Predictive and Prognostic Value of Plasma Zonulin for Gestational
                    Diabetes Mellitus in Women at 24–28 Weeks of Gestation

Zehra Yilmaz; Serkan Oral; Nazan Yurtcu; Yasam Kemal Akpak; Sebahattin Celik; Canan Caliskan

doi:10.1055/a-1936-0863

Zeitschrift für Geburtshilfe und Neonatologie, Table of Contents

Z Geburtshilfe Neonatol 2022; 226(06): 384-390
DOI: 10.1055/a-1936-0863

Original Article

Predictive and Prognostic Value of Plasma Zonulin for Gestational Diabetes Mellitus in Women at 24–28 Weeks of Gestation

Authors

Zehra Yilmaz

¹Department of Obstetrics and Gynecology, Medical Park Hospitals Group, Istanbul, Turkey
Serkan Oral

²Department of Obstetrics and Gynecology, Halic University, Beyoglu, Turkey
Nazan Yurtcu

³Department of Obstetrics and Gynecology, Sivas Cumhuriyet University, Sivas, Turkey
Yasam Kemal Akpak

⁴Department of Obstetrics and Gynecology, Tepecik Training and Research Hospital Clinics, Izmir, Turkey
Sebahattin Celik

⁵Department of Obstetrics and Gynecology, Balikesir State Hospital, Balikesir, Turkey
Canan Caliskan

⁶Department of Obstetrics and Gynecology, Samsun Education and Research Hospital, Samsun, Turkey

Abstract

Objective We aimed to examine the predictive and prognostic value of plasma zonulin for gestational diabetes mellitus (GDM) in women at 24–28 weeks of gestation.

Methods This retrospective study was carried out with pregnant women with GDM (n=98) and normal glucose tolerance (control group) (n=132). GDM was diagnosed according to American Diabetes Association (ADA) criteria with a one-step 75-g OGTT at 24–28 gestational weeks. Their serum zonulin levels measured during one-step 75-g OGTT and perinatal outcomes were compared, and the cut-off value of plasma zonulin for the prediction of GDM was calculated with receiver operating characteristic curve analysis.

Results Plasma zonulin level was significantly higher in women with GDM compared to controls (28.8±24.9 and 7.3±11.3 ng/mL, respectively). According to logistic regression analysis, plasma zonulin levels and GDM were statistically significant. The plasma zonulin cut-off value was>45.2 ng/mL. The rate of cesarean section, the rate of meconium in the amniotic fluid, and the need for admission to the neonatal intensive care unit significantly differed between women with GDM and controls.

Conclusion In pregnant women with GDM, plasma zonulin increases, and with the cut-off level of>45.2 ng/mL, it can predict GDM with values of sensitivity and specificity levels significantly higher in pregnant women with GDM, suggesting that it can be used as a tool for its screening and early diagnosis.

Key words

gestational diabetes mellitus - zonulin - perinatal outcome - prediction - biomarker

Full Text

References

References
1 Kemal Akpak Y, Gün I, Kaya N. et al. A comparison of pregnant subgroups with positive 50-gram glucose challenge test results to those with negative results in terms of obstetric and perinatal outcomes. Med Glas (Zenica) 2012; 9: 262-267 PMID: 22926361
2 Kyozuka H, Yasuda S, Murata T. et al. Adverse obstetric outcomes in early-diagnosed gestational diabetes mellitus: The Japan Environment and Children’s Study. J Diabetes Investig 2021; 12: 2071-2079
3 Tavera G, Dongarwar D, Salemi JL. et al. Diabetes in pregnancy and risk of near-miss, maternal mortality and foetal outcomes in the USA: a retrospective cross-sectional analysis. J Public Health (Oxf) 2022; 44: 549-557
4 International Diabetes Federation. IDF Diabetes Atlas, 9th ed. Brussels, Belgium: 2019. Available at: https://www.diabetesatlas.org05.17.2021
5 Aktun LH, Yorgunlar B, Karaca N. et al. Predictive risk factors in the treatment of gestational diabetes mellitus. Clin Med Insights Womens Health 2015; 8: 25-28
6 Li-Zhen L, Yun X, Xiao-Dong Z. et al. Evaluation of guidelines on the screening and diagnosis of gestational diabetes mellitus: systematic review. BMJ Open 2019; 9: e023014
7 Plows JF, Stanley JL, Baker PN. et al. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci 2018; 19: 3342
8 Mokkala K, Tertti K, Rönnemaa T. et al. Evaluation of serum zonulin for use as an early predictor for gestational diabetes. Nutr Diabetes 2017; 7: e253
9 Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011; 91: 151-175
10 Fasano A, Not T, Wang W. et al. Zonulin, a newly discovered modulator of intestinal permeability, its expression in coeliac disease. Lancet 2000; 355: 1518-1519
11 Barone MV, Gimigliano A, Castoria G. et al. Growth factor-like activity of gliadin, an alimentary protein: implications for coeliac disease. Gut 2007; 56: 480-488
12 Jauregi-Miguel A. The tight junction and the epithelial barrier in coeliac disease. Int Rev Cell Mol Biol 2021; 358: 105-132
13 Troisi J, Venutolo G, Terracciano C. et al. The therapeutic use of the zonulin inhibitor AT-1001 (Larazotide) for a variety of acute and chronic inflammatory diseases. Curr Med Chem 2021; 28: 5788-5807
14 American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018; 41: S13-S27
15 Todd DJ, Forsberg EM, Greiner DL. et al. Deficiencies in gut NK cell number and function precede diabetes onset in BB rats. J Immunol 2004; 172: 5356-5362
16 Camarero C, Eiras P, Asensio A. et al. Intraepithelial lymphocytes and coeliac disease: permanent changes in CD3-/CD7+and T cell receptor gammadelta subsets studied by flow cytometry. Acta Paediatr 2000; 89: 285-290 PMID: 10772275
17 Watts T, Berti I, Sapone A. et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A 2005; 102: 2916-2921
18 DeMeo MT, Mutlu EA, Keshavarzian A. et al. Intestinal permeation and gastrointestinal disease. J Clin Gastroenterol 2002; 34: 385-396
19 Clemente MG, De Virgiliis S, Kang JS. et al. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut 2003; 52: 218-223
20 Cui M, Qi C, Yang L. et al. A pregnancy complication-dependent change in SIgA-targeted microbiota during third trimester. Food Funct 2020; 11: 1513-1524
21 Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship. Gut 2014; 63: 1513-1521
22 Gomez-Arango LF, Barrett HL, McIntyre HD. et al. Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension 2016; 68: 974-981
23 Wickens KL, Barthow CA, Murphy R. et al. Early pregnancy probiotic supplementation with Lactobacillus rhamnosus HN001 may reduce the prevalence of gestational diabetes mellitus: a randomised controlled trial. Br J Nutr 2017; 117: 804-813
24 Luoto R, Laitinen K, Nermes M. et al. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr 2010; 103: 1792-1799
25 Agarwal MM. Consensus in gestational diabetes mellitus: looking for the Holy Grail. J Clin Med 2018; 7: 123
26 Yeral MI, Ozgu-Erdinc AS, Uygur D. et al. Prediction of gestational diabetes mellitus in the first trimester, comparison of fasting plasma glucose, two-step and one-step methods: a prospective randomized controlled trial. Endocrine 2014; 46: 512-518
27 Aziz NL, Abdelwahab S, Moussa M. et al. Maternal fructosamine and glycosylated haemoglobin in the prediction of gestational glucose intolerance. Clin Exp Obstet Gynecol 1992; 19: 235-241 PMID: 1294344
28 Ozgu-Erdinc AS, Yilmaz S, Yeral MI. et al. Prediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices. J Matern Fetal Neonatal Med 2015; 28: 1957-1962
29 Iliodromiti S, Sassarini J, Kelsey TW. et al. Accuracy of circulating adiponectin for predicting gestational diabetes: a systematic review and meta-analysis. Diabetologia 2016; 59: 692-699
30 Demir E, Ozkan H, Seckin KD. et al. Plasma zonulin levels as a non-invasive biomarker of intestinal permeability in women with gestational diabetes mellitus. Biomolecules 2019; 9: 24
31 Bawah AT, Seini MM, Yakubu YA. et al. First trimester zonulin levels and adiposity as predictive indices of gestational diabetes mellitus. Int J Diabetes Dev Ctries 2019; 39: 451-457