Academic Journal
Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme
| Title: | Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme |
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| Authors: | Raghavan, Sridharan, Jablonski, Kathleen, Delahanty, Linda M., Maruthur, Nisa M., Leong, Aaron, Franks, Paul W., Knowler, William C., Florez, Jose C., Dabelea, Dana, Diabetes Prevention Program Research Group |
| Contributors: | Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Genetic and Molecular Epidemiology, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Genetisk och molekylär epidemiologi, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EpiHealth: Epidemiology for Health, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EpiHealth: Epidemiology for Health, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EXODIAB: Excellence of Diabetes Research in Sweden, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EXODIAB: Excellence of Diabetes Research in Sweden, Originator |
| Source: | Diabetes, Obesity and Metabolism. 23(4):1030-1040 |
| Subject Terms: | Medical and Health Sciences, Clinical Medicine, Endocrinology and Diabetes, Medicin och hälsovetenskap, Klinisk medicin, Endokrinologi och diabetes, Health Sciences, Hälsovetenskap |
| Description: | 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. |
| Database: | SwePub |
| ISSN: | 14628902 14631326 |
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| DOI: | 10.1111/dom.14309 |