Many of us have seen the effects of hypercortisolism on diabetes control when prednisone is added to an acutely ill insulin-dependent diabetic. However, like many of you, I’ve never diagnosed Cushing’s Syndrome, which is distinctly rare. Nonetheless, most of us have cared for persons with diabetes who remain highly insulin-resistant and have suboptimal glycemic control despite using the latest diabetic glycemic control agents.

Hypercortisolism can negatively impact glycemic control by contributing to insulin resistance, impairing beta-cell function, inhibiting the insulinotropic effect of GLP-1 (glucagon-like peptide) and GIP (gastric inhibitory peptide), and increasing hepatic glucose output via gluconeogenesis.

The ADA has a free podcast called “Diabetes Core.” Since May, there have been 3 special podcasts on “Hypercortisolism in Difficult to Manage Diabetes” that make the case for this surprisingly being a contributing factor in about 24% of the cases in the Catalyst Study.

The CATALYST Study enrolled adults aged 18-80 who had A1C 7.5%-11.5% despite taking: 1) three or more glucose-lowering-medications, 2) taking insulin and any other glucose-lowering-medication, 3) taking two or more glucose-lowering-medications + had diabetic complications, 4) taking two or more glucose-lowering-medications and two or more blood pressure-lowering-medications. Individuals with common causes of hypercortisolism were excluded.

Hypercortisolism was detected by an overnight Dexamethasone Suppression Test (DST – Dexamethasone 1 mg at 11 p.m. and blood draw for cortisol and dexamethasone levels at 8:00 a.m. Hypercortisolism was defined as a cortisol > 1.8 ug/dl with a dexamethasone level > 140. An abdominal CT was done that detected adrenal abnormalities in 34.7% of those with hypercortisolism.

Of the 1,057 screened, 252 had unsuppressed cortisol for a prevalence of 23.8%. At baseline, 38.2% of participants were taking fast-acting insulin and 64.7% were taking long- or intermediate-acting insulin.

The phase 2 study was a placebo-controlled study of the effect of mifepristone (the glucocorticoid receptor antagonist approved for treating Cushing’s syndrome). Over 24 weeks, those on mifepristone lost 5.12 kg and 5 cm of waist circumference and were still losing weight at the end of the 24 weeks. The A1C dropped 1.3%. Anxiety and depression, which were common in this cohort, improved on mifepristone.

Mifepristone is a difficult medication to use safely. The clear message to providers is that hypercortisolism is prevalent, easy to diagnose, and could be life-changing for your patients.

I recommend the above podcasts for your review, as well as this 13-minute YouTube video featuring the lead investigator, Dr. John Buse.

Resources

• Hypercortisolism in Difficult to Manage Diabetes: https://diabetesjournals.org/journals/pages/podcasts_whats_next
• Diabetes Care gives free access (pdf available) to this study at http://bit.ly/3JoiEB9.
• YouTube Video: https://www.youtube.com/watch?v=WvtL9pf5Tro