Type 2 diabetes mellitus: from genes to disease.

The development of type 2 diabetes (T2DM) is determined by two factors: genetics and environment. The genetic background of T2DM is undoubtedly heterogeneous. Most patients with T2DM exhibit two different defects: the impairment of insulin secretion and decreased insulin sensitivity. This means that there are at least two pathophysiological pathways and at least two groups of genes that may be involved in the pathogenesis of T2DM. As far as genetic background [corrected] of T2DM is concerned, the disease may be divided into two large groups: monogenic and polygenic forms. In this review, we present genes known to cause rare monogenic forms of diabetes with predominant insulin deficiency (MODY - maturity-onset diabetes of the young, MIDD - maternally inherited diabetes with deafness) and uncommon syndromes of severe insulin resistance. We also describe some of the main approaches used to identify genes involved in the more common forms of T2D and the reasons for the lack of spectacular success in this field. Although major genes for T2DM still await to be discovered, we have probably established a "road map" that we should follow.