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 Muka & 3 others Carla J. H. van der Kallen, Giel Nijpels, Marleen M. J. van Greevenbroek

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6). 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
JournalThe Journal of clinical endocrinology and metabolism
Volume103
Issue number12
DOIs
Publication statusPublished - 2018

Cite this

't Hart, Leen M. ; Vogelzangs, Nicole ; Mook-Kanamori, Dennis O. ; Brahimaj, Adela ; Nano, Jana ; van der Heijden, Amber A. W. A. ; Willems van Dijk, Ko ; Slieker, Roderick C. ; Steyerberg, Ewout W. ; Ikram, M. Arfan ; Beekman, Marian ; Boomsma, Dorret I. ; van Duijn, Cornelia M. ; Slagboom, P. Eline ; Stehouwer, Coen D. A. ; Schalkwijk, Casper G. ; Arts, Ilja C. W. ; Dekker, Jacqueline M. ; Dehghan, Abbas ; Muka, Taulant ; van der Kallen, Carla J. H. ; Nijpels, Giel ; van Greevenbroek, Marleen M. J. / Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes. In: The Journal of clinical endocrinology and metabolism. 2018 ; Vol. 103, No. 12. pp. 4569-4579.
@article{76d26524d957485a96deca81821832a4,
title = "Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes",
abstract = "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 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95{\%} CI, 0.42 to 0.71; P = 4.5 × 10-6). 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.",
author = "{'t Hart}, {Leen M.} and Nicole Vogelzangs and Mook-Kanamori, {Dennis O.} and Adela Brahimaj and Jana Nano and {van der Heijden}, {Amber A. W. A.} and {Willems van Dijk}, Ko and Slieker, {Roderick C.} and Steyerberg, {Ewout W.} and Ikram, {M. Arfan} and Marian Beekman and Boomsma, {Dorret I.} and {van Duijn}, {Cornelia M.} and Slagboom, {P. Eline} and Stehouwer, {Coen D. A.} and Schalkwijk, {Casper G.} and Arts, {Ilja C. W.} and Dekker, {Jacqueline M.} and Abbas Dehghan and Taulant Muka and {van der Kallen}, {Carla J. H.} and Giel Nijpels and {van Greevenbroek}, {Marleen M. J.}",
year = "2018",
doi = "10.1210/jc.2018-01165",
language = "English",
volume = "103",
pages = "4569--4579",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "12",

}

't Hart, LM, Vogelzangs, N, Mook-Kanamori, DO, Brahimaj, A, Nano, J, van der Heijden, AAWA, Willems van Dijk, K, Slieker, RC, Steyerberg, EW, Ikram, MA, Beekman, M, Boomsma, DI, van Duijn, CM, Slagboom, PE, Stehouwer, CDA, Schalkwijk, CG, Arts, ICW, Dekker, JM, Dehghan, A, Muka, T, van der Kallen, CJH, Nijpels, G & van Greevenbroek, MMJ 2018, 'Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes' The Journal of clinical endocrinology and metabolism, vol. 103, no. 12, pp. 4569-4579. https://doi.org/10.1210/jc.2018-01165

Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes. / 't Hart, Leen M.; Vogelzangs, Nicole; Mook-Kanamori, Dennis O.; Brahimaj, Adela; Nano, Jana; van der Heijden, Amber A. W. A.; Willems van Dijk, Ko; Slieker, Roderick C.; Steyerberg, Ewout W.; Ikram, M. Arfan; Beekman, Marian; Boomsma, Dorret I.; van Duijn, Cornelia M.; Slagboom, P. Eline; Stehouwer, Coen D. A.; Schalkwijk, Casper G.; Arts, Ilja C. W.; Dekker, Jacqueline M.; Dehghan, Abbas; Muka, Taulant; van der Kallen, Carla J. H.; Nijpels, Giel; van Greevenbroek, Marleen M. J.

In: The Journal of clinical endocrinology and metabolism, Vol. 103, No. 12, 2018, p. 4569-4579.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes

AU - 't Hart, Leen M.

AU - Vogelzangs, Nicole

AU - Mook-Kanamori, Dennis O.

AU - Brahimaj, Adela

AU - Nano, Jana

AU - van der Heijden, Amber A. W. A.

AU - Willems van Dijk, Ko

AU - Slieker, Roderick C.

AU - Steyerberg, Ewout W.

AU - Ikram, M. Arfan

AU - Beekman, Marian

AU - Boomsma, Dorret I.

AU - van Duijn, Cornelia M.

AU - Slagboom, P. Eline

AU - Stehouwer, Coen D. A.

AU - Schalkwijk, Casper G.

AU - Arts, Ilja C. W.

AU - Dekker, Jacqueline M.

AU - Dehghan, Abbas

AU - Muka, Taulant

AU - van der Kallen, Carla J. H.

AU - Nijpels, Giel

AU - van Greevenbroek, Marleen M. J.

PY - 2018

Y1 - 2018

N2 - 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 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6). 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.

AB - 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 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6). 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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30113659

U2 - 10.1210/jc.2018-01165

DO - 10.1210/jc.2018-01165

M3 - Article

VL - 103

SP - 4569

EP - 4579

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -