Secondary diabetes mellitus in pheochromocytomas and paragangliomas.
Adrenergic phenotype
Aerobic glycolysis
Impaired insulin secretion
Noradrenergic phenotype
PPGLs
Secondary diabetes mellitus
Journal
Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
received:
28
06
2023
accepted:
10
08
2023
medline:
1
11
2023
pubmed:
21
9
2023
entrez:
21
9
2023
Statut:
ppublish
Résumé
Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.
Identifiants
pubmed: 37731140
doi: 10.1007/s12020-023-03492-7
pii: 10.1007/s12020-023-03492-7
pmc: PMC10618385
doi:
Substances chimiques
Sodium-Glucose Transporter 2 Inhibitors
0
Insulin
0
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
467-479Informations de copyright
© 2023. The Author(s).
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