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Lifestyle and metformin ameliorate insulin sensitivity independently of the genetic burden of established insulin resistance variants in Diabetes Prevention Program participants.

Hivert, Marie-France; Christophi, Costas A; Franks, Paul LU ; Jablonski, Kathleen A; Ehrmann, David A; Kahn, Steven E; Horton, Edward S; Pollin, Toni I; Mather, Kieren J and Perreault, Leigh, et al. (2016) In Diabetes 65(2). p.520-526
Abstract
Genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown if people with genetic enrichment for these IR-variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score based on 17 established IR-variants and their effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1-year of follow-up in DPP intervention (metformin and lifestyle) and control (placebo) arms. All... (More)
Genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown if people with genetic enrichment for these IR-variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score based on 17 established IR-variants and their effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1-year of follow-up in DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (β= -0.754 [SE=0.229] log-ISI per unit; P=0.001 in fully adjusted models). There was no differential effect of treatment for the association between IR-GRS on change in ISI; higher IR-GRS was associated with attenuation in ISI improvement over 1 year (β= -0.520 [SE=0.233]; P=0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin improved ISI, regardless of the genetic burden of IR-variants. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
65
issue
2
pages
520 - 526
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:26525880
  • wos:000368968000023
  • scopus:84962362095
ISSN
1939-327X
DOI
10.2337/db15-0950
language
English
LU publication?
yes
id
eb1ec7ec-b406-45f2-b46b-c6cd26d2b55a (old id 8243563)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26525880?dopt=Abstract
date added to LUP
2015-12-02 17:01:19
date last changed
2017-10-01 03:12:05
@article{eb1ec7ec-b406-45f2-b46b-c6cd26d2b55a,
  abstract     = {Genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown if people with genetic enrichment for these IR-variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score based on 17 established IR-variants and their effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1-year of follow-up in DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (β= -0.754 [SE=0.229] log-ISI per unit; P=0.001 in fully adjusted models). There was no differential effect of treatment for the association between IR-GRS on change in ISI; higher IR-GRS was associated with attenuation in ISI improvement over 1 year (β= -0.520 [SE=0.233]; P=0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin improved ISI, regardless of the genetic burden of IR-variants.},
  author       = {Hivert, Marie-France and Christophi, Costas A and Franks, Paul and Jablonski, Kathleen A and Ehrmann, David A and Kahn, Steven E and Horton, Edward S and Pollin, Toni I and Mather, Kieren J and Perreault, Leigh and Barrett-Connor, Elizabeth and Knowler, William C and Florez, Jose C},
  issn         = {1939-327X},
  language     = {eng},
  number       = {2},
  pages        = {520--526},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Lifestyle and metformin ameliorate insulin sensitivity independently of the genetic burden of established insulin resistance variants in Diabetes Prevention Program participants.},
  url          = {http://dx.doi.org/10.2337/db15-0950},
  volume       = {65},
  year         = {2016},
}