Metabolite Signature of Albuminuria

Lilian Fernandes Silva, Jagadish Vangipurapu, Ulf Smith, Markku Laakso
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 1, January 2021, Pages 143–152
https://doi.org/10.1210/clinem/dgaa661

Abstract

Objective

To investigate the metabolite signature of albuminuria in individuals without diabetes or chronic kidney disease to identify possible mechanisms that result in increased albuminuria and elevated risk of type 2 diabetes (T2D).

Research Design and Methods

The study cohort was a population-based Metabolic Syndrome In Men (METSIM) study including 8861 middle-aged and elderly Finnish men without diabetes or chronic kidney disease at baseline. A total of 5504 men participated in a 7.5-year follow-up study, and 5181 of them had metabolomics data measured by Metabolon’s ultrahigh performance liquid chromatography-tandem mass spectroscopy.

Results

We found 32 metabolites significantly (P < 5.8 × 10^-5) and positively associated with the urinary albumin excretion (UAE) rate. These metabolites were especially downstream metabolites in the amino acid metabolism pathways (threonine, phenylalanine, leucine, arginine). In our 7.5-year follow-up study, UAE was significantly associated with a 19% increase (hazard ratio 1.19; 95% confidence interval, 1.13–1.25) in the risk of T2D after the adjustment for confounding factors. Conversion to diabetes was more strongly associated with a decrease in insulin secretion than a decrease in insulin sensitivity.

Conclusions

Metabolic signature of UAE included multiple metabolites, especially from the amino acid metabolism pathways known to be associated with low-grade inflammation, and accumulation of reactive oxygen species that play an important role in the pathogenesis of UAE. These metabolites were primarily associated with an increase in UAE and were secondarily associated with a decrease in insulin secretion and insulin sensitivity, resulting in an increased risk of incident T2D.

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