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Insulin sensitivity and secretion and adipokine profile in patients with Cushing's disease treated with pasireotide
V Guarnotta1, G Pizzolanti1, A Ciresi1
1Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Diabetes, Endocrinology and Metabolism, University of Palermo, Piazza delle Cliniche 2, 90127, Palermo, Italy.
Purpose:
To evaluate the effect of pasireotide on β-cell and adipose function in patients with Cushing's disease (CD).
Methods:
Clinical and hormonal parameters, insulin secretion evaluated by HOMA-β and by the area under the curve (AUC2h) of C-peptide during a mixed meal tolerance test and insulin sensitivity, evaluated by the euglycaemic hyperinsulinaemic clamp, were evaluated in 12 patients with active CD, before and after 6 and 12 months of pasireotide. In addition, a panel of adipokines including leptin (Ob), leptin/leptin receptor ratio (Ob/Ob-R ratio), adiponectin, resistin, visfatin, adipocyte fatty acid binding protein (AFABP) and non-esterified fatty acids (NEFAs) was evaluated at baseline and after 12 months of pasireotide.
Results:
During 12 months of pasireotide treatment, a significant decrease in weight (p = 0.004), BMI (p = 0.008), waist circumference (p = 0.009), urinary free cortisol (p = 0.007), fasting insulinaemia (p = 0.007), HOMA-β (p = 0.015) and AUC2h c-peptide (p = 0.017), concomitance with an increase in fasting glycaemia (p = 0.015) and HbA1c (p = 0.030), was found. With regard to adipokines, a significant decrease in Ob (p = 0.039), Ob/Ob-R ratio (p = 0.017) and AFABP (p = 0.036) was observed concomitant with a significant increase in Ob-R (p = 0.028) after 12 months of pasireotide.
Conclusions:
12 months of treatment with pasireotide in CD is associated with an impairment of insulin secretion and an improvement of adipose function without any interference in insulin sensitivity.
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