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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

  • Jennifer A. Nettleton
  • Marie-France Hivert
  • Rozenn N. Lemaitre
  • Nicola M. McKeown
  • Dariush Mozaffarian
  • Toshiko Tanaka
  • Mary K. Wojczynski
  • Adela Hruby
  • Luc Djousse
  • Julius S. Ngwa
  • Jack L. Follis
  • Maria Dimitriou
  • Andrea Ganna
  • Denise K. Houston
  • Stavroula Kanoni
  • Vera Mikkila
  • Ani Manichaikul
  • Ioanna Ntalla
  • Frida Renström
  • Emily Sonestedt
  • Frank J. A. van Rooij
  • Stefania Bandinelli
  • Lawrence de Koning
  • Ulrika Ericson
  • Neelam Hassanali
  • Jessica C. Kiefte-de Jong
  • Kurt K. Lohman
  • Olli Raitakari
  • Constantina Papoutsakis
  • Per Sjogren
  • Kathleen Stirrups
  • Erika Ax
  • Panos Deloukas
  • Christopher J. Groves
  • Paul F. Jacques
  • Ingegerd Johansson
  • Yongmei Liu
  • Mark I. McCarthy
  • Kari North
  • Jorma Viikari
  • M. Carola Zillikens
  • Josee Dupuis
  • Albert Hofman
  • Genovefa Kolovou
  • Kenneth Mukamal
  • Inga Prokopenko
  • Olov Rolandsson
  • Ilkka Seppala
  • L. Adrienne Cupples
  • Frank B. Hu
  • Mika Kahonen
  • Andre G. Uitterlinden
  • Ingrid B. Borecki
  • Luigi Ferrucci
  • David R. Jr. Jacobs
  • Stephen B. Kritchevsky
  • Marju Orho-Melander
  • James S. Pankow
  • Terho Lehtimaki
  • Jacqueline C. M. Witteman
  • Erik Ingelsson
  • David S. Siscovick
  • George Dedoussis
  • James B. Meigs
  • Paul Franks
Publishing year: 2013
Language: English
Pages: 103-115
Publication/Series: American Journal of Epidemiology
Volume: 177
Issue: 2
Document type: Journal article review
Publisher: Oxford University Press

Abstract english

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 US 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 ( 0.004 mmol/L, 95 confidence interval: 0.005, 0.003) and FI ( 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.


  • Public Health, Global Health, Social Medicine and Epidemiology
  • diabetes
  • dietary pattern
  • gene-environment interaction
  • glucose
  • insulin


  • Genetic and Molecular Epidemiology
  • Nutrition Epidemiology
  • Diabetes and cardiovascular disease - genetic epidemiolgy
  • ISSN: 0002-9262
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49



Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00