Aims
<i>TCF7L2</i> variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. Methods
We examined the potential role of the <i>TCF7L2</i> rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. Results
We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (<i>P</i><i>P</i> = 0.003). Effects were comparable across treatment arms. Conclusions
The combination of a lack of impact of the <i>TCF7L2</i> genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin∶insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.
Reference Type
Journal Article
Periodical Full
PLoS ONE
Publication Year
2011
Volume
6
Issue
7
Other Pages
e21518
Publisher
Public Library of Science
Accession Number
journal.pone.0021518
Document Object Index
10.1371/journal.pone.0021518
URL
http://dx.doi.org/10.1371%2Fjournal.pone.0021518
PMID
21814547
PMCID
PMC3144193