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一组沙特2型糖尿病患者中循环维生素D、维生素D结合蛋白和维生素D受体表达与糖尿病肾病严重程度的关联

Association of Circulating Vitamin D, VDBP, and Vitamin D Receptor Expression with Severity of Diabetic Nephropathy in a Group of Saudi Type 2 Diabetes Mellitus Patients.

作者信息

Fawzy Manal S, Beladi Fatima I Al

出版信息

Clin Lab. 2018 Oct 1;64(10):1623-1633. doi: 10.7754/Clin.Lab.2018.180401.

Abstract

BACKGROUND

As the seventh leading cause of death by 2030, type 2 diabetes mellitus (T2DM) is considered the most common chronic metabolic disease worldwide. Vitamin D metabolic axis players were identified as good candidates for T2DM. We aimed to analyze the circulating levels of total 25-hydroxy vitamin D (25-OHD), vitamin D receptor (VDR) transcript and VD-binding protein (VDBP) in a sample of Saudi T2DM and to correlate these profiles with diabetic nephropathy and insulin resistance.

METHODS

Ninety T2DM patients, classified into normo-, micro- and macro-albuminuria groups (n = 30/each) and 50 healthy controls were studied. Serum (25-OHD) and VDBP levels were assayed by ELISA. The peripheral blood mononuclear cell (PBMN) VDR expression level was quantified by real-time RT-PCR. Insulin resistance was evaluated by the homeostasis model assessment index (HOMAI).

RESULTS

The normo-albuminuria group showed the highest levels of PBMN VDR expression, whereas the macroalbuminuria group had the lowest levels among T2DM patients. However, serum VDBP levels were significantly elevated in all patient groups. There was a significant positive correlation between PBMN VDR expression levels and serum (25-OHD) in the total patient group (r = 0.579, p < 0.001). Spearman's correlation showed significant correlations of the circulatory markers with many clinico-laboratory variables. Stepwise regression analysis indicated that serum VDBP levels, HBA1c, and BMI were independent predictors for albuminuria.

CONCLUSIONS

The study findings suggest a potential role of vitamin D metabolic players in DN, with a special concern regarding serum VDPB as a putative predictor of DN severity in type 2 DM Saudi patients. Large-scale validation studies are warranted.

摘要

背景

到2030年,2型糖尿病(T2DM)是全球第七大死因,被认为是全球最常见的慢性代谢性疾病。维生素D代谢轴相关因子被认为是T2DM的良好候选因素。我们旨在分析沙特T2DM患者样本中总25-羟基维生素D(25-OHD)、维生素D受体(VDR)转录本和维生素D结合蛋白(VDBP)的循环水平,并将这些指标与糖尿病肾病和胰岛素抵抗相关联。

方法

研究了90例T2DM患者,分为正常蛋白尿、微量白蛋白尿和大量白蛋白尿组(每组n = 30)以及50例健康对照。采用酶联免疫吸附测定法(ELISA)检测血清(25-OHD)和VDBP水平。通过实时逆转录聚合酶链反应(RT-PCR)定量外周血单个核细胞(PBMN)中VDR的表达水平。采用稳态模型评估指数(HOMAI)评估胰岛素抵抗。

结果

在T2DM患者中,正常蛋白尿组的PBMN VDR表达水平最高,而大量白蛋白尿组最低。然而,所有患者组的血清VDBP水平均显著升高。在所有患者组中,PBMN VDR表达水平与血清(25-OHD)之间存在显著正相关(r = 0.579,p < 0.001)。Spearman相关性分析显示,循环标志物与许多临床实验室变量之间存在显著相关性。逐步回归分析表明,血清VDBP水平、糖化血红蛋白(HBA1c)和体重指数(BMI)是蛋白尿的独立预测因素。

结论

研究结果表明维生素D代谢相关因子在糖尿病肾病中具有潜在作用,尤其要关注血清VDPB作为沙特2型糖尿病患者糖尿病肾病严重程度的推定预测指标。有必要进行大规模验证研究。

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