Background

Proteomics is expected to provide novel insights in the underlying pathophysiology of type 2 diabetes mellitus. In the present study, we aimed to identify and biochemically characterize proteins associated with diabetes mellitus in a Qatari population.

Methods

In a diabetes case-control study (175 cases, 164 controls; Arab, South Asian and Philippine ethnicities), we conducted a discovery study to screen 1141 blood protein levels for associations with diabetes mellitus. Additional analyses were done in controls in relation to Hb1Ac, and biochemical characterization of the main findings was performed with metabolomics (501 metabolites). We performed two-sample Mendelian Randomization to provide evidence of potential causality using data from European descent of the DIAGRAM consortium (74,124 cases of diabetes mellitus and 824,006 controls) for the identified proteins for T2D and Hb1Ac.

Results

After accounting for multiple testing, 30 protein levels were different (p-values<8.6e⁻⁵) between cases and controls. Of these, a higher Hb1Ac in controls was associated with a lower IGFBP-2 level (p-value = 4.1e⁻⁶). IGFBP-2 protein level was found lower among cases compared with controls across all ethnicities. In controls, IGFBP-2 was associated with 21 metabolite levels, but specifically connected to the metabolite citrulline in network analyses. We observed no evidence, however, that the association between IGFBP-2 and diabetes mellitus was causal.

Conclusions

We specifically identified IGFBP-2 to be associated with diabetes mellitus, although with no evidence for causality, which was specifically connected to citrulline metabolism.

中文翻译：

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卡塔尔糖尿病患者的蛋白质组学评估表明，IGFBP-2是已经存在早期血糖紊乱的危险因素。

背景

蛋白质组学有望为2型糖尿病的潜在病理生理学提供新颖的见解。在本研究中，我们旨在鉴定和生化表征卡塔尔人群中与糖尿病相关的蛋白质。

方法

在一项糖尿病病例对照研究（175例，164个对照；阿拉伯，南亚和菲律宾族裔）中，我们进行了一项发现研究，以筛查1141例血液蛋白水平与糖尿病的相关性。在与Hb1Ac有关的对照中进行了其他分析，并使用代谢组学（501种代谢物）对主要发现进行了生化表征。我们使用欧洲血统DIAGRAM协会（74,124例糖尿病患者和824,006例对照）的欧洲血统数据为T2D和Hb1Ac的鉴定蛋白进行了两次样本孟德尔随机化，以提供潜在因果关系的证据。

结果

在考虑了多次测试后，病例与对照之间的30种蛋白质水平有所不同（p值<8.6e ^-5）。其中，对照组中较高的Hb1Ac与较低的IGFBP-2水平相关（p值= 4.1e ^-6）。在所有种族中，与对照组相比，IGFBP-2蛋白水平较低。在对照中，IGFBP-2与21种代谢物水平相关，但在网络分析中与代谢物瓜氨酸特别相关。然而，我们没有观察到IGFBP-2与糖尿病之间的因果关系。

结论

尽管没有因果关系的证据，但我们明确鉴定出IGFBP-2与糖尿病有关，这与瓜氨酸代谢特别相关。