by Wei Perng, PhD
Some new evidence suggests that certain metabolite patterns in blood may actually signal future risk of disease. In 2009, Newgard et al. reported that a metabolite profile characterized by high circulating levels of branched-chain amino acids (BCAA) and related metabolites corresponds with obesity status and contributed to the development of insulin resistance in adult humans and rodents. Following this work, Wang et al. conducted a prospective cohort study in healthy middle-aged adults and discovered that the BCAA metabolite pattern preceded development of type 2 diabetes by over a decade – independently of weight status - suggesting that aberrances in BCAA metabolism may serve as an early marker of diabetes risk. This finding is especially exciting because metabolic diseases are often present years before becoming clinically apparent, but by the time they are detected considerable damage has already occurred. Taking the example of diabetes, by the time hyperglycemia manifests, substantial pancreatic cell damage has transpired, highlighting the need to identify more downstream biomarkers.
So what are the next steps? First and foremost, additional longitudinal studies examining the link between metabolite patterns and disease incidence are necessary to confirm the findings of Wang et al. There is also a need to examine these associations in pediatric populations, as most metabolic risk factors begin early in life and track into adulthood. Our research group at OPP recently conducted a cross-sectional study of 262 mother-child pairs in Project Viva, and found that obese children had higher blood BCAA than their lean counterparts. Furthermore, the BCAA metabolite pattern was directly associated with other indicators of adiposity, such as fat mass and skin-fold thicknesses, as well as with biomarkers of metabolic risk, including insulin resistance, inflammation, and altered satiety hormones. As the children get older, we hope to examine whether this metabolite pattern is associated with development of adiposity and worsening of the biomarkers.
Taken together, current evidence hints at the utility of metabolomics in metabolic risk assessment. However, whether metabolic profiling can be used regularly in the clinic depends on the strength of future study findings, and improvements in technology to lower the cost of running metabolic panels.