Dataset Information

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

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.

SUBMITTER: Li SX

PROVIDER: S-EPMC6445347 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Li Sherly X SX Imamura Fumiaki F Schulze Matthias B MB Zheng Jusheng J Ye Zheng Z Agudo Antonio A Ardanaz Eva E Aune Dagfinn D Boeing Heiner H Dorronsoro Miren M Dow Courtney C Fagherazzi Guy G Grioni Sara S Gunter Marc J MJ Huerta José María JM Ibsen Daniel B DB Jakobsen Marianne Uhre MU Kaaks Rudolf R Key Timothy J TJ Khaw Kay-Tee KT Kyrø Cecilie C Mancini Francesca Romana FR Molina-Portillo Elena E Murphy Neil N Nilsson Peter M PM Onland-Moret N Charlotte NC Palli Domenico D Panico Salvatore S Poveda Alaitz A Quirós J Ramón JR Ricceri Fulvio F Sluijs Ivonne I Spijkerman Annemieke M W AMW Tjonneland Anne A Tumino Rosario R Winkvist Anna A Langenberg Claudia C Sharp Stephen J SJ Riboli Elio E Scott Robert A RA Forouhi Nita G NG Wareham Nicholas J NJ

Diabetologia 20180317 6

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resi ...[more]

PMID: 29549418

Similar Datasets

Project description:ObjectiveTo investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.DesignProspective case-cohort study.SettingPopulations from eight European countries.Participants9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measureIncident type 2 diabetes.ResultsIn a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.ConclusionsThese findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

Project description:Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.Objective: We aimed to identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.Design: We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and P-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution.Results: Thirteen observational studies met the eligibility criteria (n < 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates.Conclusions: Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.

Dataset Information

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

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

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

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