Fluid-management strategies in acute lung injury--liberal, conservative, or both?

n engl j med 354;24 www.nejm.org june 15, 2006 2598 sulin resistance. What are the signaling pathways activated or inhibited by RBP4 that could affect insulin action? Do increased RBP4 levels cause or result from reductions in GLUT4 levels? Is genetic variation in the RBP4 gene associated with variation in the risk of insulin resistance or type 2 diabetes? Does the administration of a synthetic retinoid such as fenretinide, an agent that reduces the serum RBP4 level and totalbody retinol levels, improve insulin sensitivity in humans? The study by Graham et al. should prompt investigations to address these and other questions to define the biologic action of RBP4 in relation to insulin resistance and diabetes. Whatever the outcome of these investigations, it will take new approaches such as those used by Graham et al. to identify unanticipated mechanisms underlying type 2 diabetes and to identify better treatments for this disease.