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Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.
Diabetologia 2018; 61(6):1325-1332D

Abstract

AIMS/HYPOTHESIS

Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.

METHODS

We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution.

RESULTS

No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined.

CONCLUSIONS/INTERPRETATION

Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

Authors+Show Affiliations

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. German Center for Diabetes Research (DZD), München-Neuherberg, Germany.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.Catalan Institute of Oncology (ICO), Barcelona, Spain.Navarre Public Health Institute (ISPN), Pamplona, Spain. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. Bjørknes University College, Oslo, Norway.Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Public Health Division of Gipuzkoa, San Sebastian, Spain. Instituto BIO-Donostia, Basque Government, San Sebastian, Spain.CESP, Faculty of Medicine, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, Inserm U1018, University Paris-Saclay, Villejuif, France.CESP, Faculty of Medicine, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, Inserm U1018, University Paris-Saclay, Villejuif, France.Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.International Agency for Research on Cancer, Lyon, France.CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. National Food Institute, Division for Diet, Disease Prevention and Toxicology, Technical University of Denmark, Kongens Lyngby, Denmark.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.Cancer Epidemiology Unit, University of Oxford, Oxford, UK.Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.Danish Cancer Society, Copenhagen, Denmark.CESP, Faculty of Medicine, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, Inserm U1018, University Paris-Saclay, Villejuif, France.CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Andalusian School of Public Health, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.International Agency for Research on Cancer, Lyon, France.Department of History of Medicine, Lund University, Malmö, Sweden.Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden. Department of Nutritional Research, Umeå University, Umeå, Sweden.Public Health Directorate, Asturias, Spain.Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, (TO), Italy.Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.Danish Cancer Society Research Center, Copenhagen, Denmark.Azienda Sanitaria Provinciale di Ragusa (ASP), Ragusa, Italy. Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS), Ragusa, Italy.The Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.School of Public Health, Imperial College London, London, UK.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. nita.forouhi@mrc-epid.cam.ac.uk.MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. nick.wareham@mrc-epid.cam.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29549418

Citation

Li, Sherly X., et al. "Interplay Between Genetic Predisposition, Macronutrient Intake and Type 2 Diabetes Incidence: Analysis Within EPIC-InterAct Across Eight European Countries." Diabetologia, vol. 61, no. 6, 2018, pp. 1325-1332.
Li SX, Imamura F, Schulze MB, et al. Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries. Diabetologia. 2018;61(6):1325-1332.
Li, S. X., Imamura, F., Schulze, M. B., Zheng, J., Ye, Z., Agudo, A., ... Wareham, N. J. (2018). Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries. Diabetologia, 61(6), pp. 1325-1332. doi:10.1007/s00125-018-4586-2.
Li SX, et al. Interplay Between Genetic Predisposition, Macronutrient Intake and Type 2 Diabetes Incidence: Analysis Within EPIC-InterAct Across Eight European Countries. Diabetologia. 2018;61(6):1325-1332. PubMed PMID: 29549418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries. AU - Li,Sherly X, AU - Imamura,Fumiaki, AU - Schulze,Matthias B, AU - Zheng,Jusheng, AU - Ye,Zheng, AU - Agudo,Antonio, AU - Ardanaz,Eva, AU - Aune,Dagfinn, AU - Boeing,Heiner, AU - Dorronsoro,Miren, AU - Dow,Courtney, AU - Fagherazzi,Guy, AU - Grioni,Sara, AU - Gunter,Marc J, AU - Huerta,José María, AU - Ibsen,Daniel B, AU - Jakobsen,Marianne Uhre, AU - Kaaks,Rudolf, AU - Key,Timothy J, AU - Khaw,Kay-Tee, AU - Kyrø,Cecilie, AU - Mancini,Francesca Romana, AU - Molina-Portillo,Elena, AU - Murphy,Neil, AU - Nilsson,Peter M, AU - Onland-Moret,N Charlotte, AU - Palli,Domenico, AU - Panico,Salvatore, AU - Poveda,Alaitz, AU - Quirós,J Ramón, AU - Ricceri,Fulvio, AU - Sluijs,Ivonne, AU - Spijkerman,Annemieke M W, AU - Tjonneland,Anne, AU - Tumino,Rosario, AU - Winkvist,Anna, AU - Langenberg,Claudia, AU - Sharp,Stephen J, AU - Riboli,Elio, AU - Scott,Robert A, AU - Forouhi,Nita G, AU - Wareham,Nicholas J, Y1 - 2018/03/17/ PY - 2017/10/27/received PY - 2018/02/08/accepted PY - 2018/3/20/pubmed PY - 2019/1/9/medline PY - 2018/3/18/entrez KW - BMI KW - Body mass index KW - Diabetes KW - Diet KW - Dietary fibre KW - GRS KW - Genetic risk score KW - Insulin resistance KW - Interaction KW - Macronutrient SP - 1325 EP - 1332 JF - Diabetologia JO - Diabetologia VL - 61 IS - 6 N2 - AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. RESULTS: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. CONCLUSIONS/INTERPRETATION: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions. SN - 1432-0428 UR - https://www.unboundmedicine.com/medline/citation/29549418/Interplay_between_genetic_predisposition_macronutrient_intake_and_type_2_diabetes_incidence:_analysis_within_EPIC_InterAct_across_eight_European_countries_ L2 - https://dx.doi.org/10.1007/s00125-018-4586-2 DB - PRIME DP - Unbound Medicine ER -