Abstract
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.
Highlights
Type 1 diabetes is a chronic disease leading to hyperglycemia and high risk of developing microvascular and macrovascular complications [1]
We aimed to investigate Circulating microvesicles (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
The aims of the current study were to investigate the presence of AV+ cMVs, from different vascular origins, in children and adolescents with type 1 diabetes compared with healthy control subjects over a five-year period, and to assess associations with glycemic control and cardiovascular risk factors in the type 1 diabetes group
Summary
Type 1 diabetes is a chronic disease leading to hyperglycemia and high risk of developing microvascular and macrovascular complications [1]. Circulating microvesicles (cMVs) are extracellular and heterogenous particles shed from the plasma membrane surface on cell types like platelets, leukocytes, monocytes, neutrophils, and endothelial cells [8]. They are released upon specific (cytokine activation, apoptotic cell blebbing, and coagulation) and nonspecific (high shear stress) stimuli, which activate calcium-dependent signaling and rearrangements of the cytoskeleton [9]. 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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