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非活性基质 gla 蛋白的血浆水平与 2 型糖尿病周围神经病变有关。

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

机构信息

Sorbonne Université, Paris, France.

Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, Pitié-Salpêtrière Hospital, Paris, France.

出版信息

PLoS One. 2020 Feb 24;15(2):e0229145. doi: 10.1371/journal.pone.0229145. eCollection 2020.

Abstract

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

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)。

方法

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。

结果

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。

结论

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。

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