Dr. Ralph DeFronzo's major interests focus on the pathogenesis and treatment of type 2 diabetes mellitus and the central role of insulin resistance in the metabolic-cardiovascular cluster of disorders known collectively as the Insulin Resistance Syndrome. Using the euglycemic insulin clamp technique in combination with radioisotope turnover methodology, limb catheterization, indirect calorimetry and muscle biopsy, he has helped to define the biochemical and molecular disturbances responsible for insulin resistance and impaired glucose metabolism.