The prevalence of metabolic disorders (MDs), especially diabetes, is rapidly 
increasing worldwide, leading to an increasing risk of cardiovascular and other 
socially relevant complications. To boost MD biomarker discovery, advanced 
proteomics can harmonize metabolomics. Indeed, the rapid development of mass 
spectrometry (MS) has designated proteomics as an emerging platform to 
interrogate the plasma/serum proteome for the discovery of next-generation 
biomarkers exploitable for risk assessment, early detection and prognosis of 
MDs. Preanalytical plasma/serum treatment, such as combinatorial peptide ligand 
libraries with nano-liquid chromatography coupled with tandem MS or selected 
reaction monitoring coupled to triple-quadrupole time-of-flight instruments, are 
proven clinical laboratory techniques for quantitative analyses. New strategies, 
such as SWATH™ MS, which allows us to systematically characterize and quantify 
query sample sets of 'any protein of interest' in complex biological samples, 
may dramatically improve next-generation MD biomarkers, especially considering 
the plethora of candidates coming from the 'bioreactor' gut microbiota affecting 
MD onset and progression.