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This randomized crossover study reveals that 5 mg oral melatonin impairs glucose tolerance and disrupts insulin dynamics in healthy individuals carrying the MTNR1B G-allele diabetes risk variant. Key findings include a 40% suppression of glucose-stimulated first-phase beta-cell responsivity and dysregulated insulin negative feedback, leading to reduced early C-peptide responses and impaired glucose tolerance exclusively in risk carriers. Melatonin also prevented insulin-induced hypoglycemia in these individuals, highlighting critical genotype-dependent metabolic effects.
