Blood glucose measurement inside and outside the laboratory: both preanalytical and analytical challenges.

Glucose measurement is a critical investigation in metabolic disease management, especially in diabetes and inherited disorders. However, both laboratory-based and handheld point-of-care (HPOC) (glucometers) glucose testing face significant preanalytical and analytical challenges. In central laboratories, glycolysis in uncentrifuged samples leads to glucose consumption, which may compromise diagnostic accuracy. Although sodium fluoride (NaF) is commonly used as a glycolysis inhibitor, it has a delayed effect, requiring several hours to stabilize glucose concentrations. Recently, citrate-buffered NaF-EDTA (FCE) tubes have been introduced to inhibit glycolysis more effectively, yet they remain underused. Preanalytical variables, including sample collection, transport, and processing delays, further impact glucose stability and the diagnosis of diabetes, including gestational diabetes mellitus (GDM). HPOC devices provide an alternative by delivering rapid results and minimizing preanalytical errors, but glucose meters are prone to physiological and analytical interferences, such as hematocrit variations, environmental conditions, presence of redox-active drugs, and enzymatic specificity issues. These interferences may lead to inaccurate glucose readings, impairing clinical decision-making, especially in intensive care and emergency settings. Moreover, discrepancies between capillary and venous glucose concentrations can contribute to misdiagnosis and inappropriate glycemic management. This review provides a comprehensive analysis of glucose measurement methodologies, their limitations, and potential improvements, emphasizing the need for preanalytical harmonization in laboratory testing and a better understanding of interferences in HPOC testing. Standardization of blood sample handling and adoption of optimized collection tubes could enhance glucose measurement reliability, ultimately improving diabetes diagnosis and patient outcomes.