TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet

Katrine Grau; Stephane Cauchi; Claus Holst; Arne Astrup; J. Alfredo Martinez; Wim H.M. Saris; Ellen E Blaak; Jean-Michel Oppert; Peter Arner; Stephan Rössner; Ian A. Macdonald; Eva Klimcakova; Dominique Langin; Oluf Pedersen; Philippe Froguel; Thorkild I.A. Sørensen

doi:10.3945/ajcn.2009.27947

TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet

Katrine Grau, Stephane Cauchi, Claus Holst, Arne Astrup, J. Alfredo Martinez, Wim H.M. Saris, Ellen E Blaak, Jean-Michel Oppert, Peter Arner, Stephan Rössner, Ian A. Macdonald, Eva Klimcakova, Dominique Langin, Oluf Pedersen, Philippe Froguel, Thorkild I.A. Sørensen

43 Citationer (Scopus)

Abstract

Background: Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion. Objective: The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, lowcarbohydrate: 40-45% of energy as fat (HF); compared with lowfat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (2600 kcal/d). Design: European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-β), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146. Results: Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Δweight) (2.6 kg; P = 0.009; n = 622), smaller ΔFFM (1.6 kg; P = 0.027; n = 609), smaller ΔWC (3.3 cm; P = 0.010; n = 608), and a smaller ΔHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with ΔREE, ΔFatOx, ΔHOMA-β, or dropout. Conclusion: Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.

Originalsprog	Engelsk
Tidsskrift	American Journal of Clinical Nutrition
Vol/bind	91
Udgave nummer	2
Sider (fra-til)	472-479
Antal sider	8
ISSN	0002-9165
DOI	https://doi.org/10.3945/ajcn.2009.27947
Status	Udgivet - 1 feb. 2010

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10.3945/ajcn.2009.27947

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Grau, K., Cauchi, S., Holst, C., Astrup, A., Martinez, J. A., Saris, W. H. M., Blaak, E. E., Oppert, J-M., Arner, P., Rössner, S., Macdonald, I. A., Klimcakova, E., Langin, D., Pedersen, O., Froguel, P., & Sørensen, T. I. A. (2010). TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet. American Journal of Clinical Nutrition, 91(2), 472-479. https://doi.org/10.3945/ajcn.2009.27947

Grau, K, Cauchi, S, Holst, C, Astrup, A, Martinez, JA, Saris, WHM, Blaak, EE, Oppert, J-M, Arner, P, Rössner, S, Macdonald, IA, Klimcakova, E, Langin, D, Pedersen, O, Froguel, P & Sørensen, TIA 2010, 'TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet', American Journal of Clinical Nutrition, bind 91, nr. 2, s. 472-479. https://doi.org/10.3945/ajcn.2009.27947

@article{b0060d501d7511df8ed1000ea68e967b,

title = "TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet",

abstract = "Background: Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion. Objective: The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, lowcarbohydrate: 40-45% of energy as fat (HF); compared with lowfat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (2600 kcal/d). Design: European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-β), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146. Results: Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Δweight) (2.6 kg; P = 0.009; n = 622), smaller ΔFFM (1.6 kg; P = 0.027; n = 609), smaller ΔWC (3.3 cm; P = 0.010; n = 608), and a smaller ΔHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with ΔREE, ΔFatOx, ΔHOMA-β, or dropout. Conclusion: Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.",

author = "Katrine Grau and Stephane Cauchi and Claus Holst and Arne Astrup and Martinez, {J. Alfredo} and Saris, {Wim H.M.} and Blaak, {Ellen E} and Jean-Michel Oppert and Peter Arner and Stephan R{\"o}ssner and Macdonald, {Ian A.} and Eva Klimcakova and Dominique Langin and Oluf Pedersen and Philippe Froguel and S{\o}rensen, {Thorkild I.A.}",

year = "2010",

month = feb,

day = "1",

doi = "10.3945/ajcn.2009.27947",

language = "English",

volume = "91",

pages = "472--479",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "American Society for Nutrition",

number = "2",

}

TY - JOUR

T1 - TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet

AU - Grau, Katrine

AU - Cauchi, Stephane

AU - Holst, Claus

AU - Astrup, Arne

AU - Martinez, J. Alfredo

AU - Saris, Wim H.M.

AU - Blaak, Ellen E

AU - Oppert, Jean-Michel

AU - Arner, Peter

AU - Rössner, Stephan

AU - Macdonald, Ian A.

AU - Klimcakova, Eva

AU - Langin, Dominique

AU - Pedersen, Oluf

AU - Froguel, Philippe

AU - Sørensen, Thorkild I.A.

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Background: Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion. Objective: The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, lowcarbohydrate: 40-45% of energy as fat (HF); compared with lowfat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (2600 kcal/d). Design: European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-β), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146. Results: Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Δweight) (2.6 kg; P = 0.009; n = 622), smaller ΔFFM (1.6 kg; P = 0.027; n = 609), smaller ΔWC (3.3 cm; P = 0.010; n = 608), and a smaller ΔHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with ΔREE, ΔFatOx, ΔHOMA-β, or dropout. Conclusion: Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.

AB - Background: Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type 2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which is stimulated more by fat than by carbohydrate ingestion. Objective: The objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat and carbohydrate [high-fat, lowcarbohydrate: 40-45% of energy as fat (HF); compared with lowfat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese individuals' responses to a 10-wk hypoenergetic diet (2600 kcal/d). Design: European, obese participants (n = 771) were randomly assigned to receive an HF or an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of REE (FatOx), homeostasis model assessed insulin release (HOMA-β), and HOMA-insulin resistance (HOMA-IR) were determined at baseline and after the intervention; 739 individuals were genotyped for rs7903146. Results: Average weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between diets, NS) diet. Among individuals who were homozygous for the T-risk allele, those in the HF diet group experienced smaller weight losses (Δweight) (2.6 kg; P = 0.009; n = 622), smaller ΔFFM (1.6 kg; P = 0.027; n = 609), smaller ΔWC (3.3 cm; P = 0.010; n = 608), and a smaller ΔHOMA-IR (1.3 units; P = 0.004; n = 615) than did the LF diet group. For C allele carriers, there were no differences between the HF and LF diet groups. For the HF diet group, each additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019; n = 609). TCF7L2 rs7903146 was not associated with ΔREE, ΔFatOx, ΔHOMA-β, or dropout. Conclusion: Our results suggest that obese individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more sensitive to LF than to HF weight-loss diets.

U2 - 10.3945/ajcn.2009.27947

DO - 10.3945/ajcn.2009.27947

M3 - Journal article

C2 - 20032493

SN - 0002-9165

VL - 91

SP - 472

EP - 479

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 2

ER -

TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a 10-wk randomized hypoenergetic diet

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