Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/122730
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Type: Journal article
Title: Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study
Author: Wang, Q.
Jokelainen, J.
Auvinen, J.
Puukka, K.
Keinänen-Kiukaanniemi, S.
Järvelin, M.R.
Kettunen, J.
Mäkinen, V.P.
Ala-Korpela, M.
Citation: BMC Medicine, 2019; 17(1):1-12
Publisher: BMC
Issue Date: 2019
ISSN: 1741-7015
1741-7015
Statement of
Responsibility: 
Qin Wang, Jari Jokelainen, Juha Auvinen, Katri Puukka, Sirkka Keinänen-Kiukaanniemi ... Ville-Petteri Mäkinen ... et al.
Abstract: 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.
Keywords: Humans
Diabetes Mellitus, Type 2
Insulin Resistance
Insulin
Glucose
Blood Glucose
Triglycerides
Glucose Tolerance Test
Body Mass Index
Fasting
Administration, Oral
Cohort Studies
Follow-Up Studies
Prospective Studies
Adolescent
Adult
Middle Aged
Child
Child, Preschool
Infant
Infant, Newborn
Female
Male
Insulin Secretion
Rights: © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), 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 (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI: 10.1186/s12916-019-1440-4
Grant ID: http://purl.org/au-research/grants/nhmrc/1158958
Appears in Collections:Aurora harvest 8
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