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Role of TCF7L2 risk variant and dietary fibre intake on incident type 2 diabetes.

  • George Hindy
  • Emily Sonestedt
  • Ulrika Ericson
  • X-J Jing
  • Yuedan Zhou
  • Ola Hansson
  • Erik Renström
  • Elisabet Wirfält
  • Marju Orho-Melander
Publishing year: 2012
Language: English
Pages: 2646-2654
Publication/Series: Diabetologia
Volume: 55
Issue: 10
Document type: Journal article
Publisher: Springer

Abstract english


The T allele of transcription factor 7-like 2 gene variant, TCF7L2 rs7903146, increases the risk of type 2 diabetes by 40-50%. As TCF7L2 rs7903146 has been associated with diminished incretin effect we investigated whether interaction between dietary intake of carbohydrate, fat, protein or fibre and this variant affects the risk of type 2 diabetes.


A cohort of 24,799 non-diabetic individuals from the Malmö Diet and Cancer Study (MDCS), with dietary data obtained by a modified diet history method, were followed up for 12 years, with 1,649 recordings of incident type 2 diabetes made. Risk of type 2 diabetes in strata of diet quintiles was analysed prospectively adjusting for potential confounders. Cross-sectional analyses were performed on baseline fasting glucose and HbA(1c) levels in a subset of 5,216 randomly selected individuals from the MDCS.


The elevated risk of type 2 diabetes with rs7903146 (OR 1.44, 95% CI 1.33, 1.56, p = 4.6 × 10(-19)) increased with higher intake of dietary fibre (OR 1.24, 95% CI 1.04, 1.47 to OR 1.56, 95% CI 1.31, 1.86 from the lowest to highest quintile; p (interaction) = 0.049). High intake of dietary fibre was inversely associated with diabetes incidence only among CC genotype carriers (OR 0.74, 95% CI 0.58, 0.94 per quintile, p = 0.025). The T allele was associated with 0.027% elevated HbA(1c) (p = 0.02) and this effect increased with higher intake of fibre (from -0.021% to 0.079% for the lowest to the highest quintile, p (interaction) = 0.02). Each quintile of higher fibre intake was associated with lower HbA(1c) levels among CC and CT but not among TT genotype carriers (-0.036%, p = 6.5 × 10(-7); -0.023%, p = 0.009; and 0.012%, p = 0.52, respectively).


Our study suggests that dietary fibre intake may modify the association between TCF7L2 rs7903146 and incidence of type 2 diabetes, and that higher fibre intake may associate with protection from type 2 diabetes only among non-risk allele carriers.


  • Endocrinology and Diabetes


  • Diabetes - Cardiovascular Disease
  • Nutrition Epidemiology
  • Genomics, Diabetes and Endocrinology
  • ISSN: 1432-0428
Emily Sonestedt
E-mail: emily [dot] sonestedt [at] med [dot] lu [dot] se

Associate senior lecturer

Nutrition Epidemiology

+46 40 39 13 25

+46 73 700 71 45


Jan Waldenströms gata 35, CRC 60:13, Malmö


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