Plasma protein N-glycome composition associates with postprandial lipaemic response
(2023) In BMC Medicine 21(1).- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Metabolic response, Plasma N-glycome, Postprandial glycaemia, Postprandial lipaemia, Protein glycosylation
- in
- BMC Medicine
- volume
- 21
- issue
- 1
- article number
- 231
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:37400796
- scopus:85163881239
- ISSN
- 1741-7015
- DOI
- 10.1186/s12916-023-02938-z
- language
- English
- LU publication?
- yes
- id
- 7de30956-153d-4f09-b6b6-b7a6e9418d36
- date added to LUP
- 2023-08-25 14:34:48
- date last changed
- 2024-04-20 01:53:45
@article{7de30956-153d-4f09-b6b6-b7a6e9418d36,
abstract = {{<p>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 <sub>max</sub>), 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 <sub>max</sub> β ranging from -0.28 for low-branched glycans to 0.30 for GP26) after adjusting for covariates and multiple testing (p <sub>adjusted</sub> < 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.</p>}},
author = {{Louca, Panayiotis and Štambuk, Tamara and Frkatović-Hodžić, Azra and Nogal, Ana and Mangino, Massimo and Berry, Sarah E. and Deriš, Helena and Hadjigeorgiou, George and Wolf, Jonathan and Vinicki, Martina and Franks, Paul W. and Valdes, Ana M. and Spector, Tim D. and Lauc, Gordan and Menni, Cristina}},
issn = {{1741-7015}},
keywords = {{Metabolic response; Plasma N-glycome; Postprandial glycaemia; Postprandial lipaemia; Protein glycosylation}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Medicine}},
title = {{Plasma protein N-glycome composition associates with postprandial lipaemic response}},
url = {{http://dx.doi.org/10.1186/s12916-023-02938-z}},
doi = {{10.1186/s12916-023-02938-z}},
volume = {{21}},
year = {{2023}},
}