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

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).