Future directions and potential application of metabolite profiling in type 2 diabetes
Metabolomics approaches have unmasked a variety of metabolic pathways influenced by T2DM or insulin resistance, moving the field of metabolic physiology beyond a “glucocentric” viewpoint of these conditions. However, a difficulty in interpretation is that the fasting concentration of a metabolite only reflects a single moment in time, and etiology or tissue origins of any metabolite differences across comparator groups requires further validation. To fully elaborate the molecular and physiologic mechanisms underlying metabolite differences, future efforts will conduct systematic exploration into relevant enzymology, biochemistry, and flux measures (i.e., metabolite turnover, anabolism-catabolism events). Furthermore, efforts are underway to determine which systemic metabolites associated with metabolic diseases such as T2DM emanate from gut microbes or co-metabolism of microbe and host.
From the standpoint of clinical practice, what does metabolomics have to offer? In the future, determination of metabolic variants in drug metabolism in the clinic could be used to tailor therapeutic regimens, revolutionizing the application of “pharmacometabolomics” to individualized medicine . If applied as a tool to routinely characterize patient health, metabolomics should provide novel diagnostic and prognostic tools allowing early disease identification and intervention. While fasting samples should prove valuable in this regard, it is likely that dynamic changes in one or more analytes following OGTT or other challenges will prove even more sensitive. Comprehensive metabolite profiling of blood and tissues has already led to at least one first-generation analyte panel relevant to T2DM and metabolic disease research and medical evaluation. For instance, Quantose™is a fasting blood analyte panel available for research purposes from Metabolon (Research Triangle Park, North Carolina, USA), and includes the analytes 2-HB, 1-lineoyl-glycerophosphocholine (L-GPC), oleic acid, and insulin. The panel score reflects relative risk for T2DM and may be useful for experiments involving relative stage or severity of disease progression, or those examining efficacy of interventions. The same panel is also incorporated into a Diabetes Prevention and Management Panel offered by Health Diagnostic Laboratory (Richmond, Virginia, USA).
These early examples of tests that are based on multi-analyte platforms have their foundation in pioneering cross-sectional and prospective cohort metabolomics research. With advancements in technology and clinical uptake, it is feasible that robust predictive tests for T2DM will become commonplace, helping guide prevention strategies well before disease onset, and treatment strategies to minimize disease severity.