Evaluation of oxidative stress and proinflammatory cytokines in gestational diabetes mellitus and their correlation with pregnancy outcome

Abstract

Background: Prevalence of Gestational Diabetes Mellitus in India is increasing. In addition to performing physiological role in fetoplacental unit during pregnancy, cytokines also play pathophysiological role if expressed in abnormal amounts or sites. Objective: To estimate Proinflammatory Cytokines TNF-α, IL-6, IL-8 and anti-oxidants Glutathione Peroxidase (GTX), Superoxide dismutase (SOD), uric acid and Bilirubin levels in GDM and correlate with pregnancy outcome. Results: Pregnant women were screened for GDM using Diabetes In Pregnancy Study group, India criteria. The subjects with elevated glucose were grouped into cases ( n = 30) and with normal values were taken as controls ( n = 30). Mean Uric acid in cases was 4.53 ± 1.2 mg% whereas in controls 3.13 ± 0.58 mg%, mean TNF-α among cases was 6.06 ± 3.6 pg/ml and controls 2.81 ± 1.03 pg/ml. Antioxidants SOD and GTX were markedly decreased with mean value of 4979.21 ± 1006.3 and 13.68 ± 1.5 in cases and 9625.10 ± 1074.1 and 15.86 ± 1.2 in controls. Cytokines IL-6 (2.96 + 1.37 vs 2.88 + 1.21) and IL-8 (7.76 + 3.86 vs 2.60 + 1.45) were increased in subjects with GDM. Those with GDM developed preeclampsia (5%), Preterm labour (2%) and Polyhydromnios (5%). Foetal complications Macrosomia (13.3%) and intra uterine death (3.3%) were observed in GDM mothers. The proinflammatory cytokine levels except IL-6 were significantly increased and antioxidant markers were significantly reduced in GDM group with maternal and foetal complications. Conclusion: GDM worsens the oxidative stress and weakens anti-oxidant state. Uric acid, TNF-α and IL-8 were higher with foeto-maternal complications in GDM. Serum bilirubin, GTX and SOD is significantly lower in foeto-maternal complications. TNF-α significantly associated with preeclampsia in GDM mothers.

Role of interleukin-6 (IL-6) in predicting gestational diabetes mellitus

“…In type 2 diabetes, inflammatory cytokines may induce insulin resistance by suppressing multiple pathways in target tissues that are responsible for proper insulin signaling [ 44 ]. Insulin resistance is associated with abnormal secretion of proinflammatory cytokines, such as IL-6 [ 4 ]. In non-pregnant women, BMI and high body fat mass have been found to be associated with elevated levels of serum IL-6 [ 13 ].…”

“…Obesity and advanced maternal age are associated with the increasing prevalence of GDM worldwide. GDM heightens the potential risk of type 2 diabetes onset in the mother and her offspring [ 4 ]. The prevalence of GDM worldwide is estimated to be 17%, varying across different regions, with an estimate of 10% in North America and 25% in Southeast Asia [ 5 ].…”

“…Numerous studies have been conducted on the association of IL-6 with GDM. Some studies have shown a statistically significant association between elevated IL-6 levels and GDM [ 4 , 13 , 16 ], while others did not report such relationships [ 17 , 18 ]. To this end, considering the contradictory results regarding the association between IL-6 and GDM, and based on the literature, there is no systematic review discussing the association between IL-6 and GDM.…”

Stress adaptation is associated with insulin resistance in women with gestational diabetes mellitus

“…In addition, pregnant women are usually in a stressful condition, which together with increased requirements on oxygen and energy during pregnancy may lead to increased OS injury 9 . Is it possible that changes in stress hormones during pregnancy may also contribute to IR other than OS?…”

Undernutrition during Pregnancy

“…The increased release of pro-inflammatory cytokines and adiponectin was associated with an accumulation of adipose tissues, particularly with central obesity [19][20][21]. These releases contribute to a severe GDM, including increased glucose blood levels [22], endoplasmic reticulum stress [23], and increased insulin resistance [21,24]. Women, diagnosed with a lower adiponectin concentration at their early trimester, are likely to develop an increased insulin resistance and GDM later in their semesters [25].…”