TOPLINE

Most patients with Cushing disease had abnormal glucose metabolism. Even patients whose glucose tolerance was normal showed reduced insulin sensitivity and enhanced beta-cell activity compared with healthy control individuals, whereas patients with diabetes had impaired beta-cell compensation without a significantly lower insulin sensitivity than those with prediabetes.

METHODOLOGY

• Researchers conducted a cross-sectional study to assess glucose metabolism in patients with Cushing disease who had normal glucose tolerance, prediabetes, or diabetes and to determine factors associated with glycaemia.
• They included 50 patients with Cushing disease (mean age, 42.38 years; 78.0% women) and 52 age- and sex-matched healthy control individuals without clinical signs suggestive of hypercortisolism (mean age, 44.10 years; 80.8% women). Among patients with Cushing disease, 16 had normal glucose tolerance, 21 had prediabetes, and 13 had diabetes. All control individuals had normal glucose tolerance.
• All patients underwent blood tests to measure fasting glucose, insulin, proinsulin, C-peptide, and A1c levels. Those without prior diabetes underwent a 75-g oral glucose tolerance test (OGTT), with glucose and insulin sampled at 0, 30, 60, 90, and 120 minutes (metformin was stopped 7 days earlier). Patients with an existing diabetes diagnosis were classified on the basis of medical records and did not undergo the OGTT.
• Insulin resistance was estimated with three standard indices. Beta-cell secretory function was assessed using the ratio of insulin to glucose area under the curve, a surrogate marker.
• Anthropometric measures (BMI, waist and hip circumference, and waist to hip ratio), body composition (total and trunk fat mass), and morning cortisol levels were also assessed.

TAKEAWAY

• Overall, 68.0% of patients with Cushing disease had abnormal glucose metabolism, including prediabetes in 42.0% and diabetes in 26.0%; 10 of the 13 patients with diabetes had not been diagnosed before. Patients with Cushing disease who had normal glucose tolerance showed significantly higher mean insulin levels and had lower insulin sensitivity than control individuals.
• Patients with overt diabetes had a lower ratio of insulin to glucose area under the curve than those with prediabetes (median, 0.26 vs 0.64), without a significantly lower insulin sensitivity.
• Factors independently associated with A1c were age, morning serum cortisol levels, waist to hip ratio, and proinsulin, explaining 59.5% of its variance (P < .05 for all); age and BMI were associated with A1c in control individuals.
• In patients with Cushing disease, BMI showed no significant correlation with A1c, whereas trunk fat percentage showed a modest positive correlation.

IN PRACTICE

"[G]lycaemic status in Cushing's disease may be shaped by the combined influence of hormonal exposure, central adiposity, and beta-cell stress," the authors wrote.

SOURCE

The study was led by Przemysław Witek, Department of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw, Warsaw, Poland. It was published online on September 30, 2026, in Frontiers in Endocrinology.

LIMITATIONS

The study was small and cross-sectional, so it could not establish causality or show how glycaemia changes over time. Data on disease duration were lacking. The control group did not undergo a 1-mg dexamethasone suppression test.

DISCLOSURES

This study received support from the Medical University of Warsaw and the Military Institute of Medicine, Warsaw, Poland. The authors declared no conflicts of interest.

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