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Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes
EBioMedicine ( IF 11.1 ) Pub Date : 2021-08-20 , DOI: 10.1016/j.ebiom.2021.103550
Jose L Flores-Guerrero 1 , Marco A Grzegorczyk 2 , Margery A Connelly 3 , Erwin Garcia 3 , Gerjan Navis 1 , Robin P F Dullaart 4 , Stephan J L Bakker 1
Affiliation  

Background

The potential role of individual plasma biomarkers in the pathogenesis of type 2 diabetes (T2D) has been broadly studied, but the impact of biomarkers interaction remains underexplored. Recently, the Mahalanobis distance (MD) of plasma biomarkers has been proposed as a proxy of physiological dysregulation. Here we aimed to investigate whether the MD calculated from circulating biomarkers is prospectively associated with development of T2D.

Methods

We calculated the MD of the Principal Components (PCs) integrating the information of 32 circulating biomarkers (comprising inflammation, glycemic, lipid, microbiome and one-carbon metabolism) measured in 6247 participants of the PREVEND study without T2D at baseline. Cox proportional-hazards regression analyses were performed to study the association of MD with T2D development.

Findings

After a median follow-up of 7·3 years, 312 subjects developed T2D. The overall MD (mean (SD)) was higher in subjects who developed T2D compared to those who did not: 35·65 (26·67) and 30.75 (27·57), respectively (P = 0·002). The highest hazard ratio (HR) was obtained using the MD calculated from the first 31 PCs (per 1 log-unit increment) (1·72 (95% CI 1·42,2·07), P < 0·001). Such associations remained after the adjustment for age, sex, plasma glucose, parental history of T2D, lipids, blood pressure medication, and BMI (HRadj 1·37 (95% CI 1·11,1·70), P = 0·004).

Interpretation

Our results are in line with the premise that MD represents an estimate of homeostasis loss. This study suggests that MD is able to provide information about physiological dysregulation also in the pathogenesis of T2D.

Funding

The Dutch Kidney Foundation (Grant E.033).



中文翻译:

马氏距离,一种新的动态平衡损失统计指标与 2 型糖尿病的风险纵向相关

背景

个体血浆生物标志物在 2 型糖尿病 (T2D) 发病机制中的潜在作用已被广泛研究,但生物标志物相互作用的影响仍未得到充分探索。最近,已提出血浆生物标志物的马氏距离 (MD) 作为生理失调的代表。在这里,我们旨在调查从循环生物标志物计算的 MD 是否与 T2D 的发展有前瞻性相关。

方法

我们计算了主成分 (PC) 的 MD,它整合了在基线时没有 T2D 的 6247 名 PREVEND 研究参与者测量的 32 个循环生物标志物(包括炎症、血糖、脂质、微生物组和一碳代谢)的信息。进行 Cox 比例风险回归分析以研究 MD 与 T2D 发展的关联。

发现

中位随访 7·3 年后,312 名受试者发展为 T2D。与未发生 T2D 的受试者相比,发生 T2D 的受试者的总体 MD(平均值 (SD))更高:分别为 35·65 (26·67) 和 30.75 (27·57) ( P  = 0·002)。使用从前 31 个 PC(每 1 个对数单位增量)计算的 MD 获得最高风险比 (HR) (1·72 (95% CI 1·42,2·07), P  < 0·001)。在调整年龄、性别、血浆葡萄糖、T2D 父母史、血脂、血压药物和 BMI 后,这种关联仍然存在(HR adj 1·37 (95% CI 1·11,1·70),P  = 0· 004)。

解释

我们的结果与 MD 代表对稳态损失的估计的前提一致。这项研究表明,MD 能够在 T2D 的发病机制中提供有关生理失调的信息。

资金

荷兰肾脏基金会(Grant E.033)。

更新日期:2021-08-20
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