Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts – published 17/06/2023

Daniela Zanetti, Laurel Stell, Stefan Gustafsson, Fahim Abbasi, Philip S. Tsao, Joshua W. Knowles, RISC Investigators, Björn Zethelius, Johan Ärnlöv, Beverley Balkau, Mark Walker, Laura C. Lazzeroni, Lars Lind, John R. Petrie, Themistocles L. Assimes

The euglycaemic−hyperinsulinaemic clamp (EIC) is a reference standard for directly assessing insulin sensitivity but is invasive and time-consuming. In this issue, Zanetti et al (https://doi.org/10.1007/s00125-023-05946-z) assess the incremental value of high-throughput plasma proteomic profiling, using the proximity extension assay, in developing signatures that correlate with the M value derived from the EIC. The authors use two cohorts, the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) and the Uppsala Longitudinal Study of Adult Men (ULSAM), to show that plasma proteomic signatures of up to 67 proteins substantially improve the cross-sectional estimation of the M value over routinely available clinical variables. A smaller subset of proteins afforded much of this improvement, especially when considering predictive models applied across both cohorts. IGF-binding protein 2 was the single most consistently selected protein across all analyses and models. Zanetti and colleagues state that their approach provides opportunities to improve the identification of individuals at risk of adverse health consequences related to insulin resistance.

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