Mechanistic Pathways and Bidirectional Relationship betweenDiabetes Mellitus and Anxiety

The clinical manifestations of anxiety and diabetes mellitus are increasingly recognized as significant global public health challenges. According to current investigations, diabetes and anxiety have a mutually reinforcing relationship in which the course and outcomes of each condition are influenced by the other. To investigate the complementary effects of diabetes and anxiety, including their influence on the onset and severity of each condition, a comprehensive literature review was conducted. This review highlights the incidence of type 2 diabetes (T2D) in the coexisting stage of sarcopenia (a comorbid condition). T2D is characterized by pathophysiological disturbances, including dysregulated insulin signaling, chronic hyperglycemia, chronic inflammation, oxidative stress, insulin resistance (IR), and dyslipidemia. These factors collectively impair brain neurotransmitter function and suppress brain-derived neurotrophic factor expression, thereby predisposing individuals to anxiety. Impaired autophagy further contributes to neuronal dysfunction and metabolic imbalance, exacerbating both anxiety and T2D. Conversely, anxiety contributes to the development of IR and T2D through biological, psychological, and behavioral pathways. Chronic psychological distress disrupts the hypothalamic–pituitary–adrenal (HPA) axis, elevating cortisol levels, which in turn promote IR and accelerate T2D onset. Epidemiological data show that anxiety and T2D co-occur at approximately twice the rate compared with their independent prevalence. This review outlines essential features for analyzing the intricate link between diabetes and anxiety, focusing on incidence, shared underlying mechanisms, and highlighting potential novel biomarkers and therapeutic targets implicated in both conditions. By synthesizing current evidence, it aims to provide insights into effective management strategies and identify research gaps to enhance understanding and care for individuals affected by both diseases, thereby guiding future investigations.