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Interaction of melatonin receptor 1B (MTNR1B) genotype and type of breakfast (protein-enriched v carbohydrate-rich) on postprandial glucose response: a randomised crossover trial.

Abstract

BACKGROUND: The risk allele (G) of MTNR1B rs10830963 has been associated with impaired glucose tolerance, increased fasting glucose and type 2 diabetes (T2D). Late evening eating, when endogenous melatonin levels are elevated, is associated with impaired glucose control in MTNR1B risk carriers. Endogenous melatonin levels remain elevated into the morning so may influence glucose response to breakfast. OBJECTIVE: To investigate the interaction of MTNR1B genotype and type of breakfast on postprandial glucose response in a real-world setting. METHODS: Following an overnight fast, participants consumed either a standard carbohydrate-rich or protein-enriched porridge breakfast. Post-prandial glucose levels were recorded for two hours using a continuous glucose monitor (CGM). One week later, participants repeated the protocol consuming the alternate breakfast. A two-way mixed ANOVA determined the effect of breakfast and genotype on post-prandial glucose levels. RESULTS: Fifty-four adults completed the study. Fasting glucose was significantly higher (p&#x2009;=&#x2009;0.008) in GG (5.53&#x2009;&#xb1;&#x2009;0.43&#x2009;mmol/L) compared to CC or CG participants (5.02&#x2009;&#xb1;&#x2009;0.42 and 5.19&#x2009;&#xb1;&#x2009;0.52&#x2009;mmol/L). Post-prandial iAUC was significantly greater following the carbohydrate-rich breakfast compared to the protein-enriched breakfast (p&#x2009;<&#x2009;0.001). Following the carbohydrate-rich breakfast iAUC was significantly greater in GG participants compared to CC (p&#x2009;=&#x2009;0.026) and CG participants (p&#x2009;=&#x2009;0.029). There was no significant difference between genotype groups following the protein-enriched breakfast (p&#x2009;>&#x2009;0.05). CONCLUSION: The study findings demonstrate, in a relatively young and healthy population, MTNR1B genotype significantly affects markers associated with T2D risk. Personalised genotype-based advice to adjust timing and composition of meals consumed when endogenous melatonin levels are increased may reduce subsequent T2D risk.

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Alexandra King, Jonathan Nixon, Angeliki Kapellou, Jonathan Craven, Catherine A-M Graham, Leta Pilic, Yiannis Mavrommatis. 2026-07-28. Interaction of melatonin receptor 1B (MTNR1B) genotype and type of breakfast (protein-enriched v carbohydrate-rich) on postprandial glucose response: a randomised crossover trial.. https://doi.org/10.1038/s41430-026-01794-3

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