Gestational diabetes mellitus (GDM) represents a stage of subclinical inflammation and a risk factor for subsequent future type 2 diabetes and cardiovascular disease development. Leptin has been related with vascular and metabolic changes in GDM with heterogeneous and contradictory results with respect to their possible involvement in maternal, perinatal, and future complications. Our objective is to evaluate current evidence on the role of leptin in maternal and perinatal complications in women with GDM. PubMed, Embase, Web of Science, and Scopus databases were searched. We evaluated the studies’ quality using the Newcastle-Ottawa scale. Meta-analyses were conducted, and heterogeneity and publication bias were examined. Thirty-nine relevant studies were finally included, recruiting 2255 GDM and 3846 control pregnant women. Leptin levels were significantly higher in GDM participants than in controls (SMD = 0.57, 95%CI = 0.19 to 0.94; p < 0.001). Subgroup meta-analysis did not evidence significant differences in leptin in the different trimesters of pregnancy. Meta-regression showed a positive significant relationship for HOMA in the GDM group (p = 0.05). According to these results, it seems that high levels of leptin can be used as predictive markers in GDM.

Gestational diabetes mellitus (GDM) increases the risk of hypertensive disorders of pregnancy (HDP). We aimed to analyze the altered inflammatory markers and angiogenic factors among women with GDM to identify pregnant women at higher risk of developing HDP. Methods: This was a prospective study of 149 women without hypertension diagnosed in the third trimester with GDM. Inflammatory markers and angiogenic factors were measured at 28–32 weeks of pregnancy. Obstetric and perinatal outcomes were evaluated. Results: More than eight percent of the women developed HDP. Higher levels of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PIGF) ratio (4.9 ± 2.6 versus 2.3 ± 1.3, respectively; p < 0.001) and leptin (10.9 ± 0.8 versus 10.08 ± 1.1, respectively; p = 0.038), as well as lower levels of adiponectin (10.5 ± 1.3 versus 12.9 ± 2.7, respectively; p = 0.031), were seen in women who developed HDP versus normotensive women with GDM. A multivariable logistic regression analysis showed that adiponectin had a protective effect with 0.45-fold odds (0.23–0.83; p = 0.012), and that the sFlt-1/PIGF ratio was associated with 2.70-fold odds of developing HDP (CI 95%: 1.24–5.86; p = 0.012). Conclusion: An increase in angiogenic imbalance in the sFlt-1/PIGF ratio in women with GDM was detected and may be an indicator of developing HDP in addition to any subsequent obstetric and perinatal complications.

Dysregulation of NO production is implicated in pregnancy‐related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S‐Nitrosylation is the NO‐derived posttranslational protein modification that can modulate biological functions by forming NO‐derived complexes with longer half‐life, termed S‐nitrosothiol (SNO). Our aim was to examine the presence of endogenous S‐nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n= 8) and GDM (n= 8) pregnancies. S‐Nitrosylation was measured using the biotin‐switch assay, while the expression and protein activity were assessed by immunoblotting and colorimetric methods, respectively. Results indicated that catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas, and that was accompanied by reduced catalase activity. S‐Nitrosylation of ERK1/2 and AKT was increased in GDM placentas, and their activities were inhibited. Activities of caspase‐3 and caspase‐9 were increased, with the latter also showing diminished nitrosylation levels. These findings suggest that S‐nitrosylation is a little‐known, but critical, mechanism by which NO directly modulates key placental proteins in women with GDM and, as a consequence, maternal and fetal anomalies during pregnancy can occur.

Background: The literature provides limited evidence of cord blood leptin levels in gestational diabetes mellitus (GDM), with contradictory and inconsistent results with respect to their possible implications for maternal, perinatal, and future complications. Methods: MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched in order to investigate the state of evidence on the association of leptin profile in cord blood during perinatal complications in GDM. We critically assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed, and heterogeneity and publication bias were analyzed. Results: sixteen primary-level studies were included, recruiting 573 GDM and 1118 control pregnant women. Cord blood leptin levels were significantly higher in GDM participants compared to controls (standardized mean difference [SMD] = 0.59, 95% confidence intervals (CI) = 0.37 to 0.80, p < 0.001). All subgroups also maintained significant differences stratified by continents (Asia: SMD = 0.91, 95% CI = 0.45 to 1.37, p < 0.001; Europe: SMD = 0.38, 95% CI = 0.20 to 0.56, p < 0.001), analysis technique (ELISA: SMD = 0.70, 95% CI = 0.44 to 0.97, p < 0.001; RIA: SMD = 0.30, 95% CI = 0.11 to 0.49, p = 0.002), and sample source (plasma: SMD = 0.71, 95% CI = 0.33 to 1.09, p < 0.001; serum: SMD = 0.55, 95% CI = 0.34 to 0.77, p < 0.001). Conclusion: Cord blood leptin levels were significantly higher in GDM compared to controls. Further research is needed to clarify its role as a predictive biomarker of subsequent metabolic diseases in mothers with GDM and offspring.

Alterations in ambulatory blood pressure detected by monitoring (ABPM) have been associated with perinatal complications in hypertensive pregnant women. Aim: To establish the relationships between the blood pressure (BP) profiles detected by ABPM and adverse perinatal outcomes in normotensive women with gestational diabetes mellitus (GDM). Methods: A prospective study of normotensive women in whom 24 h ABPM was performed at 28–32 weeks of pregnancy. The obstetric and perinatal outcomes were evaluated. Results: Two hundred patients were included. Thirty-seven women with GDM and obesity had significantly higher mean systolic BP (SBP) and nocturnal SBP and diastolic BP (DBP) compared to women with only GDM (n = 86). Nocturnal SBP (OR = 1.077; p = 0.015) and obesity (OR = 1.131; p = 0.035) were risk factors for the development of hypertensive disorders of pregnancy (HDPs). Mothers of newborns with neonatal complications (n = 27) had higher nocturnal SBP (103.8 vs. 100 mmHg; p = 0.047) and DBP (62.7 vs. 59.4; p = 0.016). Women who delivered preterm (n = 10) had higher BP and a non-dipper pattern (p = 0.005). Conclusions: Nocturnal SBP was a predictor of HDPs in normotensive women with obesity or GDM. Alterations in ABPM in these patients were associated with poor obstetric and perinatal outcomes.