Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology.
The rapid rise in prevalence of type 2 diabetes mellitus (T2DM) has been driven by changes in environmental factors - primarily increased caloric intake and reduced energy expenditure - resulting in reduced whole body insulin sensitivity (often termed insulin resistance). Insulin resistance has been proposed to be a major driver of progression to T2DM. However, of 38 individual susceptibility loci for T2DM recently identified by genome wide association studies, by far the majority code for proteins involved in β-cell function. In this review, we discuss the possible reasons for the paucity of insulin resistance genes and ask whether the new genetic susceptibility data should focus attention on β-cell targets in the development of therapies for T2DM.
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G11 6TA, United Kingdom. john.petrie@glasgow.ac.uk
John R
JR
Petrie
Ewan R
ER
Pearson
Calum
C
Sutherland
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000187:drug effects