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 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.