Dataset Information

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials.

ABSTRACT: 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×treatment interaction (P = 4.3 × 10(-3)). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 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.

SUBMITTER: Papandonatos GD

PROVIDER: S-EPMC4657576 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials.

Papandonatos George D GD Pan Qing Q Pajewski Nicholas M NM Delahanty Linda M LM Peter Inga I Erar Bahar B Ahmad Shafqat S Harden Maegan M Chen Ling L Fontanillas Pierre P Wagenknecht Lynne E LE Kahn Steven E SE Wing Rena R RR Jablonski Kathleen A KA Huggins Gordon S GS Knowler William C WC Florez Jose C JC McCaffery Jeanne M JM Franks Paul W PW

Diabetes 20150807 12

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 para ...[more]

PMID: 26253612

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Project description:Background: Given the low rates of successful weight maintenance after lifestyle-induced weight loss, it is critical to develop approaches that distinguish successful weight-loss maintainers from regainers.Objective: The aim of this study was to compare published categorization criteria that differentiate maintainers and regainers via quantitative agreement.Design: The study used publicly available data from Look AHEAD (Action for Health in Diabetes; n = 1791) and Diabetes Prevention Program (DPP; n = 613) participants with ?3% initial weight loss after lifestyle interventions and 4-y follow-up data. Eight previously published criteria defining maintainers and regainers were compared with respect to number of participants and concordance via agreement statistics. Criteria were assessed separately among those with 3-9% and ?10% initial weight loss.Results: Regainers had higher body weight at year 4 than did maintainers (mean difference range: 6.6-11.9 kg in Look AHEAD; 11.5-14.6 kg in DPP; P < 0.0001). Assessing concordance among criteria, agreement was dependent on initial weight loss. Among those with 3-9% initial weight loss in both cohorts, 9 of 28 comparisons were concordant (agreement ?80%). Among those with ?10% initial weight loss, 7 of 28 comparisons in Look AHEAD and 13 of 28 in the DPP were in high agreement. The definition of successful weight-loss maintenance "regaining ?25% of initial weight loss during maintenance" showed high agreement with the most commonly used definition of "staying ?10% below initial weight" among those with ?10% initial weight loss (agreement: 85.0% in Look AHEAD; 87.4% in DPP). The same definition of ?25% regain showed high agreement with the definition of staying ?5% below initial weight among those with 3-9% initial weight loss (agreement: 91.6% in Look AHEAD; 90.5% in DPP).Conclusions: Although all of the criteria discriminated on the basis of weight loss, many showed low agreement, which limited cross-study comparisons. Among criteria with high agreement, the definition of successful weight maintenance "regaining ?25% of initial weight loss during maintenance" is a preferred definition of success, given the realistic challenges of maintaining 100% weight loss and flexible application in populations with high initial weight-loss variations. This trial was registered at clinicaltrials.gov as NCT00017953 (Look AHEAD) and NCT00004992 (DPP).

Dataset Information

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials.

Publications

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials.

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