Chronic Stress and Diabetes Mellitus: Interwoven Pathologies

Curr Diabetes Rev. 2020;16(6):546-556. doi: 10.2174/1573399815666191111152248.


Stress threatens the homeostasis and mobilizes a plethora of adaptive physiological and behavioral changes via the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The HPA axis influences the pituitary gland, hypothalamus and adrenal gland via a complex set of positive and negative feedback system. The feedback system operates in a well regulated neuroendocrine manner to reestablish the threatened body equilibrium. The HPA axis secreted major product is a glucocorticoid (cortisol) which is kept within a physiologically optimal range and serves to accomplish the various physiological functions crucial for survival. In chronically stressed individuals dishabituation of HPA axis is followed by increased release of glucocorticoids and catecholamines. Higher secretion of glucocorticoids influences glucose metabolism by promoting gluconeogenesis in the liver, suppressing glucose uptake (adipocytes and skeletal muscles), promoting lipolysis in adipocytes, suppressing insulin secretion, inflicting insulin resistance and inflammation. These biological changes alter neuroendocrine mechanisms and lead to maladaptive congregation of events that form the underlying cause of development of Type 2 diabetes (T2D). The currently reviewed evidences advocate that targeting stress mediated hypersecretion of glucocorticoids may be a viable approach for the treatment of T2D and to reinstate glucose homeostasis.

Keywords: Chronic stress; diabetes; glucocorticoids; hypothalamic-pituitary-adrenal axis; inflammation; insulin..

Publication types

  • Review

MeSH terms

  • Chronic Disease
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / psychology*
  • Glucocorticoids / adverse effects
  • Glucocorticoids / metabolism*
  • Humans
  • Hydrocortisone / adverse effects
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology
  • Insulin Resistance / physiology
  • Stress, Physiological / physiology*
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology


  • Glucocorticoids
  • Hydrocortisone