Abstract / Summary
Abstract Background Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized not only by impaired glucose regulation but also by significant interactions between physiological, psychological, and behavioral factors. While glycemic variability has emerged as an important marker of metabolic instability and diabetes-related risk, traditional approaches often emphasize biological determinants without fully integrating the influence of chronic psychological stress. Emerging evidence suggests that dysregulation of stress-response systems, including hypothalamic-pituitary-adrenal (HPA) axis activation, inflammation, and behavioral pathways, may contribute to impaired glucose regulation and increased glycemic fluctuations. Objective This narrative review examines the relationship between chronic stress dysregulation and glycemic variability in adults with T2DM and proposes an integrated psychometabolic framework incorporating neuroendocrine, inflammatory, behavioral, and digital health perspectives. Methods A comprehensive literature review was conducted examining evidence from epidemiological studies, clinical trials, mechanistic investigations, and emerging digital health research. Literature addressing chronic stress physiology, cortisol regulation, inflammation, diabetes distress, behavioral determinants, continuous glucose monitoring (CGM), and precision medicine approaches was synthesized. Results Current evidence indicates that chronic stress may contribute to glycemic instability through multiple interconnected pathways, including HPA-axis dysregulation, autonomic nervous system activation, inflammatory signaling, oxidative stress, insulin resistance, and impaired self-management behaviors. Psychological factors such as diabetes distress, depression, sleep disruption, and reduced self-efficacy may further influence metabolic outcomes. Advances in CGM technology and digital health platforms provide opportunities to characterize dynamic glucose patterns and integrate psychosocial and biological data for individualized diabetes management. Conclusion An integrated psychometabolic approach may improve understanding of the complex mechanisms underlying glycemic variability in adults with T2DM. Future research should prioritize longitudinal, multimodal investigations combining psychological assessment, biological biomarkers, behavioral measures, and continuous glucose data to develop personalized interventions targeting both metabolic regulation and stress-related pathways.