Circadian Misalignment and Chrononutrition in Type 2 Diabetes: Mechanistic Insights and Translational Gaps

Circadian rhythms regulate glucose metabolism, insulin secretion, hepatic glucose production, peripheral insulin sensitivity, nutrient handling, and energy balance. Observational studies have associated circadian timing disruption through shift work, irregular sleep, artificial light at night, social jet lag, late eating, or inconsistent meal timing with insulin resistance and type 2 diabetes mellitus (T2DM). This narrative review integrates molecular, clinical, nutritional, and pharmacological evidence linking circadian misalignment with diabetes, with emphasis on chrononutrition, time-restricted eating, glucose variability, diabetes-related complications, melatonin/MTNR1B-related susceptibility, exogenous melatonin, continuous glucose monitoring (CGM), digital phenotyping, and chronopharmacology. A structured narrative literature search was conducted to identify relevant studies on circadian biology, diabetes, meal timing, time-restricted eating, melatonin signaling, MTNR1B, circadian biomarkers, CGM, and time-informed therapeutic strategies. Mechanistic and preclinical studies establish clock-metabolism coupling, whereas controlled human physiological studies support time-of-day variation in insulin secretion, postprandial responses, and glucose handling; diabetes-specific interventional and complication-outcome evidence remains limited. Chrononutrition and time-restricted eating may support glycemic regulation only as individualized adjuncts to standard diabetes care, not as replacements for established treatment; medication review and hypoglycemia monitoring are essential, particularly for patients using insulin or insulin secretagogues. Translation into routine care requires longer diabetes-specific trials, standardized outcomes, validated biomarkers, and patient-centered implementation protocols.