University of Oulu

Mulugeta, A., Hyppönen, E., Ala-Korpela, M. et al. Cross-sectional metabolic subgroups and 10-year follow-up of cardiometabolic multimorbidity in the UK Biobank. Sci Rep 12, 8590 (2022).

Cross‑sectional metabolic subgroups and 10‑year follow‑up of cardiometabolic multimorbidity in the UK Biobank

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Author: Mulugeta, Anwar1; Hyppönen, Elina1; Ala‑Korpela, Mika2,3,4;
Organizations: 1Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia
2Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
3Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
4NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
5Computational and Systems Biology Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.7 MB)
Persistent link:
Language: English
Published: Springer Nature, 2022
Publish Date: 2023-05-05


We assigned 329,908 UK Biobank participants into six subgroups based on a self‑organizing map of 51 biochemical measures (blinded for clinical outcomes). The subgroup with the most favorable metabolic traits was chosen as the reference. Hazard ratios (HR) for incident disease were modeled by Cox regression. Enrichment ratios (ER) of incident multi‑morbidity versus randomly expected co‑occurrence were evaluated by permutation tests; ER is like HR but captures co‑occurrence rather than event frequency. The subgroup with high urinary excretion without kidney stress (HR = 1.24) and the subgroup with the highest apolipoprotein B and blood pressure (HR = 1.52) were associated with ischemic heart disease (IHD). The subgroup with kidney stress, high adiposity and inflammation was associated with IHD (HR = 2.11), cancer (HR = 1.29), dementia (HR = 1.70) and mortality (HR = 2.12). The subgroup with high liver enzymes and triglycerides was at risk of diabetes (HR = 15.6). Multimorbidity was enriched in metabolically favorable subgroups (3.4 ≤ ER ≤ 4.0) despite lower disease burden overall; the relative risk of co‑occurring disease was higher in the absence of obvious metabolic dysfunction. These results provide synergistic insight into metabolic health and its associations with cardiovascular disease in a large population sample.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 12
Article number: 8590
DOI: 10.1038/s41598-022-12198-1
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
3121 General medicine, internal medicine and other clinical medicine
Dataset Reference: The UK Biobank data are publicly available ( This study was designed and implemented according to project plan #29890.
Copyright information: © The Author(s) 2022. 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons. org/ licenses/ by/4. 0/.