Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies
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posted on 2022-03-03, 15:36 authored by Jakub Morze, Clemens Wittenbecher, Lukas Schwingshackl, Anna Danielewicz, Andrzej Rynkiewicz, Frank B Hu, Marta Guasch-Ferré<i><u>Background</u></i> Due to the
rapidly increasing availability of metabolomics data in prospective studies, an
update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.
<p><i><u>Purpose</u></i><i> </i>To conduct an updated systematic review and
meta-analysis of plasma, serum, or urine metabolite markers and incident type 2
diabetes.</p>
<p><i><u>Data Sources</u></i><i> </i>PubMed and Embase. </p>
<p><i><u>Study Selection</u></i><i> </i>Prospective observational studies investigating
the relationship between plasma, serum, or urine metabolites using high
throughput techniques and incident type 2 diabetes. </p>
<p><i><u>Data Extraction</u></i> Baseline
metabolites per-standard deviation risk estimates and 95% confidence intervals
for incident type 2 diabetes were extracted from all eligible studies.</p>
<p><i><u>Data Synthesis</u></i> Sixty-one
reports with 71,196 participants and 11,771 type 2 diabetes cases/events were
included in the updated review. Overall, 412 metabolites were meta-analyzed, of
which 123 were statistically significantly associated (FDR-P<0.05) with type
2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain,
aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and
energy-related metabolites (mannose, trehalose, pyruvate), acylcarnitines (C4DC,
C4OH, C5, C5OH, C8:1), the majority of meta-analyzed glycerolipids (di- and
triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides were
associated with higher risk of type 2 diabetes (hazard ratio [HR] 1.07-2.58). Higher levels of
glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines
were associated with lower type 2 diabetes risk (HR 0.69-0.90).</p>
<p><i><u>Limitations</u></i><i> </i>Substantial
heterogeneity <a>(I<sup>2</sup>>50%, </a>t<sup>2</sup>>0.1) was observed
for some of the metabolites.</p>
<p><i><u>Conclusions</u></i> Several
plasma and serum metabolites, including amino acids, lipids, and carbohydrates
are associated with type 2 diabetes risk. </p>
Funding
This work was supported by National Institutes of Health research grants R21AG070375-01A1, P30 DK46200, R01DK112940, and R01DK127601. MG-F is supported by American Diabetes Association grant 1-18-PMF-029. The funding sources played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication.
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