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Diabetologia. 2018 Jun;61(6):1325-1332. doi: 10.1007/s00125-018-4586-2. Epub 2018 Mar 17.

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

Author information

1
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
2
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
3
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
4
Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.
5
Catalan Institute of Oncology (ICO), Barcelona, Spain.
6
Navarre Public Health Institute (ISPN), Pamplona, Spain.
7
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
8
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
9
Bjørknes University College, Oslo, Norway.
10
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
11
Public Health Division of Gipuzkoa, San Sebastian, Spain.
12
Instituto BIO-Donostia, Basque Government, San Sebastian, Spain.
13
CESP, Faculty of Medicine, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, Inserm U1018, University Paris-Saclay, Villejuif, France.
14
Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
15
International Agency for Research on Cancer, Lyon, France.
16
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
17
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
18
National Food Institute, Division for Diet, Disease Prevention and Toxicology, Technical University of Denmark, Kongens Lyngby, Denmark.
19
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
20
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
21
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
22
Danish Cancer Society, Copenhagen, Denmark.
23
Andalusian School of Public Health, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
24
Department of History of Medicine, Lund University, Malmö, Sweden.
25
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
26
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
27
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
28
Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden.
29
Department of Nutritional Research, Umeå University, Umeå, Sweden.
30
Public Health Directorate, Asturias, Spain.
31
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
32
Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, (TO), Italy.
33
National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
34
Danish Cancer Society Research Center, Copenhagen, Denmark.
35
Azienda Sanitaria Provinciale di Ragusa (ASP), Ragusa, Italy.
36
Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS), Ragusa, Italy.
37
The Sahlgrenska Academy, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.
38
School of Public Health, Imperial College London, London, UK.
39
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.
40
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.

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.

KEYWORDS:

BMI; Body mass index; Diabetes; Diet; Dietary fibre; GRS; Genetic risk score; Insulin resistance; Interaction; Macronutrient

PMID:
29549418
PMCID:
PMC6445347
DOI:
10.1007/s00125-018-4586-2
[Indexed for MEDLINE]
Free PMC Article

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