First trimester zonulin levels and adiposity as predictive indices of gestational diabetes mellitus

  • Ahmed Tijani BawahEmail author
  • Mohammed Mustapha Seini
  • Yakubu A. Yakubu
  • Francis Abeku Ussher
  • Brodrick Yeboah Amoah
  • Huseini Alidu
Original Article



This study was aimed at determining the levels of serum zonulin during the first trimester in pregnant women and to examine the relationship between zonulin and obesity in the development of gestational diabetes mellitus (GDM). Available evidence suggests that the permeability of the gut may be associated with obesity and insulin resistance both of which are characteristics of GDM.


This was a prospective longitudinal study in which a cohort of 314 pregnant women was monitored from first trimester at the Volta Regional Hospital, Ho, Ghana. Maternal serum zonulin and lipids were analyzed during the first trimester, and body mass index (BMI) was calculated for each participant. Glucose challenge tests (GCT) and oral glucose tolerance tests (OGTT) were done between 24 and 28 weeks of pregnancy, and diagnosis of GDM was made in accordance with the American Diabetes Association (ADA) criteria.


Women who developed GDM had elevated serum zonulin levels with sensitivity, specificity, and cutoff points of 80.95%, 80.41%, and > 47.5 ng/mL respectively in predicting GDM. With positive predictive value (PPV) and negative predictive value (NPV) of 0.708 and 0.986, respectively, zonulin has been shown by this study to be a good predictor of GDM. After adjusting for maternal age and BMI, obese pregnant women with elevated plasma zonulin were 109 times likelier to develop GDM as compared to those with normal BMIs.


Zonulin levels are increased significantly during the first trimester of pregnancy in women with GDM, and these increases precede the onset of GDM.


Zonulin Obesity Dyslipidemia Gestational diabetes mellitus 



The researchers express sincere gratitude to the maternity and laboratory departments of the Volta Regional Hospital, Ho, Ghana, for granting them permission to carry out the project in the facility.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical review

The study protocol was reviewed and approved by the joint committee on human research, publications, and ethics of the Kwame Nkrumah University of Science and Technology and the Komfo Anokye Teaching Hospital, Kumasi, Ghana. Protocol number: CHRPE/AP350/14.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Sapone A, De Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55(5):1443–9.CrossRefGoogle Scholar
  2. 2.
    Żak-Gołąb A, Kocełak P, Aptekorz M, Zientara M, Juszczyk Ł, Martirosian G, et al. Gut microbiota, microinflammation, metabolic profile, and zonulin concentration in obese and normal weight subjects. Int J Endocrinol. 2013;2013:1–9.Google Scholar
  3. 3.
    Zhang D, Zhang L, Yue F, Zheng Y, Russell R. Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation. Eur J Endocrinol. 2015;172(1):29–36.CrossRefGoogle Scholar
  4. 4.
    Moreira APB, Texeira TFS, Ferreira AB, Peluzio MCG, Alfenas RCG. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr. 2012;108(5):801–9.CrossRefGoogle Scholar
  5. 5.
    Jayashree B, Bibin Y, Prabhu D, Shanthirani C, Gokulakrishnan K, Lakshmi B, et al. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem. 2014;388(1–2):203–10.CrossRefGoogle Scholar
  6. 6.
    Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernandez-Real JM. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS One. 2012;7(5):e37160.CrossRefGoogle Scholar
  7. 7.
    Carr DB, Gabbe S. Gestational diabetes: detection, management, and implications. Clin Diabetes. 1998;16(1):4.Google Scholar
  8. 8.
    Mokkala K, Tertti K, Rönnemaa T, Vahlberg T, Laitinen K. Evaluation of serum zonulin for use as an early predictor for gestational diabetes. Nutr Diabetes. 2017;7(3):e253.CrossRefGoogle Scholar
  9. 9.
    Seely EW, Solomon CG. Insulin resistance and its potential role in pregnancy-induced hypertension. J Clin Endocrinol Metab. 2003;88(6):2393–8.CrossRefGoogle Scholar
  10. 10.
    Teh WT, Teede HJ, Paul E, Harrison CL, Wallace EM, Allan C. Risk factors for gestational diabetes mellitus: implications for the application of screening guidelines. Aust N Z J Obstet Gynaecol. 2011;51(1):26–30.CrossRefGoogle Scholar
  11. 11.
    Yuan J, Cong L, Pan F-M. Risk factors of gestational diabetes mellitus. Matern Child Health Care China. 2007;33:006.Google Scholar
  12. 12.
    Park JH, Song HJ, Choun JK, Cho JJ, Paek YJ, Park KH, et al. Risk factors for gestational diabetes mellitus. Korean J Obes. 2005;14(3):178–85.Google Scholar
  13. 13.
    Asare-Anane H, Bawah AT, Osa-Andrews B, Adanu R, Ofori E, Tagoe SBRAE, et al. Lipid profile in Ghanaian women with gestational diabetes mellitus. Int J Sci Technol Res. 2013;2(4):168–75.Google Scholar
  14. 14.
    Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012;1258(1):25–33.CrossRefGoogle Scholar
  15. 15.
    Wang W, Uzzau S, Goldblum SE, Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000;113(24):4435–40.Google Scholar
  16. 16.
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(S62-S9):62.CrossRefGoogle Scholar
  17. 17.
    Jakobsdottir J, Gorin MB, Conley YP, Ferrell RE, Weeks DE. Interpretation of genetic association studies: markers with replicated highly significant odds ratios may be poor classifiers. PLoS Genet. 2009;5(2):e1000337.CrossRefGoogle Scholar
  18. 18.
    Yeboah FA, Ngala R, Bawah AT, Mbroh H. Maternal adiposity and serum leptin levels at 11-13 weeks of gestation among pregnant women with gestational diabetes mellitus. Int J Med Health Sci. 2016;5(4):197–202.Google Scholar
  19. 19.
    Zep R. SAS Macro for estimating power for ROC curves in one-sample and two-sample cases. In: 20th annual conference. 1995;1004–1006.Google Scholar
  20. 20.
    Zhang D, Zhang L, Zheng Y, Yue F, Russell R, Zeng Y. Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients. Diabetes Res Clin Pract. 2014;106(2):312–8.CrossRefGoogle Scholar
  21. 21.
    Robbins GR, Wen H, JP-Y T. Inflammasomes and metabolic disorders: old genes in modern diseases. Mol Cell. 2014;54(2):297–308.CrossRefGoogle Scholar
  22. 22.
    Noureldeen AF, Qusti SY, Al-seeni MN, Bagais MH. Maternal leptin, adiponectin, resistin, visfatin and tumor necrosis factor-alpha in normal and gestational diabetes. Indian J Clin Biochem. 2014;29(4):462–70.CrossRefGoogle Scholar
  23. 23.
    De Kort S, Keszthelyi D, Masclee A. Leaky gut and diabetes mellitus: what is the link? Obes Rev. 2011;12(6):449–58.CrossRefGoogle Scholar
  24. 24.
    Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care. 2007;30(Supplement 2):S112–9.CrossRefGoogle Scholar
  25. 25.
    Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, et al. Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care. 2007;30(8):2070–6.CrossRefGoogle Scholar
  26. 26.
    Amici RR. The history of Italian parasitology. Vet Parasitol. 2001;98(1):3–30.CrossRefGoogle Scholar
  27. 27.
    Aziz R, Mahboob T. Lipid profile and serum insulin levels in gestational diabetes. J Dow Univ Health Sci. 2008;2(3).Google Scholar
  28. 28.
    Koivunen RM, Juutinen J, Vauhkonen I, Morin-Papunen LC, Ruokonen A, Tapanainen JS. Metabolic and steroidogenic alterations related to increased frequency of polycystic ovaries in women with a history of gestational diabetes 1. J Clin Endocrinol Metab. 2001;86(6):2591–9.Google Scholar
  29. 29.
    Amraei A, Azemati M. Metabolic status of women with gestational diabetes mellitus six months after delivery. Res J Biol Sci. 2007;2(1):104–7.Google Scholar
  30. 30.
    Bronisz A, Sobiś-Żmudzińska M, Pujanek M, Junik R. An evaluation of selected lipid parameters in pregnancy complicated by gestational diabetes mellitus (part 2): differences resulting from the method of treatment. Diabetologia Doświadczalna i Kliniczna. 2007;7(6):296–5.Google Scholar
  31. 31.
    Mankuta D, Elami-Suzin M, Elhayani A, Vinker S. Lipid profile in consecutive pregnancies. Lipids Health Dis. 2010;9(1):1.CrossRefGoogle Scholar
  32. 32.
    Mazurkiewicz J, Watts G, Warburton F, Slavin B, Lowy C, Koukkou E. Serum lipids, lipoproteins and apolipoproteins in pregnant non-diabetic patients. J Clin Pathol. 1994;47(8):728–31.CrossRefGoogle Scholar
  33. 33.
    Savvidou M, Nelson SM, Makgoba M, Messow C-M, Sattar N, Nicolaides K. First-trimester prediction of gestational diabetes mellitus: examining the potential of combining maternal characteristics and laboratory measures. Diabetes. 2010;59(12):3017–22.CrossRefGoogle Scholar
  34. 34.
    Hollingsworth DR, Grundy SM. Pregnancy-associated hypertriglyceridemia in normal and diabetic women: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes. Diabetes. 1982;31(12):1092–7.CrossRefGoogle Scholar
  35. 35.
    Metzger BE, Phelps RL, Freinkel N, Navickas IA. Effects of gestational diabetes on diurnal profiles of plasma glucose, lipids, and individual amino acids. Diabetes Care. 1980;3(3):402–9.CrossRefGoogle Scholar
  36. 36.
    Son GH, Kwon JY, Kim YH, Park YW. Maternal serum triglycerides as predictive factors for large-for-gestational age newborns in women with gestational diabetes mellitus. Acta Obstet Gynecol Scand. 2010;89(5):700–4.CrossRefGoogle Scholar
  37. 37.
    Rössner S, Öhlin A. Pregnancy as a risk factor for obesity: lessons from the Stockholm pregnancy and weight development study. Obes Res. 1995;3(S2):267s–75s.CrossRefGoogle Scholar
  38. 38.
    Koukkou E, Watts G, Lowy C. Serum lipid, lipoprotein and apolipoprotein changes in gestational diabetes mellitus: a cross-sectional and prospective study. J Clin Pathol. 1996;49(8):634–7.CrossRefGoogle Scholar
  39. 39.
    Wiznitzer A, Mayer A, Novack V, Sheiner E, Gilutz H, Malhotra A, Novack L. Association of lipid levels during gestation with preeclampsia and gestational diabetes mellitus: a population-based study. Am J Obstet Gynecol 2009; 201(5):482. e481–482. e488.Google Scholar

Copyright information

© Research Society for Study of Diabetes in India 2019

Authors and Affiliations

  1. 1.Department of Medical Laboratory Sciences, School of Allied Health SciencesUniversity of Health and Allied SciencesHoGhana
  2. 2.Greater Accra Regional HospitalAccraGhana
  3. 3.School of Public HealthUniversity of Health and Allied SciencesHoGhana
  4. 4.Department of Medical Laboratory SciencesKoforidua Technical UniversityKoforiduaGhana
  5. 5.School of Biomedical and Allied Health SciencesUniversity of GhanaAccraGhana

Personalised recommendations