Publication | February 25, 2025
Plasma Lipid Metabolites, Clinical Glycemic Predictors, and Incident Type 2 Diabetes
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Read the PaperThere is a growing appreciation that the heterogeneity in disease manifestation and complications of type 2 diabetes (T2D) are not captured by conventional glycemic risk factors alone. Novel diabetes biomarkers are needed to effectively individualize disease treatment and prevention strategies by capturing aspects of T2D molecular etiology distinct from commonly used biomarkers. Metabolites are an important class of molecules from which novel etiologic diabetes biomarkers may be identified, given that T2D is a disorder of metabolism.
This study published in Diabetes Care – contributed to by Sapient’s scientists and for which Sapient provided nontargeted metabolomics data – identified diacylglycerols (DAGs) and phosphatidylcholines (PCs) that were respectively associated with increased and decreased T2D incidence.
Leveraging high-throughput mass spectrometry to measure thousands of metabolites in blood from two large prospective cohorts, the researchers were able to identify novel chemical classes of T2D risk predictors, beyond the standard metabolite glucose and its derivatives.
The findings showed that DAGs capture T2D risk information related to 2-hour postchallenge plasma glucose (2hPG) levels, while PCs capture T2D risk information independent of glycemic markers and insulin. The researchers propose that circulating DAGs in humans cause muscle-specific insulin resistance leading to impaired muscle glucose disposal as a potential mechanism for T2D risk. PCs were found to be inversely associated with T2D risk independent of fasting plasma glucose (FPG), 2hPG, HbA1c, or fasting insulin, and may exert protective effects via reduction of inflammation in metabolic tissues.
The study also used subgroup analysis to evaluate whether the identified associations of DAGs and PCs with incident T2D differed by race. They found the associations were similar and therefore represented relevant diabetes biomarkers in both European American and African American individuals.
To learn more, read the full paper and findings.
