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

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.