Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment

Abstract

Acromegaly is a rare disease due to chronic GH excess and to the consequent increase in IGF-1 levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. Indeed, chronic GH excess impairs insulin sensitivity, increases gluconeogenesis, reduces the glucose uptake in adipose tissue and muscle and alters pancreatic β cells function. As a consequence, glucose metabolism alterations are a very frequent complication in acromegaly patients, further contributing to the increased cardiovascular risk and mortality. Treatment modalities of acromegaly differently impact on glucose tolerance. Successful surgical treatment of acromegaly ameliorates glucose metabolism abnormalities. Drugs used to treat acromegaly patients may per se affect glucose homeostasis, therefore influencing patients' management. Indeed pegvisomant has been shown to positively impact on glucose metabolism, while somatostatin analogs, especially pasireotide, can cause hyperglycaemia. On the other hand, robust data on the effect of dopamine agonists on glycaemic profile are still lacking. This review summarizes the available data on diabetes mellitus in acromegaly patients, with a focus on the potential effects of the medical treatment of the disease on glucose homeostasis, providing an overview of the current state of the art.

Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases

“…One of these, Pegvisomant, has completed a phase II clinical trial for modulating insulin sensitivity in subjects with pre-diabetes (NCT02023918). Pegvisomant is used to treat acromegaly by blocking the binding of endogenous growth hormone to growth hormone receptor (GHR) [33][34][35] , and has been shown to improve insulin sensitivity in acromegaly patients 36,37 . The association between the T2D PRS and GHR levels was consistent with repurposing, suggesting Pegvisomant may reduce T2D risk by inhibiting GHR function.…”

McCune–Albright syndrome and type 1 diabetes mellitus: a novel presentation

“…Hyperglycemia can occur in MAS with the development of GH excess and/or hypercortisolemia . However, a specific association between MAS and hyperglycemia due to DM has not been established.…”

“…2 Hyperglycemia can occur in MAS with the development of GH excess and/or hypercortisolemia. 9,10 However, a specific association between MAS and hyperglycemia due to DM has not been established. Sung et al described a 23-year-old male with MAS and recently diagnosed DM treated with an oral antidiabetic medication only.…”

The Interplay Between Pituitary Health and Diabetes Mellitus – The Need for ‘Hypophyseo-vigilance’

“…On the other hand, IGF-1 improves peripheral insulin sensitivity but is not enough to override the diabetogenic action of chronic GH excess. 5 Studies have demonstrated the association of IGF-1 levels and DM as predictors of mortality in acromegaly. 6,7 Adrenocorticotrophic hormone hypersecretion Cushing's disease, or ACTH-secreting pituitary adenoma, is another recognised cause of DM.…”