Healthy nutrition plays an important role in the prevention of cardiometabolic diseases such as type 2 diabetes and cardiovascular diseases. However, not everyone responds to food in the same way; the most optimal dietary pattern for cardiometabolic health may vary from person to person. This variation seems to be partly attributed to metabolic heterogeneity, i.e. differences in metabolism between individuals. The research in this thesis demonstrates, for the first time, that refining the current general dietary guidelines according to metabolic phenotype (specifically, tissue-specific insulin resistance) may lead to greater health benefits, independent of weight loss. Therefore, our findings support precision nutrition based on metabolic phenotype as a promising strategy for the prevention of cardiometabolic diseases. Additionally, our work illustrates that further refinement of metabolic phenotypes and personalised dietary advice may optimise the effectiveness of precision nutrition, for example, based on biomarkers of lipid metabolism in the blood. The findings in this dissertation have provided leads for possible mechanisms that may be involved in the diverging effects of nutrition on cardiometabolic health. These findings can contribute to the development of future precision nutrition interventions for the prevention of type 2 diabetes and other chronic conditions.