Cortisol Levels in Patients with Obesity Predict Hypertension and Diabetes 

Researchers may have found a new way to detect hypertension and diabetes in people with obesity: an alteration in the hypothalamic-pituitary-adrenal (HPA) axis. 

One of the significant risk factors for several morbidities, including diabetes mellitus, obesity may be a result of an alteration in the hypothalamic-pituitary-adrenal (HPA) axis. This study examined the effects of the HPA axis’ negative feedback system after 1-milligram dose dexamethasone on cortisol levels to determine if there is an association with diabetes, hypertension, and cortisol. Previous studies have studied alterations in the HPA axis and investigated the significance of the axis’ role in fat tissue distribution leading to insulin resistance and response in the sympathetic nervous system, which induces high blood pressure reading in people with obesity. Researchers have hypothesized that this feedback system indirectly causes high levels of cortisol, leading to hypertension. Diabetes mellitus is thought to be closely related to hypercortisolemia produced by long-term stress and responses of hypoglycemic events often triggered by diabetes medication regimens. A previous meta-analysis discovered a decline in HPA activity in patients classified as having obesity, and that subjects of 30 to 60 years of age experienced a decrease in peripheral levels of cortisol. 

This retrospective study involved 402 patients who were classified by the World Health Organization as having obesity that underwent the dexamethasone suppression test. The test was conducted overnight and entailed administering dexamethasone 1 mg at 11 P.M., followed by drawing a fasting serum cortisol level at 8 A.M the next morning. Exclusion criteria consisted of patients with major depressive disorders or Cushing syndrome, patients utilizing glucocorticoids, estrogens, or antiepileptic medications, patients positive for human chorionic gonadotropin, people with chronic severe stress, patients with HbA1c above 8.5 deemed as having poor glycemic control, and anyone partaking in alcohol abuse. Diabetes and prediabetes were determined using the American Diabetes Associated guidelines. After the test, cortisol levels were drawn, and lab test results were evaluated. This investigation was used to determine if the difference in cortisol levels could predict the incidence of diabetes mellitus and hypertension. Patients with hypertension were diagnosed before the study and were further classified by their drug regimens and diet. This study measured ALT, serum creatinine, serum cortisol, fasting plasma glucose, HbA1c, lipids, and TSH. The cortisol cutoff for the next morning was a reading of 1.8 mcg/dL or lower. Statistical analysis involved means with standard deviations, median range values, ANOVA test, Kruskal-Wallis test, t0tests, Mann Whitney U test, and logistic regression. Data was deemed statistically significant if the P-value was less than 0.05.  

The results showed a statistical significance in comparing patients who had been diagnosed with diabetes vs. those without the disease (p < 0.001), patients with prediabetes vs. those who had not (p = 0.003), and patients with diabetes vs. patients with prediabetes (p = 0.022). The test revealed patients with hypertension had a significantly increased cortisol level (p < 0.001). There was a positive relationship between age (r = 0.319, p < 0.001), HbA1c levels (r = 0.278, p < 0.001), and fasting blood glucose (r = 0.168, p = 0.001). The presence of diabetes and hypertension can solely be predicted by the cortisol levels drawn after a 1mg dexamethasone suppression test according to the findings and the analysis involving logistic regression conducted in this study. There were no findings of a correlation between body mass index and cortisol levels.  

Patients with diabetes mellitus or hypertension who have obesity may have an altered feedback system impacting their cortisol levels. Thus, this test proved to be an effective effort in predicting these comorbidities in this patient population. Limitations of this study include the inability to obtain specific data like blood pressure readings and attributing the change in cortisol entirely to obesity. Future studies can pick up where this study left off by using direct levels of cortisol to evaluate the HPA axis. 

Practice Pearls: 

• Dexamethasone 1mg was administered as an overnight suppression test to examine cortisol correlation in patients who have obesity with hypertension and diabetes mellitus. 
• Patients with hypertension and high fasting blood glucose readings also had high serum cortisol levels post dexamethasone depression testing. 
• Metabolism of cortisol in patients with obesity may indicate diabetes mellitus or hypertension induced by the decrease in the negative feedback mechanism of the HPA axis. 

Sema Hepsen, Erkam Sencar, Davut Sakiz, et. al. “Serum cortisol level after low dose dexamethasone  suppression test may be predictive for diabetes mellitus and hypertension presence in obese patients:  A retrospective study.” Diabetes Research and Clinical Practice 161 (2020). 

Mia Flowers, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy

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