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Original Research
Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study
Clemens Wittenbecher, Tamara Štambuk, Olga Kuxhaus, Najda Rudman, Frano Vučković, Jerko Štambuk, Catarina Schiborn, Dario Rahelić, Stefan Dietrich, Olga Gornik, Markus Perola, Heiner Boeing, Matthias B. Schulze, Gordan Lauc
Diabetes Care 2020 Jan; dc191507. https://doi.org/10.2337/dc19-1507
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Abstract

OBJECTIVE Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke).

RESEARCH DESIGN AND METHODS Based on the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort (n = 27,548), we constructed case-cohorts including a random subsample of 2,500 participants and all physician-verified incident cases of type 2 diabetes (n = 820; median follow-up time 6.5 years) and CVD (n = 508; median follow-up time 8.2 years). Information on the relative abundance of 39 N-glycan groups in baseline plasma samples was generated by chromatographic profiling. We selected predictive N-glycans for type 2 diabetes and CVD separately, based on cross-validated machine learning, nonlinear model building, and construction of weighted prediction scores. This workflow for CVD was applied separately in men and women.

RESULTS The N-glycan–based type 2 diabetes score was strongly predictive for diabetes risk in an internal validation cohort (weighted C index 0.83, 95% CI 0.78–0.88), and this finding was externally validated in the Finland Cardiovascular Risk Study (FINRISK) cohort. N-glycans were moderately predictive for CVD incidence (weighted C indices men: 0.66, 95% CI 0.60–0.72; women: 0.64, 95% CI 0.55–0.73). Information on the selected N-glycans improved the accuracy of established and clinically applied risk prediction scores for type 2 diabetes and CVD.

CONCLUSIONS Selected N-glycans improve type 2 diabetes and CVD prediction beyond established risk markers. Plasma protein N-glycan profiling may thus be useful for risk stratification in the context of precisely targeted primary prevention of cardiometabolic diseases.

Footnotes

  • This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc19-1507/-/DC1.

  • Received July 29, 2019.
  • Accepted December 10, 2019.
  • © 2020 by the American Diabetes Association.
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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study
Clemens Wittenbecher, Tamara Štambuk, Olga Kuxhaus, Najda Rudman, Frano Vučković, Jerko Štambuk, Catarina Schiborn, Dario Rahelić, Stefan Dietrich, Olga Gornik, Markus Perola, Heiner Boeing, Matthias B. Schulze, Gordan Lauc
Diabetes Care Jan 2020, dc191507; DOI: 10.2337/dc19-1507

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Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study
Clemens Wittenbecher, Tamara Štambuk, Olga Kuxhaus, Najda Rudman, Frano Vučković, Jerko Štambuk, Catarina Schiborn, Dario Rahelić, Stefan Dietrich, Olga Gornik, Markus Perola, Heiner Boeing, Matthias B. Schulze, Gordan Lauc
Diabetes Care Jan 2020, dc191507; DOI: 10.2337/dc19-1507
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