Mandarino is a professor of medicine at the University of Arizona and an expert in the area of the pathogenesis of obesity and type 2 diabetes mellitus, especially as that relates to insulin resistance in skeletal muscle. Having studied insulin resistance in the Gila River Pimas as a doctoral student in physical anthropology at Arizona State University, he guided his career into a more physiological, biological and genetic track to learn more about how type 2 diabetes could become so prevalent in a number of populations world-wide. He returned to ASU in 2004 to direct the Center for Metabolic Biology, a multidisciplinary, multi-investigator unit devoted to understanding the pathogenesis of type 2 diabetes. The Center moved to the Mayo Clinic in Arizona and then finally to the University of Arizona in Tucson in 2016. His research has been continuously funded by the NIH since 1988.