Recognition of the preclinical stages of metabolic diseases such as diabetes helps to prevent full development of the disease. In our research, we alter the diet composition of pigs to create a model of human metabolic disease. The objective of the current study was to identify plasma proteins and biologic mechanisms that differed in expression between pigs fed a 'cafeteria diet' (considered unhealthy; high in saturated fats) and those fed a 'Mediterranean diet' (considered healthy; high in unsaturated fats). Pigs fed the cafeteria diet showed increased plasma levels of proteins related to LDL ('bad cholesterol'), immune processes, blood clotting, and metal binding. The Mediterranean diet was associated with increased plasma quantities of proteins associated HDL particles ('good cholesterol'), binding of LDL particles, regulation of immune processes, and glycolysis. Pigs fed a cafeteria diet showed molecular signs of diabetes and atherosclerosis-even in the absence of clinical symptoms-which seemed to protect against the development of metabolic disorders. The current results suggest potential biomarkers of the early onset of metabolic syndromes. These biomarkers can help to reveal specific metabolic changes that precede the onset of diabetes, thus enabling the initiation of patient-specific interventions early during pathophysiologic development.