Cushing disease hides metabolic trouble even when blood sugar looks normal

A new cross-sectional study out of the Medical University of Warsaw reveals that glucose metabolism is quietly going wrong in Cushing disease patients — even before blood sugar levels raise any red flags. Researchers compared 50 Cushing disease patients with 52 healthy, matched controls and found that those with normal glucose tolerance still had significantly lower insulin sensitivity and higher insulin levels than healthy individuals.

The picture gets more concerning as the disease progresses: patients who developed overt diabetes showed signs of beta-cell exhaustion — their insulin-to-glucose ratio dropped sharply compared to those with prediabetes — without a meaningfully lower insulin sensitivity, suggesting the pancreas simply can't keep up.

By the Numbers:

• 68% of Cushing disease patients had abnormal glucose metabolism
• 42% had prediabetes; 26% had diabetes
• 10 of 13 diabetic patients had never been diagnosed before
• Insulin-to-glucose ratio: 0.26 (diabetes) vs. 0.64 (prediabetes)
• Key A1c predictors: age, cortisol levels, waist-to-hip ratio, and proinsulin (explaining 59.5% of variance)

Why it matters: Clinicians managing Cushing disease patients shouldn't wait for abnormal glucose readings to start worrying about metabolic risk. Insulin resistance is already present well before diabetes develops, and most diabetic patients in this study were undiagnosed — underscoring the need for proactive metabolic screening in this population.