OBJECTIVE -Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women.RESEARCH DESIGN AND METHODS -Ten glucose-normotolerant, fertile, obese women (BMI Ͼ40 kg/m 2 , aged 38.66 Ϯ 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. RESULTS-No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P ϭ 0.05) and postobese women (P Յ 0.01) as was the decrease in dehydroepiandrosterone (P Յ 0.05 and P Յ 0.01, respectively). CBG decreased from 51.50 Ϯ 12.76 to 34.33 Ϯ 7.24 mg/l (P Յ 0.01) following BPD. FCI increased from 11.15 Ϯ 2.85 to 18.16 Ϯ 6.82 (P Յ 0.05). Insulin secretion decreased (52.04 Ϯ 16.71 vs. 30.62 Ϯ 16.32 nmol/m Ϫ2 ; P Յ 0.05), and insulin sensitivity increased by 163% (P Յ 0.0001). Serum CBG was related to BMI (r 0 ϭ 0.708; P ϭ 0.0001), body weight (r 0 ϭ 0.643; P ϭ 0.0001), body fat percent (r 0 ϭ 0.462; P ϭ 0.001), C-reactive protein (r 0 ϭ 0.619; P ϭ 0.004), and leptin (r 0 ϭ 0.579; P ϭ 0.007) and negatively to M value (r 0 ϭ Ϫ0.603; P ϭ 0.005).CONCLUSIONS -After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity. Diabetes Care 30:1494-1500, 2007N utritional status and activity of the hypothalamic-pituitary-adrenal (HPA) axis are strictly associated (1,2). However, little is known about the effect of starvation and intentional calorie deprivation on the HPA axis (3,4). The HPA axis controls the secretion of cortisol with excessive secretion being inhibited by negative feedback. Several studies suggest that abnormalities in cortisol action and HPA axis control may be a factor that links disturbances of carbohydrate metabolism (which characterize insulin resistance) and obesity (5-6). In obesity, estimation of plasma cortisol does not reflect the function of the HPA axis (7), and levels of cortisol in obese patients have been reported to be normal (8), low (9), or increased (10). On the contrary, response to different stimuli (high secretion of cortisol after laboratory stress tests or after different exo...

Two years after BPD in morbidly obese patients, comorbidities are largely corrected and insulin resistance is fully reversed despite persistent obesity. Initial fat mass, but not residual intestinal length, is the strongest predictor of weight loss after BPD.