Montserrat Broch, Maria Teresa Auguet, Rafael Ramírez, Montserrat Olona, Carmen Aguilar, Ana Megia, Maria José Alcaide, Rosa Pastor, Salomé Martínez, Enric Caubet, Antonio Garcia-España and Cristóbal Richart
Context and objective
Adipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein.
Subjects and methods
One-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): <25 kg/m2) and 89 obese (overweight/obese; BMI: ≥25<40) whose anthropometric and metabolic variables were assessed. mRNA expression was quantified by real-time PCR in subcutaneous adipose tissue (s.c.-AT) of 46 subjects.
There was a tendency for circulating RBP4 levels to positively correlate with waist circumference (β=0.29, P=0.08; R
2=0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (β=0.59, P<0.0001; R
In our population, RBP4 circulating levels were not significantly correlated with obesity-related parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 by other tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels.
Mónica Marazuela, Tomás Lucas, Cristina Alvarez-Escolá, Manel Puig-Domingo, Nuria Garcia de la Torre, Paz de Miguel-Novoa, Alejandra Duran-Hervada, Rafael Manzanares, Manuel Luque-Ramírez, Irene Halperin, Felipe F Casanueva and Ignacio Bernabeu
Pegvisomant is an effective treatment for somatostatin analogue-resistant acromegaly, but the determinants defining the response to this treatment are largely unknown.
To investigate the efficacy of pegvisomant treatment in resistant acromegalic patients (e.g. serum IGF1 at least 1.25×upper normal limit) in a clinical setting and the factors conditioning this response.
Design and setting
A retrospective cross-sectional study performed in six Spanish University hospitals from 2004 to 2007.
Forty-four acromegalic patients (61.4% female, mean age: 49±14), 95% of whom had undergone pituitary surgery and 61% having received pituitary radiotherapy. The mean follow-up was 22.7±11.2 months.
Main outcome measures
IGF1 levels reflected treatment efficacy, and the influence of gender, age, weight, previous radiotherapy and duration of treatment was assessed.
IGF1 normalisation was achieved in 84% of the patients. Male gender (P<0.05), previous irradiation (P<0.05) and the treatment duration (r=0.364, P<0.02) were associated with a better response to pegvisomant therapy. There was a significant decrease in HbA1c (P<0.001) and in the mean insulin dose (P<0.01) in acromegalic diabetic patients. Although 25% of patients experienced mild adverse events, pegvisomant was only withdrawn in four patients due to side effects (two cases of tumour growth, one liver dysfunction and one headache).
Long-term pegvisomant is a very effective therapy in resistant acromegaly. Male gender and prior radiotherapy influence the therapeutic response rate.