<b>Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes</b>
Authors: John B. Buse, Steven E. Kahn, Vanita R. Aroda, Richard J. Auchus, Timothy Bailey, Irina Bancos, Robert S. Busch, Elena A. Christofides, Ralph A. DeFronzo, Bradley Eilerman, James W. Findling, Vivian Fonseca, Oksana Hamidi, Yehuda Handelsman, Harold J. Miller, Jonathan G. Ownby, John C. Parker, Athena Philis-Tsimikas, Richard Pratley, Julio Rosenstock, Michael H. Shanik, Lance L. Sloan, Guillermo Umpierrez, Iulia Cristina Tudor, Tina K. Schlafly, Daniel Einhorn, John C. Parker, Lauren Kruszon, Robert S. Busch, Abbey Fruiterman, Yehuda Handelsman, Narges Heidarpour, Jonathan G. Ownby, Nashia Stephens, Vanita R. Aroda, Rita Gyurko, Pratibha Rao, Kelly Paulus, Mark Kipnes, Terri Ryan, Michael H. Shanik, Lisa Iannuzzi, Guillermo Umpierrez, Gloria Centeno, Timothy Bailey, Andrew Eskeland, Ronald S. Swerdloff, Elizabeth Ruiz, Jean Park, Maria Hurtado, Adline Ghazi, Mia Hamm, Harold J. Miller, Rosina Ducote, Lawrence Blonde, Shannon Williams, Kathleen Wyne, Lindsey Aldrich, Andrew Ahmann, Deborah Branigan, Samer Nakhle, Sasha Sandry, Elena A. Christofides, Jennifer Botte, Athena Philis-Tsimikas, Rosario Rosal, Bradley Eilerman, Cashmere Hardy, Lance Alan Sloan, Katia Sloan, Sam Lerman, Maria Martin, Dragana Lovre, Mary Simmons, Richard J. Auchus, Rodica Pop-Busui, Thaira Blanco Varela, John B. Buse, Franziska Gassaway, Ralph A. DeFronzo, Curtiss Puckett, Steven E. Kahn, Karen Atkinson, Michael Zimmerman, Colleen Jacobsen, Matthew Wenker, Austin Schultz, Dan Lender, Julio Rosenstock, Allison Camacho, Mark Leibowitz, Rosario Sanchez, John Delgado, Kari Jaasko, Stanley Hsia, Cecilia Rodriguez, David Guzman, Lourdes Garibay, Margaret Chang, Tatyana Nixon
Journal: Diabetes Care (2025)

OBJECTIVE Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes and HbA1c 7.5%–11.5% (58–102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure–lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol &amp;gt;1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed. RESULTS Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure–lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium–glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure–lowering medications (1.390); older age (1.316); BMI &amp;lt;30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P &amp;lt; 0.03). CONCLUSIONS Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.