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TOPLINE:

Approximately one quarter (23.8%) of patients with difficult-to-control type 2 diabetes (T2D) had hypercortisolism, with contributing factors including older age; lower body mass index (BMI); non-Latino/Hispanic ethnicity; higher hypertension medication burden; and the use of fibrates, analgesics, or newer glucose-lowering medications.

METHODOLOGY:

• Poor glycemic control can cause complications and frustration among both patients and clinicians. Although hypercortisolism is a known cause of hyperglycemia, it is rarely screened for in patients with difficult-to-control T2D because it is challenging to diagnose and is often mistakenly believed to present only as classic Cushing syndrome.
• Researchers conducted a prospective, observational study at multiple centers across the United States to assess the prevalence of hypercortisolism in 1057 adults aged 18-80 years with difficult-to-control T2D, defined as having A1c levels between 7.5% and 11.5% despite multiple standard treatments.
• All participants underwent the 1 mg dexamethasone suppression test (DST), with dexamethasone levels ≥ 140 ng/dL ensuring adequate suppression; hypercortisolism was defined by a post-DST cortisol level of > 1.8 μg/dL.
• Noncontrast abdominal CT was performed for participants with hypercortisolism, with standardized reporting criteria used across all study sites.
• The primary outcome was the prevalence of hypercortisolism; multiple logistic regression models were employed to evaluate the characteristics linked to hypercortisolism and abnormalities in adrenal imaging.

TAKEAWAY:

• Among the screened participants, 252 showed unsuppressed post-DST cortisol levels, resulting in a hypercortisolism prevalence of 23.8% (95% CI, 21.3%-26.5%), with a mean post-DST cortisol level of 3.49 µg/dL.
• The prevalence of hypercortisolism was greater than 30% among patients with cardiac disorders and those taking three or more blood pressure–lowering medications.
• Among the 219 participants with unsuppressed post-DST cortisol levels who underwent CT, adrenal imaging abnormalities were found in 34.7%, primarily involving unilateral adrenal nodules.
• The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors, maximum-dose glucagon-like peptide 1 receptor agonists, tirzepatide, or a higher number of blood pressure–lowering medications; older age; lower BMI; non-Latino/Hispanic ethnicity; and the use of fibrates or analgesics were associated with a higher prevalence of hypercortisolism (P < .03 for all).

IN PRACTICE:

“These results add to our understanding of why type 2 diabetes may be difficult to control in some individuals and suggest a potential role for screening for hypercortisolism in individuals in whom glycemic treatment targets are not met despite treatment with multiple medications,” the authors wrote.

SOURCE:

The study was led by John B. Buse, University of North Carolina School of Medicine, Chapel Hill, North Carolina. It was published online on April 18, 2025, in Diabetes Care.

LIMITATIONS:

This study recruited a highly selected phenotype exclusively from diabetes-focused practices. The results showed an association between hypercortisolism and difficult-to-control T2D but failed to establish any causation. Abnormal adrenal CT scans were categorized as “nodule(s),” “enlargement,” “nodule(s) and enlargement,” or “other imaging abnormality,” and the inclusion of the “other imaging abnormality” category may have complicated the analysis comparing normal and abnormal scans.

DISCLOSURES:

This study was funded by Corcept Therapeutics, with additional support from National Institutes of Health Clinical and Translational Science Award or Diabetes Research Center grants and the Department of Veterans. The authors disclosed serving on advisory panels as consultants for; receiving research support, grants, honoraria, and fees from; holding stocks in, and several other ties with many pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.