Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective analysis

Objective: Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement of anthropometric and metabolic parameters. The aim of the study was to evaluate the effects of DR-HC on insulin secretion and sensitivity and cardiometabolic risk, indirectly expressed by the visceral adiposity index (VAI). Design and Patients: Retrospective analysis of 49 patients, 13 with primary and 36 with secondary adrenal insufficiency (AI), respectively, on conventional glucocorticoid treatment at baseline and switched to DR-HC for 36 months. Overall, 24 patients had AI-pre–diabetes (impaired fasting glucose, impaired glucose tolerance and the combination), and 25 had AI-normal glucose tolerance (NGT). Measurements: Clinical and metabolic parameters, including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia, AUC2 h insulinaemia, oral disposition index [Dio] and ISI-Matsuda), were evaluated. Results: In patients with AI-NGT and AI-prediabetes, a significant decrease in BMI (P =.017 and P <.001), waist circumference (P =.008 and P <.001), HbA1c (P =.034 and P =.001) and a significant increase in HDL-C (P =.036 and P =.043) was, respectively, observed. In addition, in prediabetic patients, only we found a significant decrease in insulinaemia (P =.014), AUC2 h insulinaemia(P =.038) and VAI (P =.001), in concomitance with a significant increase in DIo (P =.041) and ISI-Matsuda (P =.038). Conclusions: Long-term DR-HC therapy is associated with an improvement in insulin secretion and sensitivity in patients with prediabetes. However, all patients appear to benefit from the treatment in terms of improvement of metabolic and anthropometric parameters. Larger studies are required to confirm our preliminary data.