Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study

Background. Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- and macrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis and discussed to be markers of vascula...

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Main Authors: Vibeke Bratseth, Hanna D. Margeirsdottir, Gemma Chiva-Blanch, Martin Heier, Svein Solheim, Harald Arnesen, Knut Dahl-Jørgensen, Ingebjørg Seljeflot
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2020/7216863
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author Vibeke Bratseth
Hanna D. Margeirsdottir
Gemma Chiva-Blanch
Martin Heier
Svein Solheim
Harald Arnesen
Knut Dahl-Jørgensen
Ingebjørg Seljeflot
author_facet Vibeke Bratseth
Hanna D. Margeirsdottir
Gemma Chiva-Blanch
Martin Heier
Svein Solheim
Harald Arnesen
Knut Dahl-Jørgensen
Ingebjørg Seljeflot
author_sort Vibeke Bratseth
collection DOAJ
description Background. Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- and macrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis and discussed to be markers of vascular dysfunction and hypercoagulability. Limited knowledge exists on hypercoagulability in young diabetics. We aimed to investigate cMVs over a five-year period in children/adolescents with type 1 diabetes compared with controls and any associations with glycemic control and cardiovascular risk factors. We hypothesized increased shedding of cMVs in type 1 diabetes in response to vascular activation. Methods. The cohort included type 1 diabetics (n=40) and healthy controls (n=40), mean age 14 years (range 11) at inclusion, randomly selected from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Citrated plasma was prepared and stored at -80°C until cMV analysis by flow cytometry. Results. Comparable levels of Annexin V (AV+) cMVs were observed at inclusion. At five-year follow-up, total AV+ cMVs were significantly lower in subjects with type 1 diabetes compared with controls; however, no significant differences were observed after adjusting for covariates. In the type 1 diabetes group, the total AV+, tissue factor-expressing AV+/CD142+, neutrophil-derived AV+/CD15+ and AV+/CD45+/CD15+, and endothelial-derived AV+/CD309+ and CD309+/CD34+ cMVs were inversely correlated with HbA1c (r=‐0.437, r=‐0.515, r=‐0.575, r=‐0.529, r=‐0.416, and r=‐0.445, respectively; all p≤0.01), however, only at inclusion. No significant correlations with cardiovascular risk factors were observed. Conclusions. Children/adolescents with type 1 diabetes show similar levels of AV+ cMVs as healthy controls and limited associations with glucose control. This indicates that our young diabetics on intensive insulin treatment have preserved vascular homeostasis and absence of procoagulant cMVs.
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spelling doaj-art-bc73eb837e354f188eed3e2274a718992025-02-03T01:25:17ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/72168637216863Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort StudyVibeke Bratseth0Hanna D. Margeirsdottir1Gemma Chiva-Blanch2Martin Heier3Svein Solheim4Harald Arnesen5Knut Dahl-Jørgensen6Ingebjørg Seljeflot7Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, NorwayPediatric Department, Oslo University Hospital Ullevaal, Oslo, NorwayCardiovascular Program ICCC, Institut de Recerca Hospital Santa Creu i Sant Pau-IIB Sant Pau, Sant Antoni Maria Claret, 167, 08025 Barcelona, SpainPediatric Department, Oslo University Hospital Ullevaal, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, NorwayFaculty of Medicine, University of Oslo, Oslo, NorwayCenter for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, NorwayBackground. Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- and macrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis and discussed to be markers of vascular dysfunction and hypercoagulability. Limited knowledge exists on hypercoagulability in young diabetics. We aimed to investigate cMVs over a five-year period in children/adolescents with type 1 diabetes compared with controls and any associations with glycemic control and cardiovascular risk factors. We hypothesized increased shedding of cMVs in type 1 diabetes in response to vascular activation. Methods. The cohort included type 1 diabetics (n=40) and healthy controls (n=40), mean age 14 years (range 11) at inclusion, randomly selected from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Citrated plasma was prepared and stored at -80°C until cMV analysis by flow cytometry. Results. Comparable levels of Annexin V (AV+) cMVs were observed at inclusion. At five-year follow-up, total AV+ cMVs were significantly lower in subjects with type 1 diabetes compared with controls; however, no significant differences were observed after adjusting for covariates. In the type 1 diabetes group, the total AV+, tissue factor-expressing AV+/CD142+, neutrophil-derived AV+/CD15+ and AV+/CD45+/CD15+, and endothelial-derived AV+/CD309+ and CD309+/CD34+ cMVs were inversely correlated with HbA1c (r=‐0.437, r=‐0.515, r=‐0.575, r=‐0.529, r=‐0.416, and r=‐0.445, respectively; all p≤0.01), however, only at inclusion. No significant correlations with cardiovascular risk factors were observed. Conclusions. Children/adolescents with type 1 diabetes show similar levels of AV+ cMVs as healthy controls and limited associations with glucose control. This indicates that our young diabetics on intensive insulin treatment have preserved vascular homeostasis and absence of procoagulant cMVs.http://dx.doi.org/10.1155/2020/7216863
spellingShingle Vibeke Bratseth
Hanna D. Margeirsdottir
Gemma Chiva-Blanch
Martin Heier
Svein Solheim
Harald Arnesen
Knut Dahl-Jørgensen
Ingebjørg Seljeflot
Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study
Journal of Diabetes Research
title Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study
title_full Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study
title_fullStr Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study
title_full_unstemmed Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study
title_short Annexin V+ Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study
title_sort annexin v microvesicles in children and adolescents with type 1 diabetes a prospective cohort study
url http://dx.doi.org/10.1155/2020/7216863
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