The interplay between genes and dietary factors in the aetiology of Type 2 Diabetes Mellitus

To help mitigate the escalating prevalence of Type 2 Diabetes (T2D) and alleviate society of its associated morbidity and economic burden on health care, it is crucial to understand its aetiology. Both genetic and the environmental risk factors are known to be involved. Healthy diets have been proven to reduce the risk of T2D in primary prevention trials, however, which components and exact mechanisms are involved is not fully understood, in particular, the role of macronutrient intake. Body weight, glycaemic markers and T2D are all to some extent genetically regulated. There may also be genetic influences on how people digest, absorb or metabolise macronutrients. This poses the possibility that the interplay between genes and our diet may help us unravel T2D’s aetiology. The aim of this PhD was to investigate gene-diet interactions on the risk of incident T2D, focusing primarily on macronutrient intake as the dietary factor. First, I systematically evaluated the current evidence before taking a step-wise approach (hypothesis driven to hypothesis-free) to interrogate gene-macronutrient interactions. This identified 13 publications, with 8 unique interactions reported between macronutrients (carbohydrate, fat, saturated fat, dietary fibre, and glycaemic load derived from self-report of dietary intake and circulating n-3 polyunsaturated fatty acids) and genetic variants in or near TCF7L2, GIPR, CAV2 and PEPD (p