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Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations.

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Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations. Metabolism: clinical and experimental Kho, P. F., Wary, N., Zanetti, D., Abbasi, F., Knowles, J. W., Panyard, D. J., Watson, K. T., Stell, L., Lazzeroni, L. C., Gustafsson, S., Lind, L., Petrie, J. R., Assimes, T. L. 2025: 156263

Abstract

We previously reported significant correlations between a direct measure of insulin sensitivity (IS) and blood levels of proteins measured using the Proximity Extension Assay (PEA) in two European cohorts. However, protein correlations with IS within non-European populations, in response to short-term interventions that improve IS, and any causal associations with IS have not yet been established.We measured 1470 proteins using the PEA in the plasma of 1015 ÌÇÐÄ´«Ã½ participants at Stanford University who underwent one or more direct measures of IS. Association analyses were carried out with multivariable linear regression within and across Stanford subgroups and within each of the two European cohorts. Association statistics were also meta-analyzed after transformation and harmonization of the two direct measures of IS. Lastly, we performed genome-wide association studies of IS and used genetic instruments of plasma proteins from the UK Biobank to identify candidate causal proteins for IS through Mendelian Randomization (MR) analysis.In age and sex adjusted model, 810 proteins were associated with baseline IS among 652 self-reported European participants in the Stanford cohort at a false discovery rate (FDR)?

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