Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, West Yorkshire, UK.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Diab Vasc Dis Res. 2020 Nov-Dec;17(6):1479164120963048. doi: 10.1177/1479164120963048.
Fibrin network characteristics determine predisposition to cardiovascular disease (CVD). Individuals with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have higher risk of CVD and display deranged fibrin network structure. Those with maturity onset diabetes of the young (MODY) may also be at increased risk but their fibrin clot properties have not been studied.
Plasma clots properties from 13 individuals with HNF1A-MODY, 12 matched-individuals with T2DM and 12 with T1DM were studied using a validated turbidimetric assay and confocal microscopy. Plasma levels of fibrinogen, plasminogen activator inhibitor-1, complement C3 and C-reactive protein were also measured.
MODY clot maximum absorbance was 0.37 ± 0.03 AU, similar to T1DM (0.32 ± 0.03 AU; = 0.26), but lower than T2DM (0.49 ± 0.03 AU; = 0.02), with confocal microscopy confirming structural differences. Clot lysis time in MODY was similar to T1DM (456 ± 50 and 402 ± 20 s, respectively; = 0.09) but shorter than T2DM (588 ± 58 s; = 0.006). Comparing inflammatory/thrombotic proteins in HNF1A-MODY and T2DM, C3 levels were lower in MODY than T2DM (0.58 ± 0.09 and 0.80 ± 0.1 mg/ml, respectively; < 0.01).
HNF1A-MODY fibrin network alterations are at least as pronounced as in T1DM but less thrombotic than T2DM clots. Differences in fibrin clot characteristics comparing HNF1A-MODY and T2DM may, in part, relate to lower C3 levels.
纤维蛋白网络特征决定了心血管疾病（CVD）的易感性。1 型（T1DM）和 2 型糖尿病（T2DM）患者 CVD 风险较高，且显示纤维蛋白网络结构异常。年轻起病的成人型糖尿病（MODY）患者也可能存在更高的风险，但他们的纤维蛋白凝块特性尚未得到研究。
使用经过验证的比浊法和共聚焦显微镜研究了 13 名 HNF1A-MODY 患者、12 名匹配的 T2DM 患者和 12 名 T1DM 患者的血浆凝块特性。还测量了纤维蛋白原、纤溶酶原激活物抑制剂-1、补体 C3 和 C-反应蛋白的血浆水平。
MODY 组的最大血凝块吸光度为 0.37 ± 0.03 AU，与 T1DM 相似（0.32 ± 0.03 AU； = 0.26），但低于 T2DM（0.49 ± 0.03 AU； = 0.02），共聚焦显微镜证实了结构差异。MODY 组的血凝块溶解时间与 T1DM 相似（分别为 456 ± 50 和 402 ± 20 s； = 0.09），但短于 T2DM（588 ± 58 s； = 0.006）。比较 HNF1A-MODY 和 T2DM 中的炎症/血栓形成蛋白，MODY 组的 C3 水平低于 T2DM 组（分别为 0.58 ± 0.09 和 0.80 ± 0.1 mg/ml； < 0.01）。
HNF1A-MODY 纤维蛋白网络的改变至少与 T1DM 一样明显，但血栓形成性不如 T2DM 凝块。与 T2DM 相比，HNF1A-MODY 和 T2DM 之间纤维蛋白凝块特征的差异可能部分与 C3 水平较低有关。
