University of Oulu

Ahola-Olli, A.V., Mustelin, L., Kalimeri, M. et al. Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts. Diabetologia 62, 2298–2309 (2019).

Circulating metabolites and the risk of type 2 diabetes : a prospective study of 11,896 young adults from four Finnish cohorts

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Author: Ahola-Olli, Ari V.1,2,3; Mustelin, Linda3,4,5; Kalimeri, Maria4;
Organizations: 1Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland
2Department of Internal Medicine, Satakunta Central Hospital, Sairaalantie 3, 28500, Pori, Finland
3Institute for Molecular Medicine (FIMM), University of Helsinki, Tukholmankatu 8, 00014, Helsinki, Finland
4Nightingale Health Ltd, Mannerheimintie 164a, 00300, Helsinki, Finland
5Department of Public Health, University of Helsinki, Helsinki, Finland
6Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
7Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
8NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
9Unit of Primary Health Care and Medical Research Center, Oulu University Hospital, Oulu, Finland
10Oulunkaari Primary Health Care Unit, Ii, Finland
11Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
12Nordlab Oulu, Oulu University Hospital, Oulu, Finland
13Department of Clinical Chemistry, University of Oulu, Oulu, Finland
14National Institute for Health and Welfare, Helsinki, Finland
15Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
16Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
17Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
18Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland
19Healthcare and Social Services of Selanne, Pyhasalmi, Finland
20Diabetes Unit, Healthcare Services of City of Oulu, Oulu, Finland
21Estonian Genome Center, University of Tartu, Tartu, Estonia
22Department of Epidemiology and Biostatistics, Medical Research Council–Public Health England Centre for Environment and Health, Imperial College London, London, UK
23Biocenter Oulu, University of Oulu, Oulu, Finland
24Department of Life Sciences, College of Health and Life Sciences, Brunel University, London, UK
25Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK
26Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
27Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
28Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australi
29Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
30Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2020-02-25


Aims/hypothesis: Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults.

Methods: NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up.

Results: Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years).

Conclusions/interpretation: Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.

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Series: Diabetologia
ISSN: 0012-186X
ISSN-E: 1432-0428
ISSN-L: 0012-186X
Volume: 62
Issue: 12
Pages: 2298 - 2309
DOI: 10.1007/s00125-019-05001-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was supported by the Academy of Finland (grant numbers 297338, 307247, 312476 and 312477), the Novo Nordisk Foundation (NNF17OC0026062 and 15998), Strategic Research Funding from the University of Oulu, Finland, the Sigrid Juselius Foundation, the Finnish Foundation for Cardiovascular Research, the UK Medical Research Council (MRC) via the MRC University of Bristol Integrative Epidemiology Unit (MC_UU_12013/1 and MC_UU_12013/5), and the National Health and Medical Research Council of Australia (APP1158958). The Cardiovascular Risk in YFS has been financially supported by: the Academy of Finland (286284, 134309, 126925, 121584, 124282, 129378, 117787 and 41071); the Social Insurance Institution of Finland; the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (X51001); Tampere University Hospital Supporting Foundation, Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (755320); and European Research Council (742927). NFBC 1966 received financial support from: Academy of Finland (104781, 120315, 129269, 1114194, 24300796, 85547 and 285547); Biocenter Oulu (75617); University of Oulu Grant (65354); Oulu University Hospital (2/97, 8/97); Ministry of Health and Social Affairs (23/251/97, 160/97, 190/97); National Institute for Health and Welfare, Helsinki (54121); Regional Institute of Occupational Health, Oulu (50621, 54231); ERDF European Regional Development Fund Grant (539/2010 A31592); the EU H2020-PHC-2014 DynaHEALTH action (633595); and EU H2020-HCO-2004 iHEALTH Action.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(643774) iHealth-T2D - Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes
Academy of Finland Grant Number: 297338
Detailed Information: 297338 (Academy of Finland Funding decision)
307247 (Academy of Finland Funding decision)
114194 (Academy of Finland Funding decision)
285547 (Academy of Finland Funding decision)
129269 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided 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.