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

Qin Wang, Jari Jokelainen, Juha Auvinen, Katri Puukka, Sirkka Keinänen-Kiukaanniemi, Marjo Riitta Järvelin, Johannes Kettunen, Ville-Petteri Makinen, Mika Ala-Korpela

Research output: Contribution to journalArticle

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.

LanguageEnglish
Article number217
JournalBMC Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - 29 Nov 2019

Keywords

  • Impaired fasting glucose
  • Impaired glucose tolerance
  • Insulin resistance
  • Metabolic profiling
  • Oral glucose tolerance test
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wang, Q., Jokelainen, J., Auvinen, J., Puukka, K., Keinänen-Kiukaanniemi, S., Järvelin, M. R., ... Ala-Korpela, M. (2019). Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: An interventional study. BMC Medicine, 17(1), [217]. https://doi.org/10.1186/s12916-019-1440-4
Wang, Qin ; Jokelainen, Jari ; Auvinen, Juha ; Puukka, Katri ; Keinänen-Kiukaanniemi, Sirkka ; Järvelin, Marjo Riitta ; Kettunen, Johannes ; Makinen, Ville-Petteri ; Ala-Korpela, Mika. / Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals : An interventional study. In: BMC Medicine. 2019 ; Vol. 17, No. 1.
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Wang, Q, Jokelainen, J, Auvinen, J, Puukka, K, Keinänen-Kiukaanniemi, S, Järvelin, MR, Kettunen, J, Makinen, V-P & Ala-Korpela, M 2019, 'Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: An interventional study', BMC Medicine, vol. 17, no. 1, 217. https://doi.org/10.1186/s12916-019-1440-4

Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals : An interventional study. / Wang, Qin; Jokelainen, Jari; Auvinen, Juha; Puukka, Katri; Keinänen-Kiukaanniemi, Sirkka; Järvelin, Marjo Riitta; Kettunen, Johannes; Makinen, Ville-Petteri; Ala-Korpela, Mika.

In: BMC Medicine, Vol. 17, No. 1, 217, 29.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals

T2 - BMC Medicine

AU - Wang, Qin

AU - Jokelainen, Jari

AU - Auvinen, Juha

AU - Puukka, Katri

AU - Keinänen-Kiukaanniemi, Sirkka

AU - Järvelin, Marjo Riitta

AU - Kettunen, Johannes

AU - Makinen, Ville-Petteri

AU - Ala-Korpela, Mika

PY - 2019/11/29

Y1 - 2019/11/29

N2 - 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.

AB - 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.

KW - Impaired fasting glucose

KW - Impaired glucose tolerance

KW - Insulin resistance

KW - Metabolic profiling

KW - Oral glucose tolerance test

KW - Type 2 diabetes

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