Abstract

Circadian rhythms orchestrate 24-hour cycles in behavior and physiology that are fundamental to metabolic 
homeostasis. A central clock in the suprachiasmatic nucleus and peripheral clocks in liver, adipose tissue, skeletal 
muscle, pancreas, and gut coordinate sleep–wake timing, feeding–fasting cycles, hormone secretion, and 
substrate utilization. When these clocks are misaligned with environmental and behavioral cues through shift 
work, irregular sleep, late eating, or chronic jet lag, metabolic control deteriorates. Epidemiologic data show 
that circadian disruption is associated with a higher risk of obesity and type 2 diabetes (T2D), while mechanistic 
studies link clock gene perturbations to insulin resistance, β-cell dysfunction, and altered glucose and lipid 
metabolism. This review examines circadian rhythm disruption as a convergence point in the pathogenesis of 
obesity and T2D. We outline the architecture of the circadian system and its integration with metabolic 
pathways, summarize experimental evidence that disrupting the clock induces obesity and insulin resistance, 
and synthesize epidemiologic data on shift work and social jet lag as risk factors for T2D. We then discuss 
organ-specific mechanisms linking clock dysfunction in liver, adipose tissue, muscle, and pancreatic islets to 
disturbed glucose homeostasis, and explore chrononutrition as a behavioral interface between circadian timing 
and metabolism. Finally, we consider therapeutic approaches to restore circadian alignment, including sleep 
regularity, light exposure, meal timing, and pharmacologic clock modulators, and highlight emerging 
opportunities for circadian-informed precision prevention of obesity-related diabetes.