Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

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12 Citations (Scopus)

Abstract

Aims/hypothesis. The gut incretin hormones glucagon-like
peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide
(GIP) have a major role in the pathophysiology of type 2
diabetes. Specific genetic and dietary factors have been found
to influence the release and action of incretins. We examined
the effect of interactions between seven incretin-related genetic
variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary
components (whey-containing dairy, cereal fibre, coffee and
olive oil) on the risk of type 2 diabetes in the European
Prospective Investigation into Cancer and Nutrition (EPIC)-
InterAct study.
Methods. The current case-cohort study included 8086 incident
type 2 diabetes cases and a representative subcohort of 11,035
participants (median follow-up: 12.5 years). Prentice-weighted
Cox proportional hazard regression models were used to investigate
the associations and interactions between the dietary factors
and genes in relation to the risk of type 2 diabetes.
Results. An interaction (p= 0.048) between TCF7L2 variants
and coffee intake was apparent, with an inverse association
between coffee and type 2 diabetes present among carriers of
the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95%
CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93,
0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, an
interaction (p=0.005) between an incretin-specific genetic risk
score and coffee was observed, again with a stronger inverse
association with coffee in carriers with more risk alleles (0–3
risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR
0.95 [95% CI 0.90, 0.99]). None of these associations were
statistically significant after correction for multiple testing.
Conclusions/interpretation. Our large-scale case-cohort study
provides some evidence for a possible interaction of TCF7L2
variants and an incretin-specific genetic risk score with coffee
consumption in relation to the risk of type 2 diabetes. Further
large-scale studies and/or meta-analyses are needed to confirm
these interactions in other populations.
Original languageEnglish
Pages (from-to)2613-2621
JournalDiabetologia
Volume59
Issue number12
DOIs
Publication statusPublished - 2016

Fingerprint

Incretins
Coffee
Type 2 Diabetes Mellitus
Alleles
Neoplasms
Gastric Inhibitory Polypeptide
Glucagon
Proportional Hazards Models
Meta-Analysis
Oils
Cohort Studies
Hormones

Keywords

  • Coffee
  • Dairy
  • Gene–environment interaction
  • GIPR
  • Incretins
  • KCNQ1
  • Olive oil
  • TCF7L2
  • WFS1

Cite this

@article{cea1dd6cc6444004a130dcb800667d91,
title = "Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study",
abstract = "Aims/hypothesis. The gut incretin hormones glucagon-likepeptide-1 (GLP-1) and glucose-dependent insulinotropic peptide(GIP) have a major role in the pathophysiology of type 2diabetes. Specific genetic and dietary factors have been foundto influence the release and action of incretins. We examinedthe effect of interactions between seven incretin-related geneticvariants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietarycomponents (whey-containing dairy, cereal fibre, coffee andolive oil) on the risk of type 2 diabetes in the EuropeanProspective Investigation into Cancer and Nutrition (EPIC)-InterAct study.Methods. The current case-cohort study included 8086 incidenttype 2 diabetes cases and a representative subcohort of 11,035participants (median follow-up: 12.5 years). Prentice-weightedCox proportional hazard regression models were used to investigatethe associations and interactions between the dietary factorsand genes in relation to the risk of type 2 diabetes.Results. An interaction (p= 0.048) between TCF7L2 variantsand coffee intake was apparent, with an inverse associationbetween coffee and type 2 diabetes present among carriers ofthe diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95{\%}CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95{\%} CI 0.93,0.98]); and TT: HR 0.93 [95{\%} CI 0.88, 0.98]). In addition, aninteraction (p=0.005) between an incretin-specific genetic riskscore and coffee was observed, again with a stronger inverseassociation with coffee in carriers with more risk alleles (0–3risk alleles: HR 0.99 [95{\%} CI 0.94, 1.04]; 7–10 risk alleles: HR0.95 [95{\%} CI 0.90, 0.99]). None of these associations werestatistically significant after correction for multiple testing.Conclusions/interpretation. Our large-scale case-cohort studyprovides some evidence for a possible interaction of TCF7L2variants and an incretin-specific genetic risk score with coffeeconsumption in relation to the risk of type 2 diabetes. Furtherlarge-scale studies and/or meta-analyses are needed to confirmthese interactions in other populations.",
keywords = "Coffee, Dairy, Gene–environment interaction, GIPR, Incretins, KCNQ1, Olive oil, TCF7L2, WFS1",
author = "E.J.M. Feskens and A. Kuijsten",
year = "2016",
doi = "10.1007/s00125-016-4090-5",
language = "English",
volume = "59",
pages = "2613--2621",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "12",

}

Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study. /.

In: Diabetologia, Vol. 59, No. 12, 2016, p. 2613-2621.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

AU - Feskens, E.J.M.

AU - Kuijsten, A.

PY - 2016

Y1 - 2016

N2 - Aims/hypothesis. The gut incretin hormones glucagon-likepeptide-1 (GLP-1) and glucose-dependent insulinotropic peptide(GIP) have a major role in the pathophysiology of type 2diabetes. Specific genetic and dietary factors have been foundto influence the release and action of incretins. We examinedthe effect of interactions between seven incretin-related geneticvariants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietarycomponents (whey-containing dairy, cereal fibre, coffee andolive oil) on the risk of type 2 diabetes in the EuropeanProspective Investigation into Cancer and Nutrition (EPIC)-InterAct study.Methods. The current case-cohort study included 8086 incidenttype 2 diabetes cases and a representative subcohort of 11,035participants (median follow-up: 12.5 years). Prentice-weightedCox proportional hazard regression models were used to investigatethe associations and interactions between the dietary factorsand genes in relation to the risk of type 2 diabetes.Results. An interaction (p= 0.048) between TCF7L2 variantsand coffee intake was apparent, with an inverse associationbetween coffee and type 2 diabetes present among carriers ofthe diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95%CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93,0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, aninteraction (p=0.005) between an incretin-specific genetic riskscore and coffee was observed, again with a stronger inverseassociation with coffee in carriers with more risk alleles (0–3risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR0.95 [95% CI 0.90, 0.99]). None of these associations werestatistically significant after correction for multiple testing.Conclusions/interpretation. Our large-scale case-cohort studyprovides some evidence for a possible interaction of TCF7L2variants and an incretin-specific genetic risk score with coffeeconsumption in relation to the risk of type 2 diabetes. Furtherlarge-scale studies and/or meta-analyses are needed to confirmthese interactions in other populations.

AB - Aims/hypothesis. The gut incretin hormones glucagon-likepeptide-1 (GLP-1) and glucose-dependent insulinotropic peptide(GIP) have a major role in the pathophysiology of type 2diabetes. Specific genetic and dietary factors have been foundto influence the release and action of incretins. We examinedthe effect of interactions between seven incretin-related geneticvariants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietarycomponents (whey-containing dairy, cereal fibre, coffee andolive oil) on the risk of type 2 diabetes in the EuropeanProspective Investigation into Cancer and Nutrition (EPIC)-InterAct study.Methods. The current case-cohort study included 8086 incidenttype 2 diabetes cases and a representative subcohort of 11,035participants (median follow-up: 12.5 years). Prentice-weightedCox proportional hazard regression models were used to investigatethe associations and interactions between the dietary factorsand genes in relation to the risk of type 2 diabetes.Results. An interaction (p= 0.048) between TCF7L2 variantsand coffee intake was apparent, with an inverse associationbetween coffee and type 2 diabetes present among carriers ofthe diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95%CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93,0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, aninteraction (p=0.005) between an incretin-specific genetic riskscore and coffee was observed, again with a stronger inverseassociation with coffee in carriers with more risk alleles (0–3risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7–10 risk alleles: HR0.95 [95% CI 0.90, 0.99]). None of these associations werestatistically significant after correction for multiple testing.Conclusions/interpretation. Our large-scale case-cohort studyprovides some evidence for a possible interaction of TCF7L2variants and an incretin-specific genetic risk score with coffeeconsumption in relation to the risk of type 2 diabetes. Furtherlarge-scale studies and/or meta-analyses are needed to confirmthese interactions in other populations.

KW - Coffee

KW - Dairy

KW - Gene–environment interaction

KW - GIPR

KW - Incretins

KW - KCNQ1

KW - Olive oil

KW - TCF7L2

KW - WFS1

U2 - 10.1007/s00125-016-4090-5

DO - 10.1007/s00125-016-4090-5

M3 - Article

VL - 59

SP - 2613

EP - 2621

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 12

ER -