Prevalence and Predictors of Hypercorticolism in Patients With Difficult to Control Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a major global health burden, affecting approximately 589 million adults worldwide in 2024, with the number projected to reach 853 million by 2050 .Despite advances in glucose-lowering therapy, a substantial proportion of patients remain inadequately controlled despite multiple medications . Hypercortisolism is a potentially reversible contributor to poor glycemic control. Excess cortisol promotes hepatic gluconeogenesis, impairs peripheral insulin sensitivity, and adversely affects β-cell function, thereby contributing to insulin resistance and hyperglycemia .Clinical manifestations of Cushing syndrome may overlap with common features of T2DM and obesity, making mild or clinically unapparent hypercortisolism difficult to recognize . Recent evidence has highlighted the relevance of hypercortisolism in patients with difficult-to-control T2DM. In the multicenter CATALYST study, 23.8% of 1,057 participants with inadequately controlled T2DM had an abnormal 1-mg dexamethasone suppression test (DST), defined as post-DST cortisol \>1.8 µg/dL (50 nmol/L) . However, data regarding the prevalence and clinical characteristics of hypercortisolism among Egyptian patients with difficult-to-control T2DM are lacking. The Endocrine Society recommends biochemical testing for suspected Cushing syndrome using validated first-line tests, including the 1-mg overnight DST, late-night salivary cortisol, or urinary free cortisol .Therefore, determining the prevalence and characteristics of hypercortisolism in difficult-to-control T2DM may help identify a potentially treatable contributor to persistent hyperglycemia and provide locally relevant evidence for clinical practice.

Inclusion Criteria: 1. \- Age: Adults ≥18 years and ≤70 years. 2. \- Diagnosis: Confirmed Type 2 Diabetes Mellitus ≥2 years duration according to ADA criteria. 3- Definition of Difficult-to-Control T2DM: HbA1c ≥8.5% on two separate measurements ≥3 months apart, despite adherence to ≥3 antidiabetic medications including basal insulin ≥0.5 IU/kg/day for a minimum of 6 months. 4- Treatment adherence: Confirmed medication adherence and proper insulin injection technique by clinical assessment + pharmacy refill records 5- Willingness: Signed informed consent to participate in the study and undergo 1mg DST + confirmatory tests Exclusion Criteria: 1. Type 1 DM or any other specific types of diabetes. 2. Pregnancy or lactation- due to physiological hypercortisolism. 3. Current or recent use \