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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Hindy
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Sonestedt
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Ericson
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Jing
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Zhou
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Hansson
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Renström
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden.
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Wirfält
Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö, Sweden. Marju.Orho-Melander@med.lu.se.|Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre 91:12, Jan Waldenströms gata 35, 20502, Malmö, Sweden. Marju.Orho-Melander@med.lu.se.
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Orho-Melander
D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D004043:Dietary Fiber / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
D004043:Dietary Fiber; D006442:Glycated Hemoglobin; D058118:Transcription Factor 7-Like 2 Protein; C544894:TCF7L2 protein, human