A Significantly Higher Glucose Concentration in Plasma Collected with Glycolytic Inhibitors than in Serum: Impact of Insulin Resistance

<b>Objectives</b>: This study aimed to identify factors influencing the magnitude of the difference between plasma glucose concentration (Glu(P)) and serum glucose concentration (Glu(S)). <b>Methods</b>: A total of 333 healthy Japanese adults aged 22-29 years (212 males and 121 females) were enrolled. Plasma samples were collected using glycolytic inhibitors, whereas serum samples were obtained without glycolytic inhibitors and kept at room temperature. Glu(P) and Glu(S) were measured and compared. <b>Results</b>: The median difference between Glu(P) and Glu(S), defined as Glu(P-S), was 4 mg/dL across all participants, with no gender-related differences. A strong positive correlation was observed between Glu(P) and Glu(S). Glu(P-S) was positively correlated with body mass index, Glu(P), triglyceride-glucose index, white blood cell count, serum sodium, magnesium, and zinc levels. In contrast, Glu(P-S) was negatively correlated with Glu(S), hemoglobin A1c (HbA1c), homeostasis model assessment of beta-cell function, and high-density lipoprotein cholesterol (HDL-C). Multiple regression analysis demonstrated that HDL-C and HbA1c were independent determinants of Glu(P-S) in the overall cohort. Among females, HDL-C, triglyceride, low-density lipoprotein cholesterol, ferritin, and <i>C</i>-reactive protein independently influenced Glu(P-S), whereas no independent determinants were identified in males. <b>Conclusions</b>: Plasma glucose concentrations measured with glycolytic inhibitors were significantly higher than serum glucose concentrations measured without inhibitors at room temperature. The magnitude of Glu(P-S) appears to be associated with markers of insulin resistance, particularly HDL-C levels.