Diurnal Cortisol Patterns, Future Diabetes, and Impaired Glucose Metabolism in the Whitehall II Cohort Study.

Abstract

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. The aim was to examine the association of diurnal cortisol secretion with future T2D and impaired glucose metabolism in a community-dwelling population. 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). The occupational cohort was originally recruited in 1985-1988. A total of 3270 men and women with an average age of 60.85 years at phase 7 (2002-2004). Incident T2D and impaired fasting glucose in 2012-2013 were measured. 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). In this nonclinical population, alterations in diurnal cortisol patterns were predictive of future glucose disturbance.