Post-dexamethasone cortisol levels rise gradually in adults with difficult-to-treat type 2 diabetes (T2D), increasing cardiometabolic burden. These findings were presented at EASD 2025, highlighting the significance of cortisol even below current hypercortisolism cutoffs.

The CATALYST study examined 1,057 adults with difficult-to-treat type 2 diabetes (T2D). Participants underwent a 1-mg dexamethasone suppression test (DST), and post-DST cortisol values were categorized as <1.2 μg/dL, 1.2–1.8 μg/dL, and >1.8 μg/dL.

Analyses revealed that 24% of participants exceeded the current hypercortisolism cutoff of 1.8 μg/dL. Higher cortisol levels correlated with more cardiac comorbidities (33% vs 17% in <1.2 μg/dL) and greater use of ≥3 blood-pressure medications (38% vs 21%). Individuals with intermediate cortisol levels (1.2–1.8 μg/dL) shared multiple characteristics with those above the 1.8 μg/dL threshold, suggesting a continuum of cardiometabolic risk.

Multivariate analysis identified ethnicity, fibrate therapy, and blood-pressure medication use as independent predictors of post-DST cortisol >1.8 μg/dL. These findings indicate that current guidelines may overlook patients with mild cortisol elevation who carry similar risk profiles.