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The relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes.Adults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay.We recruited 333 subjects (186 females and 147 males), aged 56.1 +/- 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p0.0001) and lasted until 2 h (p0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = -0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPGor = 5.55 mmol/l (p = 0.025) but not in those with FPG5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference.Serum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.