Although the liver is the major site of LDL clearance, peripheral tissues, such as the pancreas, also have LDL receptors and clear LDL particles (appendix 2 p 9).32 Moreover, experimentally increasing cholesterol uptake or reducing cholesterol efflux produces islet cell dysfunction with reduced insulin secretion and cell proliferation.33–38 All of these findings are consistent with the hypothesis that increased uptake of LDL particles by the LDL pathway could contribute to the pathogenesis of type 2 diabetes. This evidence concerns the gene INS and type 2 diabetes mellitus.