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.
Highlights
Type 2 diabetes mellitus (T2DM) develops as a consequence of the interplay between genetic and lifestyle factors
The aim of this study is to describe the complex effect of changes in lifestyle factors known to impact on the risk of developing T2DM whilst considering genetic predisposition and other intrinsic factors on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme
As reported for the full cohort in the primary analysis [11], the mean change in weight, glucose, HOMA-B and HOMA-IR in response to the intervention were all significantly greater in the commercial weight loss programme (CP) compared to the standard care (SC) treatment groups (Table 1) in this subset of participants
Summary
Type 2 diabetes mellitus (T2DM) develops as a consequence of the interplay between genetic and lifestyle factors. There is known to be a strong heritable component for T2DM with genetic factors explaining around 25% of the variation in disease risk and approximately 60% of variation in impaired glucose tolerance [1]. Overweight and obesity, physical inactivity, and diets with a high proportion of saturated fat and low non-starch polysaccharide (NSP) are the lifestyle factors identified with convincing or probable evidence of increased risk of developing T2DM [9]. Weight loss has been shown to improve insulin sensitivity and glycaemic control in people with impaired glucose tolerance or T2DM [10, 11], and when combined with reductions in saturated fat, increases in dietary fibre and increases in physical activity can reduce the incidence of developing T2DM [12,13,14]. There is substantial inter-individual variation in the improvements in insulin sensitivity and glycaemia for a given change in lifestyle factors which may reflect intrinsic characteristics such as genotype
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