Patidar Ashish, Singh Dhruv K, Thakur Shori, Winocour Peter, Farrington Ken, Baydoun Anwar R
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K.
Renal Unit, Lister Hospital, Coreys Mill Lane, Stevenage SG1 4AB, U.K.
Clin Sci (Lond). 2017 May 1;131(10):991-1000. doi: 10.1042/CS20160882. Epub 2017 Mar 20.
Although vascular calcification (VC) is prevalent in Type 2 diabetes mellitus (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) on serum, enabling it to induce VC outside the disease milieu. We, therefore, investigated the CP of serum from controls and subjects with T2DM with and without VC Samples from 20 healthy controls and 44 age- and sex-matched patients with T2DM with modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) > 60 ml·min were analysed for CP using rat aortic smooth muscle cells CT scans of femoral arteries identified individuals with calcification. Serum from subjects with T2DM revealed significantly greater CP than controls. This was further enhanced in the presence of VC. Addition of β-glycerophosphate (β-GP) plus CaCl increased the CP of T2DM serum but not of controls. Along with age, CP was an independent predictor of the presence of VC. In receiver operator curve (ROC) analysis, CP was a significant predictor of femoral arterial VC (C-statistic 0.70: =0.009). The distribution of CP was bimodal around a cutoff of 100 nmoles of Ca protein mg, with a higher proportion of Type 2 diabetes subjects with calcification (T2DM+) sera above the cutoff value. This group also showed elevated levels of osteoprotegerin (OPG) and matrix Gla protein (MGP). Diabetes confers CP on the serum which is enhanced by the presence of VC. The CP acquired may be dependent on levels of OPG and MGP. These findings may be clinically relevant for early identification of individuals at risk of VC and for informing therapeutic strategies.
尽管血管钙化（VC）在2型糖尿病（T2DM）中普遍存在，但其潜在机制仍不清楚。T2DM是否赋予血清钙化潜能（CP），使其能够在疾病环境之外诱导VC也尚不清楚。因此，我们研究了有或无VC的对照组和T2DM患者血清的CP。分析了20名健康对照者以及44名年龄和性别匹配的T2DM患者（肾病饮食改良估算肾小球滤过率（MDRD-4 eGFR）>60 ml·min）的样本，使用大鼠主动脉平滑肌细胞检测CP。股动脉CT扫描确定有钙化的个体。T2DM患者的血清显示出比对照组显著更高的CP。在存在VC的情况下，这种情况进一步增强。添加β-甘油磷酸酯（β-GP）加氯化钙可增加T2DM血清的CP，但对照组血清则无此现象。与年龄一起，CP是VC存在的独立预测因子。在受试者工作特征曲线（ROC）分析中，CP是股动脉VC的显著预测因子（C统计量0.70：P=0.009）。CP的分布在100纳摩尔钙/毫克蛋白的临界值周围呈双峰分布，钙化的2型糖尿病受试者（T2DM+）血清高于临界值的比例更高。该组还显示骨保护素（OPG）和基质Gla蛋白（MGP）水平升高。糖尿病赋予血清CP，而VC的存在会增强这种CP。获得的CP可能取决于OPG和MGP的水平。这些发现可能在临床上与早期识别有VC风险的个体以及为治疗策略提供信息相关。
