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Title:   Author  item
                                            Adams, Seanitem
                                            Newman, John
  Submitted to: Book Chapter
                                    Publication Type: Book / Chapter
                                    Publication Acceptance Date: 5/13/2014
                                    Publication  Date: 3/6/2015
                                    Citation: Adams, S.H., Newman, J.W. 2015. Metabolomics:  Insulin Resistance and Type 2 Diabetes Mellitus. Book Chapter. DOI: 10.1002/9781118387658.ch18.Interpretive Summary: Type 2 diabetes mellitus (T2DM) develops over many years, providing an opportunity to consider early prognostic tools that guide interventions to thwart disease.  Advancements in analytical chemistry enable quantitation of hundreds of metabolites in biofluids and tissues (metabolomics), providing insights about the broad metabolic perturbations that take place when insulin resistance is evident.  T2DM itself also impacts multiple metabolic pathways in parallel or in addition to deteriorating blood sugar control.  When coupled to statistical, chemoinformatic, and metabolic physiology expertise, metabolomics is a powerful discovery tool to generate new hypotheses.  Recent results have shown that T2DM progression is marked by inefficient fat combustion, altered amino acid utilization in tissues (e.g., higher branched chain and aromatic amino acids, probably due to less efficient tissue uptake and/or oxidative catabolism), and altered blood bile acids and choline-containing phospholipids.  Previously under-appreciated pathway perturbations identify new opportunities for therapeutic intervention.  In addition, first-generation clinical blood test panels spawned by metabolomics are now being implemented to aid in T2DM and cardiometabolic disease risk assessments.
                                Technical Abstract: Type 2 diabetes mellitus (T2DM) develops over many years, providing an opportunity to consider early prognostic tools that guide interventions to thwart disease.  Advancements in analytical chemistry enable quantitation of hundreds of metabolites in biofluids and tissues (metabolomics), providing insights about the broad metabolic perturbations that take place when insulin resistance is evident.  T2DM itself also impacts multiple metabolic pathways in parallel or in addition to deteriorating blood sugar control.  When coupled to statistical, chemoinformatic, and metabolic physiology expertise, metabolomics is a powerful discovery tool to generate new hypotheses.  Recent results have shown that T2DM progression is marked by incomplete ß-oxidation (e.g., altered blood acylcarnitine profiles), altered amino acids (e.g., higher branched chain and aromatic amino acids, probably due to less efficient tissue uptake and/or oxidative catabolism), and altered blood bile acids and choline-containing phospholipids.  Previously under-appreciated pathway perturbations identify new opportunities for therapeutic intervention.  In addition, first-generation clinical blood test panels spawned by metabolomics are now being implemented to aid in T2DM and cardiometabolic disease risk assessments.


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