Unexpectedly High Prevalence of Hypercortisolism in Patients with Poorly Controlled Type 2 Diabetes

Core Concepts

A surprisingly high proportion of patients with poorly controlled type 2 diabetes have hypercortisolism, suggesting the need to rethink screening and management approaches for this patient population.

Abstract

The CATALYST trial, a study investigating the prevalence of hypercortisolism in patients with poorly controlled type 2 diabetes, found that 24% of the 1,055 enrolled participants had the condition. This was much higher than the expected prevalence of around 8% based on previous reports. The study enrolled patients with an A1c between 7.5-11.5%, who were taking multiple antihyperglycemic and antihypertensive medications. Rigorous screening using the 1-mg dexamethasone overnight suppression test was employed to detect endogenous hypercortisolism, which was then verified through further lab tests and imaging. Interestingly, 66% of the participants with hypercortisolism had no abnormality on imaging, suggesting the condition may present subtly in this population. The risk of hypercortisolism was highest in those taking two or more antihyperglycemic and two or more antihypertensive medications, as well as those taking three or more blood pressure-lowering drugs, with 35% of this subgroup found to have the condition. The investigators were surprised by the high prevalence and noted that if extrapolated, it could mean over a million people in the US with poorly controlled diabetes may have hypercortisolism. They suggest clinicians may need to rethink their approach to screening and managing these patients, though more data from the ongoing second phase of the CATALYST trial is needed before making definitive recommendations.

Stats

24% of the 1,055 participants with poorly controlled type 2 diabetes had hypercortisolism. The risk of hypercortisolism was highest in those taking two or more antihyperglycemic and two or more antihypertensive medications (OR 1.871, 95% CI 1.406-2.491). 35% of participants taking three or more blood pressure-lowering medications had hypercortisolism.

Quotes

"The investigators were shocked that it was 24% in this study." "As endocrinologists, we've gotten hung up with cutpoints. We should think of hypercortisolism as a continuum."

Key Insights Distilled From

Hypercortisolism Prevalence High in Poorly Controlled T2D

by Alicia Ault at www.medscape.com 06-28-2024

https://www.medscape.com/viewarticle/hypercortisolism-prevalence-high-poorly-controlled-t2d-2024a1000c2q

Deeper Inquiries

What are the potential underlying mechanisms driving the high prevalence of hypercortisolism in this patient population with poorly controlled type 2 diabetes?

The high prevalence of hypercortisolism in patients with poorly controlled type 2 diabetes could be attributed to several factors. Firstly, hypercortisolism, also known as Cushing syndrome, can be a driver of type 2 diabetes, indicating a bidirectional relationship between the two conditions. The chronic exposure to elevated cortisol levels can lead to insulin resistance, impaired glucose metabolism, and ultimately contribute to the development and exacerbation of diabetes. Additionally, the stress response triggered by hypercortisolism can further dysregulate glucose homeostasis, worsening glycemic control in individuals with diabetes. Moreover, the use of multiple antihyperglycemic and antihypertensive medications, common in patients with poorly controlled diabetes, may also play a role in the dysregulation of cortisol levels, potentially exacerbating hypercortisolism in this population.

How might the management of type 2 diabetes need to be adjusted if hypercortisolism is more common than previously thought in this group?

The increased recognition of hypercortisolism in patients with poorly controlled type 2 diabetes suggests a need for adjustments in the management of diabetes in this group. Clinicians may need to consider screening for hypercortisolism in individuals with inadequately controlled diabetes, especially those on multiple antihyperglycemic and antihypertensive medications. Given the potential impact of hypercortisolism on glycemic control, identifying and addressing this condition early could lead to more effective management of diabetes. Furthermore, a shift towards viewing hypercortisolism as a continuum rather than a binary diagnosis may prompt a more nuanced approach to screening and treatment in this patient population. Integrating screening for hypercortisolism into routine diabetes care protocols for individuals with persistent glycemic challenges could improve outcomes and quality of life for these patients.

What are the broader implications of these findings for our understanding of the interplay between metabolic disorders, endocrine dysfunction, and multimorbidity?

The findings regarding the high prevalence of hypercortisolism in patients with poorly controlled type 2 diabetes have significant implications for our understanding of the complex interplay between metabolic disorders, endocrine dysfunction, and multimorbidity. Firstly, these results underscore the intricate relationship between diabetes and hypercortisolism, highlighting the bidirectional influence these conditions exert on each other. This interplay suggests that addressing both metabolic and endocrine factors concurrently may be crucial for optimizing patient outcomes in individuals with comorbid diabetes and hypercortisolism. Additionally, the association between medication burden, particularly the use of multiple antihyperglycemic and antihypertensive agents, and the risk of hypercortisolism emphasizes the importance of considering the broader health context and potential interactions between medications in patients with multimorbidity. These findings call for a more holistic and integrated approach to managing complex metabolic and endocrine conditions, taking into account the interconnected nature of these disorders in individuals with multiple comorbidities.