Depression and type 2 diabetes (T2D) are clinically associated and the causes of the association are still under investigation. We aimed at identifying what is known about the stress response and cortisol pathway and the clinical association of depression and T2D, and at hypothesizing the link of the association. In this review, we report independent studies on stress response, cortisol pathway, depression, T2D, and independent studies on stress and cortisol pathway in depression, and in T2D. We focus and integrate the stress and cortisol pathway hypothesis to explain the clinical association of depression and T2D. We hypothesize that the corticotropin-releasing hormone receptors are one of the missing linking factor of the cortisol pathway underlying the clinical association of depression and T2D. We state what studies are still needed to confirm or rule out our hypothesis.
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