Growth hormone and glycemic metabolism.

Abstract

Growth hormone (GH) is secreted in a pulsatile pattern and exerts pleiotropic effects on growth and metabolism. Beyond its role in somatic development, GH is a key regulator of glucose homeostasis through its influence on insulin signaling, lipid mobilization, and substrate partitioning. Chronic disturbances of the GH-IGF-1 axis profoundly affect glucose metabolism. In acromegaly, sustained GH and IGF-1 excess induces systemic insulin resistance via direct antagonism of insulin receptor signaling, increased lipolysis, and elevated free fatty acids, ultimately leading to impaired glucose tolerance or overt diabetes in up to half of patients. Conversely, GH deficiency is characterized by visceral adiposity, low IGF-1, and reduced lean mass, changes that also impair insulin sensitivity through distinct mechanisms. These contrasting phenotypes highlight the dual role of GH in modulating insulin action and glucose control. Notably, insulin resistance in acromegaly is paradoxical in that it occurs despite reduced adipose tissue mass, whereas in GH deficiency it is driven by increased fat accumulation. Therapeutic interventions targeting the GH axis -such as transsphenoidal surgery, somatostatin analogues, GH receptor antagonists, and dopamine agonists- have differential effects on glucose homeostasis, ranging from improvement of insulin sensitivity to further impairment depending on the agent. Recognition of these divergent metabolic consequences is critical for personalized management of patients with acromegaly or GH deficiency. Looking ahead, advances in understanding GH-IGF-1-insulin cross-talk and the molecular drivers of insulin resistance may guide the development of novel therapies aimed at optimizing metabolic outcomes in disorders of the GH axis.