Identifying blood metabolites for type 2 diabetes risk
A new study in Nature Medicine combines metabolomic, genetic and lifestyle data to identify 235 metabolites, 67 of which previously unreported, that act as biomarkers for a heightened risk of type 2 diabetes.
Diabetes is a health concern for millions of people across the world. Recent studies estimate that there are 589 million adults living with diabetes globally. This number is anticipated to rise to over 850 million in 2050. 90% of those currently living with diabetes suffer from the iteration of the condition known as type 2 (T2D). T2D manifests in middle or older age patients and its onset is linked to myriad factors including, but not limited to, diet, lifestyle and genetic predisposition. High blood sugar, caused by an increased resistance to the hormone insulin, is a T2D fingerprint for pathophysiologists. However, T2D can also affect several other metabolic pathways in the body, leading to a unique group of small molecules in the blood stream alongside abnormally high glucose levels.
A new study, published in Nature Medicine, a culmination of decades of research by academics from across the United States, sought to establish an understating of T2D mechanisms and the telltale metabolites and metabolic pathways associated with not only T2D but with the risk of developing the disease. The authors analyzed the plasma samples of 23,364 study participants from ten cohorts. Over the three decades of study, nearly 4,000 members of the original cohorts developed T2D.
Liquid chromatography–tandem mass spectrometry (LC–MS) was utilized for metabolomic profiling. Research teams used complimentary LC–MS methods, including hydrophilic interaction chromatography (HILIC) and both positive and negative ion modes for the analyses of 469 metabolites. From the 469 identified metabolites, 235 small molecules were found to be associated with T2D risk, including 67 previously unreported associations across various metabolic pathways.
Researchers also integrated diet, genetic and lifestyle data when analyzing the results of the study. Genetic analysis suggested that many metabolites identified were subject to strong genetic regulation. This opens the door to future studies to explore the mechanisms underpinning metabolites and T2D.
You may also be interested in:
- Marking World Diabetes Day with treatment progress in 2025
- Hidden biomarkers uncovered for diabetes early warning signs
- Analysis of semaglutide from human plasma by LC-MS/MS
The incorporation of lifestyle data, together with metabolomic and genetic results demonstrated the correlation between these risk-associated metabolites and diet and lifestyle choices. Results indicated that obesity, physical activity and quality of diet can significantly affect the metabolome. The study yielded several threads for future research to follow on to further probe the mechanism linking lifestyle decisions with metabolic pathways associated with T2D.
The authors close the paper by acknowledging that whilst the study is a significant landmark in the journey to fully understand the risk factors and pathophysiology of T2D, there is still much more work to be done, in both the laboratory and the clinic to fully investigate the pathways. They also hope that their identified metabolites may be used as biomarkers in prevention and early mitigation of T2D.
