Diabetes CareType 2 DiabetesCohortDecember 1, 2025

Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes.

Buse JB, Kahn SE, Aroda VR, Auchus RJ, Bailey T, Bancos I, Busch RS, Christofides EA, DeFronzo RA, Eilerman B, Findling JW, Fonseca V, Hamidi O, Handelsman Y, Miller HJ, Ownby JG, Parker JC, Philis-Tsimikas A, Pratley R, Rosenstock J, Shanik MH, Sloan LL, Umpierrez G, Tudor IC, Schlafly TK, Einhorn D, CATALYST Investigators*

View on PubMed DOI: 10.2337/dc24-2841

Key Finding

Nearly 1 in 4 people (23.8%) with hard-to-control type 2 diabetes have excess cortisol production, which may explain why their blood sugar stays high despite multiple medications.

What This Study Found

Think of cortisol as your body's stress hormone - it's like having your car's accelerator stuck down, constantly flooding your system with signals to raise blood sugar. This study looked at over 1,000 people whose type 2 diabetes wasn't responding well to treatment (HbA1c between 7.5-11.5% despite being on 2+ diabetes medications) and found that nearly a quarter had hypercortisolism - their bodies were producing too much cortisol. It's like trying to put out a fire while someone keeps pouring gasoline on it. The researchers used a dexamethasone suppression test, which is like giving the body a signal to turn off cortisol production overnight - if cortisol stays high the next morning, it suggests the system is stuck in overdrive. The problem was even more common in certain groups: about 1 in 3 people with heart problems had excess cortisol, and over 1 in 3 people taking three or more blood pressure medications had it. Interestingly, people taking newer diabetes medications like SGLT2 inhibitors, maximum-dose GLP-1 drugs, or tirzepatide were more likely to have hypercortisolism - possibly because doctors were already throwing everything they could at these particularly challenging cases.

Statistics Decoded

23.8% prevalence (95% CI 21.3-26.5%): Out of 1,057 people studied, 252 had hypercortisolism - this probably wasn't just luck, like flipping heads 20 times in a row. The real prevalence in similar patients is very likely between 21-27%. 33.3% in cardiac patients and 36.6% in those on 3+ BP meds: These subgroups had even higher rates. 34.7% had adrenal abnormalities on imaging: About 1 in 3 people with excess cortisol also had visible problems with their adrenal glands. Odds ratios ranging from 1.316 to 3.718: Non-Latino/Hispanic ethnicity had nearly 4x higher odds, while older age increased odds by about 32%. All P-values <0.03 means these associations probably weren't due to chance.

Why This Matters

This could be a game-changer for thousands of diabetes patients whose blood sugar won't budge despite multiple medications - screening for excess cortisol might reveal a treatable cause that's been flying under the radar. For doctors, this suggests that when diabetes becomes really stubborn, it might be time to look beyond just adding more diabetes drugs and investigate whether stress hormones are sabotaging treatment efforts.

Original Abstract

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. 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 >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. 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 <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 < 0.03). Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.