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

Citation
Raghavan, S., et al. “Interaction Of Diabetes Genetic Risk And Successful Lifestyle Modification In The Diabetes Prevention Programme.”. Diabetes, Obesity & Metabolism, pp. 1030-1040.
Center University of Colorado Denver
Author Sridharan Raghavan, Kathleen Jablonski, Linda M Delahanty, Nisa M Maruthur, Aaron Leong, Paul W Franks, William C Knowler, Jose C Florez, Dana Dabelea, Diabetes Prevention Program Research Group
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 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.

Year of Publication
2021
Journal
Diabetes, obesity & metabolism
Volume
23
Issue
4
Number of Pages
1030-1040
Date Published
04/2021
ISSN Number
1463-1326
DOI
10.1111/dom.14309
Alternate Journal
Diabetes Obes Metab
PMID
33394545
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