The metabolomics imprint of controlled modification of carbohydrate quality elucidates long-term impact on cardiometabolic disease risk and facilitates precision prevention approaches

The glycemic response to carbohydrate (CHO) intake varies, depending on the dietary CHO quality and individual metabolic predisposition.

However, the long-term metabolic adaptation to dietary CHO quality and the effect on cardiometabolic disease risk remain elusive, and molecular determinants of potential interpersonal effect heterogeneity are largely unknown.We propose a multi-study multi-omics design to examine how dietary CHO quality affects the metabolome and subsequent diabetes, heart disease, and stroke risk.

We will use a diet intervention trial with different levels of CHO’s glycemic index (GI) but otherwise consistent diet, to generate a multi-metabolite score (MMS) of dietary GI.

Then, we will examine if this MMS associates with self-reported GI of the habitual diet in deep-phenotyping observational studies, and test potential interactions with the microbiome and genetic background.

In the Swedish SIMPLER and the US Harvard cohorts, we will assess the association of this MMS with cardiometabolic disease incidence.

We will also conduct a comparability study to harmonize the metabolomics data between the Scandinavian and US studies.We expect to elucidate the metabolic adaption to different CHO quality and implications for cardiometabolic disease risk.

We also aim to develop biomarkers of dietary CHO quality and individual metabolic vulnerability, potentially facilitating precision nutrition prevention of cardiometabolic diseases.