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This article explores the bidirectional relationship between type 2 diabetes mellitus (T2DM) and depression, focusing on their shared pathophysiological mechanisms, including immune-inflammatory responses, gut-brain axis dysregulation, metabolic abnormalities, and neuroendocrine modulation. Research indicates that T2DM contributes to anxiety and depression through chronic low-grade inflammation, insulin resistance, gut microbiota imbalance, and hyperactivation of the hypothalamic-pituitary-adrenal axis. Conversely, depression may increase the risk of T2DM via lifestyle disruption, immune activation, and neurotransmitter imbalance. Additionally, metabolic pathway disturbances - such as reduced adiponectin, impaired insulin signaling, and altered amino acid metabolism - may influence mood regulation and cognition. The article further examines emerging therapeutic strategies targeting these shared mechanisms, including anti-inflammatory treatments, gut microbiota modulation, hypothalamic-pituitary-adrenal axis interventions, metabolic therapies (e.g. , glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors), and multidisciplinary integrative management. Emphasizing the multisystem nature of diabetes-depression comorbidity, this work highlights the importance of incorporating mental health strategies into diabetes care to optimize outcomes and enhance patient quality of life.
Luo et al. (Tue,) studied this question.