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Previously Associated Type 2 Diabetes Variants May Interact With Physical Activity to Modify the Risk of Impaired Glucose Regulation and Type 2 Diabetes A Study of 16,003 Swedish Adults

Brito, Ema C.; Lyssenko, Valeriya; Renstrom, Frida; Berglund, Göran LU ; Nilsson, Peter LU ; Groop, Leif LU and Franks, Paul LU (2009) In Diabetes 58(6). p.1411-1418
Abstract
OBJECTIVE-Recent advances in type 2 diabetes genetics have culminated in the discovery and confirmation of multiple risk variants. Two important, and largely unanswered questions are whether this information can be used to identify individuals most susceptible to the adverse consequences of sedentary behavior and to predict their response to lifestyle intervention; such evidence Would be mechanistically informative and provide a rationale for targeting genetically susceptible subgroups of the population. RESEARCH DESIGN AND METHODS-Gene X physical activity interactions were assessed for 17 polymorphisms ill a prospective population-based cohort of initially nondiabetic middle-aged adults. Outcomes were 1) impaired glucose regulation (IGR)... (More)
OBJECTIVE-Recent advances in type 2 diabetes genetics have culminated in the discovery and confirmation of multiple risk variants. Two important, and largely unanswered questions are whether this information can be used to identify individuals most susceptible to the adverse consequences of sedentary behavior and to predict their response to lifestyle intervention; such evidence Would be mechanistically informative and provide a rationale for targeting genetically susceptible subgroups of the population. RESEARCH DESIGN AND METHODS-Gene X physical activity interactions were assessed for 17 polymorphisms ill a prospective population-based cohort of initially nondiabetic middle-aged adults. Outcomes were 1) impaired glucose regulation (IGR) versus normal glucose regulation determined with either fasting or 2-h plasma glucose concentrations (n = 16,003), 2) glucose intolerance (in mmol/l, n = 8,860), or 3) incident, type 2 diabetes (n = 2,063 events). RESULTS-Tests of gene X physical activity interactions oil IGR risk for 3 of the 17 polymorphisms were nominally statistically significant: CDKNT2A/B rs10811661 (P-interaction = 0.015), HNF1B rs4430796 (P-interaction = 0.026), and PPARG rs1801282 (P-interaction = 0.04). Consistent interactions were observed for the CDKN2A/B (P-interaction = 0.013) and HNF1B (P-interaction = 0.0009) variants on 2-h glucose concentrations. Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant, (P-interaction = 0.0004). The interaction effects for HNF1B on IGR risk and incident diabetes remained significant after correction for multiple testing (P-interaction = 0.015 and 0.0068, respectively). CONCLUSIONS-Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle. Diabetes 58:1411-1418, 2009 (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
58
issue
6
pages
1411 - 1418
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000266347500020
  • scopus:66649093212
ISSN
1939-327X
DOI
10.2337/db08-1623
language
English
LU publication?
yes
id
c00981fd-ac57-42b5-9690-ad110a3eec7b (old id 1425310)
date added to LUP
2009-07-02 16:18:29
date last changed
2017-12-10 04:14:46
@article{c00981fd-ac57-42b5-9690-ad110a3eec7b,
  abstract     = {OBJECTIVE-Recent advances in type 2 diabetes genetics have culminated in the discovery and confirmation of multiple risk variants. Two important, and largely unanswered questions are whether this information can be used to identify individuals most susceptible to the adverse consequences of sedentary behavior and to predict their response to lifestyle intervention; such evidence Would be mechanistically informative and provide a rationale for targeting genetically susceptible subgroups of the population. RESEARCH DESIGN AND METHODS-Gene X physical activity interactions were assessed for 17 polymorphisms ill a prospective population-based cohort of initially nondiabetic middle-aged adults. Outcomes were 1) impaired glucose regulation (IGR) versus normal glucose regulation determined with either fasting or 2-h plasma glucose concentrations (n = 16,003), 2) glucose intolerance (in mmol/l, n = 8,860), or 3) incident, type 2 diabetes (n = 2,063 events). RESULTS-Tests of gene X physical activity interactions oil IGR risk for 3 of the 17 polymorphisms were nominally statistically significant: CDKNT2A/B rs10811661 (P-interaction = 0.015), HNF1B rs4430796 (P-interaction = 0.026), and PPARG rs1801282 (P-interaction = 0.04). Consistent interactions were observed for the CDKN2A/B (P-interaction = 0.013) and HNF1B (P-interaction = 0.0009) variants on 2-h glucose concentrations. Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant, (P-interaction = 0.0004). The interaction effects for HNF1B on IGR risk and incident diabetes remained significant after correction for multiple testing (P-interaction = 0.015 and 0.0068, respectively). CONCLUSIONS-Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle. Diabetes 58:1411-1418, 2009},
  author       = {Brito, Ema C. and Lyssenko, Valeriya and Renstrom, Frida and Berglund, Göran and Nilsson, Peter and Groop, Leif and Franks, Paul},
  issn         = {1939-327X},
  language     = {eng},
  number       = {6},
  pages        = {1411--1418},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Previously Associated Type 2 Diabetes Variants May Interact With Physical Activity to Modify the Risk of Impaired Glucose Regulation and Type 2 Diabetes A Study of 16,003 Swedish Adults},
  url          = {http://dx.doi.org/10.2337/db08-1623},
  volume       = {58},
  year         = {2009},
}