TCF7L2 Polymorphism, Weight Loss and Proinsulin: Insulin Ratio in the Diabetes Prevention Program
(2011) In PLoS ONE 6(7).- Abstract
- Aims: TCF7L2 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 TCF7L2 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... (More)
- Aims: TCF7L2 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 TCF7L2 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 (P, 0.001), higher baseline proinsulin: insulin ratio (p<0.0001) and increased proinsulin: insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. Conclusions: The combination of a lack of impact of the TCF7L2 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. (Less)
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https://lup.lub.lu.se/record/2071751
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 6
- issue
- 7
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000293175100004
- scopus:79960780846
- pmid:21814547
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0021518
- language
- English
- LU publication?
- yes
- id
- 66601380-806f-4049-a03e-b9a076380bb3 (old id 2071751)
- date added to LUP
- 2016-04-01 13:13:14
- date last changed
- 2022-04-21 20:24:22
@article{66601380-806f-4049-a03e-b9a076380bb3, abstract = {{Aims: TCF7L2 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 TCF7L2 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 (P, 0.001), higher baseline proinsulin: insulin ratio (p<0.0001) and increased proinsulin: insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. Conclusions: The combination of a lack of impact of the TCF7L2 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.}}, author = {{McCaffery, Jeanne M. and Jablonski, Kathleen A. and Franks, Paul and Dagogo-Jack, Sam and Wing, Rena R. and Knowler, William C. and Delahanty, Linda and Dabelea, Dana and Hamman, Richard and Shuldiner, Alan R. and Florez, Jose C.}}, issn = {{1932-6203}}, language = {{eng}}, number = {{7}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS ONE}}, title = {{TCF7L2 Polymorphism, Weight Loss and Proinsulin: Insulin Ratio in the Diabetes Prevention Program}}, url = {{https://lup.lub.lu.se/search/files/3237489/2213089.pdf}}, doi = {{10.1371/journal.pone.0021518}}, volume = {{6}}, year = {{2011}}, }