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

Abstract EN

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.