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This work aims to detect the associations of C-peptide and the homeostasis model assessment of beta-cells function (HOMA2-B%) with inflammatory biomarkers in pregnant-women in comparison with non-pregnant women. Sera of 28 normal pregnant women at late pregnancy versus 27 matched age non-pregnant women (control), were used to estimate C-peptide, triiodothyronine (T3), and thyroxin (T4) by Enzyme-linked-immunosorbent assay (ELISA), fasting blood sugar (FBS) by automatic analyzer Biolis 24i, hematology-tests by hematology analyzer and the calculation of HOMA2-B% and homeostasis model assessment of insulin sensitivity (HOMA2-S%) by using C-peptide values instead of insulin. The comparisons, correlations, regression analysis tests were performed by the software of statistical package for the social sciences (SPSS). In pregnant women group, HOMA2-B%, T3, T4, white blood cell (WBC), MID cells, granulocytes (GRAN) increased significantly (p-values˂0.05), while C-peptide level raised about 11% compared to control. Lymphocytes, red blood cells (RBC), platelets (PLT) and hemoglobin (HGB) decreased significantly (p-values˂0.05). Lymphocytes predicted both HOMA2-B% and C-peptide level during pregnancy (R2 =0.516, p ˂0.0004; R2=0.31, p ˂0.009 respectively). Prediction of HOMA2-B% and C-peptide levels by lymphocytes account clarifies that the adaptation in beta-cells might be a part of the defense system mechanism of the body against oxidative stress, and this highlights new insight on the proliferation of beta-cells during pregnancy and insulin sensitivity.
Published Online First 20/1/2022
This work is licensed under a Creative Commons Attribution 4.0 International License.
Genevay M, Pontes H, Meda P. Beta cell adaptation in pregnancy: A major difference between humans and rodents? Diabetologia. 2010;53(10):2089–92.
Lorenzo PI, Martín-Montalvo A, Vuilleumier NC, Gauthier BR. Molecular modelling of islet β-cell adaptation to inflammation in pregnancy and gestational diabetes mellitus. Int J Mol Sci. 2019;20(24).
Leighton E, Sainsbury CA, Jones GC. A Practical Review of C-Peptide Testing in Diabetes. Diabetes Ther. 2017;8(3):475–87.
Kim JD, Kang SJ, Lee MK, Park SE, Rhee EJ, Park CY, et al. C-peptide-based index is more related to incident type 2 diabetes in non-diabetic subjects than insulin-based index. Endocrinol Metab. 2016;31(2):320–7.
Faber OK, Hagen C, Binder C, Markussen J, Naithani VK, Blix PM, et al. Kinetics of human connecting peptide in normal and diabetic subjects. J Clin Invest. 1978;62(1):197–203.
Melles E, Bergman T, Alvelius G, Jonsson A, Ekberg K, Wahren J, et al. Proinsulin C-peptide and its C-terminal pentapeptide: Degradation in human serum and Schiff base formation with subsequent CO2 incorporation. Cell Mol Life Sci. 2003;60(5):1019–25.
Sima AAF, Zhang W, Kreipke CW, Rafols JA, Hoffman WH. Inflammation in diabetic encephalopathy is prevented by C-peptide. Rev Diabet Stud. 2009;6(1):37–42.
Vish MG, Mangeshkar P, Piraino G, Denenberg A, Hake PW, O’Connor M, et al. Proinsulin c-peptide exerts beneficial effects in endotoxic shock in mice. Crit Care Med. 2007;35(5):1348–55.
Ryk A, Łosiewicz A, Michalak A, Fendler W. Biological activity of c-peptide in microvascular complications of type 1 diabetes—time for translational studies or back to the basics? Int J Mol Sci. 2020;21(24):1–18.
Murad Y, El Sayed M, Abdel Gayed A, El Shalakany A. Serum insulin and C-peptide levels as markers of pre-eclampsia in pregnant women. Menoufia Med J. 2015;28(1):233.
Williams K V., Becker DJ, Orchard TJ, Costacou T. Persistent C-peptide levels and microvascular complications in childhood onset type 1 diabetes of long duration. J. Diabetes Complicat. 2019;33(9):657–61.
Fink NR, Chawes B, Bønnelykke K, Thorsen J, Stokholm J, Rasmussen MA, et al. Levels of Systemic Low-grade Inflammation in Pregnant Mothers and Their Offspring are Correlated. Sci Rep. 2019;9(1):1–9.
Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med [Internet]. 2012;18(9):1407–12. Available from: http://dx.doi.org/10.1038/nm.2885
Bas FY, Tola EN, Sak S, Cankaya BA. The role of complete blood inflammation markers in the prediction of spontaneous abortion. Pakistan J Med Sci. 2018;34(6):1381–5.
Araújo J, Schettini DC, Virgílio T, Claudeir G, Júnior S. Evaluation of Immunological Parameters in Pregnant Women : Low Levels of B and NK Cells. Rev Bras Ginecol Obstet. 2019;41:213–219.
Chandra S, Tripathi AK, Mishra S, Amzarul M, Vaish AK. Physiological changes in hematological parameters during pregnancy. Indian J Hematol Blood Transfus. 2012;28(3):144–6.
Chen Y, Zhong H, Zhao Y, Luo X, Gao W. Role of platelet biomarkers in inflammatory response. Biomark Res. 2020;8(1):2–8.
Zhuang Y, Zhang J, Li Y, Gu H, Zhao J, Sun Y, et al. B Lymphocytes Are Predictors of Insulin Resistance in Women with Gestational Diabetes Mellitus. Endocrine, Metab Immune Disord - Drug Targets. 2019;19(3):358–66.
Perrotta C, Buldorini M, Assi E, Cazzato D, De Palma C, Clementi E, et al. The thyroid hormone triiodothyronine controls macrophage maturation and functions: Protective role during inflammation. Am J Pathol [Internet]. 2014;184(1):230–47. Available from: http://dx.doi.org/10.1016/j.ajpath.2013.10.006
Wang CY, Yu TY, Shih SR, Huang KC, Chang TC. Low total and free triiodothyronine levels are associated with insulin resistance in non-diabetic individuals. Sci Rep. 2018;8(1):1–8.
Mannaerts D, Faes E, Cos P, Briedé JJ, Gyselaers W, Cornette J, et al. Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function. PLoS One. 2018;13(9):1–14.
Gillespie SL, Porter K, Christian LM. Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women. J Reprod Immunol. 2016;114:27–31.
Bhatt MP, Lim YC, Kim YM, Ha KS. C-peptide activates AMPKα and prevents ROS-mediated mitochondrial fission and endothelial apoptosis in diabetes. Diabetes. 2013;62(11):3851–62.
Luppi P, Cifarelli V, Tse H, Piganelli J, Trucco M. Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-κB pathway. Diabetologia. 2008;51(8):1534–43.
Wallerath T, Kunt T, Forst T, Closs EI, Lehmann R, Flohr T, et al. Stimulation of endothelial nitric oxide synthase by proinsulin C-peptide. Nitric Oxide - Biol Chem. 2003;9(2):95–102.
Walcher D, Aleksic M, Jerg V, Hombach V, Zieske A, Homma S, et al. C-peptide induces chemotaxis of human CD4-positive cells: Involvement of pertussis toxin-sensitive G-proteins and phosphoinositide 3-kinase. Diabetes. 2004;53(7):1664–70.
Winer DA, Winer S, Shen L, Chng MHY, Engleman EG. B lymphocytes as emerging mediators of insulin resistance. Int J Obes Suppl [Internet]. 2012;2(S1):S4–7. Available from: http://dx.doi.org/10.1038/ijosup.2012.2
Parretti E, Mecacci F, Papini M, Cioni R, Carignani L, Mignosa M, et al. Third-Trimester Maternal Glucose Levels From Diurnal Profiles in Nondiabetic Pregnancies. Diabetes Care. 2001;24(8):1319–23.
Chen X, Stein TP, Steer RA, Scholl TO. Individual free fatty acids have unique associations with inflammatory biomarkers , insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women. BMJ Open Diabetes Res Care. 2019;1–9.
Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S. Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab. 2017;6(9):943–57.
Eftekharian MM, Karimi J, Safe M, Sadeghian A, Borzooei S, Siahpoushi E. Investigation of the correlation between some immune system and biochemical indicators in patients with type 2 diabetes. Hum Antibodies. 2016;24(1–2):25–31.
Yang S, Shi FT, Leung PCK, Huang HF, Fan J. Low thyroid hormone in early pregnancy is associated with an increased risk of gestational diabetes mellitus. J Clin Endocrinol Metab. 2016;101(11):4237–43.
Klecha AJ, Genaro AM, Gorelik G, Barreiro Arcos ML, Silberman DM, Schuman M, et al. Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: Thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway. J Endocrinol. 2006;189(1):44–55.