LAUSR

A plethora of metabolic profiling studies have identified several metabolic signatures in the patient’s biofluids and tissues to be correlated with type 2 diabetes (T2D) and its comorbidities. However, the association between specific metabolite-based markers and occurrence of mitochondrial dysfunction among T2D subjects has not been adequately addressed. Therefore, the current study sought to determine whether circulating metabolite signatures in cultured myotubes and fasting plasma of T2D subjects are associated with mitochondrial dysfunction. A cellular disease model was first established using human myotubes treated with antimycin A, an oxidative phosphorylation inhibitor. The cultured sample of these intracellular-defined metabolites on treated myotubes was analyzed using mass spectrometry based approaches. Further, a targeted metabolic profiling of fasting blood plasma from normal (n=83) and T2D (n=92) subjects in a cross sectional study was validated. Multivariable-adjusted conditional logical regression analysis was computed to estimate odds ratios (ORs) and 95% confidence intervals for verifying differentiating metabolites correlated with T2D. Several metabolites were considerably altered in cultured myotubes with reduced mitochondrial function. Targeted metabolic fingerprinting of fasting blood plasma adjusted for age, sex and body mass index (BMI) revealed 20 significant robust metabolites (P