Naslov
Plasma protein N-glycans as emerging biomarkers of cardiometabolic risk

Autori
Pavić, Tamara ; Wittenbecher, Clemens ; Selak, Najda ; Kuxhaus, Olga ; Vučković, Frano ; Štambuk, Jerko ; Schiborn, Catarina ; Dietrich, Stefan ; Gornik, Olga ; Boeing, Heiner ; Schulze, Matthias ; Lauc, Gordan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
13th Jenner Glycobiology and Medicine Symposium book of abstracts / - , 2019, 42-42

Skup
13th Jenner Glycobiology and Medicine Symposium

Mjesto i datum
Cambridge (MA), Sjedinjene Američke Države, 04.05.2019. - 07.05.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
plasma N-glycome, type 2 diabetes, cardiovascular diseases

Sažetak
Cardiometabolic diseases represent a major clinical burden, rendering the recognition of at-risk individuals extremely important. In this regard, N-glycans offer a novel perspective. Herein, we evaluated the predictive value of plasma N-glycome for incident type 2 diabetes (T2D) and cardiovascular diseases (CVD), in baseline- healthy participants from EPIC-Potsdam cohort. Endpoint-specific case-cohorts within EPIC- Potsdam consisted of 2, 813 participants including 743 incident cases for T2D and 2, 558 participants including 418 incident cases for CVD. Cross-validated machine learning and non- linear modelling techniques were used to select robust disease predictors and construct weighted prediction scores from all age- adjusted N- glycans. Type 2 diabetes risk score (GST2D) was constructed using six N-glycan residuals, giving a hazard ratio (HR) of 3.73 (95 % CI 3.00-4.63) per standard deviation (SD). Moreover, GST2D successfully predicted incident T2D in internal validation cohort with C-Index of 0.83 (95 % CI 0.78-0.88). Higher GST2D was also significantly associated with increased CVD risk in men (HR per SD 1.23, 95% CI 1.09-1.40), but not in women. Therefore, sex-stratified CVD glycan scores (GSCVD) were built. For men, GSCVD represented a weighted combination of GST2D and two additional glycan residuals, showing a HR of 1.89 (95 % CI 1.57- 2.27) and moderate predictive performance for incident CVD (C-Index 0.66, 95% CI 0.60-0.72). For women, only one N-glycan peak (GP5) was independently associated with incident CVD (HR per SD 0.70, 95% CI 0.57-0.86), with moderate prediction value (C-index 0.64, 95% CI 0.55- 0.73). Moreover, inclusion of the aforementioned glycan predictors improved the accuracy of established risk prediction models for both T2D and CVD. Taken altogether, this research showed that plasma N-glycome profiling generates highly informative predictors of incident cardiometabolic diseases. Glycan-based risk scores have the potential to complement the toolbox of novel biomarkers that are considered for risk stratification in precision prevention approaches.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti, Kliničke medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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