These authors contributed equally to this work.
Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes
Article first published online: 20 AUG 2012
© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG
BJOG: An International Journal of Obstetrics & Gynaecology
Volume 119, Issue 12, pages 1512–1520, November 2012
How to Cite
Yu, Y., Hanssen, K., Kalyanaraman, V., Chirindel, A., Jenkins, A., Nankervis, A., Torjesen, P., Scholz, H., Henriksen, T., Lorentzen, B., Garg, S., Menard, M., Hammad, S., Scardo, J., Stanley, J., Wu, M., Basu, A., Aston, C. and Lyons, T. (2012), Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes. BJOG: An International Journal of Obstetrics & Gynaecology, 119: 1512–1520. doi: 10.1111/j.1471-0528.2012.03463.x
- Issue published online: 11 OCT 2012
- Article first published online: 20 AUG 2012
- Accepted 25 June 2012. Published Online 20 August 2012.
- Advanced glycation end-products;
- soluble RAGE
Please cite this paper as: Yu Y, Hanssen K, Kalyanaraman V, Chirindel A, Jenkins A, Nankervis A, Torjesen P, Scholz H, Henriksen T, Lorentzen B, Garg S, Menard M, Hammad S, Scardo J, Stanley J, Wu M, Basu A, Aston C, Lyons T. Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes. BJOG 2012;119:1512–1520.
Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE.
Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset.
Setting Antenatal clinics.
Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21).
Methods Maternal serum levels of sRAGE (total circulating pool), Nε-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays.
Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE−).
Results In DM PE+ versus DM PE−, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates.
Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM.