Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes

Leen M. 't Hart*, Nicole Vogelzangs, Dennis O. Mook-Kanamori, Adela Brahimaj, Jana Nano, Amber A. W. A. van der Heijden, Ko Willems van Dijk, Roderick C. Slieker, Ewout W. Steyerberg, M. Arfan Ikram, Marian Beekman, Dorret I. Boomsma, Cornelia M. van Duijn, P. Eline Slagboom, Coen D. A. Stehouwer, Casper G. Schalkwijk, Ilja C. W. Arts, Jacqueline M. Dekker, Abbas Dehghan, Taulant MukaCarla J. H. van der Kallen, Giel Nijpels, Marleen M. J. van Greevenbroek

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Objective: We studied whether blood metabolomic measures in people with type 2 diabetes (T2D) are associated with insufficient glycemic control and whether this association is influenced differentially by various diabetes drugs. We then tested whether the same metabolomic profiles were associated with the initiation of insulin therapy.

Methods: A total of 162 metabolomic measures were analyzed using a nuclear magnetic resonance-based method in people with T2D from four cohort studies (n = 2641) and one replication cohort (n = 395). Linear and logistic regression analyses with adjustment for potential confounders, followed by meta-analyses, were performed to analyze associations with hemoglobin A1c levels, six glucose-lowering drug categories, and insulin initiation during a 7-year follow-up period (n = 698).

Results: After Bonferroni correction, 26 measures were associated with insufficient glycemic control (HbA1c >53 mmol/mol). The strongest association was with glutamine (OR, 0.66; 95% CI, 0.61 to 0.73; P = 7.6 x 10(-19)). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P

Conclusion: Blood metabolomic measures were associated with present and future glycemic control and might thus provide relevant cues to identify those at increased risk of treatment failure.

Original languageEnglish
Pages (from-to)4569-4579
Number of pages11
JournalJournal of Clinical Endocrinology & Metabolism
Issue number12
Publication statusPublished - Dec 2018


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