Genetic determinants of type 2 diabetes mellitus

Type 2 diabetes refers to a group of disparate metabolic diseases, which ar e typically characterized by insulin resistance in peripheral tissues, toge ther with impaired insulin secretion from pancreatic beta -cells. The compl exity of type 2 diabetes is related to factors such as genetic heterogeneit y, interactions between genes, and the modulating role played by the enviro nment. Recent progress has included defining the molecular basis of monogen ic forms of type 2 diabetes, such as familial partial lipodystrophy and the subtypes of maturity-onset diabetes of the young (MODY), and also the iden tification of chromosomal regions that may harbor type 2 diabetes susceptib ility genes. Many common variants in functional and positional candidate ge nes, including ADRB3, PPARG, ENPP1, and CAPN10, have also been studied for their possible role as determinants of type 2 diabetes, with varying levels of agreement between studies. The availability of a relatively complete se quence of the human genome will increase the amount of genetic information that can be used to evaluate hypotheses for the genetic basis of type 2 dia betes. To make sense of human type 2 diabetes in the post-genomic era, it i s essential to have well-defined phenotypes in addition to sufficient numbe rs of individuals with the appropriate pedigree structure from families and /or communities.