Unravelling the associations between insulin sensitivity and brain metabolites in prediabetic individuals, and exploring the therapeutic impact of exercise as an early intervention

Insulin resistance (IR) has been linked to obesity, type 2 diabetes mellitus, and recently Alzheimer’s
disease. However, it is strikingly prevalent, even among young and lean individuals who are typically not considered at risk, making it a serious public health issue. Since the related pathologies are all linked to altered neurometabolism, early warning signs could already be observable in the prediabetic state. Because research on IR and brain metabolites is currently scarce and methodologically heterogeneous, the aim of the proposed project is to explore this relationship between the peripheral and central metabolic profiles. An age- and gender-stratified lifespan sample (N=64) will undergo blood sampling to measure their IR, as well as magnetic resonance spectroscopy to measure the full spectra of neurometabolites at a 3T magnetic field. Potential moderators of the relationship will be inserted into the multivariate regression analysis, to approximate how much variance can be explained by factors like body composition and physical fitness. Moreover, once the phenotype of IR associated with an unfavourable brain metabolic profile has been identified, these criteria will be used to recruit another sample (N=25) that will undergo a 12-week high-intensity interval training intervention, to test whether the peripheral and central metabolic profiles can be improved. Taken together, this would generate vital data and tools for the early detection and treatment of IR.
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