Siena, Siena, Italy
| | - Domenico Sergi
- Division of Cardiology, University Hospital "Tor Vergata", Rome, RM, Italy
| | - Alberto Palazzuoli
- Cardiovascular Diseases Unit, Department of Internal Medicine, S. Maria Alle Scotte Hospital, University of Siena, Siena, Italy
| | - Francesco Romeo
- Division of Cardiology, University Hospital "Tor Vergata", Rome, RM, Italy
- Unicamillus International University, Rome, RM, Italy
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Ludvigsson J, Sumnik Z, Pelikanova T, Nattero Chavez L, Lundberg E, Rica I, Martínez-Brocca MA, Ruiz de Adana M, Wahlberg J, Katsarou A, Hanas R, Hernandez C, Clemente León M, Gómez-Gila A, Lind M, Lozano MF, Sas T, Samuelsson U, Pruhova S, Dietrich F, Puente Marin S, Nordlund A, Hannelius U, Casas R. Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial. Diabetes Care 2021; 44:1604-1612. [PMID: 34021020 PMCID: PMC8323180 DOI: 10.2337/dc21-0318] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 04/15/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7-193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
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Affiliation(s)
- Johnny Ludvigsson
- Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children's Hospital, Linköping University, Linköping, Sweden
| | - Zdenek Sumnik
- Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | - Terezie Pelikanova
- Diabetes Centre of the Institute of Clinical and Experimental Medicine, Prague, Czech Republic
| | - Lia Nattero Chavez
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Elena Lundberg
- Institution of Clinical Science, Department of Pediatrics, Umeå University, Norrland University Hospital, Umeå, Sweden
| | - Itxaso Rica
- Department of Pediatric Endocrinology, Cruces University Hospital, CIBERDEM, Bilbao, Spain
| | | | - Marisol Ruiz de Adana
- Department of Adult Endocrinology and Diabetology, General University Hospital, Instituto de Biomedicina de Málaga, CIBERDEM, Malaga, Spain
| | - Jeanette Wahlberg
- Departments of Endocrinology Region Östergötland and Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | | | - Ragnar Hanas
- Department of Pediatrics, NU Hospital Group, Uddevalla, Sweden
| | - Cristina Hernandez
- Department of Endocrinology and Nutrition, Vall d'Hebron Hospital, CIBERDEM, Barcelona, Spain
| | - Maria Clemente León
- Department of Endocrinology and Nutrition, Vall d'Hebron Hospital, CIBERDEM, Barcelona, Spain
| | - Ana Gómez-Gila
- Pediatric Endocrinology Service, Virgen del Rocío University Hospital, Sevilla, Spain
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.,Department of Medicine, Department of Medicine, Uddevalla, Sweden
| | - Marta Ferrer Lozano
- Department of Pediatric Endocrinology, Miguel Servet University Hospital, Zaragoza, Spain
| | - Theo Sas
- Diabeter, National Treatment and Research Center for Children, Adolescents and Young Adults With Type 1 Diabetes, and Department of Pediatric Endocrinology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Ulf Samuelsson
- Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children's Hospital, Linköping University, Linköping, Sweden
| | - Stepanka Pruhova
- Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | - Fabricia Dietrich
- Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | - Sara Puente Marin
- Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | | | | | - Rosaura Casas
- Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
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9
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Serés-Noriega T, Giménez M, Perea V, Blanco J, Vinagre I, Pané A, Ruiz S, Cofán M, Mesa A, Esmatjes E, Conget I, Ortega E, Amor AJ. Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes. Nutr Metab Cardiovasc Dis 2021; 31:2099-2108. [PMID: 34039504 DOI: 10.1016/j.numecd.2021.03.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 03/23/2021] [Accepted: 03/23/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIMS Glycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. METHODS AND RESULTS We selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7-55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p < 0.05), with no association in patients receiving this drug (p for interaction <0.05; in ≥2 plaques). Finally, in models adjusted for other classical and T1D-specific risk factors, GlycA and GlycB H/W ratios remained associated with carotid plaque (OR 1.39 [1.12-1.90] and OR 6.89 [1.85-25.62], respectively). CONCLUSION In T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.
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Affiliation(s)
- Tonet Serés-Noriega
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain
| | - Marga Giménez
- Diabetes Unit, Endocrinology and Nutrition Department, Institut d'Investigacions BiomèdiquesAugust Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Verónica Perea
- Endocrinology and Nutrition Department, Hospital Universitari Mútua de Terrassa, Terrassa, Spain
| | - Jesús Blanco
- Diabetes Unit, Endocrinology and Nutrition Department, Institut d'Investigacions BiomèdiquesAugust Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Irene Vinagre
- Diabetes Unit, Endocrinology and Nutrition Department, Institut d'Investigacions BiomèdiquesAugust Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain
| | - Adriana Pané
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain
| | - Sabina Ruiz
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain
| | - Monserrat Cofán
- Endocrinology and Nutrition Department, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Alex Mesa
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain
| | - Enric Esmatjes
- Diabetes Unit, Endocrinology and Nutrition Department, Institut d'Investigacions BiomèdiquesAugust Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Ignacio Conget
- Diabetes Unit, Endocrinology and Nutrition Department, Institut d'Investigacions BiomèdiquesAugust Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Emilio Ortega
- Endocrinology and Nutrition Department, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Antonio J Amor
- Diabetes Unit, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain.
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Rajbhandari J, Fernandez CJ, Agarwal M, Yeap BXY, Pappachan JM. Diabetic heart disease: A clinical update. World J Diabetes 2021; 12:383-406. [PMID: 33889286 PMCID: PMC8040078 DOI: 10.4239/wjd.v12.i4.383] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/27/2021] [Accepted: 03/13/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) significantly increases the risk of heart disease, and DM-related healthcare expenditure is predominantly for the management of cardiovascular complications. Diabetic heart disease is a conglomeration of coronary artery disease (CAD), cardiac autonomic neuropathy (CAN), and diabetic cardiomyopathy (DCM). The Framingham study clearly showed a 2 to 4-fold excess risk of CAD in patients with DM. Pathogenic mechanisms, clinical presentation, and management options for DM-associated CAD are somewhat different from CAD among nondiabetics. Higher prevalence at a lower age and more aggressive disease in DM-associated CAD make diabetic individuals more vulnerable to premature death. Although common among diabetic individuals, CAN and DCM are often under-recognised and undiagnosed cardiac complications. Structural and functional alterations in the myocardial innervation related to uncontrolled diabetes result in damage to cardiac autonomic nerves, causing CAN. Similarly, damage to the cardiomyocytes from complex pathophysiological processes of uncontrolled DM results in DCM, a form of cardiomyopathy diagnosed in the absence of other causes for structural heart disease. Though optimal management of DM from early stages of the disease can reduce the risk of diabetic heart disease, it is often impractical in the real world due to many reasons. Therefore, it is imperative for every clinician involved in diabetes care to have a good understanding of the pathophysiology, clinical picture, diagnostic methods, and management of diabetes-related cardiac illness, to reduce morbidity and mortality among patients. This clinical review is to empower the global scientific fraternity with up-to-date knowledge on diabetic heart disease.
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Affiliation(s)
- Jake Rajbhandari
- College of Medical and Dental Sciences, University of Birmingham Medical School, Birmingham B15 2TH, United Kingdom
| | | | - Mayuri Agarwal
- Department of Endocrinology and Metabolism, Pilgrim Hospital, Boston PE21 9QS, United Kingdom
| | - Beverly Xin Yi Yeap
- Department of Medicine, The University of Manchester Medical School, Manchester M13 9PL, United Kingdom
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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11
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Ahmed MO, Byrne RE, Pazderska A, Segurado R, Guo W, Gunness A, Frizelle I, Sherlock M, Ahmed KS, McGowan A, Moore K, Boran G, McGillicuddy FC, Gibney J. HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study. Diabetologia 2021; 64:656-667. [PMID: 33169205 DOI: 10.1007/s00125-020-05320-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 09/09/2020] [Indexed: 01/02/2023]
Abstract
AIMS/HYPOTHESIS The prevalence of atherosclerosis is increased in type 1 diabetes despite normal-to-high HDL-cholesterol levels. The cholesterol efflux capacity (CEC) of HDL is a better predictor of cardiovascular events than static HDL-cholesterol. This cross-sectional study addressed the hypothesis that impaired HDL function contributes to enhanced CVD risk within type 1 diabetes. METHODS We compared HDL particle size and concentration (by NMR), total CEC, ATP-binding cassette subfamily A, member 1 (ABCA1)-dependent CEC and ABCA1-independent CEC (by determining [3H]cholesterol efflux from J774-macrophages to ApoB-depleted serum), and carotid intima-media thickness (CIMT) in 100 individuals with type 1 diabetes (37.6 ± 1.2 years; BMI 26.9 ± 0.5 kg/m2) and 100 non-diabetic participants (37.7 ± 1.1 years; 27.1 ± 0.5 kg/m2). RESULTS Compared with non-diabetic participants, total HDL particle concentration was lower (mean ± SD 31.01 ± 8.66 vs 34.33 ± 8.04 μmol/l [mean difference (MD) -3.32 μmol/l]) in participants with type 1 diabetes. However, large HDL particle concentration was greater (9.36 ± 3.98 vs 6.99 ± 4.05 μmol/l [MD +2.37 μmol/l]), resulting in increased mean HDL particle size (9.82 ± 0.57 vs 9.44 ± 0.56 nm [MD +0.38 nm]) (p < 0.05 for all). Total CEC (14.57 ± 2.47%CEC/4 h vs 12.26 ± 3.81%CEC/4 h [MD +2.31%CEC/4 h]) was greater in participants with type 1 diabetes relative to non-diabetic participants. Increased HDL particle size was independently associated with increased total CEC; however, following adjustment for this in multivariable analysis, CEC remained greater in participants with type 1 diabetes. Both components of CEC, ABCA1-dependent (6.10 ± 2.41%CEC/4 h vs 5.22 ± 2.57%CEC/4 h [MD +0.88%CEC/4 h]) and ABCA1-independent (8.47 ± 1.79% CEC/4 h vs 7.05 ± 1.76% CEC/4 h [MD +1.42% CEC/4 h]) CEC, were greater in type 1 diabetes but the increase in ABCA1-dependent CEC was less marked and not statistically significant in multivariable analysis. CIMT was increased in participants with type 1 diabetes but in multivariable analysis it was only associated negatively with age and BMI. CONCLUSIONS/INTERPRETATION HDL particle size but not HDL-cholesterol level is independently associated with enhanced total CEC. HDL particle size is greater in individuals with type 1 diabetes but even after adjusting for this, total and ABCA1-independent CEC are enhanced in type 1 diabetes. Further studies are needed to understand the mechanisms underlying these effects, and whether they help attenuate progression of atherosclerosis in this high-risk group. Graphical abstract.
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Affiliation(s)
- Mohamad O Ahmed
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Rachel E Byrne
- Diabetes Complications Research Centre, School of Medicine, University College Dublin, Belfield, Dublin, Ireland
| | - Agnieszka Pazderska
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Ricardo Segurado
- School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Belfield, Dublin, Ireland
| | - Weili Guo
- Diabetes Complications Research Centre, School of Medicine, University College Dublin, Belfield, Dublin, Ireland
| | - Anjuli Gunness
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Isolda Frizelle
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Mark Sherlock
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Khalid S Ahmed
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Anne McGowan
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Kevin Moore
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland
| | - Gerard Boran
- Department of Chemical Pathology, Tallaght University Hospital, Dublin, Ireland
| | - Fiona C McGillicuddy
- Diabetes Complications Research Centre, School of Medicine, University College Dublin, Belfield, Dublin, Ireland
| | - James Gibney
- Robert Graves Institute of Endocrinology, Tallaght University Hospital, Dublin, Ireland.
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12
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Bebu I, Braffett BH, Schade D, Sivitz W, Malone JI, Pop-Busui R, Lorenzi GM, Lee P, Trapani VR, Wallia A, Herman WH, Lachin JM. An Observational Study of the Equivalence of Age and Duration of Diabetes to Glycemic Control Relative to the Risk of Complications in the Combined Cohorts of the DCCT/EDIC Study. Diabetes Care 2020; 43:2478-2484. [PMID: 32788280 PMCID: PMC7510046 DOI: 10.2337/dc20-0226] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 07/13/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This epidemiological analysis of the pooled Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort describes the equivalence of a 1-percentage point increase in HbA1c (such as from 7% to 8%) and years of additional age or duration of type 1 diabetes (T1D) relative to the risk of complications. RESEARCH DESIGN AND METHODS Separate Cox proportional hazards models determined the number of additional years of age and/or duration of T1D that would result in the same increase in risk of microvascular (retinopathy, nephropathy, and neuropathy) and cardiovascular complications and mortality as a 1-percentage point increase in HbA1c. RESULTS The risk of any cardiovascular disease associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 4.3 (95% CI 2.7-5.9) additional years of age or 5.6 (95% CI 2.7-6.5) additional years' duration of T1D. The risk of estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or end-stage renal disease associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 12.1 (95% CI 8.3-15.9) additional years of age or 18.0 (95% CI 4.3-31.7) additional years' duration of T1D. The proliferative diabetic retinopathy risk associated with a 1-percentage point increase in HbA1c was equivalent to the risk associated with 6.4 (95% CI 5.3-7.4) additional years' duration of T1D, while for mortality risk, it was equivalent to the risk associated with 12.9 (95% CI 6.6-19.3) additional years of age. CONCLUSIONS Our results help evaluate the impact of glycemia on advanced complications in a way that may be more interpretable to health care providers and individuals with T1D.
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Affiliation(s)
- Ionut Bebu
- Biostatistics Center, The George Washington University, Rockville, MD
| | | | | | | | | | | | | | - Pearl Lee
- University of Michigan, Ann Arbor, MI
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Ludvigsson J, Routray I, Elluru S, Leanderson P, Larsson HE, Rathsman B, Hanås R, Carlsson A, Ek T, Samuelsson U, Torbjörnsdotter T, Åman J, Örtqvist E, Badwal K, Beam C, Casas R. Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial. Future Sci OA 2020. [PMID: 32802401 DOI: 10.2144/fsoa‐2020‐0078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Aim Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D). Methods 64 patients (T1D since <4 months, age 10-17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1-90 400 mg/day Ibuprofen, D1-450 vitamin D 2000 IU/day, D15, 45 sc. 20 μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40 μg GAD-alum D15, 45; placebo. Results Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24 h with change in C-peptide AUC at 15 months (r = -0.776, p < 0.0001). Conclusion Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov).
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Affiliation(s)
- Johnny Ludvigsson
- Department of Biomedical & Clinical Sciences, Crown Princess Victoria Children´s Hospital & Div of Pediatrics, Linköping University, SE-58185, Linköping, Sweden
| | - Indusmita Routray
- Department of Biomedical & Clinical Sciences, Division of Pediatrics, Linköping University, SE 58185 Linköping, Sweden
| | - Sriramulu Elluru
- Department of Biomedical & Clinical Sciences, Division of Pediatrics, Linköping University, SE 58185 Linköping, Sweden
| | - Per Leanderson
- Department of Clinical & Experimental Medicine, Occupational & Environmental Medicine Center, Linköping University, Linköping S-58185, Sweden
| | - Helena E Larsson
- Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund University, Sweden & Department of Pediatrics, Skåne University Hospital, SE-21428 Malmö, Sweden
| | - Björn Rathsman
- Sachska Pediatric Hospital, Södersjukhuset, SE-11861 Stockholm, Sweden
| | - Ragnar Hanås
- Department of Pediatrics, NU Hospital Group, SE 45153 Uddevalla, Sweden & Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, SE 41346 Gothenburg, Sweden
| | - Annelie Carlsson
- Pediatric Autoimmunity, Department of Clinical Sciences Lund, Lund University, Sweden, Skåne University Hospital, SE-22242 Lund, Sweden
| | - Torben Ek
- Department of Pediatrics, Hospital of Halland, SE 30233 Halmstad, Sweden
| | - Ulf Samuelsson
- Department of Biomedical & Clinical Sciences, Crown Princess Victoria Children´s Hospital & Div of Pediatrics, Linköping University, SE-58185, Linköping, Sweden.,Department of Biomedical & Clinical Sciences, Division of Pediatrics, Linköping University, SE 58185 Linköping, Sweden
| | - Torun Torbjörnsdotter
- Department of Women & Child Health, Astrid Lindgrens Children's Hospital at Karolinska University Hospital, Karolinska Institutet, SE 17164 Stockholm, Sweden
| | - Jan Åman
- Department of Pediatrics, University Hospital, SE 70382 Örebro, Sweden
| | - Eva Örtqvist
- Department of Women & Child Health, Astrid Lindgren Children's Hospital at Karolinska University Hospital, Karolinska Institutet, SE 17164 Stockholm, Sweden
| | - Karun Badwal
- Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, USA
| | - Craig Beam
- Department of Biomedical Sciences, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, USA
| | - Rosaura Casas
- Department of Biomedical & Clinical Sciences, Division of Pediatrics, Linköping University, SE 58185 Linköping, Sweden
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Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type I diabetes: lessons from the DIABGAD randomized pilot trial. Future Sci OA 2020; 6:FSO604. [PMID: 32802401 PMCID: PMC7421935 DOI: 10.2144/fsoa-2020-0078] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Aim: Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D). Methods 64 patients (T1D since <4 months, age 10–17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1–90 400 mg/day Ibuprofen, D1–450 vitamin D 2000 IU/day, D15, 45 sc. 20 μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40 μg GAD-alum D15, 45; placebo. Results: Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24 h with change in C-peptide AUC at 15 months (r = -0.776, p < 0.0001). Conclusion: Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov). In many countries, Type I diabetes with insufficient own insulin secretion is a common life-threatening disease in children and adults. There is no prevention and no cure. In spite of very intense treatment, the disease leads to serious complications. There is no efficaceous method to save own insulin secretion without serious risks and adverse events, but autoantigen treatment with glutamic acid decarboxylase has shown some efficacy. We have tried a combination therapy with vitamin D and anti-inflammatory treatment (ibuprofen). Vitamin D in combination with glutamic acid decarboxylase-alum seems to have beneficial effects, but not Ibuprofen. The effect is influenced by basal clinical and immunological status.
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15
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Fagninou A, Nekoua MP, Sossou D, Moutairou K, Fievet N, Yessoufou A. Th2-Immune Polarizing and Anti-Inflammatory Properties of Insulin Are Not Effective in Type 2 Diabetic Pregnancy. J Immunol Res 2020; 2020:2038746. [PMID: 32626786 PMCID: PMC7312550 DOI: 10.1155/2020/2038746] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 05/21/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The implication of the immune system in the physiopathology of pregnancy complicated by diabetes has been reported. Here, we investigated the effects of insulin treatment on the frequencies of immune cell subpopulations as well as T cell-derived cytokines in type 2 diabetic (T2D) pregnancy compared to gestational diabetes mellitus (GDM). METHODS Fifteen (15) women with GDM, twenty (20) insulin-treated T2D pregnant women, and twenty-five (25) pregnant controls were selected. Immune cell subpopulation frequencies were determined in blood using flow cytometry. The proliferative capacity of T cells was performed, and serum and cell culture supernatant cytokine levels were also quantified. RESULTS The frequencies of total CD3+ and CD4+ T cells and nonclassical monocytes significantly increased in insulin-treated T2D pregnant women compared to pregnant controls. The proportions of CD4+ T cells as well as B cells were significantly higher in women with GDM than in pregnant controls. GDM was associated with high frequencies of total CD3+ and CD4+ T cells and B cell expansion, suggesting a concomitant activation of cellular and humoral immunity. Concomitantly, Th1/Th2 ratio, determined as IFN-γ/IL-4, was shifted towards Th1 phenotype in women with GDM and insulin-treated T2D pregnant women. Besides, isolated T cells elicited similar proliferative capacity in the three groups of women. Insulin-treated T2D pregnant women and women with GDM exhibited a low serum IL-10 level, without any change in the number of Treg cells. CONCLUSION Our study showed that, despite insulin treatment, pregnant women with T2D displayed a proinflammatory status consistent with high proportions of CD3+ and CD4+ T cells, upregulation of Th1 cytokines, and low IL-10 production, suggesting a reduced immune-suppressive activity of regulatory T cells. However, GDM, although associated with proinflammatory status, has shown increased humoral immunity consistent with high proportion of CD19+ B cells. Thus, the lack of response to insulin in diabetes during pregnancy and clinical implications of these immunological parameters deserves further investigations.
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Affiliation(s)
- Adnette Fagninou
- Faculty of Sciences and Technology (FAST), University of Abomey-Calavi, Institute of Applied Biomedical Sciences (ISBA), Laboratory of Cell Biology and Physiology, 01 BP 526 Cotonou, Benin
| | - Magloire Pandoua Nekoua
- Faculty of Sciences and Technology (FAST), University of Abomey-Calavi, Institute of Applied Biomedical Sciences (ISBA), Laboratory of Cell Biology and Physiology, 01 BP 526 Cotonou, Benin
| | - Darius Sossou
- Center for Study and Research on Malaria Associated with Pregnancy and Childhood (CERPAGE) and IRD-UMR261, Cotonou, Benin
| | - Kabirou Moutairou
- Faculty of Sciences and Technology (FAST), University of Abomey-Calavi, Institute of Applied Biomedical Sciences (ISBA), Laboratory of Cell Biology and Physiology, 01 BP 526 Cotonou, Benin
| | - Nadine Fievet
- Center for Study and Research on Malaria Associated with Pregnancy and Childhood (CERPAGE) and IRD-UMR261, Cotonou, Benin
| | - Akadiri Yessoufou
- Faculty of Sciences and Technology (FAST), University of Abomey-Calavi, Institute of Applied Biomedical Sciences (ISBA), Laboratory of Cell Biology and Physiology, 01 BP 526 Cotonou, Benin
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Ludvigsson J. Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route. Int J Mol Sci 2020; 21:E1598. [PMID: 32111075 PMCID: PMC7084272 DOI: 10.3390/ijms21051598] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/19/2020] [Accepted: 02/21/2020] [Indexed: 12/11/2022] Open
Abstract
Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.
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Affiliation(s)
- Johnny Ludvigsson
- Crown Princess Victoria Children´s Hospital and Div of Pediatrics, Dept of Biomedical and Clinical Sciences, Lnköping university, SE 58185 Linköping, Sweden
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17
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Kiss Z, Rokszin G, Abonyi-Tóth Z, Jermendy G, Kempler P, Barkai L, Wittmann I. Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary. Diabetes Metab Res Rev 2019; 35:e3190. [PMID: 31140677 DOI: 10.1002/dmrr.3190] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 04/11/2019] [Accepted: 05/22/2019] [Indexed: 11/06/2022]
Abstract
BACKGROUND There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40). METHODS We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period. RESULTS The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes. CONCLUSIONS A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.
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Affiliation(s)
- Zoltán Kiss
- 2nd Department of Medicine and Nephrological Center, Faculty of Medicine, University of Pécs, Pécs, Hungary
| | | | - Zsolt Abonyi-Tóth
- RxTarget Ltd., Szolnok, Hungary
- University of Veterinary Medicine, Budapest, Hungary
| | | | - Péter Kempler
- 1st Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - László Barkai
- Institute of Theoretical Health Sciences, Faculty of Health Care, University of Miskolc, Miskolc, Hungary
- Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovakia
| | - István Wittmann
- 2nd Department of Medicine and Nephrological Center, Faculty of Medicine, University of Pécs, Pécs, Hungary
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18
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Šuran D, Kanič V, Naji F, Krajnc I, Čokolič M, Zemljič E, Sinkovič A. Predictors of early cardiac changes in patients with type 1 diabetes mellitus: An echocardiography-based study. Bosn J Basic Med Sci 2019; 19:384-391. [PMID: 31215855 DOI: 10.17305/bjbms.2019.4250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 06/12/2019] [Indexed: 11/16/2022] Open
Abstract
In patients with type 1 diabetes mellitus (T1DM) imaging studies have demonstrated an increased prevalence of left ventricular diastolic dysfunction and increased left ventricular mass (LVM) unrelated to arterial hypertension and ischemic heart disease. The aim of our study was to identify potential predictors of early subclinical changes in cardiac chamber size and function in such patients. Sixty-one middle-aged asymptomatic normotensive patients with T1DM were included in the study. Conventional and tissue Doppler echocardiography was performed and fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, and creatinine were measured. We found moderate bivariate correlations of body mass index (BMI) with left atrial volume (r = 0.47, p < 0.01), LVM (r = 0.42, p < 0.01), left ventricular relative wall thickness (r = 0.32, p = 0.01), and all observed parameters of diastolic function of both ventricles. The five-year average value of HbA1c weakly correlated with the Doppler index of left ventricular filling pressure E/e´sept (r = 0.27, p = 0.04). We found no significant association of diabetes duration, five-year trend of HbA1c, serum lipids, and glomerular filtration rate with cardiac structure and function. After adjusting for other parameters, BMI remained significantly associated with left atrial volume, LVM as well as with the transmitral Doppler ratio E/A. In our study, BMI was the only observed parameter significantly associated with subclinical structural and functional cardiac changes in the asymptomatic middle-aged patients with T1DM.
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Affiliation(s)
- David Šuran
- Department of Cardiology and Angiology, University Medical Centre Maribor, Maribor, Slovenia.
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Deola S, Guerrouahen BS, Sidahmed H, Al-Mohannadi A, Elnaggar M, Elsadig R, Abdelalim EM, Petrovski G, Gadina M, Thrasher A, Wels WS, Hunger SP, Wang E, Marincola FM, Maccalli C, Cugno C. Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28-29 2017, Doha, Qatar). J Transl Med 2018; 16:276. [PMID: 30305089 PMCID: PMC6180452 DOI: 10.1186/s12967-018-1652-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 10/01/2018] [Indexed: 02/07/2023] Open
Abstract
New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called “living drugs”. Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report.
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Affiliation(s)
- Sara Deola
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar
| | | | - Heba Sidahmed
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar
| | - Anjud Al-Mohannadi
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar
| | - Muhammad Elnaggar
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar
| | - Ramaz Elsadig
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar
| | - Essam M Abdelalim
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha, Qatar
| | | | | | - Adrian Thrasher
- UCL Great Ormond Street Institute of Child Health, London, UK
| | - Winfried S Wels
- Georg Speyer Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany
| | | | - Ena Wang
- Immune Oncology Discovery and System Biology, AbbVie, Redwood City, CA, USA
| | | | | | - Cristina Maccalli
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar
| | - Chiara Cugno
- Research Department, Clinical Research Center, Sidra Medicine, Doha, Qatar.
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Moström P, Ahlén E, Imberg H, Hansson PO, Lind M. Adherence of self-monitoring of blood glucose in persons with type 1 diabetes in Sweden. BMJ Open Diabetes Res Care 2017; 5:e000342. [PMID: 28611921 PMCID: PMC5387961 DOI: 10.1136/bmjdrc-2016-000342] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Revised: 12/13/2016] [Accepted: 12/26/2016] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE The primary aim was to evaluate the extent to which persons with type 1 diabetes perform self-monitoring of blood glucose (SMBG) according to guidelines. Secondary objectives were to investigate predictors for good SMBG adherence, reasons for non-adherence, and association between SMBG frequency and hemoglobin A1c (HbA1c). METHODS This was a survey-based cross-sectional study. Questionnaires were sent out to 600 random patients at five sites. Patients were included if they were diagnosed with type 1 diabetes and ≥18 years old and excluded if they were currently using continuous glucose monitoring (CGM). Analysis of data was performed separately for the three sites where the answer frequency was ≥70%. RESULTS In total, 138 of 314 study participants, 43.9% (95% CI 38.5% to 49.4%) performed SMBG ≥4 times per day. For the three clinics where ≥70% of surveyed patients were included in the analysis, results were similar, 41.3% (95% CI 34.7% to 47.8%). Top three reported reasons for not performing more frequent SMBG were lack of time, not remembering, and self-consciousness. Frequency of SMBG was associated with HbA1c levels (p<0.0001). 30% of patients believed that ≤3 SMBG/day was recommended by healthcare providers. CONCLUSIONS Less than 50% of patients in Sweden follow guidelines of SMBG ≥4 times per day, despite glucose meters and strips being generally available at no cost. This indicates a need for further support in performing SMBG and increased availability of other tools for glucose monitoring.
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Affiliation(s)
- Peter Moström
- Department of Internal Medicine, Alingsås Lasarett, Alingsås, Sweden
| | - Elsa Ahlén
- Department of Medicine, Värnamo Hospital, Värnamo, Sweden
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Henrik Imberg
- Statistiska Konsultgruppen, Gothenburg, Sweden
- Department of Mathematical Sciences, Chalmers University of Technology and the University of Gothenburg, Gothenburg, Sweden
| | - Per-Olof Hansson
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Marcus Lind
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Abstract
In spite of modern techniques, the burden for patients with type 1 diabetes mellitus will not disappear, and type 1 diabetes will remain a life-threatening disease causing severe complications and increased mortality. We have to learn of ways to stop the destructive process, preserve residual insulin secretion or even improve the disease via β-cell regeneration. This will give a milder disease, a more stable metabolism, simpler treatment and perhaps even cure. Therapies based on single drugs have not shown sufficient efficacy; however, there are several treatments with encouraging efficacy and no apparent, or rather mild, adverse events. As the disease process is heterogeneous, treatments have to be chosen to fit relevant subgroups of patients, and step by step efficacy can possibly be improved by the use of combination therapies. Thus immunosuppressive therapies like anti-CD3 and anti-CD20 monoclonal antibodies might be combined with fusion proteins such as etanercept [tumor necrosis factor (TNF)-α inhibitor] and/or abatacept (CTLA4-Ig) early after onset to stop the destructive process, supported by β-cell protective agents. The effect may be prolonged by using autoantigen therapy [glutamate decarboxylase (GAD) proinsulin], and by adding agents facilitating β-cell regeneration [e.g. glucagon-like peptide-1 (GLP-1)] there should be a good chance to make the disease milder, perhaps leading to cure in some patients.
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Affiliation(s)
- Johnny Ludvigsson
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, 58185, Linköping, Sweden.
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Abstract
Managing severe insulin resistance (IR) in patients with type 1 diabetes (T1DM) can be challenging for both clinicians and patients. As average weight for patients with T1DM has increased in recent decades, IR in this population has become more widespread. Currently, almost 50 % of patients with T1DM are overweight or obese. While intensive insulin therapy is associated with reduction in complications, aggressive treatment can lead to weight gain. With increasing weight, insulin can become less effective to control glycemia, resulting in higher insulin doses and hence more weight gain. Novel strategies to break this vicious cycle are needed. This review will investigate current research on insulin formulations, lifestyle modification, adjunct therapies, and surgery that may help better manage patients with T1DM and IR.
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Mameli C, Mazzantini S, Ben Nasr M, Fiorina P, Scaramuzza AE, Zuccotti GV. Explaining the increased mortality in type 1 diabetes. World J Diabetes 2015; 6:889-895. [PMID: 26185597 PMCID: PMC4499523 DOI: 10.4239/wjd.v6.i7.889] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 04/07/2015] [Accepted: 04/20/2015] [Indexed: 02/05/2023] Open
Abstract
Despite large improvements in the management of glucose levels and in the treatment of cardiovascular risk factors, the mortality rate in individuals with type 1 diabetes (T1D) is still high. Recently, Lind et al found that T1D individuals with glycated hemoglobin levels of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that is twice as high as the risk for matched controls. T1D is a chronic disease with an early onset (e.g., pediatric age) and thus in order to establish a clear correlation between death rate and the glycometabolic control, the whole history of glycemic control should be considered; particularly in the early years of diabetes. The switch from a normo- to hyperglycemic milieu in an individual with T1D in the pediatric age, represents a stressful event that may impact outcomes and death rate many years later. In this paper we will discuss the aforementioned issues, and offer our view on these findings, paying a particular attention to the several alterations occurring in the earliest phases of T1D and to the many factors that may be associated with the chronic history of T1D. This may help us to better understand the recently published death rate data and to develop future innovative and effective preventive strategies.
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