Diurnal Cortisol Patterns, Future Diabetes, and Impaired Glucose Metabolism in the Whitehall II Cohort Study
Open accessAbstract
CONTEXT: The hypothalamic pituitary-adrenal axis is thought to play a role in type 2 diabetes (T2D). However, evidence for an association between cortisol and future glucose disturbance is sparse. OBJECTIVE: The aim was to examine the association of diurnal cortisol secretion with future T2D and impaired glucose metabolism in a community-dwelling population. DESIGN: This is a prospective cohort study of salivary cortisol measured at the 2002-2004 clinical examination of the Whitehall II study, United Kingdom. We measured cortisol (nmol/l) from six saliva samples obtained over the course of a day: at waking, +30 minutes, +2.5 hours, +8 hours, +12 hours, and bedtime. Participants who were normoglycemic in 2002-2004 (phase 7) were reexamined in 2012-2013 (phase 11). SETTING: The occupational cohort was originally recruited in 1985-1988. PARTICIPANTS: A total of 3270 men and women with an average age of 60.85 years at phase 7 (2002-2004). OUTCOME MEASURES: Incident T2D and impaired fasting glucose in 2012-2013 were measured. RESULTS: Raised evening cortisol at phase 7 was predictive of new-onset T2D at phase 11 (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37) with a trend for a flatter slope in participants with incident T2D (odds ratio, 1.15; 95% CI, 0.99-1.33). When expanding this analysis to a broader category of glucose disturbance we found that a flattened diurnal cortisol slope at phase 7 was predictive of future impaired fasting glucose or T2D at phase 11 (OR, 1.12; 95% CI, 1.02-1.22), as was high bedtime cortisol (OR, 1.10; 95% CI, 1.01-1.20). CONCLUSIONS: In this nonclinical population, alterations in diurnal cortisol patterns were predictive of future glucose disturbance.
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In an analysis of 3,270 initially healthy individuals from the Whitehall II cohort, raised evening levels of cortisol predicted new onset T2DM over a 9 year follow-up period independent of covariates.
“In this analysis of 3,270 initially healthy individuals from the Whitehall II cohort, raised evening levels of cortisol predicted new onset T2DM over a 9 year follow-up period independent of covariates.”
From Type 2 diabetes mellitus and psychological stress — a modifiable risk factor (2017) · cites this paper as [36]
No associations were detected between morning levels of cortisol or the CAR and T2DM onset.
“No associations were detected between morning levels of cortisol or the CAR and T2DM onset.”
From Type 2 diabetes mellitus and psychological stress — a modifiable risk factor (2017) · cites this paper as [36]
When the analysis was expanded to include prediabetes, raised evening concentrations of cortisol and a flatter slope in cortisol across the day predicted the combined outcome.
“When the analysis was expanded to a broader category of glucose disturbance to include prediabetes, raised evening concentrations of cortisol and a flatter slope in cortisol across the day were found to predict the combined outcome.”
From Type 2 diabetes mellitus and psychological stress — a modifiable risk factor (2017) · cites this paper as [36]
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- Authors
- Hackett, R. A., Kivimäki, M., Kumari, M., & Steptoe, A.
- Affiliations
- University of Essex (GB)
- Corresponding author
- Hackett, Ruth A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-02
- Volume
- 101
- Issue
- 2
- Pages
- 619-625
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4880118
- OpenAlex
- W2194195225
- Cited by
- 121
- References
- 10
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 8 · 2023: 12 · 2022: 13 · 2021: 15 · 2020: 18 · 2019: 11 · 2018: 8 · 2017: 14 · 2016: 9
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Access at Essex (University of Essex) (submittedVersion)
- Funders
- British Heart Foundation (RG/10/005/28296)
- University College London
- Medical Research Council (MR/K013351/1)
- Economic and Social Research Council (ES/J023299/1)
- National Institute on Aging (R01AG034454, AG 13196, R37AG013196, R01AG013196)
- National Heart, Lung, and Blood Institute (HL36310, R01HL036310)
- 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
- diurnal cortisol, type 2 diabetes, impaired fasting glucose, impaired glucose metabolism, salivary cortisol, hypothalamic-pituitary-adrenal axis, cortisol slope, diabetes risk prediction, Whitehall II cohort
- MeSH terms
- Aged, Algorithms, Blood Glucose, Circadian Rhythm, Diabetes Mellitus, Type 2, Female, Glucose, United Kingdom, Humans, Hydrocortisone, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Saliva, Cohort Studies
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