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Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme
Author(s) -
Raghavan Sridharan,
Jablonski Kathleen,
Delahanty Linda M.,
Maruthur Nisa M.,
Leong Aaron,
Franks Paul W.,
Knowler William C.,
Florez Jose C.,
Dabelea Dana
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14309
Subject(s) - diabetes mellitus , medicine , lifestyle modification , gerontology , endocrinology
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.