Urinary Peptides Associated Closely with Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is a common disease of pregnant women, which has a higher incidence in recent years. The purpose of this study is to explore urinary biomarkers that could predict and monitor gestational diabetes mellitus (GDM). Urine samples from 30 normal pregnant women and 78 GDM patients were collected and purified by weak cationic exchange magnetic beads (MB-WCX), then analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The urinary peptide signatures of the two groups were compared by BioExplorer software. The potential ability of the differently expressed peptides to distinguish GDM patients from normal pregnant women was evaluated by receiver operating characteristic (ROC) analysis. At last, the differently expressed peptides were identified by liquid chromatography tandem mass spectrometry (LC-MS). There were four differently expressed peptides (m/z 1000.5, 1117.5, 1142.9, and 2022.9) between two groups, which were identified as fragments of urinary albumin, α2-macroglobulin, human hemopexin, and α1-microglobulin, respectively. The diagnostic efficacy of m/z 1142.9 was better than the other peptides. The area under the curve (AUC) of the m/z 1142.9 was 0.690 (95% CI: 0.583-0.796). The discovery of urinary polypeptides provides the possibility for the early prediction of GDM and the monitoring of glucose metabolism in GDM patients by a noninvasive method.

Establishment of clinical diagnostic models using glucose, lipid, and urinary polypeptides in gestational diabetes mellitus

“…The clinical characteristics of all the subjects and the levels of lipid metabolism markers were compared (Table 1). There were no significant differences in age, pre‐pregnancy body mass index, average gestational age, and average number of pregnancies and births, between the two groups ( p > 0.05) 8 . The serum TRIG and HDL‐C levels in the first trimester were significantly different ( p < 0.05) between the GDM and N groups.…”

“…The AUC of the 11 indexes were 0.704, 0.565, 0.698, 0.769, 0.612, 0.621, 0.670, 0.641, 0.612, 0.690, and 0.600, respectively. ROC analyses of ALBU, A2MG, HEMO, and AMBP have been reported 8 …”

“…The serum triglyceride (TRIG) and high‐density lipoprotein cholesterol (HDL‐C) values in the first trimester (8–12 weeks), and values of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) of OGTT in the second trimester (24–28 weeks) were collected by the laboratory information system (LIS) at our hospital. Seven GDM‐related urinary peptide markers were successfully identified in previous studies, including coagulation factor IX (F IX), TBC1 family member 5 isoform a (Homosapiens) (TBC1D5a), human immunoglobulin kappa constant (human C_k gene), urine albumin (ALBU), alpha‐2‐macroglobulin (A2MG), human hemopexin (HEMO), and alpha‐1‐Microglobulin (AMBP) 8,9 . The peak values of the seven urine polypeptides were retrospectively analyzed.…”

“…Seven GDM‐related urinary peptide markers were successfully identified in previous studies, including coagulation factor IX (F IX), TBC1 family member 5 isoform a (Homosapiens) (TBC1D5a), human immunoglobulin kappa constant (human C_k gene), urine albumin (ALBU) , alpha‐2‐macroglobulin (A2MG), human hemopexin (HEMO) , and alpha‐1‐Microglobulin (AMBP). 8 , 9 The peak values of the seven urine polypeptides were retrospectively analyzed.…”

“…Based on the screening of GDM‐related clinical indexes and urine polypeptides, 7 , 8 , 9 the clinical diagnostic value of each index was compared horizontally, and the diagnostic models of different statistical classification methods were established in combination with each index. We hope that through the establishment of the diagnosis model, clinical, and research indexes can be applied to the clinical prevention, diagnosis, and dynamic monitoring of GDM.…”