Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes
Open accessAbstract
Psychological stress may contribute to type 2 diabetes but mechanisms are still poorly understood. In this study, we examined whether stress responsiveness is associated with glucocorticoid and mineralocorticoid sensitivity in a controlled experimental comparison of people with type 2 diabetes and non-diabetic participants. Thirty-seven diabetes patients and 37 healthy controls underwent psychophysiological stress testing. Glucocorticoid (GR) and mineralocorticoid sensitivity (MR) sensitivity were measured by dexamethasone- and prednisolone-inhibition of lipopolysaccharide (LPS)-induced interleukin (IL) 6 levels, respectively. Blood pressure (BP) and heart rate were monitored continuously, and we periodically assessed salivary cortisol, plasma IL-6 and monocyte chemotactic protein (MCP-1). Following stress, both glucocorticoid and mineralocorticoid sensitivity decreased among healthy controls, but did not change in people with diabetes. There was a main effect of group on dexamethasone (F(1,74)=6.852, p=0.013) and prednisolone (F(1,74)=7.295, p=0.010) sensitivity following stress at 45 min after tasks. People with diabetes showed blunted stress responsivity in systolic BP, diastolic BP, heart rate, IL-6, MCP-1, and impaired post-stress recovery in heart rate. People with Diabetes had higher cortisol levels as measured by the total amount excreted over the day and increased glucocorticoid sensitivity at baseline. Our study suggests that impaired stress responsivity in type-2 diabetes is in part due to a lack of stress-induced changes in mineralocorticoid and glucocorticoid sensitivity.
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This state contributes to elevated circulating pro-inflammatory cytokines, suggesting a mechanistic link between HPA axis dysfunction and increased autoimmune and metabolic disease risk in chronically stressed populations.
“This state contributes to elevated circulating pro-inflammatory cytokines, suggesting a mechanistic link between HPA axis dysfunction, and increased autoimmune and metabolic disease risk in chronically stressed populations [46].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [46]
The Discussion (page unavailable) says insufficient corticosteroid signalling may release inflammatory markers from glucocorticoid control and reports increased pro-inflammatory cytokines in patients with diabetes. This supports a possible link between HPA-axis dysfunction, inflammation, and altered glucose metabolism, but the paper does not establish increased autoimmune disease risk or extend the finding to chronically stressed populations generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn individuals with chronic conditions such as type 2 diabetes, dysregulation of the HPA axis leads to reduced glucocorticoid sensitivity.
“For instance, in individuals with chronic conditions such as type 2 diabetes, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis leads to reduced glucocorticoid sensitivity.”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [46]
The Introduction links altered HPA-axis feedback in diabetes to possible impairment of corticosteroid receptor sensitivity. But the Discussion reports higher glucocorticoid sensitivity at baseline in the diabetes group and a lack of stress-induced change, not an overall reduction in sensitivity. It also states that the cross-sectional study cannot establish that HPA-axis dysregulation causes the observed response. (LLM, conf=0.88)
Experimental — accuracy not yet measuredChronic HPA axis activation and stress hormone imbalance contribute to immune dysfunction, promoting aging and increasing susceptibility to inflammatory, autoimmune, metabolic, and neuropsychiatric disorders.
“Collectively, these findings underscore how chronic HPA axis activation and stress hormone imbalance contribute to immune dysfunction, promoting aging and increasing susceptibility to inflammatory, autoimmune, metabolic, and neuropsychiatric disorders [46].”
From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [46]
The Introduction (page unavailable) links HPA-axis disturbance in people with diabetes to inflammation and complications. The Discussion (page unavailable) suggests that insufficient corticosteroid signaling may increase inflammatory markers and alter glucose metabolism. It does not establish that chronic HPA-axis activation promotes aging or increases susceptibility to autoimmune and neuropsychiatric disorders; the citing sentence extends a diabetes-focused, hedged account into a broader causal claim. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Self-citationChronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation
Nunez, S. G., Rabelo, S. P., Subotic, N., Caruso, J. W., & Knezevic, N. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26209994 · Cited by 138 · see citing works
“This state contributes to elevated circulating pro-inflammatory cytokines, suggesting a mechanistic link between HPA axis dysfunction, and increased autoimmune and metabolic disease risk in chronically stressed populations [46].”
- Authors
- Carvalho, L. A., Urbanova, L., Hamer, M., Hackett, R. A., Lazzarino, A. I., & Steptoe, A.
- Affiliations
- University College London (GB)
- Corresponding author
- Carvalho, Livia A.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 51
- Pages
- 209-218
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4275581
- OpenAlex
- W2121974327
- Cited by
- 48
- References
- 9
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 4
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation (RG/10/05/28296, RG/10/005/28296)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- type 2 diabetes, psychological stress, glucocorticoid sensitivity, stress responsivity, dexamethasone suppression, interleukin-6, MCP-1, salivary cortisol, blood pressure, heart rate, stress recovery, psychoneuroimmunology
- MeSH terms
- Aged, Blood Pressure, Dexamethasone, Diabetes Mellitus, Type 2, Female, Glucocorticoids, Heart Rate, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Prednisolone, Saliva, Stress, Psychological, Interleukin-6, Chemokine CCL2
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