Obesity and type 2 diabetes (T2D) are major global health concerns, yet long-term outcomes of dietary prevention strategies remain suboptimal. One limitation is that current nutritional guidelines fail to account for individual metabolic variability. Variations in insulin resistance (IR) across diverse tissues, including adipose tissue, muscle, and liver, exert a pivotal influence on cardiometabolic risk, modulating the body’s nutrient processing in response to dietary interventions. Even within cohorts exhibiting overweight and normal glucose tolerance, discernible phenotypes of liver or muscle IR can be delineated, characterized by distinct microbial, metabolomic, lipidomic, and adipose tissue transcriptome profiles.
Specifically, dietary intervention tailored to liver (LIR) or muscle insulin resistance (MIR) phenotypes led to improved insulin sensitivity and cardiometabolic health (PERSON), independent of weight loss, demonstrating the potential of precision nutrition. To further refine this approach, we employed data-driven clustering to stratify individuals based on glucose homeostasis and body composition. Using an iterative Hierarchical Clustering of Principal Components on a large cohort (The Maastricht Study), we identified six metabotypes. These were validated and classified with high accuracy (71–75%) using a Random Forest model and inform a current precision nutrition study.
Obesity and T2D correlate with microbial dysbiosis, with initial microbial composition emerging as a potential determinant in lifestyle-induced cardiometabolic health outcomes. Indeed, a small part of the benefits of metabotype-tailored diets in PERSON may be mediated by gut microbial metabolism. Nevertheless, to induce pronounced effects on host metabolism through microbial modulation, a more robust approach may be required based on the amount and type of dietary fibers. These insights into microbiota and host tissue metabolism will be deliberated within the framework of devising targeted lifestyle strategies to ameliorate cardiometabolic health in individuals with obesity.
Keywords: obesity, precision lifestyle strategies, insulin resistant phenotype, nutrition, microbiota composition, diet, cardiometabolic health