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超重/肥胖人群中维生素 D 与组织特异性胰岛素敏感性的关系。

Vitamin D and Tissue-Specific Insulin Sensitivity in Humans With Overweight/Obesity.

机构信息

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.

Department of Nutrition Science, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia.

出版信息

J Clin Endocrinol Metab. 2019 Jan 1;104(1):49-56. doi: 10.1210/jc.2018-00995.

DOI:10.1210/jc.2018-00995
PMID:30137362
Abstract

CONTEXT

Vitamin D deficiency in obesity has been linked to insulin resistance. However, studies that examined the association between plasma 25-hydroxyvitamin D3 [25(OH)D3] as well as plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and tissue-specific insulin sensitivity are scarce. Furthermore, vitamin D receptor (VDR) and vitamin D-metabolizing enzymes [cytochrome 450 (CYP)] expression in adipose tissue (AT) might affect AT insulin sensitivity.

OBJECTIVE

To investigate the association between body mass index (BMI) and plasma 25(OH)D3 and 1,25(OH)2D3, AT VDR; between plasma 25(OH)D3, 1,25(OH)2D3, AT VDR, and tissue-specific insulin sensitivity in individuals with overweight/obesity.

DESIGN AND PATIENTS

This analysis included 92 adult individuals (BMI, >25 kg/m2). A two-step hyperinsulinemic-euglycemic clamp with a [6,6-2H2]-glucose tracer was performed to assess tissue-specific insulin sensitivity. Abdominal subcutaneous AT (SAT) mRNA expression of VDR and CYP was determined by using quantitative RT-PCR.

SETTING

University medical center.

MAIN OUTCOME MEASURES

Plasma 25(OH)D3, 1,25(OH)2D3, 1,25(OH)2D3/25(OH)D3 ratio, SAT VDR and CYPs mRNA, and tissue-specific insulin sensitivity.

RESULTS

BMI was inversely associated with plasma 25(OH)D3 (β = -0.274; P = 0.011) but not with plasma 1,25(OH)2D3. Plasma 25(OH)D3 was not related to CYPs or VDR expression in SAT. Plasma 1,25(OH)2D3 and 25(OH)D3 were not related to tissue-specific insulin sensitivity. Interestingly, SAT VDR mRNA was negatively associated with AT insulin sensitivity (β = -0.207; P = 0.025).

CONCLUSIONS

BMI was inversely associated with 25(OH)D3 concentrations, which could not be explained by alterations in SAT VDR and CYP enzymes. Plasma vitamin D metabolites were not related to tissue-specific insulin sensitivity. However, VDR expression in SAT was negatively associated with AT insulin sensitivity.

摘要

背景

肥胖症患者的维生素 D 缺乏与胰岛素抵抗有关。然而,目前关于血浆 25-羟维生素 D3 [25(OH)D3]和血浆 1,25-二羟维生素 D3 [1,25(OH)2D3]与组织特异性胰岛素敏感性之间的关联的研究很少。此外,脂肪组织(AT)中的维生素 D 受体(VDR)和维生素 D 代谢酶(细胞色素 450(CYP))的表达可能会影响 AT 胰岛素敏感性。

目的

研究超重/肥胖个体的体重指数(BMI)与血浆 25(OH)D3 和 1,25(OH)2D3、AT VDR 之间的关系;血浆 25(OH)D3、1,25(OH)2D3、AT VDR 与组织特异性胰岛素敏感性之间的关系。

设计和患者

本分析包括 92 名成年个体(BMI>25kg/m2)。采用两步法高胰岛素正葡萄糖钳夹技术联合[6,6-2H2]-葡萄糖示踪剂评估组织特异性胰岛素敏感性。采用实时定量 RT-PCR 法测定腹部皮下脂肪组织(SAT)中 VDR 和 CYP 的 mRNA 表达。

地点

大学医学中心。

主要观察指标

血浆 25(OH)D3、1,25(OH)2D3、1,25(OH)2D3/25(OH)D3 比值、SAT VDR 和 CYPmRNA 及组织特异性胰岛素敏感性。

结果

BMI 与血浆 25(OH)D3 呈负相关(β=-0.274;P=0.011),但与血浆 1,25(OH)2D3 无关。血浆 25(OH)D3 与 SAT 中的 CYP 或 VDR 表达无关。血浆 1,25(OH)2D3 和 25(OH)D3 与组织特异性胰岛素敏感性无关。有趣的是,SAT VDR mRNA 与 AT 胰岛素敏感性呈负相关(β=-0.207;P=0.025)。

结论

BMI 与 25(OH)D3 浓度呈负相关,而这不能用 SAT VDR 和 CYP 酶的改变来解释。血浆维生素 D 代谢物与组织特异性胰岛素敏感性无关。然而,SAT 中的 VDR 表达与 AT 胰岛素敏感性呈负相关。

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