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Plasma protein N-glycome composition associates with postprandial lipaemic response

Title: Plasma protein N-glycome composition associates with postprandial lipaemic response
Authors: Louca P.; Stambuk T.; Frkatovic-Hodzic A.; Nogal A.; Mangino M.; Berry S. E.; Deris H.; Hadjigeorgiou G.; Wolf J.; Vinicki M.; Franks P. W.; Valdes A. M.; Spector T. D.; Lauc G.; Menni C.
Contributors: P. Louca; T. Stambuk; A. Frkatovic-Hodzic; A. Nogal; M. Mangino; S.E. Berry; H. Deri; G. Hadjigeorgiou; J. Wolf; M. Vinicki; P.W. Frank; A.M. Valde; T.D. Spector; G. Lauc; C. Menni
Publisher Information: BioMed Central Ltd
Publication Year: 2023
Collection: The University of Milan: Archivio Istituzionale della Ricerca (AIR)
Subject Terms: Metabolic response; Plasma N-glycome; Postprandial glycaemia; Postprandial lipaemia; Protein glycosylation; Settore MED/01 - Statistica Medica
Description: Background: A dysregulated postprandial metabolic response is a risk factor for chronic diseases, including type 2 diabetes mellitus (T2DM). The plasma protein N-glycome is implicated in both lipid metabolism and T2DM risk. Hence, we first investigate the relationship between the N-glycome and postprandial metabolism and then explore the mediatory role of the plasma N-glycome in the relationship between postprandial lipaemia and T2DM. Methods: We included 995 individuals from the ZOE-PREDICT 1 study with plasma N-glycans measured by ultra-performance liquid chromatography at fasting and triglyceride, insulin, and glucose levels measured at fasting and following a mixed-meal challenge. Linear mixed models were used to investigate the associations between plasma protein N-glycosylation and metabolic response (fasting, postprandial (C max), or change from fasting). A mediation analysis was used to further explore the relationship of the N-glycome in the prediabetes (HbA1c = 39–47mmol/mol (5.7–6.5%))–postprandial lipaemia association. Results: We identified 36 out of 55 glycans significantly associated with postprandial triglycerides (C max β ranging from -0.28 for low-branched glycans to0.30 for GP26) after adjusting for covariates and multiple testing (p adjusted < 0.05). N-glycome composition explained 12.6% of the variance in postprandial triglycerides not already explained by traditional risk factors. Twenty-seven glycans were also associated with postprandial glucose and 12 with postprandial insulin. Additionally, 3 of the postprandial triglyceride–associated glycans (GP9, GP11, and GP32) also correlate with prediabetes and partially mediate the relationship between prediabetes and postprandial triglycerides. Conclusions: This study provides a comprehensive overview of the interconnections between plasma protein N-glycosylation and postprandial responses, demonstrating the incremental predictive benefit of N-glycans. We also suggest a considerable proportion of the effect of prediabetes on postprandial ...
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/37400796; info:eu-repo/semantics/altIdentifier/wos/WOS:001022895400011; volume:21; issue:1; firstpage:1; lastpage:11; numberofpages:11; journal:BMC MEDICINE; https://hdl.handle.net/2434/1093890
DOI: 10.1186/s12916-023-02938-z
Availability: https://hdl.handle.net/2434/1093890; https://doi.org/10.1186/s12916-023-02938-z
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.CB7E7C49
Database: BASE