Journal
DIABETES
Volume 64, Issue 12, Pages 4312-4321Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db15-0441
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK072041-02, DK056992-14S1]
- Department of Veterans Affairs
- Doris Duke Charitable Foundation Clinical Scientist Development Award
- Swedish Heart-Lung Foundation
- Novo Nordisk Foundation
- Swedish Research Council
- EXODIAB
- Swedish Diabetes Association
- NIDDK of the National Institutes of Health (NIH)
- NIDDK
- Indian Health Service
- NIH Office of Research on Minority Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute on Aging
- Centers for Disease Control and Prevention
- NIH Office of Research on Women's Health
- American Diabetes Association
- Intramural Research Program of the NIDDK
- Novo Nordisk Fonden [NNF13OC0005781, NNF12OC1016167, NNF14OC0011039, NNF11OC1014855] Funding Source: researchfish
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Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2-4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism x treatment interaction (P = 4.3 x 10(-3)). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 x 10(-4)). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle.
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