Dataset Information

Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes.

ABSTRACT:

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 (HR_adj 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).

SUBMITTER: Flores-Guerrero JL

PROVIDER: S-EPMC8379628 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes.

Flores-Guerrero Jose L JL Grzegorczyk Marco A MA Connelly Margery A MA Garcia Erwin E Navis Gerjan G Dullaart Robin P F RPF Bakker Stephan J L SJL

EBioMedicine 20210820

<h4>Background</h4>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.<h4>Methods</h4>We calculated the MD o ...[more]

PMID: 34425309

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Dataset Information

Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes.

Background

Methods

Findings

Interpretation

Funding

Publications

Mahalanobis distance, a novel statistical proxy of homeostasis loss is longitudinally associated with risk of type 2 diabetes.

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