Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts.

Journal Article (Journal Article;Review)

Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 U.S. and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG (β = -0.004 mmol/L, 95% confidence interval: -0.005, -0.003) and FI (β = -0.008 ln-pmol/L, 95% confidence interval: -0.009, -0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

Full Text

Duke Authors

Cited Authors

  • Nettleton, JA; Hivert, M-F; Lemaitre, RN; McKeown, NM; Mozaffarian, D; Tanaka, T; Wojczynski, MK; Hruby, A; Djoussé, L; Ngwa, JS; Follis, JL; Dimitriou, M; Ganna, A; Houston, DK; Kanoni, S; Mikkilä, V; Manichaikul, A; Ntalla, I; Renström, F; Sonestedt, E; van Rooij, FJA; Bandinelli, S; de Koning, L; Ericson, U; Hassanali, N; Kiefte-de Jong, JC; Lohman, KK; Raitakari, O; Papoutsakis, C; Sjogren, P; Stirrups, K; Ax, E; Deloukas, P; Groves, CJ; Jacques, PF; Johansson, I; Liu, Y; McCarthy, MI; North, K; Viikari, J; Zillikens, MC; Dupuis, J; Hofman, A; Kolovou, G; Mukamal, K; Prokopenko, I; Rolandsson, O; Seppälä, I; Cupples, LA; Hu, FB; Kähönen, M; Uitterlinden, AG; Borecki, IB; Ferrucci, L; Jacobs, DR; Kritchevsky, SB; Orho-Melander, M; Pankow, JS; Lehtimäki, T; Witteman, JCM; Ingelsson, E; Siscovick, DS; Dedoussis, G; Meigs, JB; Franks, PW

Published Date

  • January 15, 2013

Published In

Volume / Issue

  • 177 / 2

Start / End Page

  • 103 - 115

PubMed ID

  • 23255780

Pubmed Central ID

  • PMC3707424

Electronic International Standard Serial Number (EISSN)

  • 1476-6256

Digital Object Identifier (DOI)

  • 10.1093/aje/kws297


  • eng

Conference Location

  • United States