Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus

Joshua J. Joseph, Sherita H. Golden

Research output: Contribution to journalReview articlepeer-review

134 Scopus citations


Controversy exists over the role of stress and depression in the pathophysiology of type 2 diabetes mellitus. Depression has been shown to increase the risk for progressive insulin resistance and incident type 2 diabetes mellitus in multiple studies, whereas the association of stress with diabetes is less clear, owing to differences in study designs and in forms and ascertainment of stress. The biological systems involved in adaptation that mediate the link between stress and physiological functions include the hypothalamic–pituitary–adrenal (HPA) axis and the autonomic nervous and immune systems. The HPA axis is a tightly regulated system that represents one of the body's mechanisms for responding to acute and chronic stress. Depression is associated with cross-sectional and longitudinal alterations in the diurnal cortisol curve, including a blunted cortisol awakening response and flattening of the diurnal cortisol curve. Flattening of the diurnal cortisol curve is also associated with insulin resistance and type 2 diabetes mellitus. In this article, we review and summarize the evidence supporting HPA axis dysregulation as an important biological link between stress, depression, and type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)20-34
Number of pages15
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - Mar 2017


  • cortisol
  • depression
  • diabetes
  • hypothalamic–pituitary–adrenal axis
  • stress

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science


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