Project Title: Role of genetic makeup in the modulation of early prediabetic dysglycemia and its interaction with gut microbiome

Project No: lzp-2022/1-0386

Period: 1 January 2023 – 31 December 2025

Project costs: 300 000, 00 EUR

Principle Investigator: Dr.biol. Jānis Kloviņš

Summary

In the last decade, large-scale genome-wide association studies (GWAS) have identified more than 500 genetic loci associated with T2D risk and glycemic traits. However, there is a limited understanding of how these genetic loci influence the development of early dysglycemia and its further progression to type 2 diabetes (T2D). Also, from the clinical perspective, little is known about the correlation between lifestyle change mediated prevention efficiency and inherited genetic risk. From the gut microbiome perspective, recent research suggests that major gut microbiota and metabolome alterations might begin long before clinical onset. We, therefore, propose to study the effect of T2D-associated genetic loci and their interaction with the gut microbiome in the cohort of metabolic syndrome patients with early dysglycemia and evaluate its correlation with phenotypic and clinical outcomes. We will also perform a diet intervention on two groups of patients with the highest and lowest extremes of polygenic risk score (PRS) distribution, assessing the improvements in glucose variability and changes in microbial and metabolic profiles. As a result, we will establish a set of genetic, microbial, and metabolic biomarkers predicting the intervention-associated short-term and long-term outcomes and evaluate the association of these biomarkers with clinical and phenotypic data from existing population and T2D cohorts.

Information published 02.01.2023.