Blood metabolomic measures associate with present and future glycemic control in type 2 diabetes.

TitleBlood metabolomic measures associate with present and future glycemic control in type 2 diabetes.
Publication TypeJournal Article
Year of Publication2018
AuthorsHart LM 't, Vogelzangs N, Mook-Kanamori DO, Brahimaj A, Nano J, van der Heijden AAWA, van Dijk KWillems, Slieker RC, Steyerberg E, Ikram AM, Beekman M, Boomsma DI, van Duijn CM, Slagboom EP, Stehouwer CDA, Schalkwijk CG, Arts ICW, Dekker JM, Dehghan A, Muka T, van der Kallen CJH, Nijpels G, van Greevenbroek M
JournalJ Clin Endocrinol Metab
Date Published2018 Aug 02
ISSN1945-7197
Abstract

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

Methods: One-hundred-and-sixty-two metabolomic measures were analyzed using a NMR-based method in people with type 2 diabetes from four cohort studies (n=2641) and one replication cohort (n=395). Linear and logistic regression with adjustment for potential confounders followed by meta-analyses was done to analyze associations with HbA1c levels, six glucose-lowering drug categories, and insulin initiation during seven year follow-up (n=698).

Results: After Bonferroni correction twenty-six measures were associated with insufficient glycemic control (HbA1c>53 mmol/mol). The strongest association was with glutamine (OR=0.66 (95%CI 0.61;0.73), P=7.6x10-19). In addition when compared to treatment naïve patients thirty-one metabolomic measures were associated with glucose-lowering drugs use (representing various metabolite categories, all P≤3.1x10-4). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (ApoA1 and M-HDL subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. With the strongest association observed for M-HDL-CE (OR=0.54 (95%CI=0.42;0.71); P=4.5x10-6).

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

DOI10.1210/jc.2018-01165
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID30113659