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Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme

Raghavan, Sridharan ; Jablonski, Kathleen ; Delahanty, Linda M. ; Maruthur, Nisa M. ; Leong, Aaron ; Franks, Paul W. LU ; Knowler, William C. ; Florez, Jose C. and Dabelea, Dana (2021) In Diabetes, Obesity and Metabolism 23(4). p.1030-1040
Abstract

Aim: To test whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. Materials and methods: We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the Diabetes Prevention Programme who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (≥7% weight loss, ≥150 min/wk of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. Results: A lower GRS and achieving each or all three ILS goals were each associated... (More)

Aim: To test whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. Materials and methods: We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the Diabetes Prevention Programme who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (≥7% weight loss, ≥150 min/wk of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. Results: A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all P < 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (P < 0.001), physical activity goal (P = 0.02), and all three ILS goals (P < 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 (95% CI 0.3, 3.4), 3.1 (95% CI 1.5, 4.7), and 3.9 (95% CI 1.6, 6.2) fewer diabetes cases/100-person-years in the first, second and third GRS tertiles (P < 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (P < 0.001), but not for weight loss (P = 0.18) or physical activity (P = 0.62) goals. Conclusions: Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes.

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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes, Obesity and Metabolism
volume
23
issue
4
pages
1030 - 1040
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:33394545
  • scopus:85100581782
ISSN
1462-8902
DOI
10.1111/dom.14309
language
English
LU publication?
yes
id
5a28356f-753f-4b30-81dc-0428f9fd131a
date added to LUP
2021-02-26 14:38:35
date last changed
2025-04-19 18:57:51
@article{5a28356f-753f-4b30-81dc-0428f9fd131a,
  abstract     = {{<p>Aim: To test whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. Materials and methods: We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the Diabetes Prevention Programme who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (≥7% weight loss, ≥150 min/wk of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. Results: A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all P &lt; 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (P &lt; 0.001), physical activity goal (P = 0.02), and all three ILS goals (P &lt; 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 (95% CI 0.3, 3.4), 3.1 (95% CI 1.5, 4.7), and 3.9 (95% CI 1.6, 6.2) fewer diabetes cases/100-person-years in the first, second and third GRS tertiles (P &lt; 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (P &lt; 0.001), but not for weight loss (P = 0.18) or physical activity (P = 0.62) goals. Conclusions: Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes.</p>}},
  author       = {{Raghavan, Sridharan and Jablonski, Kathleen and Delahanty, Linda M. and Maruthur, Nisa M. and Leong, Aaron and Franks, Paul W. and Knowler, William C. and Florez, Jose C. and Dabelea, Dana}},
  issn         = {{1462-8902}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1030--1040}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Diabetes, Obesity and Metabolism}},
  title        = {{Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme}},
  url          = {{http://dx.doi.org/10.1111/dom.14309}},
  doi          = {{10.1111/dom.14309}},
  volume       = {{23}},
  year         = {{2021}},
}