Clinical Significance of Emerging Metabolic Biomarkers in Early Prediction of Insulin Resistance and Type 2 Diabetes Mellitus: A review study

This review outlines the growing clinical importance of emerging metabolic biomarkers to the early detection of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Due to the long period of T2DM, there is an urgent necessity to identify biomarkers that can identify metabolic derangement at a preclinical stage. The data collected herein shows that lipid metabolic changes, alterations in the amino-acid profile, intermediate metabolites of the energy-generating pathways, and both inflammatory and adipokine signalling changes predetermine the overt hyperglycaemia by a few years. Markers derived by lipidomics, discrete amino-acids, and their metabolites, glucose and mitochondrial energy pathway substrates, and inflammatory mediators all reflect major pathophysiology underlying IR and T2DM, i.e. impaired insulin signalling, pancreatic β-cell dysfunction, gluconeogenic excess of the liver, ectopic lipid accrual, mitochondrial inefficiency, and chronic low-grade inflammation. It is always indicated in prospective cohort studies that these biomarkers significantly add to the risk stratification that is not sufficiently achieved with the conventional clinical determinants, and thus, it is easier to identify people who are at high risk earlier. The review also elaborates on mechanistic interconnections between biomarkers and disease pathogenesis and the issues surrounding the assay normalisation, population heterogeneity, cost-effectiveness, confounding variables, and the ethical issues. Altogether, the evidence supports the promise of multi-omics and metabolite-targeted interventions to transform the paradigm of early detection and preventive in T2DM; however, large-scale, longitudinal, ethnically diverse researches, as well as standardised assays and intervention trials based on biomarkers are all critical requirements before a routine translation into clinical practice.