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Incretin Response to Mixed Meal Challenge in Active Cushing's Disease and after Pasireotide Therapy.
Barbot, Mattia; Mondin, Alessandro; Regazzo, Daniela; Guarnotta, Valentina; Basso, Daniela; Giordano, Carla; Scaroni, Carla; Ceccato, Filippo.
Afiliación
  • Barbot M; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile 105, 35128 Padova, Italy.
  • Mondin A; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile 105, 35128 Padova, Italy.
  • Regazzo D; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile 105, 35128 Padova, Italy.
  • Guarnotta V; Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", UOC di Malattie Endocrine, del Ricambio e della Nutrizione, Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
  • Basso D; Laboratory Medicine Unit, Department of Medicine DIMED, University-Hospital of Padova, 35128 Padova, Italy.
  • Giordano C; Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", UOC di Malattie Endocrine, del Ricambio e della Nutrizione, Università degli Studi di Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy.
  • Scaroni C; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile 105, 35128 Padova, Italy.
  • Ceccato F; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile 105, 35128 Padova, Italy.
Int J Mol Sci ; 23(9)2022 May 06.
Article en En | MEDLINE | ID: mdl-35563608
ABSTRACT
Cushing's disease (CD) causes diabetes mellitus (DM) through different mechanisms in a significant proportion of patients. Glucose metabolism has rarely been assessed with appropriate testing in CD; we aimed to evaluate hormonal response to a mixed meal tolerance test (MMTT) in CD patients and analyzed the effect of pasireotide (PAS) on glucose homeostasis. To assess gastro-entero-pancreatic hormones response in diabetic (DM+) and non-diabetic (DM−) patients, 26 patients with CD underwent an MMTT. Ten patients were submitted to a second MMTT after two months of PAS 600 µg twice daily. The DM+ group had significantly higher BMI, waist circumference, glycemia, HbA1c, ACTH levels and insulin resistance indexes than DM− (p < 0.05). Moreover, DM+ patients exhibited increased C-peptide (p = 0.004) and glucose area under the curve (AUC) (p = 0.021) during MMTT, with a blunted insulinotropic peptide (GIP) response (p = 0.035). Glucagon levels were similar in both groups, showing a quick rise after meals. No difference in estimated insulin secretion and insulinglucagon ratio was found. After two months, PAS induced an increase in both fasting glycemia and HbA1c compared to baseline (p < 0.05). However, this glucose trend after meal did not worsen despite the blunted insulin and C-peptide response to MMTT. After PAS treatment, patients exhibited reduced insulin secretion (p = 0.005) and resistance (p = 0.007) indexes. Conversely, glucagon did not change with a consequent impairment of insulinglucagon ratio (p = 0.009). No significant differences were observed in incretins basal and meal-induced levels. Insulin resistance confirmed its pivotal role in glucocorticoid-induced DM. A blunted GIP response to MMTT in the DM+ group might suggest a potential inhibitory role of hypercortisolism on enteropancreatic axis. As expected, PAS reduced insulin secretion but also induced an improvement in insulin sensitivity as a result of cortisol reduction. No differences in incretin response to MMTT were recorded during PAS therapy. The discrepancy between insulin and glucagon trends while on PAS may be an important pathophysiological mechanism in this iatrogenic DM; hence restoring insulinglucagon ratio by either enhancing insulin secretion or reducing glucagon tone can be a potential therapeutic target.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) / Diabetes Mellitus / Diabetes Mellitus Tipo 2 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) / Diabetes Mellitus / Diabetes Mellitus Tipo 2 Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Italia