How Do Serum Zonulin Levels Change in Gestational Diabetes Mellitus, Pregnancy Cholestasis, and the Coexistence of Both Diseases?

Abstract

We investigated the question of how serum zonulin levels change in intrahepatic cholestasis of pregnancy (ICP) and gestational diabetes mellitus (GDM) and, in the case of the coexistence of ICP and GDM, evaluated the eventual increase in zonulin plasmatic levels. Participants were enrolled for the study between 25 February 2021 and 20 August 2021. The prospective case-control study included: group 1 of 95 pregnant women diagnosed with ICP; group 2 of 110 pregnant women diagnosed with GDM; group 3 of 16 women diagnosed with both GDM and ICP; group 4 of 136 healthy pregnant women as the control group. The groups were compared in terms of age, body mass index (BMI), gravidity, parity, gestational week of delivery, plasma zonulin levels, delivery type, birth weight, first- and fifth-minute APGAR scores, newborn intensive care unit (NICU) admission, and meconium staining of amniotic fluid parameters. The results suggested that the plasma zonulin levels of ICP (group 1), GDM (group 2), and GDM with ICP (group 3) patients were higher than those of the healthy pregnant women of group 4 (p < 0.001). Among the patient groups, the highest median plasma zonulin levels were found in group 3 (110.33 ng/mL). Zonulin levels were also associated with the severity of ICP and adverse pregnancy outcomes. High serum zonulin levels were related to GDM, ICP, and adverse perinatal outcomes. The coexistence of GDM and ICP led to higher serum zonulin concentrations.

Changes in Oxidative Stress and Intestinal Permeability during Pregnancy in Women with Gestational Diabetes Mellitus Treated with Metformin or Insulin and Healthy Controls: A Randomized Controlled Trial

“…Mokkala et al [36] reported an increase in serum zonulin concentration from early to late pregnancy, suggesting that intestinal permeability is increased as pregnancy proceeds. Previous studies, such as Daneshvar et al [16] or Guvey et al [35], have demonstrated the relationship between zonulin and GDM, showing higher serum zonulin levels in women with GDM compared to non-diabetic pregnant women. Our data showed a significant increase in zonulin during the follow-up in both healthy controls and GDM women treated with insulin; nevertheless, it remained the same in those women with GDM treated with metformin, probably due to the beneficial changes in the composition of gut microbiota.…”

“…Dysbiosis produces an increase in intestinal permeability regulated by zonulin, among others. The stimulation of a zonulin release leads to the dissociation of the zonula occludens-1 protein from tight junctions between intestinal epithelial cells, resulting in increased intestinal permeability [35], which can favor the movement of LPS, which are strong inducers of inflammation [17]. Mokkala et al [36] reported an increase in serum zonulin concentration from early to late pregnancy, suggesting that intestinal permeability is increased as pregnancy proceeds.…”

Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions

“…The association between zonulin levels and impaired glucose metabolism has also been described in patients with obesity [ 62 , 141 , 142 , 143 , 144 ] or insulin resistance associated with polycystic ovary syndrome (PCOS) [ 145 , 146 ]. Moreover, it has recently been shown that elevated levels of zonulin could be a potential predictor of complications related to pregnancy, including gestational diabetes (GDM), intrahepatic cholestasis (ICP), hypertensive disorders (HDP), and adverse perinatal outcomes [ 131 , 147 , 148 , 149 , 150 , 151 , 152 ].…”

Colestasis intrahepática en el embarazo: una revisión actualizada

“…Es una condición benigna para la paciente, ya que se asocia a náuseas, pérdida de apetito y dolor en el cuadrante superior derecho del abdomen, asociándose con un buen pronóstico en general. Sin embargo, puede afectar negativamente al feto ya que se ha relacionado con parto pre término, sufrimiento fetal agudo, líquido amniótico meconial y óbito (Güvey et al, 2021;López-Pérez et al, 2022). Se considera que esta afección es de origen multifactorial, ya que se ha asociado a condiciones hormonales, ambientales y genéticas (Ferreiro-Fernando et al, 2020).…”