Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies

<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>