Objective

Subjects with low vitamin D levels are at risk of cardiometabolic disease. The aim of this study was to identify novel serological markers linking vitamin D status with cardiometabolic profile in non-diabetic adults with obesity.

Methods

For the discovery phase, we used quantitative serum proteomics in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25–35 kg/m²] and low [25(OH)D < 50 nmol/L] vs. high vitamin D status [25(OH)D > 50 nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort with similar characteristics (n = 179).

Results

We identified 423 and 549 differentially expressed proteins in the high vs. low vitamin D groups of the male and female cohorts, respectively. The small molecule biochemistry protein networks and the glycolysis|gluconeogenesis pathway were significantly enriched in the DEPs of both sexes. As surrogate markers to these processes, the insulin-like growth factor binding protein -2 (IGFBP-2) was upregulated in males, whereas IGFBP-3 was upregulated in females from the high Vitamin D status. This sex-specific trend was confirmed using Luminex ELISA to an independent but clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p = 0.03).

Conclusions

The high Vitamin D status correlated with the serological upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may constitute surrogate markers of risk reduction of cardiometabolic disease.

中文翻译：

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肥胖成年人中IGFBP-2和IGFBP-3与维生素D状态的性别特异性相关性：一项横断面血清蛋白质组学研究

客观的

维生素D水平低的受试者有罹患心脏代谢疾病的风险。这项研究的目的是确定非糖尿病成年人肥胖症中维生素D状况与心脏代谢曲线相关的新型血清学标志物。

方法

在发现阶段，我们对肥胖[BMI：25–35 kg / m ² ]和低[25（OH）D <50 nmol / L]的肥胖，性别匹配，年龄匹配和BMI匹配的受试者使用了定量的血清蛋白质组学与高维生素D状态[25（OH）D> 50 nmol / L]（n  = 16）。对于验证阶段，我们在具有相似特征（n  = 179）的更大队列中进行了ELISA 。

结果

我们分别在男性和女性队列中的高维生素D和低维生素D组中鉴定了423和549个差异表达的蛋白质。该小分子生物化学 蛋白质网络和 糖酵解|糖异生通路在两性的分别的DEP丰富显著。作为这些过程的替代标志物，胰岛素样生长因子结合蛋白-2（IGFBP-2）在男性中被上调，而在女性中，IGFBP-3在高维生素D状态下被上调。使用Luminex ELISA对男性（n  = 84，p  =  0.002）和女性（n  = 95，p  =  0.03）的一个独立但临床相似的队列证实了这种性别特异性趋势。

结论

维生素D的高水平与肥胖男性中IGFBP-2的血清学上调和女性肥胖中IGFBP-3的血清学上调有关，可能构成降低心血管疾病风险的替代指标。