From the Research
Low cortisol levels can indeed increase insulin resistance, as evidenced by the most recent and highest quality study available, which suggests that restoring physiological cortisol levels can improve insulin sensitivity and secretion in patients with adrenal insufficiency. When cortisol levels are chronically low, as seen in conditions like adrenal insufficiency, the body's ability to regulate blood glucose becomes impaired. Cortisol plays an important role in maintaining glucose homeostasis by promoting gluconeogenesis (production of new glucose) in the liver and enhancing the body's sensitivity to insulin. Without adequate cortisol, cells become less responsive to insulin's signals to take up glucose from the bloodstream, resulting in insulin resistance. This relationship is complex because while acute high cortisol can cause temporary insulin resistance, chronically low cortisol disrupts the normal feedback mechanisms that regulate glucose metabolism.
Some key points to consider include:
- The study published in 2018 1 found that dual-release hydrocortisone treatment improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency.
- The study published in 2015 2 found that continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve and prevented a continuous decrease in glucose during the night, without compromising insulin sensitivity.
- The study published in 2021 3 found that morning serum cortisol levels can predict central adrenal insufficiency diagnosed by insulin tolerance test, highlighting the importance of cortisol in glucose regulation.
The underlying mechanism involves cortisol's role in regulating inflammatory pathways and energy metabolism, as insufficient cortisol leads to dysregulated inflammatory responses that contribute to insulin resistance at the cellular level. Patients with adrenal insufficiency often require cortisol replacement therapy (such as hydrocortisone at physiological doses of 15-25 mg daily divided into 2-3 doses) to restore normal glucose metabolism.
In terms of specific treatment, the study published in 2018 1 suggests that dual-release hydrocortisone treatment can improve insulin sensitivity and secretion in patients with adrenal insufficiency. However, it is essential to note that the optimal treatment approach may vary depending on individual patient needs and circumstances.
Overall, the evidence suggests that low cortisol levels can contribute to insulin resistance, and restoring physiological cortisol levels can improve insulin sensitivity and secretion in patients with adrenal insufficiency.