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TCF7L2, dietary carbohydrate, and risk of type 2 diabetes in US women.

ABSTRACT: BACKGROUND:TCF7L2 is the strongest type 2 diabetes (T2D) locus identified to date, and evidence suggests it plays an important role in insulin synthesis, processing, and secretion. Dietary factors that increase the insulin demand might enhance the risk of T2D associated with TCF7L2 variants. OBJECTIVE:The objective was to determine whether the risk of T2D associated with TCF7L2 is modified by the glycemic load (GL), glycemic index (GI), cereal fiber content, and total carbohydrate content of the diet. DESIGN:T2D cases (n = 1140) and controls (n = 1915) from the Nurses' Health Study were genotyped for TCF7L2 (rs12255372). Dietary intake was assessed with a semiquantitative food-frequency questionnaire. RESULTS:Significant differences in odds ratios (ORs) of T2D associated with the TCF7L2 genotype between high and low strata of GL (P = 0.03) and GI (P = 0.05) were suggested. Compared with the GG genotype, multivariate-adjusted ORs (95% CI) of T2D associated with the TT genotype were 2.71 (1.64, 4.46) and 2.69 (1.64, 4.43) among individuals in the highest tertile of GL and GI, respectively. Corresponding ORs (95% CIs) among individuals in the lowest tertiles of GL and GI were 1.66 (0.95, 2.88) and 1.82 (1.11, 3.01). The risk of T2D associated with the TCF7L2 single nucleotide polymorphism did not significantly differ by cereal fiber or carbohydrate intake. CONCLUSION:Carbohydrate quality and quantity modified risk of T2D associated with TCF7L2, which suggests that changes in risk attributable to the TCF7L2 variant are magnified under conditions of increased insulin demand.

SUBMITTER: Cornelis MC

PROVIDER: S-EPMC2667467 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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TCF7L2, dietary carbohydrate, and risk of type 2 diabetes in US women.

Cornelis Marilyn C MC Qi Lu L Kraft Peter P Hu Frank B FB

The American journal of clinical nutrition 20090211 4

<h4>Background</h4>TCF7L2 is the strongest type 2 diabetes (T2D) locus identified to date, and evidence suggests it plays an important role in insulin synthesis, processing, and secretion. Dietary factors that increase the insulin demand might enhance the risk of T2D associated with TCF7L2 variants.<h4>Objective</h4>The objective was to determine whether the risk of T2D associated with TCF7L2 is modified by the glycemic load (GL), glycemic index (GI), cereal fiber content, and total carbohydrate ...[more]

PMID: 19211816

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Project description:Aims/hypothesisThe 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.MethodsA 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.ResultsThe 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/interpretationOur 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.

Dataset Information

TCF7L2, dietary carbohydrate, and risk of type 2 diabetes in US women.

Publications

TCF7L2, dietary carbohydrate, and risk of type 2 diabetes in US women.

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