Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research funded by grants of the Romanian Ministry of Education and Research, CNCS-UEFISCDI, project no. PN-III-P1-1.2-PCCDI-2017–0527 (Contract no. 83PCCDI/2018), project no. PN-III-P1-1.1-TE-2019–0811, within PNCDI III” (Contract no. TE 97/2020) Background Dislypidemia is a major risk factor for cardiovascular diseases as well as for diabetes where often leads to severe microvascular complications. Reportedly, microRNAs (miRNAs) associated with microvesicles (MVs) regulate cellular mechanisms in the progression of diabetic dyslipidemia. We hypothesised that detection of the changes in plasma MV components could be used as early biomarkers to prevent the irreversible effects of diabetic dyslipidemia. Purpose: of this study was to search whether in diabetic dyslipidemia with/without microvascular complications there are modifications of the circulating MVs and plasma miRNAs and whether these changes could be predictive of the disease evolution. Methods Plasma/sera was collected from diabetic patients with dyslipidemia with/without microvascular complications and the main parameters and the inflammatory markers were assessed. Results showed that, compared to either diabetes or dyslipidemia alone, in the diabetic dyslipidemic patients, significant increases in plasma glucose, cholesterol, LDL-cholesterol, triglyceride concentrations, systolic blood pressure were present. In addition, high levels of circulating IL-6 and MVs-derived from endothelial cells (CD144+), platelets (CD41+), macrophages (CD14+), and leucocytes (CD18+) were detected. Significant changes were found in plasma miRNAs and MV-associated miRNAs: 122,-132,-143,-200b,-212, decreased miR-34a,-155,-218 expressions in MVs, and reduced miR-21,-34a,-132,-143 expressions in plasma. Notably, when microvascular complications were associated to diabetic dyslipidemia, we found significant changes such as increased expression of miR-21,-34a,-122,-126,-143,-218,-223 in MV and plasma miR-143,-132 and decreased miR-200b,-212 in MVs and plasma miR-223. Conclusion In patients with diabetic dyslipidemia and, in particular, with diabetic dyslipidemia associated with microvascular complications, a significant modification in the plasma MV content and miRNAs occur suggesting that they could turn into biomarkers and potential diagnostic tool for diabetic dyslipidemia and its complications.

中文翻译：

---

循环微泡和血浆中的 microRNA 作为补充糖尿病血脂异常及其并发症临床诊断的生物标志物

资金致谢 资金来源类型：公共拨款——仅限国家预算。主要资金来源：由罗马尼亚教育和研究部资助的研究，CNCS-UEFISCDI，项目编号。PN-III-P1-1.2-PCCDI-2017–0527（合同编号 83PCCDI/2018），项目编号。PN-III-P1-1.1-TE-2019-0811，在 PNCDI III 内”（合同号 TE 97/2020） 背景 血脂异常是心血管疾病和糖尿病的主要危险因素，糖尿病通常会导致严重的微血管并发症。据报道，与微泡 (MV) 相关的 microRNA (miRNA) 在糖尿病血脂异常的进展中调节细胞机制。我们假设检测血浆 MV 成分的变化可用作早期生物标志物，以防止糖尿病血脂异常的不可逆影响。目的：这项研究的目的是研究在伴有/不伴有微血管并发症的糖尿病血脂异常中是否存在循环 MV 和血浆 miRNA 的修饰，以及这些变化是否可以预测疾病的演变。方法 采集伴有/不伴有微血管并发症的糖尿病血脂异常患者血浆/血清，评估主要参数和炎症标志物。结果表明，与单独的糖尿病或血脂异常相比，糖尿病血脂异常患者的血糖、胆固醇、低密度脂蛋白胆固醇、甘油三酯浓度、收缩压显着升高。此外，检测到高水平的循环 IL-6 和源自内皮细胞 (CD144+)、血小板 (CD41+)、巨噬细胞 (CD14+) 和白细胞 (CD18+) 的 MV。在血浆 miRNA 和 MV 相关 miRNA 中发现了显着变化：122、-132、-143、-200b、-212，降低了 MV 中 miR-34a、-155、-218 的表达，降低了 miR-21、-34a， -132,-143 血浆中的表达式。值得注意的是，当微血管并发症与糖尿病血脂异常相关时，我们发现了显着变化，例如 MV 和血浆 miR-143 中 miR-21、-34a、-122、-126、-143、-218、-223 的表达增加，- 132 并降低 MV 和血浆 miR-223 中的 miR-200b,-212。结论 在糖尿病血脂异常患者中，特别是与微血管并发症相关的糖尿病血脂异常患者中，血浆 MV 含量和 miRNA 发生显着改变，表明它们可以成为糖尿病血脂异常及其并发症的生物标志物和潜在诊断工具。