Inflammatory protein signatures as predictors of insulin resistance and cognitive function: a one-year longitudinal study in the

Background: Large-scale studies have demonstrated a temporal relationship between insulin resistance (IR) and peripheral inflammation, with emerging evidence also suggesting a link to cognitive decline. However, most of the existing research has focused on individual inflammatory proteins, while the role of inflammatory protein signatures associated with IR and cognition remains unexplored. Aim: In this study, we investigated a) whether specific inflammatory protein signatures are associated with IR; b) whether baseline inflammatory protein signatures predict changes in Homeostatic Model Assessment for IR (HOMA-IR) after one-year follow-up, and c) whether baseline IR and/or specific inflammatory signatures predicted cognitive performance at follow-up. Methods: In 110 healthy adults from the Results: Next to the cumulative score, two inflammatory protein signatures were identified, related to 1) cytokine signalling, 2) immune cell migration. At baseline, the cytokine signalling signature correlated with HOMA-IR; together with BMI, CCL7 and CCL4 were consistently selected in >99% of models, with the penalised regression signature explaining 38,2% of HOMA-IR variance (mean out of sample R Conclusion: Our findings contribute to a better understanding of the specific inflammatory proteins involved in the temporal association between IR and inflammation: while CRP predicts HOMA-IR, the more specific signature linked to cytokine-signalling did not; instead, a high HOMA-IR predicted higher inflammation related to immune cell migration. We discovered proteins including CCL4, CCL7 and IL-10 associated with HOMA-IR, which should be explored further.