Serum Levels and Placental Expression of NGAL in Gestational Diabetes Mellitus

Abstract

Objectives. The aim was to investigate neutrophil gelatinase-associated lipocalin (NGAL) levels in the serum and term placentas and its potential role in gestational diabetes mellitus (GDM). Methods. A total of 49 GDM subjects and 39 age-matched women with normal pregnancies were recruited. We examined serum concentrations of NGAL and tumor necrosis factor-α (TNF-α) in maternal blood and cord blood and their expression levels in the term placentas and umbilical cord. Results. Serum NGAL levels were significantly higher in GDM patients than in normal pregnant controls both in the maternal blood (4.80 ± 1.99 vs. 3.66 ± 1.13, P=0.001) and the cord blood (4.70 ± 2.08 vs. 3.85 ± 1.44, P=0.027). Moreover, serum NGAL levels exhibited a positive correlation with various parameters of insulin resistance. Maternal serum NGAL levels positively correlated with the NGAL levels found in the cord blood of the control (r = 0.399, P=0.012) and the GDM subjects (r = 0.349, P=0.014). Finally, the expression of NGAL protein levels in the placenta (1.22 ± 0.39 vs. 0.65 ± 0.23, P<0.001) and umbilical cord (0.65 ± 0.23 vs. 0.25 ± 0.10, P<0.001) were higher in GDM women than those noted in the control subjects. In the GDM group, maternal serum NGAL levels exhibited a positive correlation with placental NGAL mRNA and protein levels (r = 0.848, P=0.008; r = 0.636, P=0.011, respectively). Conclusions. NGAL may be an important adipokine involved in GDM and fetal development. The oversecretion of NGAL from the placenta may contribute to the elevated levels of serum NGAL in gestational diabetes mellitus.

Circulating neutrophil gelatinase-associated lipocalin and gestational diabetes mellitus: a meta-analysis

“…[12,39]. By pooling the current evidence, our results were in chord with findings from previous studies mainly conducted in Chinese population [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30], showing that circulating NGAL levels were higher in GDM cases compared to healthy controls. For instance, in a cohort study involving 41 women with a singleton pregnancy, who developed GDM in the past 12 months, and healthy group of 82 normal pregnancies, the levels of circulating NGAL were significantly higher in those with GDM than that of control group [51.3 ng/mL (39.8-66.1) vs. 17.8 ng/mL (15.5-20.9); p < 0.001] in the first trimester [13].…”

“…For instance, in a cohort study involving 41 women with a singleton pregnancy, who developed GDM in the past 12 months, and healthy group of 82 normal pregnancies, the levels of circulating NGAL were significantly higher in those with GDM than that of control group [51.3 ng/mL (39.8-66.1) vs. 17.8 ng/mL (15.5-20.9); p < 0.001] in the first trimester [13]. Furthermore, another study including 49 GDM subjects and 39 age-matched women with heathy pregnancies not only reported significantly higher level of serum NGAL in GDM women compared with the control in maternal blood (4.80 ± 1.99 vs. 3.66 ± 1.13, p = 0.001) and cord blood (4.70 ± 2.08 vs. 3.85 ± 1.44, p = 0.027), but also found positive correlation between NGAL levels and different clinical markers of insulin resistance (Pearson's correlation coefficient or Spearman's corre-lation coefficient ranged from 0.253 to 0.624, all p < 0.05) [30]. Consistently, a Chinese study involving 260 pregnant women showed that, plasma NGAL concentrations tended to be statistically higher in women with GDM and normal prepregnancy BMI (group 2) and in those with GDM and overweighted BMI (group 3) compared with healthy pregnant women with normal BMI (group 1) (p < 0.001 for both group comparisons) [22].…”

“…After reviewing the title and abstract, 101 articles were excluded and the full texts of 32 articles were identified, and 15 articles were further excluded because they did not meet the selection criteria. In total, 17 articles (19 results) met the criteria and were finally included in our analysis [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”

“…Neutrophil gelatinase-associated lipocalin (NGAL), also named lipocalin-2, first identified as a matrix protein of specific granules of human neutrophils [11], was found to exert an effect on the regulation of insulin sensitivity and was associated with insulin resistance [12]. To further investigate the potential role of NGAL in the GDM development, a broad range of studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] was conducted to evaluated the differences of circulating NGAL levels between GDM cases and healthy pregnant women. But large variations in the results were observed across studies, a little difference was obtained from studies by Sweeting AN et al [28] and Wang YY et al [29] compared to the relatively significant differences obtained from most studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”

Clinical application value of serum neutrophil gelatinase-associated lipocalin in neonatal sepsis

“…The NGAL is a lipocalin superfamily member, which was first discovered and named by Lars Kjeldsen in 1993 (12). Normally, NGAL is released from a small amount of neutrophils in bone marrow while under pathological conditions, and it is also upregulated and released by a variety of other cells, such as activated neutrophils, macrophages, and non-hematopoietic epithelial cells (13,14). Meanwhile NGAL is a novel marker of AKI (15,16), and it has been identified as a highly sensitive and nonspecific predictor of AKI injury in pediatric septic shock (17).…”