Macronutrient Composition and Plasma Metabolites in Relation to Cardiometabolic Disease

Abstract

The connection between macronutrient composition, metabolic pathways, and cardiometabolic disease has been a popular target of investigation. However, there exist large research gaps relating to macronutrient composition, especially relating to protein and carbohydrates, and incident coronary heart disease, macronutrient composition and survival among individuals in type 2 diabetes, as well as metabolic pathways that may lead to incident diabetes. Furthermore, the origin of these macronutrients (i.e. whether they are derived primarily from plant or animal sources), may also be key factors in these relationships. In this dissertation, I attempted to address these largely unexplored research questions by through the use of longitudinal data analysis in several rich cohorts. In Chapter 1, I examine the use of the dietary protein to carbohydrate ratio, which has become a subject of great interest in animal studies, using population data from the Nurses’ Health Study I and the Health Professionals’ Follow-Up Study, and find that a total protein to carbohydrate ratio is not predictive of coronary heart disease, but that one based primarily on plant protein may reduce risk. In Chapter 2, I examine whether adherence to a low carbohydrate diet is associated with prolonged survival after diagnosis with type 2 diabetes. I find that adherence to either a total or plant-based low carbohydrate diet is predictive of longer survival post-type 2 diabetes, and that this relationship further holds for an animal based low carbohydrate diet when looking at cardiovascular-specific mortality. In Chapter 3, I examined whether plasma arginine-based metabolites, which may be involved in nitric oxide synthesis, may be associated with incident type 2 diabetes. I find that 1-year changes in arginine are associated with lower risk of type 2 diabetes, and that unfavorable changes in N-monomethyl-l-arginine may be offset by consuming a Mediterranean dietary pattern characterized by high intake of plant foods. Overall, macronutrient source in addition to composition must be considered when designing public health guidelines. Plant-based diets in particular are promising interventions to reduce cardiometabolic disease.