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Epidemiology and Population Health

Serum vascular adhesion protein-1 is up-regulated in hyperglycemia and is associated with incident diabetes negatively



Vascular adhesion protein-1 (VAP-1) can enhance tissue glucose uptake in cell studies and normalize hyperglycemia in animal studies. However, serum VAP-1 concentration (sVAP-1) is higher in subjects with diabetes in cross-sectional studies. In this cohort study, we test our hypothesis that sVAP-1 is increased in prediabetes to counteract hyperglycemia and is associated with incident diabetes negatively.


From 2006 to 2012, 600 subjects without diabetes from Taiwan Lifestyle Study were included and followed regularly. Diabetes was diagnosed if FPG ≥ 126 mg/dL (7 mmol/L), 2-h plasma glucose (2hPG) during an oral glucose tolerance test (OGTT) ≥ 200 mg/dL (11.1 mmol/L), or hemoglobin A1c (HbA1c) ≥ 6.5%, or if the subject received anti-diabetic medications. Abdominal fat areas were measured by abdominal computed tomography and sVAP-1 was analyzed by ELISA.


sVAP-1 was higher in subjects with prediabetes (p < 0.05) and increased during an OGTT (p < 0.001). Fasting sVAP-1 was associated with the response of sVAP-1 during an OGTT (p < 0.001). Besides, sVAP-1 was associated negatively with body mass index (BMI, r = −0.1449, p = 0.003), waist circumference (r = −0.1425, p = 0.004), abdominal visceral (r = −0.1457, p = 0.003), and subcutaneous (r = −0.1025, p = 0.035) fat areas, and serum high-sensitivity C-reactive protein (hsCRP) concentration (r = −0.2035, p < 0.0001), and positively with plasma adiponectin concentration (r = 0.2086, p < 0.0001), adjusted for age and gender. After 4.7 ± 2.6 years, 73 subjects (12.2%) developed incident diabetes. High sVAP-1 predicted a lower incidence of diabetes, adjusted for age, gender, BMI, family history of diabetes, HbA1c, HOMA2-%B and HOMA2-IR (HR = 0.66, 95% CI = 0.50–0.88, p < 0.01).


sVAP-1 is increased in response to hyperglycemia. It is associated with obesity and serum hsCRP concentration negatively, and plasma adiponectin concentration positively. Besides, a high sVAP-1 is associated with a lower incidence of diabetes in human.

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This work is supported in part by the grant from the National Science Council, Taiwan (NSC 101-2314-B-002-069-MY3). The authors would like to thank the staff of the eighth Core Lab, Department of Medical Research, National Taiwan University Hospital for their technical and computing assistance.

Author contributions

CH Kuo researched data, contributed to the discussion, and drafted the manuscript. JN Wei researched data, contributed to the discussion, wrote/reviewed the manuscript. CY Yang, HY Ou, HT Wu, KC Fan, SH Wang, CH Hsiao, MK Lee researched data, contributed to the discussion, and reviewed/edited the manuscript. CH Hua provided laboratory assistance and contributed to the discussion. HY Li researched data, contributed to the discussion, and wrote/reviewed/edited the manuscript. HY Li is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Hung-Yuan Li.

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