Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes.
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.


METHODS
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.


METHODS
Antenatal clinics.


METHODS
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), N(ε)-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays.


METHODS
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.
Harold Hamm Diabetes Center and Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK 73104, USA.
Y
Y
Yu
K F
KF
Hanssen
V
V
Kalyanaraman
A
A
Chirindel
A J
AJ
Jenkins
A J
AJ
Nankervis
P A
PA
Torjesen
H
H
Scholz
T
T
Henriksen
B
B
Lorentzen
S K
SK
Garg
M K
MK
Menard
S M
SM
Hammad
J A
JA
Scardo
J R
JR
Stanley
M
M
Wu
A
A
Basu
C E
CE
Aston
T J
TJ
Lyons
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007093:Imidazoles / Q000097:blood; D016014:Linear Models; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood*; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C117197:imidazolone; C048496:N(6)-carboxymethyllysine; D008239:Lysine