Cortisol and Type 2 Diabetes: Recognizing the Signs

In the third episode of our insights series, Cortisol and Type 2 Diabetes: What Patients Need to Know, John Buse, M.D., Ph.D., explores the subtle, everyday signs of chronically elevated cortisol from a practical patient perspective. Buse notes that medicine is in the "early days" of recognizing a massive clinical shift. Classically, medical students were taught to look for extreme visual markers of Cushing's syndrome — such as a dorsocervical fat pad, deep purple stretch marks and a distinctively round "moon face." However, Buse reveals that the typical patient dealing with diabetes-related hypercortisolism looks entirely normal, perhaps presenting with central obesity or slightly flushed cheeks that are only noticeable in retrospect.

Instead of obvious physical traits, Buse explains that the true primary indicator of hypercortisolism is a body that simply refuses to respond to standard medical treatments as expected. In a practical setting, a physician might suspect high cortisol when a patient with new-onset diabetes is prescribed metformin, but their A1C barely budges from an 8 to a 7.8, rather than dropping to a typical 6.9. Even after adding a thiazolidinedione and an advanced GLP-1 receptor agonist like Tirzepatide, the patient may only lose a few pounds while their A1C stubbornly refuses to enter the safe zone of the sixes. A similar pattern occurs in the hypertension space, where "resistant hypertension" is defined as a patient requiring four or more blood pressure medications (or three drugs including a diuretic at reasonable doses) yet their blood pressure remains stubbornly higher than 130.

The episode provides crucial guidance on how patients can distinguish between normal daily stress and a deeper issue requiring medical evaluation. While acknowledging that behavioral health professionals are best equipped to draw these lines, Buse advises patients to seek additional care if stress actively disrupts their daily lives, making it hard to get through the day, handle responsibilities, or stay focused at work and home. He cautions against the common tendency to lean immediately on prescription drugs like benzodiazepines, advocating instead for the immense value of behavioral therapy. For long-term stress management, Dr. Buse recommends highly effective non-pharmaceutical approaches, ranging from at-home practices like meditation and mindfulness therapy to deeper, structured interventions with a psychologist, such as Cognitive Behavioral Therapy (CBT).