Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients
An adaptive phenomenon?
- Melania Manco, MD, PHD1,
- José M. Fernández-Real2,
- Maria E. Valera-Mora3,
- Henri Déchaud4,
- Giuseppe Nanni5,
- Vincenzo Tondolo5,
- Menotti Calvani3,
- Marco Castagneto5,
- Michel Pugeat4 and
- Geltrude Mingrone3
- 1Liver Unit, “Bambino Gesù” Hospital and Research Institute, Rome, Italy
- 2Department of Diabetes, Endocrinology, and Nutrition, University Hospital of Girona, Girona, Spain
- 3Department of Internal Medicine, Catholic University, Rome, Italy
- 4Fédèration d'Endocrinologie, Hospital Neuro-Cardiologique, Hospices Civils, Lyon, France
- 5Department of Surgery, Catholic University; Rome, Italy
- Address correspondence and reprint requests to Melania Manco, MD, PhD, via Pineta Sacchetti, 484, 00168, Rome, Italy. E-mail: melaniamanco{at}tiscali.it
Abstract
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 >40 kg/m2, aged 38.66 ± 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 = 0.05) and postobese women (P ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m−2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = −0.603; P = 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.
- BPD, biliopancreatic diversion
- CBG, cortisol-binding globulin
- CRP, C-reactive protein
- DEX, dexamethasone
- DEX-ST, DEX suppression test
- FCI, free cortisol index
- FFM, fat-free mass
- HPA, hypothalamic-pituitary-adrenal
- OGTT, oral glucose tolerance test
- RIA, radioimmunoassay
Footnotes
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M.C. is employed by Sigma-Tau (Italy).
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted December 21, 2006.
- Received June 30, 2006.
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