Genetic etiology of type 2 diabetes mellitus: a review

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes characterized by elevated levels of plasma glucose caused by impairment in both insulin secretion and action. It is becoming an epidemic leading to various complications and its prevalence and incidence are increasing at an alarming rate in developing countries like India, raising a major public health concern. Both the genetic and environmental factors play a strong role in the manifestation of this complex genetic disorder. In the recent years, there has been a spate of molecular genetic investigations, including whole genome scans, to test the association of genetic variants with T2DM in different patho-physiological pathways. A large number of candidate genes have been identified to be associated with T2DM, albeit only a couple of them show consistency in association in different populations/ethnic groups. Given relatively high risk for T2DM in India and immense genetic heterogeneity and substructure of the constituent populations, the number of studies is too small to be able to characterize the genetic basis of the disease in India. The recent dramatic increase in number of affected people indicates that lifestyle factors related to urbanization and sedentary occupations may be particularly important in triggering the genetic elements that cause this type of diabetes. Therefore, it is imperative to precisely establish the underlying genetic and environmental factors behind this complex genetic disorder so that preventive measures can be initiated. We have attempted to review the molecular genetic studies conducted, till date, globally on T2DM along with the epidemiological, environmental and ethnic factors implicated in the manifestation of T2DM.