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Plasma N-glycome shows continuous deterioration as the diagnosis of insulin resistance approaches.

  • Cvetko, Ana1
  • Mangino, Massimo2, 3
  • Tijardović, Marko1
  • Kifer, Domagoj1
  • Falchi, Mario2
  • Keser, Toma1
  • Perola, Markus4
  • Spector, Tim D2
  • Lauc, Gordan1, 5
  • Menni, Cristina2
  • Gornik, Olga6
  • 1 University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia. , (Croatia)
  • 2 Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • 3 NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
  • 4 National Institute for Health and Welfare, Helsinki, Finland. , (Finland)
  • 5 Genos Glycoscience Research Laboratory, Zagreb, Croatia. , (Croatia)
  • 6 University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia [email protected] , (Croatia)
Published Article
BMJ Open Diabetes Research & Care
Publication Date
Sep 01, 2021
DOI: 10.1136/bmjdrc-2021-002263
PMID: 34518155


Prediction of type 2 diabetes mellitus (T2DM) and its preceding factors, such as insulin resistance (IR), is of great importance as it may allow delay or prevention of onset of the disease. Plasma protein N-glycome has emerged as a promising predictive biomarker. In a prospective longitudinal study, we included patients with a first diagnosis of impaired glucose metabolism (IR or T2DM) to investigate the N-glycosylation's predictive value years before diabetes development. Plasma protein N-glycome was profiled by hydrophilic interaction ultra-performance liquid chromatography in 534 TwinsUK participants free from disease at baseline. This included 89 participants with incident diagnosis of IR or T2DM during the follow-up period (7.14±3.04 years) whose last sample prior to diagnosis was compared using general linear regression with 445 age-matched unrelated controls. Findings were replicated in an independent cohort. Changes in N-glycome have also been presented in connection with time to diagnosis. Eight groups of plasma N-glycans were different between incident IR or T2DM cases and controls (p<0.05) after adjusting for multiple testing using Benjamini-Hochberg correction. These differences were noticeable up to 10 years prior to diagnosis and are changing continuously as becoming more expressed toward the diagnosis. The prediction model was built using significant glycan traits, displaying a discriminative performance with an area under the receiver operating characteristic curve of 0.77. In addition to previous studies, we showed the diagnostic potential of plasma N-glycome in the prediction of both IR and T2DM development years before the clinical manifestation and indicated the continuous deterioration of N-glycome toward the diagnosis. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

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