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 = 39–47 mmol/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 to 0.30 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 triglycerides is mediated by some plasma N-glycans.

Plasma protein N-glycome composition associates with postprandial lipaemic response / P. Louca, T. Stambuk, A. Frkatovic-Hodzic, A. Nogal, M. Mangino, S.E. Berry, H. Deris, G. Hadjigeorgiou, J. Wolf, M. Vinicki, P.W. Franks, A.M. Valdes, T.D. Spector, G. Lauc, C. Menni. - In: BMC MEDICINE. - ISSN 1741-7015. - 21:1(2023), pp. 231.1-231.11. [10.1186/s12916-023-02938-z]

Plasma protein N-glycome composition associates with postprandial lipaemic response

C. Menni
Ultimo
2023

Abstract

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 = 39–47 mmol/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 to 0.30 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 triglycerides is mediated by some plasma N-glycans.
Metabolic response; Plasma N-glycome; Postprandial glycaemia; Postprandial lipaemia; Protein glycosylation
Settore MED/01 - Statistica Medica
2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1093890
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