, Volume 50, Issue 1, pp 5-7
Date: 11 Nov 2006

TCF7L2 and type 2 diabetes—we WNT to know

This is an excerpt from the content

The initial report by Grant et al. [1] that variants in the TCF7L2 gene are strongly associated with risk of developing type 2 diabetes has now been robustly reproduced in many other populations. In fact, variants in this gene contribute more powerfully to the risk of developing type 2 diabetes than any other gene identified to date (see also [2]).

Since the population-attributable risk is also substantial, we need to understand whether the TCF7L2 variants are causally related to type 2 diabetes, and if so, what the pathogenetic mechanisms are.

The phenotype of individuals carrying the susceptibility variants seems to be slightly at odds with the typical individual at risk, in that the BMI is reduced relative to non-risk variants rather than increased. Virtually all reports have shown impaired insulin secretion following a glucose tolerance test, although the degree of insulin sensitivity has not been stringently defined. Using the minimal model analysis following an IVGTT in non-diabeti ...