The Cortisol–Diabetes Connection

In the second episode of our insights series, Cortisol and Type 2 Diabetes: What Patients Need to Know, John Buse, M.D., Ph.D., addresses the complex question of whether cortisol is a direct cause of type 2 diabetes or a contributing factor. Buse explains that even with massive exposure to steroids — such as during high-dose chemotherapy for lymphoma or abrupt autoimmune disease onset — cortisol alone is generally not enough to cause diabetes in a completely normal or diabetes-resistant individual. Instead, it acts as a powerful catalyst in people who already carry an underlying, background risk for the disease. While a large portion of the population is fundamentally at risk because their bodies cannot secrete enough insulin to compensate for increased insulin resistance, individual sensitivity to steroids varies wildly; some individuals can gain significant weight and maintain normal glucose tolerance, while others might develop hyperglycemia from a quick steroid taper for something as simple as poison ivy.

The episode goes on to explore the multiple biological mechanisms through which cortisol contributes to high blood sugar. Buse breaks down how cortisol disrupts normal metabolism on several fronts: it increases insulin resistance specifically in the muscles to decrease glucose uptake, spikes hepatic glucose production in the liver and triggers lipolysis, which is the breakdown of fat cells. Furthermore, excess cortisol reduces direct insulin secretion and negatively impacts the production of incretin hormones. By systematically interfering with how these different organs and hormones process energy, cortisol builds a multi-layered path toward hyperglycemia.

Finally, Buse tackles the relationship between chronic stress, hypercortisolism and insulin resistance, noting that the relationship is far more intricate than most patients realize. While chronic stress is associated with elevated cortisol, Buse clarifies that the severe level of excess cortisol causing difficult-to-control type 2 diabetes involves a more complex bodily process than just daily lifestyle stress alone. Because cortisol receptors are active in every single cell in the body, excess levels can trigger a dozen or more disruptive mechanisms simultaneously. This widespread impact allows cortisol to interfere not only with glucose metabolism, but also with blood pressure regulation, vascular biology, and bone health, illustrating just how deeply intertwined hormonal balance is with a patient’s total cardiovascular and metabolic wellness.