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Diabetes DOI:10.2337/db15-0441

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

Publication TypeJournal Article
Year of Publication2015
AuthorsPapandonatos, GD, Pan, Q, Pajewski, NM, Delahanty, LM, Peter, I, Erar, B, Ahmad, S, Harden, M, Chen, L, Fontanillas, P, Wagenknecht, LE, Kahn, SE, Wing, RR, Jablonski, KA, Huggins, GS, Knowler, WC, Florez, JC, McCaffery, JM, Franks, PW
Corporate AuthorsGIANT Consortium, Diabetes Prevention Program and the Look AHEAD Research Groups
JournalDiabetes
Volume64
Issue12
Pages4312-21
Date Published2015 Dec
ISSN1939-327X
KeywordsBody Mass Index, Combined Modality Therapy, Diabetes Mellitus, Type 2, Diet, Reducing, Eukaryotic Initiation Factors, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Life Style, Longitudinal Studies, Male, Middle Aged, Mitochondrial Proteins, Motor Activity, Obesity, Overweight, Polymorphism, Single Nucleotide, Prediabetic State, Recurrence, Risk, Weight Gain, Weight Loss
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

URLhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26253612
DOI10.2337/db15-0441
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26253612?dopt=Abstract

Alternate JournalDiabetes
PubMed ID26253612
PubMed Central IDPMC4657576
Grant ListU01 DK048437 / DK / NIDDK NIH HHS / United States
U01 DK048406 / DK / NIDDK NIH HHS / United States
U01 DK048407 / DK / NIDDK NIH HHS / United States
U01 DK048412 / DK / NIDDK NIH HHS / United States
U01 DK048375 / DK / NIDDK NIH HHS / United States
U01 DK048434 / DK / NIDDK NIH HHS / United States
U01 DK048413 / DK / NIDDK NIH HHS / United States
U01 DK056992 / DK / NIDDK NIH HHS / United States
R01 DK072041 / DK / NIDDK NIH HHS / United States
DK056992-14S1 / DK / NIDDK NIH HHS / United States
U01 DK048397 / DK / NIDDK NIH HHS / United States
U01 DK048381 / DK / NIDDK NIH HHS / United States
U01 DK048514 / DK / NIDDK NIH HHS / United States
U01 DK048485 / DK / NIDDK NIH HHS / United States
U01 DK048411 / DK / NIDDK NIH HHS / United States
U01 DK048443 / DK / NIDDK NIH HHS / United States
R01 DK072041-02 / DK / NIDDK NIH HHS / United States
U01 DK048380 / DK / NIDDK NIH HHS / United States
U01 DK048400 / DK / NIDDK NIH HHS / United States
P30 DK026687 / DK / NIDDK NIH HHS / United States
U01 DK048468 / DK / NIDDK NIH HHS / United States
U01 DK048387 / DK / NIDDK NIH HHS / United States
U01 DK048404 / DK / NIDDK NIH HHS / United States
U01 DK048489 / DK / NIDDK NIH HHS / United States
U01 DK048349 / DK / NIDDK NIH HHS / United States
U01 DK048377 / DK / NIDDK NIH HHS / United States
P30 DK017047 / DK / NIDDK NIH HHS / United States