Although the mechanism of comorbidities between diabetes and depression is still unclear, we speculate based on some available evidence that the comorbidities between diabetes and depression may be related to the activation of certain inflammatory pathways, such as NLRP3 (NOD-like receptor protein 3) inflammatory bodies, which can accept the stimulation of metabolic stress signals and further cause the activation of Caspase-1 and a series of inflammatory factors. The gene discussed is CASP1; the disease is major depressive disorder.