• Panayiotis Louca, Tamara Štambuk, Azra Frkatović-Hodžić, Ana Nogal, Massimo Mangino, Sarah E Berry, Helena Deriš, George Hadjigeorgiou, Jonathan Wolf, Martina Vinicki, Paul W Franks, Ana M Valdes, Tim D Spector, Gordan Lauc, and Cristina Menni.
• Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, Westminster Bridge Road, London, SE1 7EH, UK.
• Bmc Med. 2023 Jul 3; 21 (1): 231231.

BackgroundA 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.MethodsWe 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 (Cmax), 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.ResultsWe identified 36 out of 55 glycans significantly associated with postprandial triglycerides (Cmax β ranging from -0.28 for low-branched glycans to 0.30 for GP26) after adjusting for covariates and multiple testing (padjusted < 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.ConclusionsThis 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.© 2023. The Author(s).

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