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Association of Diurnal Patterns in Salivary Cortisol With Type 2 Diabetes in the Whitehall II Study
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CONTEXT: The hypothalamic pituitary-adrenal axis is thought to play a role in Type 2 Diabetes (T2D). However, the evidence for an association between diurnal cortisol patterns and T2D is equivocal. OBJECTIVE: The aim was to examine the association of cortisol patterns throughout the day with T2D status in a community-dwelling population. DESIGN: This was a cross-sectional study of T2D status and salivary cortisol from phase 7 (2002-2004) of the Whitehall II study, United Kingdom. SETTING: The occupational cohort was originally recruited in 1985-1988. PARTICIPANTS: Three-thousand, five-hundred eight white men and women including 238 participants with T2D aged 50-74 years with complete information on cortisol secretion participated. OUTCOME MEASURES: We measured diurnal cortisol (nmol/L) patterns from six saliva samples obtained over the course of a normal day: at waking, +30 min, +2.5, +8, +12 hours, and bedtime. The cortisol awakening response and slope in diurnal secretion were calculated. RESULTS: T2D status was associated with a flatter slope in cortisol decline across the day (b = 0.004; confidence interval [CI], 0.001-0.007; P = .014) and greater bedtime cortisol (b = 0.063; CI, 0.010-0.117; P = 0.020) independent of a wide range of covariates measured at the time of cortisol assessment. There was no association between morning cortisol, the cortisol awakening response, and T2D (P > .05). CONCLUSIONS: In this nonclinical population, T2D was associated with a flatter slope in cortisol levels across the day and raised bedtime cortisol values.
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“The largest study to date, which included over 3,500 individuals from the Whitehall II epidemiological cohort, reported that people with T2DM had a flatter slope in levels of cortisol across the day and raised evening concentrations of cortisol compared with healthy individuals 30”
From Type 2 diabetes mellitus and psychological stress — a modifiable risk factor (2017) · cites this paper as [30]
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“For example, flatter slopes have previously been reported in specific disease groups, including metastatic breast cancer (Abercrombie et al., 2004) and diabetes mellitus (Hackett et al., 2014), relative to healthy controls.”
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“Changes in hypothalamic–pituitary–adrenal (HPA) axis cortisol levels have been linked with increased risk of type 2 diabetes, obesity, metabolic syndrome, and cardiovascular mortality (Björntorp and Rosmond, 2000; Brunner et al., 2002; Kumari et al., 2011; Champaneri et al., 2012, 2013; Hackett et al., 2014).”
BackgroundGan, L., Li, N., Heizhati, M., Li, M., Yao, L., Hong, J., Wu, T., Wang, H., Liu, M., & Maitituersun, A. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad184 · Cited by 10
Pre-Operative Cognitive Functioning and Inflammatory and Neuroendocrine Responses to Cardiac Surgery
Poole, L., Ronaldson, A., Kidd, T., Leigh, E. S., Jahangiri, M., & Steptoe, A. (2016) · Annals of Behavioral Medicine · doi:10.1007/s12160-016-9779-7 · Cited by 10
“For example, in the cardiac literature, elevated cortisol has been linked to cardiac risk factors such as hypercholesterolemia, diabetes, abdominal obesity and hypertension by some [18, 19], but not all [20], authors.”
BackgroundSelf-citationIs the hypothalamic–pituitary–adrenal axis disrupted in type 2 diabetes mellitus?
Raff, H., & Magill, S. B. (2016) · Endocrine · doi:10.1007/s12020-016-1108-1 · Cited by 10
“More importantly for this Editorial, patients with T2DM may have altered HPA axis activity in the absence of frank hypercortisolism [7].”
BackgroundYang, C., Ye, T. T., & Gao, Y. (2025) · PLoS ONE · doi:10.1371/journal.pone.0326193 · Cited by 10
Exercise timing and circadian regulation of metabolism in type 2 diabetes
Hansen, S. S. K., Zierath, J. R., & Wallberg‐Henriksson, H. (2026) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2026.01.015 · Cited by 8
Johar, H., Spieler, D., Bidlingmaier, M., Herder, C., Rathmann, W., Köenig, W., Peters, A., Kruse, J., & Ladwig, K. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10132751 · Cited by 9
Hitomi, T., & Kataoka, H. (2024) · Analytica—A Journal of Analytical Chemistry and Chemical Analysis · doi:10.3390/analytica5020015 · Cited by 8
“…stress [6], autism spectrum disorders [7], Alzheimer’s disease [8] and cognitive dysfunction [9] in old age, Parkinson’s disease [10], diabetes [11], cardiovascular disease [12], cancer [13–15], primary aldosteronism [16], hypogonadism [17,18], ovarian disorders [19–21], Cushing syndrome…”
BackgroundNovak, N. L., Wang, X., Clarke, P. J., Hajat, A., Needham, B. L., Sánchez, B. N., Rodríguez, C. J., Seeman, T. E., Castro‐Diehl, C., Golden, S. H., et al. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.08.018 · Cited by 8
“…in turn to health and mortality risk; for example, a flatter decline in cortisol throughout the day has been associated with higher risk for obesity, diabetes, and cardiovascular disease and higher all-cause mortality (Champaneri et al., 2012; Hackett et al., 2014; Kumari et al., 2011, 2010).”
BackgroundInfluentialPan, L., Sun, Q., Liu, G., & Guo, J. (2019) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2019/1394641 · Cited by 8
“0e association of cortisol with T2DM was shown when it was found that there was a significant upward trend in the cortisol level before bedtime in T2DM patients [49], and the circadian rhythm of cortisol secretion was found to be the main determinant of glycemic control in humans [50].”
BackgroundScribante, A., Pellegrini, M., Ghizzoni, M., Pulicari, F., Giannì, A. B., & Spadari, F. (2024) · The Open Dentistry Journal · doi:10.2174/0118742106346940241212104004 · Cited by 9
Utilization of Mind–Body Intervention for Integrative Health Care of COVID-19 Patients and Survivors
Yang, H., Setou, N., & Koh, E. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116618 · Cited by 7
“Indeed, a large epidemiological study involving 3500 individuals revealed that people with T2DM had a flatter slope of cortisol level during the day and greater evening levels of cortisol compared with healthy people [94].”
BackgroundApolipoprotein A-IV constrains HPA and behavioral stress responsivity in a strain-dependent manner
Packard, A. E. B., Zhang, J., Myers, B., Ko, C., Wang, F., Tso, P., & Ulrich‐Lai, Y. M. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.08.025 · Cited by 6
“, 2017), and type 2 diabetes is associated with increased neuroendocrine responses to stress, as well as a higher incidence of stress-related disorders including depression (Hackett et al., 2014; Siddiqui et al., 2015; Tabák et al., 2014).”
Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional Reactivity
Wolf, T., Tsenkova, V. K., Ryff, C. D., Davidson, R. J., & Willette, A. A. (2018) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000582 · Cited by 7
“Another study showed that individuals with type 2 diabetes had flattened cortisol during the day compared with others in the study who did not have type 2 diabetes (71).”
Isaac, A. J., Bufferd, S. J., & Mekawi, Y. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107416 · Cited by 6
Sanchís-Soler, G., Tortosa‐Martínez, J., Manchado, C., & Cortell-Tormo, J. M. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.01.002 · Cited by 6
Salivary cortisol is not associated with incident insulin resistance or type 2 diabetes mellitus
Gariani, K., Marques-Vidal, P. M., Waeber, G., Vollenweider, P., & Jornayvaz, F. R. (2019) · Endocrine Connections · doi:10.1530/ec-19-0251 · Cited by 6
Weigensberg, M. J., Wen, C. K. F., Sanogo, F., Toledo‐Corral, C. M., & Ding, L. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106053 · Cited by 4
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Radin, J. M., Al‐Delaimy, W. K., Kritz‐Silverstein, D. C., Wingard, D. L., Barrett-Connor, E. L., & Laughlin, G. A. (2022) · Global Journal of Epidemiology and Public Health · doi:10.12974/2313-0946.2016.03.01.1 · Cited by 4
“Several studies have reported an association between elevated cortisol and diabetes in older adults [4-8].”
BackgroundEvaluating the Interrelationship Between Salivary Cortisol and Glycemia in Type 2 Diabetics
Kumar, T. V., Vasanthi, V., Dineshkumar, T., Narayan, M., Divya, B., Krishnan, R. K., & Ramadoss, R. (2022) · Journal of Orofacial Sciences · doi:10.4103/jofs.jofs_96_22 · Cited by 3
Toledo‐Corral, C. M., Ding, L., Morales, J. C., Chapman, T. M., Romero, M. B., & Weigensberg, M. J. (2023) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2022.0091 · Cited by 3
Shared genetic architecture between sleep traits and cardiometabolic diseases
Zhang, Y., Jian, S., Ouyang, H., Purushotham, Y., Yu, Q., Tang, B., Gottlieb, D. J., Sofer, T., & Yi, M. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106220 · Cited by 2
“103 In addition, individuals with T2D exhibit a modified diurnal cortisol rhythm in contrast to individuals without the condition, 104,105 and elevated evening cortisol levels are indicative of the beginning of T2D in initially healthy populations.”
Cortisol awakening response in bipolar patients with comorbid type 2 diabetes mellitus
Monteleone, A. M., D’Agostino, G., Cascino, G., Marciello, F., Monteleone, P., & Maj, M. (2021) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2021.1973280 · Cited by 2
“2015) or a normal CAR with a flattened diurnal cortisol rhythm (Lederbogen et al. 2011; Hackett et al. 2014) or with a flatter early-decline cortisol (Champaneri et al.”
BackgroundResultDysregulated responses to stress and weight in people with type 2 diabetes
Hackett, R. A., Gareddu, A., Panagi, L., Steptoe, A., & Poole, L. (2023) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2023.111354 · Cited by 2
“Changes in diurnal cortisol output have been implicated in the pathogenesis of both obesity [25] and T2D [26] in observational studies.”
BackgroundSelf-citationEffects of multiple stress events at different stages of life on the incidence of metabolic syndrome
Li, N., Gao, Y., Zhao, X., Wang, L., Wang, R., Mei, S., Hu, P., Lu, W., Zhao, T., Huang, F., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1419443 · Cited by 1
“Elevated basal plasma cortisol levels are highly associated with type 2 diabetes and obesity (23, 24).”
BackgroundEgorov, A. I., Xue, W., Kobylanski, J., Fuzawa, M., Griffin, S. M., Wade, T. J., & Nye, M. (2025) · BMC Research Notes · doi:10.1186/s13104-024-07056-4 · Cited by 1
“It exhibits a diurnal pattern with a pronounced post awakening peak [28].”
Diurnal cortisol cycle and cognitive performance in older people with Type 2 diabetes
Vallejo, L., Zapater‐Fajarí, M., Montoliu, T., Hidalgo, V., & Salvador, A. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107718 · Cited by 1
Metadata
- Authors
- Hackett, R. A., Steptoe, A., & Kumari, M.
- Affiliations
- University of Essex (GB)
- University College London (GB)
- Corresponding author
- Hackett, Ruth A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-12
- Volume
- 99
- Issue
- 12
- Pages
- 4625-4631
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4255120
- OpenAlex
- W2000289373
- Semantic Scholar
- bada6d524b4ece58518ad130479f04ef95924d01
- Cited by
- 118
- References
- 48
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 8 · 2021: 7 · 2020: 15 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 15 · 2015: 10
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Access at Essex (University of Essex) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation (RG/10/005/28296)
- University College London
- Medical Research Council (MR/K013351/1, WC1E 6BT)
- Economic and Social Research Council (ES/K005146/1, RES 596-28-0001, ES/J023299/1)
- National Institute on Aging (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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- type 2 diabetes, salivary cortisol, diurnal cortisol rhythm, hypothalamic-pituitary-adrenal axis, cortisol awakening response, Whitehall II study, occupational cohort
- MeSH terms
- Aged, Arousal, Circadian Rhythm, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Hydrocortisone, Male, Middle Aged, Saliva, Cohort Studies
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