Abstract
IntroductionPatients with type 1 diabetes have high risk of developing microvascular complications, and microangiopathy contributes to premature cardiovascular disease in this population. The role that microvesicles (MVs) may play in the development of microangiopathy in type 1 diabetes remains unclear. Materials and methodsPlasma levels of endothelial MVs (EMVs) and platelet MVs (PMVs) in 130 patients with type 1 diabetes without microangiopathy, 106 patients with microangiopathy and 100 matched healthy controls were analyzed using flow cytometry. MV expression of procoagulant phosphatidylserine (PS) and proinflammatory high mobility group box-1 protein (HMGB1) was also assessed. ResultsPatients with type 1 diabetes had markedly elevated levels of EMVs and PS+ EMVs as well as PMVs and PS+ PMVs compared to healthy controls (p < .001 for all). Furthermore, HMGB1+ EMVs and HMGB1+ PMVs were significantly increased in patients (p < .001 for all). After adjusting for potential confounders, there were no clear differences between patients with or without microvascular complications for any of the MV parameters. ConclusionType 1 diabetes is a prothrombotic and proinflammatory disease state that, regardless of the presence of clinical microangiopathy, is associated with elevated levels of plasma MVs, in particular those of an endothelial origin. We have for the first time demonstrated that patients with type 1 diabetes have higher levels of HMGB1+ MVs. HMGB1 is an alarmin with potent proinflammatory effects that drive endothelial dysfunction, and it would therefore be of interest to further study the role of HMGB1+ MVs in the development of macrovascular complications in type 1 diabetes.
Highlights
Patients with type 1 diabetes have high risk of developing microvascular complications, and mi croangiopathy contributes to premature cardiovascular disease in this population
Patients had significantly higher systolic- and diastolic blood pressure, high-density lipoprotein (HDL) cholesterol, platelet concentration as well as fasting glucose but lower total and low-density lipoprotein (LDL) cho lesterol levels compared to healthy controls, whereas there was no difference in age, sex distribution, tobacco use or body mass index (BMI). High-sensitivity C-reactive protein (hsCRP) tended to be higher among patients, but the difference did not reach statistical significance
We have demonstrated that patients with type 1 diabetes have significantly higher levels of high mobility group box-1 protein (HMGB1) expressing endothelial MVs (EMVs) and platelet MVs (PMVs) compared to healthy controls
Summary
Patients with type 1 diabetes have high risk of developing microvascular complications, and mi croangiopathy contributes to premature cardiovascular disease in this population. We have for the first time demonstrated that patients with type 1 diabetes have higher levels of HMGB1+ MVs. HMGB1 is an alarmin with potent proinflammatory effects that drive endothelial dysfunction, and it would be of interest to further study the role of HMGB1+ MVs in the development of macro vascular complications in type 1 diabetes. The importance of EV exposure of procoagulant molecules such as the negatively-charged phospholipid phosphatidylserine (PS) [14,15] and inflammatory med iators such as high mobility group box-1 protein (HMGB1) [17,18] to the development of microvascular disease remains unclear. HMGB1 acts as an alarmin with a range of proinflammatory effects
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