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

Health Data Sci. 2021 Nov 3:2021:9897048. doi: 10.34133/2021/9897048. eCollection 2021.

Authors

Tao Huang^{1

2

3

4}, Zhenhuang Zhuang¹, Yoriko Heianza⁵, Dianjianyi Sun⁵, Wenjie Ma⁶, Wenxiu Wang¹, Meng Gao¹, Zhe Fang¹, Emilio Ros^{7

8}, Liana C Del Gobbo⁹, Jordi Salas-Salvadó^{8

10}, Miguel A Martínez-González^{6

8

11}, Jan Polak¹², Markku Laakso¹³, Arne Astrup¹⁴, Dominique Langin¹⁵, Jorg Hager¹⁶, Gabby Hul¹⁷, Torben Hansen¹⁸, Oluf Pedersen¹⁸, Jean-Michel Oppert¹⁹, Wim H M Saris¹⁷, Peter Arner²⁰, Montserrat Cofán^{7

8}, Sujatha Rajaram²¹, Jaakko Tuomilehto^{22

23

24}, Jaana Lindström²², Vanessa D de Mello²⁵, Alena Stancacova¹³, Matti Uusitupa²⁵, Mathilde Svendstrup^{18

26}, Thorkild I A Sørensen^{18

27}, Christopher D Gardner⁹, Joan Sabaté²¹, Dolores Corella^{8

28}, J Alfredo Martinez^{8

29}, Lu Qi^{5

6}

Affiliations

¹ Department of Epidemiology & Biostatistics, School of Public Health, Peking University, China.
² Department of Global Health, School of Public Health, Peking University, China.
³ Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education, China.
⁴ Global Health Institute Peking University, China.
⁵ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
⁶ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Department of Endocrinology & Nutrition, Institut d'Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain.
⁸ CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
⁹ Stanford Prevention Research Center, Stanford University, Stanford CA, USA.
¹⁰ Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain.
¹¹ University of Navarra, Department of Preventive Medicine and Public Health, Medical School & IDISNA, Pamplona, Spain.
¹² Department for the Study of Obesity and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
¹³ Department of Medicine, University of Eastern Finland, Kuopio, Finland.
¹⁴ University of Copenhagen, Department of Nutrition, Exercise and Sports, Faculty of Science, Copenhagen, Denmark.
¹⁵ Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Institute of Metabolic and Cardiovascular Diseases, University of Toulouse and Paul Sabatier University, Toulouse, France.
¹⁶ Nestlé Institute of Health Sciences, Lausanne, Switzerland.
¹⁷ Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Maastricht, Netherlands.
¹⁸ Section of Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹⁹ Sorbonne Université, Institute of Cardiometabolism and Nutrition (ICAN), Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
²⁰ Department of Medicine, Unit for Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
²¹ School of Public Health, Loma Linda University, Loma Linda, CA, USA.
²² Department of Chronic Disease Prevention, Finnish National Institute for Health and Welfare, HelsinkiFinland.
²³ Department of Public Health, University of Helsinki, Helsinki, Finland.
²⁴ Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
²⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
²⁶ Danish Diabetes Academy Odense, Denmark.
²⁷ Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
²⁸ Department of Preventive Medicine, University of Valencia, Valencia, Spain.
²⁹ Department of Nutrition Food Science and Physiology, University of Navarra, IDISNA, Pamplona and IMDEA, Madrid, Spain.

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: $I^{2} = 45.1 %$ , $p < 0.05$ ; $z = 2.20$ , $p = 0.028$ ) 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.