title: Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.
abstract: The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Celia G
authors.initials: CG
authors.lastname: Walker
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Solis-Trapala
authors.affiliation: Else Kroener-Fresenius-Center for Nutritional Medicine, Faculty of Medicine, Technische Universität München, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Holzapfel
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Gina L
authors.initials: GL
authors.lastname: Ambrosini
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney, NSW, Australia.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Fuller
authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, The Genetics of Obesity and Related Metabolic Traits Programme, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.affiliation: Else Kroener-Fresenius-Center for Nutritional Medicine, Faculty of Medicine, Technische Universität München, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney, NSW, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Caterson
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Jebb
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D008954:Models, Biological; D019655:Quantitative Trait, Heritable; D012044:Regression Analysis; D012307:Risk Factors; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D004041:Dietary Fats