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. 2022 Sep 22;28(11):2309–2320. doi: 10.1038/s41591-022-01980-3

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a–c, Calibration curves for CPH models, including baseline parameter sets Age+Sex, ASCVD and PANEL, as well as their combinations with the metabolomic state (Age+Sex + MET) for the endpoints T2D (a), dementia (b) and heart failure (c). d–f, Endpoint-specific net benefit curves standardized by endpoint prevalence, where horizontal solid gray lines indicate ‘treat none’ and vertical solid gray lines indicate ‘treat all’; T2D (d), dementia (e) and heart failure (f). The standardized net benefits of sets Age+Sex, ASCVD and PANEL are compared with Age+Sex + MET and additional non-laboratory predictors of PANEL (PANELnoLaboratory). Green and blue color-filled areas indicate the added benefit of the combination of the metabolomic state and Age+Sex and PANELnoLaboratory, respectively. g–i, Standardized net benefit curves comparing the performance of PANEL + MET against baselines Age+Sex, ASCVD and PANEL; T2D (g), dementia (h) and heart failure (i). Decision curves were derived from n = 111,745 (T2D), n = 117,245 (dementia) and n = 113,636 (heart failure) individuals.