Variation in maturity-onset diabetes of the young genes influence response to interventions for diabetes prevention
(2017) In Journal of Clinical Endocrinology and Metabolism 102(8). p.2678-2689- Abstract
Context: Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits. Objectives: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. Design and Setting: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP. Participants and Interventions: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n =... (More)
Context: Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits. Objectives: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. Design and Setting: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP. Participants and Interventions: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944). Main Outcome Measures: Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-Cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism 3 treatment interaction (Pint, 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits. Results: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-Cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups. Conclusions: These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2017-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 102
- issue
- 8
- pages
- 12 pages
- publisher
- Oxford University Press
- external identifiers
-
- pmid:28453780
- wos:000407009500004
- scopus:85026913235
- ISSN
- 0021-972X
- DOI
- 10.1210/jc.2016-3429
- language
- English
- LU publication?
- yes
- id
- 7fd08be3-041e-4222-96c7-8638e41333f9
- date added to LUP
- 2017-08-23 15:03:02
- date last changed
- 2024-03-31 15:09:01
@article{7fd08be3-041e-4222-96c7-8638e41333f9,
abstract = {{<p>Context: Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits. Objectives: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. Design and Setting: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP. Participants and Interventions: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944). Main Outcome Measures: Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-Cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism 3 treatment interaction (Pint, 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits. Results: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-Cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups. Conclusions: These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.</p>}},
author = {{Billings, Liana K. and Jablonski, Kathleen A and Warner, A. Sofia and Cheng, Yu Chien and McAteer, Jarred B. and Tipton, Laura and Shuldiner, Alan R. and Ehrmann, David A and Manning, Alisa K. and Dabelea, Dana and Franks, Paul W. and Kahn, Steven E and Pollin, Toni I and Knowler, William C and Altshuler, David and Florez, Jose C.}},
issn = {{0021-972X}},
language = {{eng}},
month = {{08}},
number = {{8}},
pages = {{2678--2689}},
publisher = {{Oxford University Press}},
series = {{Journal of Clinical Endocrinology and Metabolism}},
title = {{Variation in maturity-onset diabetes of the young genes influence response to interventions for diabetes prevention}},
url = {{http://dx.doi.org/10.1210/jc.2016-3429}},
doi = {{10.1210/jc.2016-3429}},
volume = {{102}},
year = {{2017}},
}