Postprandial metabolite profiles associated with type 2 diabetes clearly stratify individuals with impaired fasting glucose

Ruifang Li-Gao; Renée de Mutsert; Patrick C N Rensen; Jan Bert van Klinken; Cornelia Prehn; Jerzy Adamski; Astrid van Hylckama Vlieg; Martin den Heijer; Saskia le Cessie; Frits R Rosendaal; Ko Willems van Dijk; Dennis O Mook-Kanamori

doi:10.1007/s11306-017-1307-7

Postprandial metabolite profiles associated with type 2 diabetes clearly stratify individuals with impaired fasting glucose

Metabolomics. 2018;14(1):13. doi: 10.1007/s11306-017-1307-7. Epub 2017 Dec 12.

Authors

Ruifang Li-Gao¹, Renée de Mutsert², Patrick C N Rensen^{3

4}, Jan Bert van Klinken^{4

5}, Cornelia Prehn⁶, Jerzy Adamski^{6

7

8}, Astrid van Hylckama Vlieg², Martin den Heijer², Saskia le Cessie^{2

9}, Frits R Rosendaal², Ko Willems van Dijk^{3

4

5}, Dennis O Mook-Kanamori^{2

10}

Affiliations

¹ Department of Clinical Epidemiology, Leiden University Medical Center, P. O. Box 9600, 2300 RC, Leiden, The Netherlands. r.li@lumc.nl.
² Department of Clinical Epidemiology, Leiden University Medical Center, P. O. Box 9600, 2300 RC, Leiden, The Netherlands.
³ Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
⁷ German Center for Diabetes Research, Neuherberg, Germany.
⁸ Lehrstul für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
⁹ Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
¹⁰ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

Introduction: Fasting metabolite profiles have been shown to distinguish type 2 diabetes (T2D) patients from normal glucose tolerance (NGT) individuals.

Objectives: We investigated whether, besides fasting metabolite profiles, postprandial metabolite profiles associated with T2D can stratify individuals with impaired fasting glucose (IFG) by their similarities to T2D.

Methods: Three groups of individuals (age 45-65 years) without any history of IFG or T2D were selected from the Netherlands Epidemiology of Obesity study and stratified by baseline fasting glucose concentrations (NGT (n = 176), IFG (n = 186), T2D (n = 171)). 163 metabolites were measured under fasting and postprandial states (150 min after a meal challenge). Metabolite profiles specific for a high risk of T2D were identified by LASSO regression for fasting and postprandial states. The selected profiles were utilised to stratify IFG group into high (T2D probability ≥ 0.7) and low (T2D probability ≤ 0.5) risk subgroups. The stratification performances were compared with clinically relevant metabolic traits.

Results: Two metabolite profiles specific for T2D (n_fasting = 12 metabolites, n_postprandial = 4 metabolites) were identified, with all four postprandial metabolites also being identified in the fasting state. Stratified by the postprandial profile, the high-risk subgroup of IFG individuals (n = 72) showed similar glucose concentrations to the low-risk subgroup (n = 57), yet a higher BMI (difference: 3.3 kg/m² (95% CI 1.7-5.0)) and postprandial insulin concentrations (21.5 mU/L (95% CI 1.8-41.2)).

Conclusion: Postprandial metabolites identified T2D patients as good as fasting metabolites and exhibited enhanced signals for IFG stratification, which offers a proof of concept that metabolomics research should not focus on the fasting state alone.

Keywords: Fasting; Impaired fasting glucose; LASSO regularised logistic regression; Metabolomics; Postprandial; Risk stratification; Type 2 diabetes.