Mary Aurélien, Hartemann Agnes, Liabeuf Sophie, Aubert Carole Elodie, Kemel Salim, Salem Joe Elie, Cluzel Philippe, Lenglet Aurélie, Massy Ziad A, Lalau Jean-Daniel, Mentaverri Romuald, Bourron Olivier, Kamel Saïd
INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France.
Amiens University Medical Center, Pharmacy, 80054, Amiens, France.
Cardiovasc Diabetol. 2017 Feb 15;16(1):24. doi: 10.1186/s12933-017-0509-7.
Vascular calcification (VC) is common in type 2 diabetes, and is associated with cardiovascular complications. Recent preclinical data suggest that metformin inhibits VC both in vitro and in animal models. However, metformin's effects in patients with diabetic VC have not previously been characterized. The present study investigated the association between metformin use and lower-limb arterial calcification in patients with type 2 diabetes and high cardiovascular risk.
The DIACART cross-sectional cohort study included 198 patients with type 2 diabetes but without severe chronic kidney disease. Below-the-knee calcification scores were assessed by computed tomography and supplemented by colour duplex ultrasonography. Data on anti-diabetic drugs were carefully collected from the patients' medical records and during patient interviews. Biochemical and clinical data were studied as potential confounding factors.
Metformin-treated patients had a significantly lower calcification score than metformin-free patients (mean ± standard deviation: 2033 ± 4514 and 4684 ± 9291, respectively; p = 0.01). A univariate analysis showed that metformin was associated with a significantly lower prevalence of severe below-the-knee arterial calcification (p = 0.02). VC was not significantly associated with the use of other antidiabetic drugs, including sulfonylureas, insulin, gliptin, and glucagon like peptide-1 analogues. A multivariate logistic regression analysis indicated that the association between metformin use and calcification score (odds ratio [95% confidence interval] = 0.33 [0.11-0.98]; p = 0.045) was independent of age, gender, tobacco use, renal function, previous cardiovascular disease, diabetes duration, neuropathy, retinopathy, HbA levels, and inflammation.
In patients with type 2 diabetes, metformin use was independently associated with a lower below-the-knee arterial calcification score. This association may contribute to metformin's well-known vascular protective effect. Further prospective investigations of metformin's potential ability to inhibit VC in patients with and without type 2 diabetes are now needed to confirm these results.
血管钙化（VC）在2型糖尿病中很常见，且与心血管并发症相关。最近的临床前数据表明，二甲双胍在体外和动物模型中均能抑制血管钙化。然而，二甲双胍对糖尿病性血管钙化患者的影响此前尚未得到明确阐述。本研究调查了2型糖尿病且心血管风险高的患者使用二甲双胍与下肢动脉钙化之间的关联。
DIACART横断面队列研究纳入了198例2型糖尿病但无严重慢性肾病的患者。通过计算机断层扫描评估膝下钙化评分，并辅以彩色双功超声检查。从患者的病历和患者访谈中仔细收集有关抗糖尿病药物的数据。研究生化和临床数据作为潜在的混杂因素。
接受二甲双胍治疗的患者钙化评分显著低于未使用二甲双胍的患者（均值±标准差分别为2033±4514和4684±9291；p = 0.01）。单因素分析显示，二甲双胍与严重膝下动脉钙化的患病率显著降低相关（p = 0.02）。血管钙化与使用其他抗糖尿病药物（包括磺脲类、胰岛素、格列汀和胰高血糖素样肽-1类似物）无显著关联。多因素逻辑回归分析表明，使用二甲双胍与钙化评分之间的关联（比值比[95%置信区间]=0.33[0.11 - 0.98]；p = 0.045）独立于年龄、性别、吸烟、肾功能、既往心血管疾病、糖尿病病程、神经病变、视网膜病变、糖化血红蛋白水平和炎症。
在2型糖尿病患者中，使用二甲双胍与较低的膝下动脉钙化评分独立相关。这种关联可能有助于二甲双胍众所周知的血管保护作用。现在需要进一步对二甲双胍在有或无2型糖尿病患者中抑制血管钙化的潜在能力进行前瞻性研究，以证实这些结果。
