Researchers have identified hundreds of blood metabolites that predict a person’s risk of type 2 diabetes over and above traditional risk factors.
Their study suggests that these small molecules—generated through the metabolism—may mediate how dietary and lifestyle choices link with type 2 diabetes.
Specifically, the results suggest that these metabolites reflect a dysregulated metabolism driven by both genetics and modifiable risk factors.
The findings, in Nature Medicine, have been used to create a unique metabolomic signature for risk stratification and as a monitoring biomarker.
“A better understanding of the biological pathways behind disease can help drive the development of new treatments,” explained Qibin Qi, PhD, from Albert Einstein College of Medicine in New York.
“Our findings lay the groundwork for a deeper understanding of type 2 diabetes and may help inform the development of precision preventive strategies targeting specific metabolic pathways.”
The study is the largest and most comprehensive investigation of blood metabolomic profiles associated with the risk of type 2 diabetes, integrating genomic, diet and lifestyle data in people from diverse ethnic backgrounds.
It included 23,634 people from 10 prospective cohorts, who were initially free from type 2 diabetes and followed for up to 26 years.
Among 469 metabolites studied in blood samples, 235 were associated with elevated or decreased risk of developing type 2 diabetes, after adjusting for demographic, socioeconomic and clinical factors that included body mass index and waist–hip ratio.
Of these metabolites, 168 were previously reported associations and 67 were new discoveries that spanned bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine, and histidine pathways.
Metabolites associated with type 2 diabetes were genetically linked with signaling pathways and clinical traits relevant to the pathophysiology of type 2 diabetes, including insulin resistance, glucose/insulin response, ectopic fat deposition, energy/lipid regulation, and liver function.
Lifestyle factors—particularly physical activity, obesity, and diet—explained greater variations in metabolites associated with type 2 diabetes than differences in metabolites not associated with the condition.
The investigators then used their results to develop a unique signature of 44 metabolites that improved the prediction of future risk for type 2 diabetes beyond conventional risk factors.
“As a resource, our findings may aid mechanistic and clinical research to investigate pathways underlying [type 2 diabetes] pathophysiology,” the researchers concluded.
“Our metabolomic signature may serve as a powerful tool for risk stratification and as a monitoring biomarker to inform precision [type 2 diabetes] prevention and early intervention.”
