Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide

Tao Huang; Zhenhuang Zhuang; Yoriko Heianza; Dianjianyi Sun; Wenjie Ma; Wenxiu Wang; Meng Gao; Zhe Fang; Emilio Ros; Liana C. Del Gobbo; Jordi Salas-Salvadó; Miguel A. Martínez-González; Jan Polak; Markku Laakso; Arne Astrup; Dominique Langin; Jorg Hager; Gabby Hul; Torben Hansen; Oluf Pedersen; Jean Michel Oppert; Wim H.M. Saris; Peter Arner; Montserrat Cofán; Sujatha Rajaram; Jaakko Tuomilehto; Jaana Lindström; Vanessa D. de Mello; Alena Stancacova; Matti Uusitupa; Mathilde Svendstrup; Thorkild I.A. Sørensen; Christopher D. Gardner; Joan Sabaté; Dolores Corella; J. Alfredo Martinez; Lu Qi

doi:10.34133/2021/9897048

Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide

Tao Huang^*, Zhenhuang Zhuang, Yoriko Heianza, Dianjianyi Sun, Wenjie Ma, Wenxiu Wang, Meng Gao, Zhe Fang, Emilio Ros, Liana C. Del Gobbo, Jordi Salas-Salvadó, Miguel A. Martínez-González, Jan Polak, Markku Laakso, Arne Astrup, Dominique Langin, Jorg Hager, Gabby Hul, Torben Hansen, Oluf PedersenJean Michel Oppert, Wim H.M. Saris, Peter Arner, Montserrat Cofán, Sujatha Rajaram, Jaakko Tuomilehto, Jaana Lindström, Vanessa D. de Mello, Alena Stancacova, Matti Uusitupa, Mathilde Svendstrup, Thorkild I.A. Sørensen, Christopher D. Gardner, Joan Sabaté, Dolores Corella, J. Alfredo Martinez, Lu Qi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n = 4, 114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2 = 45:1%, p < 0:05; z = 2:20, p = 0:028) per one copy of the TCF7L2 T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele. Conclusions. Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.

Original language	English
Article number	9897048
Journal	Health Data Science
Volume	2021
DOIs	https://doi.org/10.34133/2021/9897048
Publication status	Published - 1 Jan 2021

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10.34133/2021/9897048Licence: CC BY

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Huang, T., Zhuang, Z., Heianza, Y., Sun, D., Ma, W., Wang, W., Gao, M., Fang, Z., Ros, E., Del Gobbo, L. C., Salas-Salvadó, J., Martínez-González, M. A., Polak, J., Laakso, M., Astrup, A., Langin, D., Hager, J., Hul, G., Hansen, T., ... Qi, L. (2021). Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide. Health Data Science, 2021, Article 9897048. https://doi.org/10.34133/2021/9897048

@article{dd8e5880f2364ec9afc65cf71794be8b,

title = "Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide",

abstract = "Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n = 4, 114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2 = 45:1%, p < 0:05; z = 2:20, p = 0:028) per one copy of the TCF7L2 T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele. Conclusions. Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.",

author = "Tao Huang and Zhenhuang Zhuang and Yoriko Heianza and Dianjianyi Sun and Wenjie Ma and Wenxiu Wang and Meng Gao and Zhe Fang and Emilio Ros and {Del Gobbo}, {Liana C.} and Jordi Salas-Salvad{\'o} and Mart{\'i}nez-Gonz{\'a}lez, {Miguel A.} and Jan Polak and Markku Laakso and Arne Astrup and Dominique Langin and Jorg Hager and Gabby Hul and Torben Hansen and Oluf Pedersen and Oppert, {Jean Michel} and Saris, {Wim H.M.} and Peter Arner and Montserrat Cof{\'a}n and Sujatha Rajaram and Jaakko Tuomilehto and Jaana Lindstr{\"o}m and {de Mello}, {Vanessa D.} and Alena Stancacova and Matti Uusitupa and Mathilde Svendstrup and S{\o}rensen, {Thorkild I.A.} and Gardner, {Christopher D.} and Joan Sabat{\'e} and Dolores Corella and {Alfredo Martinez}, J. and Lu Qi",

note = "Funding Information: The study was supported by grants from the National Key R&D Program of China (2020YFC2003401). The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002). POUNDS Lost was supported by NIH grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States-Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Overseas Research Fellowship from the JSPS. DIETFITS was supported by grant 1R01DK091831 from the National Institute of Diabetes and Digestive and Kidney Diseases; grant T32HL007034 from the Nutrition Science Initiative; grant 1K12GM088033 from the National Heart, Lung, and Blood Institute; and the Stanford Clinical and Translational Science Award. The Diogenes Project is supported by a contract FP6-2005-513946 from the European commission under the Food Quality and Safety Priority of the Sixth Framework Programme. WAHA was supported by a grant from the California Walnut Commission and CIBER Fisiopatolog{\'i}a de la Obesidad y Nutrici{\'o}n (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. DPS was supported by Academy of Finland (128315, 129330, and 283454), the Finnish Diabetes Research Foundation, the Juho Vainio Foundation (to J.L.), the Novo Nordisk Foundation (to J.L.), The EVO-fund of Kuopio University Hospital (5106, 5168, 5254 [to M.U.]), and the Ministry of Education of Finland, Sigrid Juselius Foundation. PREDIMED-Reus was supported by the CIBEROBN, ISCIII, Madrid; Fundaci{\'o} la Marat{\'o}-TV3 and Generalitat Valenciana (Grant PROMETEO-17/2017), Spain. NUGENOB was supported by the European Community (Contract no. QLK1-CT-2000-00618). Dr. Astrup receives payment as Associate Editor of The American Journal of Clinical Nutrition and as a member of the Editorial Committee of Annual Review of Nutrition. Dr. Astrup is advisor to or a member of advisory boards for a number of food and pharmaceutical producers: Acino, Switzerland; BioCare Copenhagen, DK; Dutch Beer Institute, NL; Gelesis, USA; Groupe {\'E}thique et Sant{\'e}, France; McCain Foods Limited, USA; Navamedic, DK; Novo Nordisk, DK; Saniona, DK; Weight Watchers, USA. Dr. Astrup is recipient of stock options in Gelesis, USA. He does not own stock in or has other ownership interests in any of the other companies to which he provides scientific advice, or in any nutrition company other than those companies whose stock is held by various mutual fund retirement accounts. Dr. Astrup's recent research at the University of Copenhagen, Denmark, has received funding via unrestricted grants from or contracts with DC-Ingredients, Denmark, Danish Dairy Foundation, Global Dairy Platform, and Gelesis AS, USA. Dr. Astrup is recipient of honoraria as speaker for a wide range of Danish and international concerns and receives royalties from textbooks and from popular diet and cookery books. Dr. Astrup is coinventor of a number of patents, including methods of inducing weight loss, treating obesity and preventing weight gain (licensee Gelesis, USA), and biomarkers for predicting degree of weight loss (licensee Nestec SA, CH), owned by the University of Copenhagen, in accordance with Danish law. Dr. Astrup is cofounder and coowner of the University of Copenhagen spin-out companies Mobile Fitness A/S, Personalized Weight Management Research Consortium ApS (Gluco-diet.dk), and Flaxslim ApS, where he is also member of the board. The funding organization had no role in the preparation of the manuscript. The authors listed in the byline are from the Gene-lifestyle Intervention Working Group. This is the first manuscript from this working group. Funding Information: The study was supported by grants from the National Key R&D Program of China (2020YFC2003401). The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002). POUNDS Lost was supported by NIH grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States– Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Overseas Research Fellowship from the JSPS. DIETFITS was supported by grant 1R01DK091831 from the National Institute of Diabetes and Digestive and Kidney Diseases; grant T32HL007034 from the Nutrition Science Initiative; grant 1K12GM088033 from the National Heart, Lung, and Blood Institute; and the Stanford Clinical and Translational Sci- ence Award. The Diogenes Project is supported by a contract FP6-2005-513946 from the European commission under the Food Quality and Safety Priority of the Sixth Framework Programme. WAHA was supported by a grant from the California Walnut Commission and CIBER Fisiopatolog{\'i}a de la Obesidad y Nutrici{\'o}n (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. DPS was supported by Academy of Finland (128315, 129330, and 283454), the Finnish Diabetes Research Foundation, the Juho Vainio Foundation (to J.L.), the Novo Nordisk Foundation (to J.L.), The EVO-fund of Kuopio University Hospital (5106, 5168, 5254 [to M.U.]), and the Ministry of Education of Finland, Sigrid Juselius Foundation. PREDIMED-Reus was supported by the CIBEROBN, ISCIII, Madrid; Fundaci{\'o} la Marat{\'o}-TV3 and Generalitat Valenciana (Grant PROME-TEO-17/2017), Spain. NUGENOB was supported by the European Community (Contract no. QLK1-CT-2000-00618). Dr. Astrup receives payment as Associate Editor of The American Journal of Clinical Nutrition and as a member of the Editorial Committee of Annual Review of Nutrition. Dr. Astrup is advisor to or a member of advisory boards for a number of food and pharmaceutical producers: Acino, Switzerland; BioCare Copenhagen, DK; Dutch Beer Institute, NL; Gelesis, USA; Groupe {\'E}thique et Sant{\'e}, France; McCain Foods Limited, USA; Navamedic, DK; Novo Nordisk, DK; Saniona, DK; Weight Watchers, USA. Dr. Astrup is recipient of stock options in Gelesis, USA. He does not own stock in or has other ownership interests in any of the other companies to which he provides scientific advice, or in any nutrition company other than those companies whose stock is held by various mutual fund retirement accounts. Dr. Astrup{\textquoteright}s recent research at the University of Copenhagen, Denmark, has received funding via unrestricted grants from or contracts with DC-Ingredients, Denmark, Danish Dairy Foundation, Global Dairy Platform, and Gelesis AS, USA. Dr. Astrup is recipient of honoraria as speaker for a wide range of Danish and international concerns and receives royalties from textbooks and from popular diet and cookery books. Dr. Astrup is coinventor of a number of patents, including methods of inducing weight loss, treating obesity and preventing weight gain (licensee Gelesis, USA), and biomarkers for predicting degree of weight loss (licensee Nestec SA, CH), owned by the University of Copenhagen, in accordance with Danish law. Dr. Astrup is cofounder and coowner of the University of Copenhagen spin-out companies Mobile Fitness A/S, Personalized Weight Management Research Consortium ApS (Gluco-diet.dk), and Flaxslim ApS, where he is also member of the board. The funding organization had no role in the preparation of the manuscript. The authors listed in the byline are from the Gene-lifestyle Intervention Working Group. This is the first manuscript from this working group. Publisher Copyright: Copyright {\textcopyright} 2021 Tao Huang et al. Exclusive Licensee Peking University Health Science Center. Distributed under a Creative Commons Attribution License (CC BY 4.0).",

year = "2021",

month = jan,

day = "1",

doi = "10.34133/2021/9897048",

language = "English",

volume = "2021",

journal = "Health Data Science",

issn = "2097-1095",

publisher = "American Association for the Advancement of Science",

}

Huang, T, Zhuang, Z, Heianza, Y, Sun, D, Ma, W, Wang, W, Gao, M, Fang, Z, Ros, E, Del Gobbo, LC, Salas-Salvadó, J, Martínez-González, MA, Polak, J, Laakso, M, Astrup, A, Langin, D, Hager, J, Hul, G, Hansen, T, Pedersen, O, Oppert, JM, Saris, WHM, Arner, P, Cofán, M, Rajaram, S, Tuomilehto, J, Lindström, J, de Mello, VD, Stancacova, A, Uusitupa, M, Svendstrup, M, Sørensen, TIA, Gardner, CD, Sabaté, J, Corella, D, Alfredo Martinez, J & Qi, L 2021, 'Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide', Health Data Science, vol. 2021, 9897048. https://doi.org/10.34133/2021/9897048

Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide. / Huang, Tao; Zhuang, Zhenhuang; Heianza, Yoriko et al.
In: Health Data Science, Vol. 2021, 9897048, 01.01.2021.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults

T2 - Big Data from Seven Randomized Controlled Trials Worldwide

AU - Huang, Tao

AU - Zhuang, Zhenhuang

AU - Heianza, Yoriko

AU - Sun, Dianjianyi

AU - Ma, Wenjie

AU - Wang, Wenxiu

AU - Gao, Meng

AU - Fang, Zhe

AU - Ros, Emilio

AU - Del Gobbo, Liana C.

AU - Salas-Salvadó, Jordi

AU - Martínez-González, Miguel A.

AU - Polak, Jan

AU - Laakso, Markku

AU - Astrup, Arne

AU - Langin, Dominique

AU - Hager, Jorg

AU - Hul, Gabby

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Oppert, Jean Michel

AU - Saris, Wim H.M.

AU - Arner, Peter

AU - Cofán, Montserrat

AU - Rajaram, Sujatha

AU - Tuomilehto, Jaakko

AU - Lindström, Jaana

AU - de Mello, Vanessa D.

AU - Stancacova, Alena

AU - Uusitupa, Matti

AU - Svendstrup, Mathilde

AU - Sørensen, Thorkild I.A.

AU - Gardner, Christopher D.

AU - Sabaté, Joan

AU - Corella, Dolores

AU - Alfredo Martinez, J.

AU - Qi, Lu

N1 - Funding Information: The study was supported by grants from the National Key R&D Program of China (2020YFC2003401). The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002). POUNDS Lost was supported by NIH grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States-Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Overseas Research Fellowship from the JSPS. DIETFITS was supported by grant 1R01DK091831 from the National Institute of Diabetes and Digestive and Kidney Diseases; grant T32HL007034 from the Nutrition Science Initiative; grant 1K12GM088033 from the National Heart, Lung, and Blood Institute; and the Stanford Clinical and Translational Science Award. The Diogenes Project is supported by a contract FP6-2005-513946 from the European commission under the Food Quality and Safety Priority of the Sixth Framework Programme. WAHA was supported by a grant from the California Walnut Commission and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. DPS was supported by Academy of Finland (128315, 129330, and 283454), the Finnish Diabetes Research Foundation, the Juho Vainio Foundation (to J.L.), the Novo Nordisk Foundation (to J.L.), The EVO-fund of Kuopio University Hospital (5106, 5168, 5254 [to M.U.]), and the Ministry of Education of Finland, Sigrid Juselius Foundation. PREDIMED-Reus was supported by the CIBEROBN, ISCIII, Madrid; Fundació la Marató-TV3 and Generalitat Valenciana (Grant PROMETEO-17/2017), Spain. NUGENOB was supported by the European Community (Contract no. QLK1-CT-2000-00618). Dr. Astrup receives payment as Associate Editor of The American Journal of Clinical Nutrition and as a member of the Editorial Committee of Annual Review of Nutrition. Dr. Astrup is advisor to or a member of advisory boards for a number of food and pharmaceutical producers: Acino, Switzerland; BioCare Copenhagen, DK; Dutch Beer Institute, NL; Gelesis, USA; Groupe Éthique et Santé, France; McCain Foods Limited, USA; Navamedic, DK; Novo Nordisk, DK; Saniona, DK; Weight Watchers, USA. Dr. Astrup is recipient of stock options in Gelesis, USA. He does not own stock in or has other ownership interests in any of the other companies to which he provides scientific advice, or in any nutrition company other than those companies whose stock is held by various mutual fund retirement accounts. Dr. Astrup's recent research at the University of Copenhagen, Denmark, has received funding via unrestricted grants from or contracts with DC-Ingredients, Denmark, Danish Dairy Foundation, Global Dairy Platform, and Gelesis AS, USA. Dr. Astrup is recipient of honoraria as speaker for a wide range of Danish and international concerns and receives royalties from textbooks and from popular diet and cookery books. Dr. Astrup is coinventor of a number of patents, including methods of inducing weight loss, treating obesity and preventing weight gain (licensee Gelesis, USA), and biomarkers for predicting degree of weight loss (licensee Nestec SA, CH), owned by the University of Copenhagen, in accordance with Danish law. Dr. Astrup is cofounder and coowner of the University of Copenhagen spin-out companies Mobile Fitness A/S, Personalized Weight Management Research Consortium ApS (Gluco-diet.dk), and Flaxslim ApS, where he is also member of the board. The funding organization had no role in the preparation of the manuscript. The authors listed in the byline are from the Gene-lifestyle Intervention Working Group. This is the first manuscript from this working group. Funding Information: The study was supported by grants from the National Key R&D Program of China (2020YFC2003401). The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002). POUNDS Lost was supported by NIH grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States– Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Overseas Research Fellowship from the JSPS. DIETFITS was supported by grant 1R01DK091831 from the National Institute of Diabetes and Digestive and Kidney Diseases; grant T32HL007034 from the Nutrition Science Initiative; grant 1K12GM088033 from the National Heart, Lung, and Blood Institute; and the Stanford Clinical and Translational Sci- ence Award. The Diogenes Project is supported by a contract FP6-2005-513946 from the European commission under the Food Quality and Safety Priority of the Sixth Framework Programme. WAHA was supported by a grant from the California Walnut Commission and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. DPS was supported by Academy of Finland (128315, 129330, and 283454), the Finnish Diabetes Research Foundation, the Juho Vainio Foundation (to J.L.), the Novo Nordisk Foundation (to J.L.), The EVO-fund of Kuopio University Hospital (5106, 5168, 5254 [to M.U.]), and the Ministry of Education of Finland, Sigrid Juselius Foundation. PREDIMED-Reus was supported by the CIBEROBN, ISCIII, Madrid; Fundació la Marató-TV3 and Generalitat Valenciana (Grant PROME-TEO-17/2017), Spain. NUGENOB was supported by the European Community (Contract no. QLK1-CT-2000-00618). Dr. Astrup receives payment as Associate Editor of The American Journal of Clinical Nutrition and as a member of the Editorial Committee of Annual Review of Nutrition. Dr. Astrup is advisor to or a member of advisory boards for a number of food and pharmaceutical producers: Acino, Switzerland; BioCare Copenhagen, DK; Dutch Beer Institute, NL; Gelesis, USA; Groupe Éthique et Santé, France; McCain Foods Limited, USA; Navamedic, DK; Novo Nordisk, DK; Saniona, DK; Weight Watchers, USA. Dr. Astrup is recipient of stock options in Gelesis, USA. He does not own stock in or has other ownership interests in any of the other companies to which he provides scientific advice, or in any nutrition company other than those companies whose stock is held by various mutual fund retirement accounts. Dr. Astrup’s recent research at the University of Copenhagen, Denmark, has received funding via unrestricted grants from or contracts with DC-Ingredients, Denmark, Danish Dairy Foundation, Global Dairy Platform, and Gelesis AS, USA. Dr. Astrup is recipient of honoraria as speaker for a wide range of Danish and international concerns and receives royalties from textbooks and from popular diet and cookery books. Dr. Astrup is coinventor of a number of patents, including methods of inducing weight loss, treating obesity and preventing weight gain (licensee Gelesis, USA), and biomarkers for predicting degree of weight loss (licensee Nestec SA, CH), owned by the University of Copenhagen, in accordance with Danish law. Dr. Astrup is cofounder and coowner of the University of Copenhagen spin-out companies Mobile Fitness A/S, Personalized Weight Management Research Consortium ApS (Gluco-diet.dk), and Flaxslim ApS, where he is also member of the board. The funding organization had no role in the preparation of the manuscript. The authors listed in the byline are from the Gene-lifestyle Intervention Working Group. This is the first manuscript from this working group. Publisher Copyright: Copyright © 2021 Tao Huang et al. Exclusive Licensee Peking University Health Science Center. Distributed under a Creative Commons Attribution License (CC BY 4.0).

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n = 4, 114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2 = 45:1%, p < 0:05; z = 2:20, p = 0:028) per one copy of the TCF7L2 T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele. Conclusions. Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.

AB - Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n = 4, 114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2 = 45:1%, p < 0:05; z = 2:20, p = 0:028) per one copy of the TCF7L2 T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele. Conclusions. Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.

U2 - 10.34133/2021/9897048

DO - 10.34133/2021/9897048

M3 - Article

SN - 2097-1095

VL - 2021

JO - Health Data Science

JF - Health Data Science

M1 - 9897048

ER -

Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide

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