Sorbonne Université, Paris, France.
Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, Pitié-Salpêtrière Hospital, Paris, France.
PLoS One. 2020 Feb 24;15(2):e0229145. doi: 10.1371/journal.pone.0229145. eCollection 2020.
AIMS/HYPOTHESIS: Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP.
198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA.
In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (β = -0.26, p = 0.045) after integrating effects of height (β = -0.38, p = 0.01), insulin treatment (β = 0.42, p = 0.002), retinopathy treated by laser (β = 0.26, p = 0.02), and total cholesterol levels (β = 0.3, p = 0.03) by multivariable analysis.
The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy.
目的/假设：糖尿病周围神经病变是糖尿病的一种常见且严重的并发症。由于基质 Gla 蛋白（MGP）在神经系统的几个组成部分中表达，并参与一些神经疾病，因此 MGP 可能在周围神经系统稳态中发挥作用。本研究旨在评估与 2 型糖尿病敏感糖尿病神经病变相关的因素，特别是 MGP 的无活性形式去磷酸化非羧化 MGP（dp-ucMGP）。
纳入 198 例 2 型糖尿病患者。通过神经病变残疾评分（NDS）≥6 定义存在敏感的糖尿病神经病变。通过 ELISA 测定 dp-ucMGP 的血浆水平。
在该队列中，平均年龄为 64±8.4 岁，80%的患者为男性。15.7%的患者存在周围神经病变，与 dp-ucMGP 水平显著相关（r=0.51，p<0.0001）（β=-0.26，p=0.045），经多变量分析校正身高（β=-0.38，p=0.01）、胰岛素治疗（β=0.42，p=0.002）、激光治疗的视网膜病变（β=0.26，p=0.02）和总胆固醇水平（β=0.3，p=0.03）后。
糖尿病神经病变与 MGP 无活性形式之间的关联表明存在新的病理生理途径需要探索。需要进一步的研究来确定 dp-ucMGP 是否可作为敏感神经病变的生物标志物。由于 dp-ucMGP 是维生素 K 状态不佳的标志物，因此需要进行临床研究来探索高维生素 K 摄入对糖尿病周围神经病变的潜在保护作用。
