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Open Access 08-03-2023 | Acromegaly | Review

Secondary diabetes mellitus in acromegaly

Authors: Melpomeni Moustaki, Stavroula A. Paschou, Paraskevi Xekouki, Kalliopi Kotsa, Melpomeni Peppa, Theodora Psaltopoulou, Sophia Kalantaridou, Andromachi Vryonidou

Published in: Endocrine | Issue 1/2023

Abstract

Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.

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Title: Secondary diabetes mellitus in acromegaly
Authors: Melpomeni Moustaki
Stavroula A. Paschou
Paraskevi Xekouki
Kalliopi Kotsa
Melpomeni Peppa
Theodora Psaltopoulou
Sophia Kalantaridou
Andromachi Vryonidou
Publication date: 08-03-2023
Publisher: Springer US
Keywords: Acromegaly
Insulins
Lipolysis
Hyperglycemia
Lipolysis
Diabetes
Insulins
Published in: Endocrine / Issue 1/2023
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-023-03339-1

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