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

Authors: NETTLETON, JENNIFER - University Of Texas Health Science Center; HIVERT, MARIE-FRANCE - Harvard Medical School; LEMAITRE, ROZENN - University Of Washington; MCKEOWN, NICOLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MOZAFFARIAN, DARIUSH - Harvard University; TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH); WOJCZYNSKI, MARY - Washington University; HRUBY, ADELA - Harvard University; DJOUSSE, LUC - Brigham & Women'S Hospital; NGWA, JULIUS - Brigham & Women'S Hospital; FOLLIS, JACK - University Of Texas Health Science Center; DIMITRIOUS, MARIA - University Of Marmara; GANNA, ANDREA - Emory University; HOUSTON, DENISE - University Of Georgia; KANONI, STAVROULA - Wellcome Trust Sanger Institute; MIKKILA, VERA - University Of Tampere Medical School; MANICHAIKUL, ANI - University Of Washington; NTALLA, IONNA - Harokopio University Of Athens; RENSTROM, FRIDA - Lund University; SONESTEDT, EMILY - Lund University; VAN ROOJI, FRANK - Netherlands Genomics Initiative; BANDINELLI, STEFANI - Tuscany Regional Health Agency; DE KONING, LAWRENCE - University Of Calgary; ERICSON, ULRIKA - Lund University; HASSANALI, NEELAM - University Of Oxford; KIEFTE-DE JONG, JESSICA - Erasmus Medical Center; LOHMAN, KURT - California Pacific Medical Center; RAITAKARI, OLLI - University Of Turku; POPOUTSAKIS, CONSTANTINA - University Of Athens; SJOGREN, PER - Copenhagen University; STIRRUPS, KATHLEEN - University Of Cambridge; AX, ERIKA - Uppsala University; DELOUKAS, PANOS - William Harvey Research Institute; GROVES, CHRISTOPHER - University Of Oxford; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JOHANSSON, INGEGERD - University Of Umea; LIU, YONGMEI - Wake Forest University; MCCARTHY, MARK - University Of Oxford; NORTH, KARI - University Of North Carolina; VIIKARI, JORMA - University Of Turku; ZILLIKENS, M CAROLA - Ghent University; DUPUIS, JOSEE - Boston University; HOFMAN, ALBERT - University Medical Center - Utrecht; KOLOVOU, GENOVEFA - Onassis Cardiac Surgery Center; MUKAMAL, KENNETH - Beth Israel Deaconess Medical Center; PROKOPENKO, INGA - University Of Oxford; ROLANDSSON, OLOV - University Of Helsinki; SEPPALA, LLKKA - University Of Tampere Medical School; CUPPLES, L ADRIENNE - Boston University; HU, FRANK - Brigham & Women'S Hospital; KAHONEN, MIKA - Tampere University Hospital; UITTERLINDEN, ANDRE - Erasmus Medical Center; BORECKI, INGRID - Washington University; FERNUCCI, LUIGI - National Institute On Aging (NIA, NIH); JACOBS, DAVID - University Of Minnesota; KRITCHEVSKY, STEPHEN - Wake Forest University; ORHO-MELANDER, MARJU - Lund University; PANKOW, JAMES - University Of Minnesota; LEHTIMAKI, TERHO - University Of Tampere Medical School; WITTEMAN, JACQUELINE C M - Erasmus Medical Center; INGELSSON, ERIK - University Of Oxford; SISCOVICK, DAVID - University Of Washington; DEDOUSSIS, GEORGE - Harokopio University Of Athens; MEIGS, JAMES - Harvard University; FRANKS, PAUL - Lund University

Submitted to: American Journal of Epidemiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2012
Publication Date: 12/19/2012
Citation: Nettleton, J.A., Hivert, M., Lemaitre, R.N., Mckeown, N.M., Mozaffarian, D., Tanaka, T., Wojczynski, M.K., Hruby, A., Djousse, L., Ngwa, J.S., Follis, J., Dimitrious, M., Ganna, A., Houston, D.K., Kanoni, S., Mikkila, V., Manichaikul, A., Ntalla, I., Renstrom, F., Sonestedt, E., Van Rooji, F.J., Bandinelli, S., De Koning, L., Ericson, U., Hassanali, N., Kiefte-De Jong, J.C., Lohman, K.K., Raitakari, O., Popoutsakis, C., Sjogren, P., Stirrups, K., Ax, E., Deloukas, P., Groves, C.J., Jacques, P.F., Johansson, I., Liu, Y., Mccarthy, M.I., North, K., Viikari, J., Zillikens, M., Dupuis, J., Hofman, A., Kolovou, G., Mukamal, K., Prokopenko, I., Rolandsson, O., Seppala, L., Cupples, L., Hu, F., Kahonen, M., Uitterlinden, A.G., Borecki, I.B., Fernucci, L., Jacobs, D.R., Kritchevsky, S.B., Orho-Melander, M., Pankow, J.S., Lehtimaki, T., Witteman, J., Ingelsson, E., Siscovick, D.S., Dedoussis, G., Meigs, J.B., Franks, P.W. 2012. 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. American Journal of Epidemiology. 177(2):103-115.

Interpretive Summary: Recent advances have allowed us to conduct genome-wide association studies (GWAS), which investigate the complex interactions between human genetics and diseases such as type 2 diabetes. One important question that GWAS studies raise is whether lifestyle choices, such as adhering to a healthier diet, can offset genetic risks of disease? It is well-established that certain dietary patterns are associated with lower risk of disease. For example, diets comprised largely of plant foods (e.g., whole grains, fruits, vegetables), rather than red meats and foods high in sugar, salt, and refined grains are associated with lower risk of type 2 diabetes and cardiovascular disease. However, how genetic risk plays into this relationship between diabetes and dietary patterns is not well-established. The purpose of this study was to: 1) evaluate if and how dietary patterns are associated with two markers of type 2 diabetes: fasting insulin and fasting glucose and 2) evaluate whether genetic factors, known to be associated with fasting insulin and glucose, modify the association between dietary patterns and fasting glucose and insulin. The study utilized data from 15 previously conducted studies in the United States and Europe, comprising over 51,000 total people without diabetes. We found that healthier diets were associated with lower fasting glucose and insulin regardless of genetic factors (genotype). These results suggest that adhering to a healthy diet is important for everyone and that, from a public health standpoint, population-based dietary recommendations can be beneficial to all individuals, regardless of genetics. In addition, since our study, as is the case with all GWAS studies, examines only specific genetic variants, future research should continue to examine interactions between other potential genetic factors and diet and lifestyle behaviors.

Technical Abstract: 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 (beta = -0.004 mmol/L, 95% confidence interval: -0.005, -0.003) and FI (beta = -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.