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Diet/Lifestyle Intervention Influences Genetic Effect of TCF7L2 Genotype on Glycemic Control and Adiposity Among 4,114 Individuals Enrolled in Seven Randomized Controlled Trials

29 Pages Posted: 8 Oct 2018

See all articles by Tao Huang

Tao Huang

Peking University - Department of Epidemiology and Biostatistics

Yoriko Heianza

Tulane University - School of Public Health and Tropical Medicine

Dianjianyi Sun

Tulane University - Department of Epidemiology

Wenjie Ma

Harvard University - Department of Nutrition

Zhe Fang

Peking University - School of Public Health

Meng Gao

Peking University - School of Public Health

Emilio Ros

Institut d'Investigacions Biomèdiques August Pi Sunyer

Liana C. Del Gobbo

Stanford University

Jordi Salas-Salvadó

Carlos III Institute of Health

Miguel A. Martínez-González

University of Navarra - Department of Preventive Medicine and Public Health; Carlos III Institute of Health - Center for Biomedical Research in Network-Physiopathology of Obesity and Nutrition (CIBEROBN); IdiSNA, Navarra Institute for Health Research; Harvard University - T.H. Chan School of Public Health

Jan Polak

Charles University in Prague - Faculty of Medicine

Markku Laakso

University of Eastern Finland

Arne Astrup

University of Copenhagen

Dominique Langin

University of Toulouse 3, Paul Sabatier University

Jorg Hager

Nestlé Institute of Health Sciences

Gabby Hul

Maastricht University - Medical Center

Torben Hansen

University of Copenhagen - Faculty of Health and Medical Sciences

Oluf Pedersen

University of Copenhagen - Faculty of Health and Medical Sciences

Jean-Michel Oppert

Université Paris I Panthéon-Sorbonne

Wim Saris

Maastricht University - Medical Center

Peter Arner

Karolinska Institutet - Department of Medicine

Montserrat Cofán

Institut d'Investigacions Biomèdiques August Pi Sunyer

Sujatha Rajaram

Loma Linda University

Jaakko Tuomilehto

Government of the Republic of Finland - National Institute for Health and Welfare

Jaana Lindström

Government of the Republic of Finland - National Institute for Health and Welfare

Vanessa D. de Mello

University of Eastern Finland

Alena Stancacova

University of Eastern Finland

Matti I. Uusitupa

University of Eastern Finland

Mathilde Svendstrup

University of Copenhagen - Faculty of Health and Medical Sciences

Thorkild Sørensen

University of Copenhagen - Faculty of Health and Medical Sciences

Christopher Gardner

Stanford University

Joan Sabaté

Loma Linda University

Dolores Corella

Stanford University

J. Alfredo Martinez

Stanford University

Lu Qi

Tulane University - Department of Epidemiology; Harvard University - Department of Nutrition

More...

Abstract

Background: The transcription factor 7-like 2 gene (TCF7L2) is the strongest locus associated by the variant rs7903146 with type 2 diabetes (T2D) identified to date. Whether diet/lifestyle intervention modifies genetic effect of TCF7L2 variant on glucose homeostasis and adiposity is still controversial.

Objective: To quantify the modification effects of the diet/lifestyle interventions on genetic association of TCF7L2 variant rs7903146 with glycemic control and adiposity changes in randomized controlled trials (RCTs). Design A large collaborative analysis of individual-participant data from seven RCTs. Setting RCTs conducted in adults reporting changes in glycemic traits, body weight, or waist circumference by TCF7L2 rs7903146 after dietary/lifestyle-based interventions. Gene-treatment interaction models were fitted to individual participant data from all studies, using allele dose coding for genetic effects and a common set of covariates.

Results: We included seven eligible RCTs for the joint analysis (n=4,114 participants). Overall, a significant interaction between TCF7L2 rs7903146 and diet/lifestyle interventions on decrease in fasting glucose was observed. Compared with control, diet/lifestyle interventions reduced fasting glucose by -0.17 (95% CI, -0.32 to -0.02) mmol/L (test for heterogeneity: I2=45.1%, p<0.05; test for overall effect: z=2.20, p=0.028) for each copy of the TCF7L2 T risk allele. In addition, diet/lifestyle interventions reduced waist circumference regardless of genetic risk. However, changes in other glycemic traits, body weight and waist circumference for one copy of TCF7L2 risk allele in response to diet/lifestyle interventions were not significant.

Conclusions: This large collaborative analysis suggests that carrying the TCF7L2 T risk allele confers modestly greater benefit in improving glycemic control in response to diet/lifestyle interventions.

Funding Statement: The study was supported by grants from the Peking University Start-up Grant (BMU2018YJ002), the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616), the Boston Obesity Nutrition Research Center (DK46200), and United States-Israel Binational Science Foundation Grant 2011036.

Declaration of Interests: All authors declare: no support from companies for the submitted work; no relationships with companies that might have an interest in the submitted work in the previous three years; no spouses, partners, or children have no financial relationships that may be relevant to the submitted work; no non-financial interests that may be relevant to the submitted work.

Ethics Approval Statement: Participants from all participating trials provided written, informed consent, and ethical approval was granted by local institutional review boards (see Supplemental Table 1).

Keywords: Diet/lifestyle intervention; genetic effect; TCF7L2 genotype; glycemic control; adiposity; randomized controlled trials

Suggested Citation

Huang, Tao and Heianza, Yoriko and Sun, Dianjianyi and Ma, Wenjie and Fang, Zhe and Gao, Meng and Ros, Emilio and Del Gobbo, Liana C. and Salas-Salvadó, Jordi and Martínez-González, Miguel A. and Polak, Jan and Laakso, Markku and Astrup, Arne and Langin, Dominique and Hager, Jorg and Hul, Gabby and Hansen, Torben and Pedersen, Oluf and Oppert, Jean-Michel and Saris, Wim and Arner, Peter and Cofán, Montserrat and Rajaram, Sujatha and Tuomilehto, Jaakko and Lindström, Jaana and de Mello, Vanessa D. and Stancacova, Alena and Uusitupa, Matti I. and Svendstrup, Mathilde and Sørensen, Thorkild and Gardner, Christopher and Sabaté, Joan and Corella, Dolores and Martinez, J. Alfredo and Qi, Lu, Diet/Lifestyle Intervention Influences Genetic Effect of TCF7L2 Genotype on Glycemic Control and Adiposity Among 4,114 Individuals Enrolled in Seven Randomized Controlled Trials (April 10, 2018). Available at SSRN: https://ssrn.com/abstract=3260786

Tao Huang

Peking University - Department of Epidemiology and Biostatistics ( email )

No. 38 Xueyuan Road
Haidian District
Beijing, Beijing 100871
China

Yoriko Heianza

Tulane University - School of Public Health and Tropical Medicine

New Orleans, LA 70112
United States

Dianjianyi Sun

Tulane University - Department of Epidemiology

New Orleans, LA 70112
United States

Wenjie Ma

Harvard University - Department of Nutrition

Boston, MA 02115
United States

Zhe Fang

Peking University - School of Public Health

No. 38 Xueyuan Road
Haidian District
Beijing, 100871
China

Meng Gao

Peking University - School of Public Health

No. 38 Xueyuan Road
Haidian District
Beijing, 100871
China

Emilio Ros

Institut d'Investigacions Biomèdiques August Pi Sunyer

Spain

Liana C. Del Gobbo

Stanford University

Stanford, CA 94305
United States

Jordi Salas-Salvadó

Carlos III Institute of Health

Spain

Miguel A. Martínez-González

University of Navarra - Department of Preventive Medicine and Public Health

c/ Irunlarrea, 1
Pamplona, 31008
Spain

Carlos III Institute of Health - Center for Biomedical Research in Network-Physiopathology of Obesity and Nutrition (CIBEROBN)

C/ Monforte de Lemos 3-5
Pabellón 11. Planta 0
Madrid, 28029
Spain

IdiSNA, Navarra Institute for Health Research

C/Irunlarrea, 3
Pamplona, 31008
Spain

Harvard University - T.H. Chan School of Public Health

677 Huntington Avenue
Boston, MA MA 02115
United States

Jan Polak

Charles University in Prague - Faculty of Medicine

Celetná 13
Praha 1, 116 36
Czech Republic

Markku Laakso

University of Eastern Finland ( email )

PO Box 111
Joensuu, 80100
Finland

Arne Astrup

University of Copenhagen ( email )

Nørregade 10
Copenhagen, København DK-1165
Denmark

Dominique Langin

University of Toulouse 3, Paul Sabatier University ( email )

118 Route de Narbonne
Toulouse cedex 9, F-31062
France

Jorg Hager

Nestlé Institute of Health Sciences

Switzerland

Gabby Hul

Maastricht University - Medical Center

Maastricht
Netherlands

Torben Hansen

University of Copenhagen - Faculty of Health and Medical Sciences

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Oluf Pedersen

University of Copenhagen - Faculty of Health and Medical Sciences

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Jean-Michel Oppert

Université Paris I Panthéon-Sorbonne

17, rue de la Sorbonne
Paris, IL 75005
France

Wim Saris

Maastricht University - Medical Center

Maastricht
Netherlands

Peter Arner

Karolinska Institutet - Department of Medicine ( email )

Sweden

Montserrat Cofán

Institut d'Investigacions Biomèdiques August Pi Sunyer

Spain

Sujatha Rajaram

Loma Linda University

Loma Linda, CA 92350
United States

Jaakko Tuomilehto

Government of the Republic of Finland - National Institute for Health and Welfare

Helsinki
Finland

Jaana Lindström

Government of the Republic of Finland - National Institute for Health and Welfare

Helsinki
Finland

Vanessa D. De Mello

University of Eastern Finland

PO Box 111
Joensuu, 80100
Finland

Alena Stancacova

University of Eastern Finland

PO Box 111
Joensuu, 80100
Finland

Matti I. Uusitupa

University of Eastern Finland ( email )

PO Box 111
Joensuu, 80100
Finland

Mathilde Svendstrup

University of Copenhagen - Faculty of Health and Medical Sciences ( email )

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Thorkild Sørensen

University of Copenhagen - Faculty of Health and Medical Sciences ( email )

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Christopher Gardner

Stanford University ( email )

Stanford, CA 94305
United States

Joan Sabaté

Loma Linda University

Loma Linda, CA 92350
United States

Dolores Corella

Stanford University

Stanford, CA 94305
United States

J. Alfredo Martinez

Stanford University

Stanford, CA 94305
United States

Lu Qi (Contact Author)

Tulane University - Department of Epidemiology

New Orleans, LA 70112
United States

Harvard University - Department of Nutrition

Boston, MA 02115
United States

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