Gestational diabetes as an inter-generational cardiometabolic risk factor: spotlight on emerging exerkines.

Abstract

Gestational diabetes mellitus (GDM) is an increasingly prevalent global health condition, driven by rising maternal age and the obesogenic environment, currently affecting approximately 14% of pregnancies worldwide. GDM is associated with adverse perinatal outcomes as well as a substantial increase in long-term cardiometabolic risk. Women with a history of GDM exhibit a markedly elevated risk of developing type 2 diabetes (T2D) within the first decade postpartum, together with an approximately twofold higher risk of major cardiovascular events. Importantly, offspring of mothers with GDM are also predisposed to obesity and T2D later in life, underscoring the role of GDM as a major intergenerational determinant of cardiometabolic disease. Physical activity is recommended as an effective non-pharmacological strategy for the prevention and management of GDM; however, the molecular mechanisms underlying its benefits remain only partially understood. Exerkines, bioactive molecules modulated by exercise, have emerged as important regulators of systemic metabolic and cardiovascular adaptations. In addition to the well-characterised exerkines such as leptin, adiponectin, and irisin, emerging evidence supports the relevance of additional mediators, including chemerin, members of the FGF19 subfamily, and adipsin, as contributors to the pathophysiology of GDM and cardiovascular risk. This narrative review summarises the current evidence on these emerging exerkines, focusing on their biological mechanisms and clinical relevance in GDM. A deeper understanding of the exerkine network may provide novel insights into the interplay between exercise, metabolic regulation, and pregnancy, ultimately supporting improved GDM management and long-term cardiometabolic risk stratification across generations.