Endocrine–metabolic regulation during the transition period in dairy cows: mechanisms, biomarkers, and emerging diagnostics for subclinical ketosis

The transition period from late gestation to early lactation represents a phase of marked endocrine and metabolic adjustment in dairy cows, driven by rapidly increasing energy demands associated with the onset of milk production. Alterations in circulating insulin, growth hormone, insulin-like growth factor-1, and cortisol promote nutrient partitioning toward lactation, enhance adipose tissue lipolysis, and increase the release of non-esterified fatty acids (NEFAs) into the bloodstream. When hepatic oxidative capacity and triglyceride export mechanisms are exceeded, excess NEFA uptake favors ketogenesis and accumulation of ketone bodies, particularly β-hydroxybutyrate, resulting in subclinical ketosis (SCK). Although SCK lacks overt clinical signs, it is highly prevalent during early lactation and is associated with impaired immune function, increased susceptibility to postpartum disorders, reduced milk yield, and compromised reproductive performance. This review summarizes current knowledge on the endocrine regulation of lipid mobilization, hepatic metabolic flexibility, and immunometabolic adaptations that contribute to the development of SCK in transition dairy cows. Diagnostic approaches are discussed with emphasis on established biomarkers such as NEFA and β-hydroxybutyrate, milk-based infrared spectroscopy, and emerging biosensor-based technologies, highlighting their advantages, limitations, and applicability for herd-level monitoring. The review also integrates evidence on the economic consequences of SCK and recent advances in precision nutrition, molecular profiling, and machine-learning-based prediction tools that may support earlier detection and targeted management. This synthesis is intended to provide a consolidated overview of endocrine-metabolic mechanisms and diagnostic strategies relevant to subclinical ketosis in dairy cattle during the transition period.