University of Oulu

Wang, Q., Jokelainen, J., Auvinen, J. et al. Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study. BMC Med 17, 217 (2019).

Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals : an interventional study

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Author: Wang, Qin1,2,3,4; Jokelainen, Jari3,5; Auvinen, Juha3,6;
Organizations: 1Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
2Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
3Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
4Biocenter Oulu, University of Oulu, Oulu, Finland
5Unit of Primary Care and Medical Research Center, Oulu University Hospital, Oulu, Finland
6Oulunkaari Health Center, Ii, Finland
7NordLab Oulu, Oulu University Hospital and Department of Clinical Chemistry, University of Oulu, Oulu, Finland
8Health and Wellfare Center, Oulu, Finland
9Healthcare and Social Services of Selänne, Pyhäjärvi, Finland
10Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
11Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, Middlesex, UK
12National Institute for Health and Welfare, Helsinki, Finland
13Computational and Systems Biology Program, Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia
14Hopwood Centre for Neurobiology, Lifelong Health Theme, SAHMRI, Adelaide, Australia
15MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
16Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
17NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
18Department 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, VIC, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
Persistent link:
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-03-25


Background: Insulin resistance (IR) is predictive for type 2 diabetes and associated with various metabolic abnormalities in fasting conditions. However, limited data are available on how IR affects metabolic responses in a non-fasting setting, yet this is the state people are mostly exposed to during waking hours in the modern society. Here, we aim to comprehensively characterise the metabolic changes in response to an oral glucose test (OGTT) and assess the associations of these changes with IR.

Methods: Blood samples were obtained at 0 (fasting baseline, right before glucose ingestion), 30, 60, and 120 min during the OGTT. Seventy-eight metabolic measures were analysed at each time point for a discovery cohort of 4745 middle-aged Finnish individuals and a replication cohort of 595 senior Finnish participants. We assessed the metabolic changes in response to glucose ingestion (percentage change in relative to fasting baseline) across the four time points and further compared the response profile between five groups with different levels of IR and glucose intolerance. Further, the differences were tested for covariate adjustment, including gender, body mass index, systolic blood pressure, fasting, and 2-h glucose levels. The groups were defined as insulin sensitive with normal glucose (IS-NGT), insulin resistant with normal glucose (IR-NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and new diabetes (NDM). IS-NGT and IR-NGT were defined as the first and fourth quartile of fasting insulin in NGT individuals.

Results: Glucose ingestion induced multiple metabolic responses, including increased glycolysis intermediates and decreased branched-chain amino acids, ketone bodies, glycerol, and triglycerides. The IR-NGT subgroup showed smaller responses for these measures (mean + 23%, interquartile 9–34% at 120 min) compared to IS-NGT (34%, 23–44%, P < 0.0006 for difference, corrected for multiple testing). Notably, the three groups with glucose abnormality (IFG, IGT, and NDM) showed similar metabolic dysregulations as those of IR-NGT. The difference between the IS-NGT and the other subgroups was largely explained by fasting insulin, but not fasting or 2 h glucose. The findings were consistent after covariate adjustment and between the discovery and replication cohort.

Conclusions: Insulin-resistant non-diabetic individuals are exposed to a similar adverse postprandial metabolic milieu, and analogous cardiometabolic risk, as those with type 2 diabetes. The wide range of metabolic abnormalities associated with IR highlights the necessity of diabetes diagnostics and clinical care beyond glucose management.

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Series: BMC medicine
ISSN: 1741-7015
ISSN-E: 1741-7015
ISSN-L: 1741-7015
Volume: 17
Issue: 1
Article number: 217
DOI: 10.1186/s12916-019-1440-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work is supported by grants from the National Health and Medical Research Council of Australia (APP1158958); the UK Medical Research Council (MC_UU_12013/1); the Academy of Finland (grant numbers 297338 and 307247); the Novo Nordisk foundation (NNF17OC0027034 and NNF17OC0026062); the Health and Wellfare Center, City of Oulu, Finland; the Sigrid Juselius Foundation; the ERDF European Regional Development Fund (grant no. 539/2010 A31592); and the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 633595; DynaHEALTH). The Baker Institute is supported in part by the Victorian Government’s Operational Infrastructure Support Program.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
Academy of Finland Grant Number: 297338
Detailed Information: 297338 (Academy of Finland Funding decision)
307247 (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. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.