GlycA, a marker of acute phase glycoproteins, and the risk of incident type 2 diabetes mellitus: PREVEND study

Connelly, Margery A.; Gruppen, Eke G.; Wolak-Dinsmore, Justyna; Matyus, Steven P.; Riphagen, Ineke J.; Shalaurova, Irina; Bakker, Stephan J. L.; Otvos, James D.; Dullaart, Robin

doi:10.1016/j.cca.2015.11.001

Cited by 81 publications

(85 citation statements)

References 40 publications

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“…One notable exception was GlycA, a complex NMR signal of N-acetyl methyl group protons of mobile glycan residues of glycoproteins [44], which was markedly higher in obese GDM women at both time points. Plasma glycoproteins are predominantly acute-phase proteins and GlycA is associated with conditions associated with an inflammatory response, including type 2 diabetes [45]. This novel observation suggests that GlycA might also be a useful marker for GDM.…”

Section: Discussionmentioning

confidence: 87%

Metabolic profiling of gestational diabetes in obese women during pregnancy

et al. 2017

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Aims/hypothesis Antenatal obesity and associated gestational diabetes (GDM) are increasing worldwide. While pre-existing insulin resistance is implicated in GDM in obese women, the responsible metabolic pathways remain poorly described. Our aim was to compare metabolic profiles in blood of obese pregnant women with and without GDM 10 weeks prior to and at the time of diagnosis by OGTT. Methods We investigated 646 women, of whom 198 developed GDM, in this prospective cohort study, a secondary analysis of UK Pregnancies Better Eating and Activity Trial (UPBEAT), a multicentre randomised controlled trial of a complex lifestyle intervention in obese pregnant women. Multivariate regression analyses adjusted for multiple testing, and accounting for appropriate confounders including study intervention, were performed to compare obese women with GDM with obese non-GDM women. We measured 163 analytes in serum, plasma or whole blood, including 147 from a targeted NMR metabolome, at time point 1 (mean gestational age 17 weeks 0 days) and time point 2 (mean gestational age 27 weeks 5 days, at time of OGTT) and compared them between groups. Results Multiple significant differences were observed in women who developed GDM compared with women without GDM (false discovery rate corrected p values <0.05). Most were evident prior to diagnosis. Women with GDM demonstrated raised lipids and lipoprotein constituents in VLDL subclasses, greater triacylglycerol enrichment across lipoprotein particles, higher branched-chain and aromatic amino acids and different fatty acid, ketone body, adipokine, liver and inflammatory marker profiles compared with those without GDM. Conclusions/interpretation Among obese pregnant women, differences in metabolic profile, including exaggerated dyslipidaemia, are evident at least 10 weeks prior to a diagnosis of GDM in the late second trimester.

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Section: Discussionmentioning

confidence: 87%

Metabolic profiling of gestational diabetes in obese women during pregnancy

et al. 2017

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“…In addition, GlycA was shown to be associated with future major adverse coronary events and mortality in two different cohorts of patients undergoing coronary angiography [1,52,74]. Of note, the association of GlycA with incident T2DM remained statistically significant both in the WHS and PREVEND even after adjusting for traditional diabetes risk factors and hsCRP [43,75,76]. Thus evidence is accumulating that GlycA may be a useful biomarker for the assessment of CVD and T2DM risk.…”

Section: Glycoprotein Assays and Cardiometabolic Disordersmentioning

confidence: 91%

“…Proton ( 1 H) NMR, another high-throughput technological platform that is able to quantify inflammatory glycoproteins based on their glycans, was recently introduced to the clinical laboratory setting [38][39][40][41][42][43]. Although it is not possible to identify and quantify individual proteins via NMR, it is possible to measure subsets of glycoproteins based on their shared glycan moieties [38,39,42].…”

Section: Assays Of Glycoproteins In Biological Fluids and Developmentmentioning

confidence: 98%

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Connelly

Gruppen

Otvos

et al. 2016

Clinica Chimica Acta

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The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity.

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“…GlycA is regarded as a marker of low-grade systemic inflammation (16)(17)(18). Evidence has been accumulating that GlycA may predict CVD as well as incident type 2 diabetes mellitus (T2DM) (17,(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

GlycA, a novel proinflammatory glycoprotein biomarker, and high-sensitivity C-reactive protein are inversely associated with sodium intake after controlling for adiposity: the Prevention of Renal and Vascular End-Stage Disease study

Gruppen

Connelly

Vart

et al. 2016

The American Journal of Clinical Nutrition

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GlycA, a marker of acute phase glycoproteins, and the risk of incident type 2 diabetes mellitus: PREVEND study

Abstract: The performance characteristics of the GlycA test reveal that it is suitable for clinical applications, including assessment of the risk of future T2DM.

Cited by 81 publications

References 40 publications

Metabolic profiling of gestational diabetes in obese women during pregnancy

Metabolic profiling of gestational diabetes in obese women during pregnancy

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

GlycA, a novel proinflammatory glycoprotein biomarker, and high-sensitivity C-reactive protein are inversely associated with sodium intake after controlling for adiposity: the Prevention of Renal and Vascular End-Stage Disease study

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