Clinical Implications of Interleukin-10 and Interleukin-6 Dysregulation in Gestational Diabetes

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DOI: 10.21522/TIJPH.2013.12.02.Art005

Authors : Parameswari. R. P, A. N. Nithish Varman, Mohammed Farooq, Lakshmi Thangavelu

Abstract:

Gestational diabetes (GDM) can result in short-term and lasting health problems for the pregnant mother and the developing foetus. Instead of a sudden inflammatory response, GDM might trigger a chronic, low-level inflammation called "meta-inflammation." This persistent inflammation could play a role in the future development of diabetes, obesity, and cardiovascular issues for both the mother and child. Given this, the present study is an attempt to investigate the association between GDM and inflammation by evaluating the levels of interleukins. The study involved a total of 50 individuals, 25 pregnant women in gestational age 24 to 28 weeks as calculated by LMP and dating scan with gestational diabetes and 25 healthy pregnant women. Interleukin-10 and interleukin-6 levels were estimated by ELISA analysis. The plasma level of the anti-inflammatory marker IL-10 was significantly lower in the GDM group than in the healthy subjects group. Concomitantly the levels of pro-inflammatory cytokine IL-6 were found to be markedly increased in the GDM subjects in comparison to that of healthy subjects. Enhanced inflammatory response has been observed in GDM, suggesting that inflammatory markers could serve as predictive indicators for GDM. Delayed diagnosis could result in significant consequences for both the mother and the child, both in the short and long term. Hence, there is a pressing requirement for early markers of GDM to facilitate timely intervention and treatment. Exploring these inflammatory signals in greater detail presents an opportunity to enhance maternal health outcomes by creating focused and efficient therapeutic approaches.

References:

[1].   Chorell, E., Hall, U. A., Gustavsson, C., Berntorp, K., Puhkala, J., Luoto, R., Olsson, T., and Holmäng, A., 2017, Pregnancy to Postpartum Transition of Serum Metabolites in Women with Gestational Diabetes. Metabolism, 72, pp.27-36.

[2].   Kim, S. Y., Sappenfield, W., Sharma, A. J., Wilson, H. G., Bish, C. L., Salihu, H. M., and England, L. J., 2013, Racial/Ethnic Differences in the Prevalence of Gestational Diabetes Mellitus and Maternal Overweight and Obesity by Nativity Florida, 2004‐2007, Obesity, 21(1), pp.E33-E40.

[3].   Kim, C., Newton, K. M., and Knopp, R. H., 2002, Gestational Diabetes and the Incidence of Type 2 Diabetes: A Systematic Review, Diabetes Care, 25(10), pp.1862-1868.

[4].   Hotamisligil, G. S., 200, Inflammation and Metabolic Disorders, Nature, 444(7121), pp. 860-867.

[5].   Shoelson, S. E., Herrero, L. and Naaz, A., 2007, Obesity, Inflammation, and Insulin Resistance. Gastroenterology, 132(6), pp.2169-2180.

[6].   Donath, M. Y. and Shoelson, S. E., 2011, Type 2 Diabetes as an Inflammatory Disease. Nature Reviews Immunology, 11(2), pp.98-107.

[7].   Ehses, J. A., Perren, A., Eppler, E., Ribaux, P., Pospisilik, J. A., Maor-Cahn, R., Gueripel, X., Ellingsgaard, H., Schneider, M. K., Biollaz, G. and Fontana, A., 2007, Increased Number of Islet-Associated Macrophages in Type 2 Diabetes, Diabetes, 56(9), pp. 2356-2370.

[8].   Sobrevia, L., Salsoso, R., Fuenzalida, B., Barros, E., Toledo, L., Silva, L., Pizarro, C., Subiabre, M., Villalobos, R., Araos, J., and Toledo, F., 2016, Insulin is a Key Modulator of Fetoplacental Endothelium Metabolic Disturbances in Gestational Diabetes Mellitus, Frontiers in Physiology, 7, p.119.

[9].   Hajam, Y. A., Rai, S., Pandi-Perumal, S. R., Brown, G. M., Reiter, R. J. and Cardinali, D. P., 2022, Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function. Neuroendocrinology, 112(8), pp.807-822.

[10].  Varadaiah, Y. G. C., Sivanesan, S., Nayak, S. B. and Thirumalarao, K. R., 2022, Purine Metabolites can Indicate Diabetes Progression, Archives of Physiology and Biochemistry, 128(1), pp.87-91.

[11].  Christian, L. M., and Porter, K., 2014, Longitudinal Changes in Serum Proinflammatory Markers Across Pregnancy and Postpartum: Effects of Maternal Body Mass Index, Cytokine, 70(2), pp.134-140.

[12].  Gomes, C. P., Torloni, M. R., Gueuvoghlanian‐Silva, B. Y., Alexandre, S. M., Mattar, R., and Daher, S., 2013, Cytokine Levels in Gestational Diabetes Mellitus: A Systematic Review of the Literature, American Journal of Reproductive Immunology, 69(6), pp.545-557.

[13].  Thorand, B., Kolb, H., Baumert, J., Koenig, W., Chambless, L., Meisinger, C., Illig, T., Martin, S. and Herder, C., 2005, Elevated Levels of Interleukin-18 Predict the Development of Type 2 Diabetes: Results from the Monica/Kora Augsburg Study, 1984–2002, Diabetes, 54(10), pp.2932-2938.

[14].  Brauner, H., Lüthje, P., Grünler, J., Ekberg, N. R., Dallner, G., Brismar, K., and Brauner, A., 2014, Markers of Innate Immune Activity in Patients with Type 1 and Type 2 Diabetes Mellitus and the Effect of the Anti-Oxidant Coenzyme Q10 On Inflammatory Activity, Clinical & Experimental Immunology, 177(2), pp.478-482.

[15].  Kang, J., Lee, C. N., Li, H. Y., Hsu, K. H., Wang, S. H. and Lin, S. Y., 2018, Association of Interleukin-10 Methylation Levels with Gestational Diabetes in a Taiwanese Population, Frontiers in genetics, 9, p. 222.

[16].  Elenkov, I. J., Wilder, R. L., Bakalov, V. K., Link, A. A., Dimitrov, M. A., Fisher, S., Crane, M., Kanik, K. S. and Chrousos, G. P., 2001, IL-12, TNF-α, and Hormonal Changes During Late Pregnancy and Early Postpartum: Implications for Autoimmune Disease Activity During these times, The Journal of Clinical Endocrinology & Metabolism, 86(10), pp.4933-4938.

[17].  Ni, J., Wang, Y., Zhu, J., Zheng, T., Yu, J. and Xiong, Y., 2022, Interleukin-10 Levels and Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis, The Journal of Maternal-Fetal & Neonatal Medicine, 35(25), pp.7609-7616.

[18].  Van Exel, E., Gussekloo, J., de Craen, A. J., Frolich, M., Bootsma-Van Der Wiel, A. and Westendorp, R. G., 2002, Low Production Capacity of Interleukin-10 Associates with the Metabolic Syndrome and Type 2 Diabetes: The Leiden 85-Plus Study, Diabetes, 51(4), pp. 1088-1092.

[19].  Atègbo, J. M., Grissa, O., Yessoufou, A., Hichami, A., Dramane, K. L., Moutairou, K., Miled, A., Grissa, A., Jerbi, M., Tabka, Z. and Khan, N. A., 2006, Modulation of Adipokines and Cytokines in Gestational Diabetes And Macrosomia, The Journal of Clinical Endocrinology & Metabolism, 91(10), pp.4137-4143.

[20].  Al-Shukaili, A., Al-Ghafri, S., Al-Marhoobi, S., Al-Abri, S., Al-Lawati, J. and Al-Maskari, M., 2013, Analysis of Inflammatory Mediators in Type 2 Diabetes Patients, International Journal of Endocrinology, 2013.

[21].  Richardson, A. C. and Carpenter, M. W., 2007, Inflammatory Mediators in Gestational Diabetes Mellitus, Obstetrics and gynecology clinics of North America, 34(2), pp. 213-224.

[22].  Aktulay, A., Engin-Ustun, Y., Sahin Ozkan, M., Erkaya, S., Kara, M., Kaymak, O. and Danisman, N., 2015, Gestational Diabetes Mellitus Seems to be Associatied with Inflammation, Acta Clinica Croatica, 54(4.), pp.475-478.

[23].  Vrachnis, N., Belitsos, P., Sifakis, S., Dafopoulos, K., Siristatidis, C., Pappa, K. I. and Iliodromiti, Z., 2012, Role of Adipokines and Other Inflammatory Mediators in Gestational Diabetes Mellitus and Previous Gestational Diabetes Mellitus, International Journal of Endocrinology, 2012.

[24].  Wolf, M., Sauk, J., Shah, A., Smirnakis, K. V., Jimenez-Kimble, R., Ecker, J. L. and Thadhani, R., 2004, Inflammation and Glucose Intolerance. A Prospective Study of Gestational Diabetes Mellitus, Clinical Diabetology, 5(2), pp.85-94.

[25]. Xuan Nguyen, K., Bui Minh, T., Dinh, H. T., Viet Tran, T., Dinh Le, T., Phi Thi Nguyen, N., Tran, T. T. H., Hien Vu, T., Ho Thi Nguyen, L., Trung Nguyen, K., and Huy Thong, N., 2023, Low-Grade Inflammation in Gestational Diabetes Mellitus and its Correlation with Maternal Insulin Resistance and Fetal Growth Indices, International Journal of General Medicine, pp.1429-1436.