The hypothalamic–pituitary–adrenal axis is a tightly regulated system that represents one of the body’s mechanisms for responding to acute and chronic stress. Prolonged stress and/or inadequate regulation of the stress system can lead to a condition of chronic hypercortisolism or, in some cases, a blunted cortisol response to stress, contributing to insulin resistance, increased adiposity and type 2 diabetes mellitus. Moreover, acute and chronic stress can exacerbate or worsen metabolic conditions by supporting an inflammatory state and a tight relationship between stress, inflammation and adipose tissue has been reported and has been a growing subject of interest in recent years. We reviewed and summarized the evidence supporting hypothalamic–pituitary–adrenal axis dysregulation as an important biological link between stress, obesity, inflammation and type 2 diabetes mellitus. Furthermore, we emphasized the possible role of infectious-related stress such as SarsCov2 infection in adrenal axis dysregulation, insulin resistance and diabetes in a bidirectional link. Understanding and better defining the links between stress and obesity or diabetes could contribute to further definition of the pathogenesis and the management of stress-related complications, in which the HPA axis dysregulation has a primary role.
Significance of hypothalamic-pituitary-adrenal axis dysfunction and functional hypercorticosolism syndrome in metabolic syndrome and type 2 diabetes mellitus
