Comorbid depression and glycemic instability in adolescent type 1 diabetes: Clinical insights into suicide risk

Figure 2 Hypothalamic-pituitary-adrenal axis dysfunction and stress susceptibility. The cascade from glycemic variability to psychological despair. A: Extreme glucose fluctuations act as physiological stressors; B: Triggering excessive hypothalamic-pituitary-adrenal axis activation and flattening cortisol rhythms; C: Elevated cortisol inhibits brain-derived neurotrophic factor expression, impairing synaptic plasticity; D: This biological state translates into “learned helplessness”, a core psychological driver of suicidal ideation in type 1 diabetes. HPA: Hypothalamic-pituitary-adrenal; BDNF: Brain-derived neurotrophic factor; IL: Interleukin; TNF: Tumor necrosis factor.