Cortisol secretion and abnormalities of glucose metabolism in nondiabetic patients with hypertension

Abstract

Objective: Glycometabolic changes are associated with hypercortisolism in Cushing's syndrome. Because impaired glucose tolerance (IGT) and insulin resistance are frequently detected in patients with essential hypertension, we hypothesized that in these patients, early glycometabolic abnormalities might be related to differences in regulation of cortisol secretion. Methods: In a cross-sectional study, we included 155 nondiabetic, essential hypertensive patients who were free of organ complications. The homeostasis model assessment (HOMA) index and the area under the curve of plasma glucose (AUC-glucose) and insulin (AUC-insulin) concentration following an oral glucose tolerance test were measured, together with daily plasma cortisol (8 a.m., 3 p.m. and 12 a.m.; AUC-cortisol) and 8 a.m. cortisol after 1 mg overnight dexamethasone suppression test (DST). Results: IGT was present in 27% of patients who were older and had higher BMI, plasma triglycerides and uric acid, AUC-cortisol and DST-cortisol, and lower HDL-cholesterol. Frequency of IGT increased progressively across tertiles of DST-cortisol, together with levels of glycated hemoglobin, fasting insulin and C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. AUC-cortisol and DST-cortisol were directly correlated with insulin, C-peptide, HOMA-index, AUC-glucose, and AUC-insulin. Multivariate regression analysis showed that DST-cortisol was directly and independently correlated with HOMA index, AUC-glucose, and AUC-insulin. In a logistic regression model, both AUC-cortisol and DST-cortisol independently predicted IGT. Conclusion: Daily cortisol and cortisol response to DST are independent determinants of IGT and insulin resistance in nondiabetic patients with hypertension, suggesting that even subtle differences in regulation of cortisol secretion might increase the risk of these patients to develop diabetes.

Predictive Modeling of Resistant Hypertension Risk: Incorporating the TyG Index and Clinical Factors

“…Existing clinical studies have also found that IR is an independent risk factor for autonomic imbalance based on 6-month follow-up observations [28]. Furthermore, research has shown a close relationship between IR and cortisol levels as well as pro-inflammatory factors; suggesting involvement of hypothalamic-pituitary-adrenal axis activity and macrophages in fat mobilization [29][30].…”

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension

“…Thus, differences in cortisol secretion within a physiological range could contribute to a prothrombotic state and thereby to hypertensive organ damage. Also, to this point it should be noticed that minor differences in regulation of cortisol secretion were previously found to be associated with impaired glucose metabolism in nondiabetic hypertensive patients ( 36 ) and greater left ventricular mass ( 30 ), suggesting additional mechanisms that might mediate detrimental cardiovascular effects of cortisol in essential hypertension.…”

“…Plasma cortisol was measured by immunoassay (Electro Chemiluminescence ECLIA, Elecsys cortisol II, Roche Diagnostics, Basel, Switzerland) with an intraassay and interassay coefficient of variation of 1.7% and 2.3%, respectively, and the lowest detection limit of 1.5 nmol/L. The area under the curve of daily cortisol (8 AM, 3 PM, 12 AM; AUC-cortisol) was calculated by the trapezoidal rule ( 36 ). Duplicate 24-hour urinary collections were obtained for measurement of free cortisol excretion with a direct chemiluminescence technique (ADVIA Centaur Cortisol Immunoassay System, Siemens Healthcare, Milan, Italy; detection range, 14–2069 nmol/l) and the average value was considered.…”