B Lymphocytes Are Predictors of Insulin Resistance in Women with Gestational Diabetes Mellitus

Author(s): Yan Zhuang, Jin Zhang, Yiwei Li, Hongqin Gu, Jinyan Zhao, Ya Sun, Rencheng Wang, Chunyan Zhang, Wen Chen, Jianrong Weng, Lan Qi, Huifang Lu, Jiarong Zhang, Qin Liu, Yinyan He*, Xianming Xu

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 19 , Issue 3 , 2019

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Graphical Abstract:


Backgroud: The present study aimed to investigate the association between immune cells and gestational diabetes mellitus (GDM) and identify a reasonable predictor of insulin resistance in women with GDM.

Objective: The clinical and biochemical characteristics of 124 women with GDM and 168 healthy pregnant women were compared.

Methods: The percentage of immune cells in the blood of the subjects was analyzed by flow cytometry. Pearson’s correlation analysis revealed the correlation between the percentage of B lymphocytes and insulin resistance. A cutoff point was determined for the percentage of B lymphocytes, based on insulin resistance, using receiver operating characteristic (ROC) curves.

Results: Compared to the healthy pregnant women, the percentages of B lymphocytes and IgA produced by B-cells were significantly different in women with GDM. The percentage of B lymphocytes was positively related to insulin resistance.The number of 14.05% of B lymphocytes was an optimal cutoff point that predicted the insulin resistance in women with GDM.

Conclusion: The percentage of B lymphocytes was positively associated with insulin resistance, and hence, might serve as an appropriate predictor of insulin resistance in women with GDM.

Keywords: B lymphocytes, insulin resistance, inflammation, GDM, immune, IgA, flow cytometry.

Zhu, Y.; Zhang, C. Prevalence of gestational diabetes and risk of progression to Type 2 diabetes: A global perspective. Curr. Diab. Rep., 2016, 1, 7.
Chiefari, E.; Arcidiacono, B.; Foti, D.; Brunetti, A. Gestational diabetes mellitus: An updated overview. J. Endocrinol. Invest., 2017, 40, 899-909.
Basri, N.I.; Mahdy, Z.A.; Ahmad, S.; Abdul Karim, A.K.; Shan, L.P.; Abdul Manaf, M.R.; Ismail, N.A.M. The World Health Organization (WHO) versus The International Association of Diabetes and Pregnancy Study Group (IADPSG) diagnostic criteria of gestational diabetes mellitus (GDM) and their associated maternal and neonatal outcomes. Horm. Mol. Biol. Clin. Investig., 2018, 34(1) pii: /j/hmbci.2018.34.issue-1/hmbci-2017-0077/hmbci-2017-0077.xml. doi: 10.1515/hmbci-2017-0077.
[http://dx.doi.org/10.1515/hmbci-2017- 0077]
Buchanan, T.A.; Xiang, A.H.; Page, K.A. Gestational diabetes mellitus: Risks and management during and after pregnancy. Nat. Rev. Endocrinol., 2012, 8, 639-649.
Kendrick, J.M. Screening and diagnosing gestational diabetes mellitus revisited: Implications from HAPO. J. Perinat. Neonatal Nurs., 2011, 25(3), 226-232; quiz 233-234.
Weinert, L.S. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy: Comment to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel. Diabetes Care, 2010, 33(7), e9.
Talukdar, S.; Oh, D.Y.; Bandyopadhyay, G.; Li, D.; Xu, J.; McNelis, J. Lu, Min.; Li, P.; Yan, Q.; Zhu, Y.; Ofrencio.; Lin, M.; Brenner, M.B.; Olefsky, J.M. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat. Med., 2012, 18, 1407-1412.
Justin, I.O.; Ajay, C. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science, 2013, 339(6116), 172-177.
Satoshi, N.; Ichiro, M.; Mika, N.; Koji, E.; Hiroshi, Y.; Mitsuru, O.; Makoto, O.; Kazuo, H.; Kohjiro, U.; Seiryo, S.; Kotaro, Y.; Takashi, K.; Ryozo, N. CD8 + effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med., 2009, 15(8), 914-920.
Winer, D.A.; Winer, S.; Shen, L.; Wadia, P.P.; Yantha, J.; Paltser, G.; Tsui, H.; Wu, P.; Davidson, M.G.; Alonso, M.N.; Leong, H.; Glassford, A.; Caimol, M.; Kenkel, J.A.; Tedder, T.F.; McLaughlin, T.; Miklos, D.B.; Dosch, H.M.; Engleman, E.G. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med., 2011, 17, 610-617.
Winer, D.A.; Winer, S.; Chng, M.H.; Shen, L.; Engleman, E.G.B. Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell. Mol. Life Sci., 2014, 71, 1033-1043.
Nikolajczyk, B.S.; Jagannathan-Bogdan, M.; Shin, H.; Gyurko, R. State of the union between metabolism and the immune system in type 2 diabetes. Genes Immun., 2011, 12, 239-250.
Palming, J.; Gabrielsson, B.G.; Jennische, E.; Smith, U.; Carlsson, B.; Carlsson, L.M.; Lonn, M. Plasma cells and Fc receptors in human adipose tissue--lipogenic and anti-inflammatory effects of immunoglobulins on adipocytes. Biochem. Biophys. Res. Commun., 2006, 343, 43-48.
Bhatia, D.; Sinha, A.; Hari, P.; Sopory, S.; Saini, S.; Puraswani, M.; Saini, H.; Mitra, D.K.; Bagga, A. Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome. Pediatr. Res., 2018, 84(4), 520-526.
Adamo, L.; Staloch, L.; Rocha-Resende, C.; Matkovich, S.J.; Jiang, W.; Bajpai, G.; Weinheimer, C.J.; Kovacs, A.; Schilling, J.D.; Barger, P.M.; Bhattacharya, D.; Mann, D.L. Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury. JCI Insight, 2018, 3(11), e120137.
Gelsinger, S.L.; Smith, A.M.; Jones, C.M.; Heinrichs, A.J. Technical note: Comparison of radial immunodiffusion and ELISA for quantification of bovine immunoglobulin G in colostrum and plasma. J. Dairy Sci., 2015, 98(6), 4084-4089.
Aune, D.; Sen, A.; Henriksen, T.; Saugstad, O.D.; Tonstad, S. Physical activity and the risk of gestational diabetes mellitus: A systematic review and dose-response meta-analysis of epidemiological studies. Eur. J. Epidemiol., 2016, 31, 967-997.
West, N.A.; Crume, T.L.; Maligie, M.A.; Dabelea, D. Cardiovascular risk factors in children exposed to maternal diabetes in utero. Diabetologia, 2011, 54, 504-507.
Tam, W.H.; Ma, R.C.; Yang, X.; Ko, G.T.; Tong, P.C.; Cockram, C.S.; Sahota, D.S.; Rogers, M.S.; Chan, J.C.N. Glucose intolerance and cardiometabolic risk in children exposed to maternal gestational diabetes mellitus in utero. Pediatrics, 2008, 122, 1229-1234.
DiCianni, G.; Miccoli, R.; Volpe, L.; Lencioni, C.; Del Prato, S. Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab. Res. Rev., 2003, 19, 259-270.
Harlev, A.; Wiznitzer, A. New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr. Diab. Rep., 2010, 10, 242-247.
Olefsky, J.M.; Glass, C.K. Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol., 2010, 72, 219-246.
Odegaard, J.I.; Chawla, A. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science, 2013, 339, 172-177.
Schober, L.; Radnai, D.; Spratte, J.; Kisielewicz, A.; Schmitt, E.; Mahnke, K.; Fluhr, H.; Uhlmann, L.; Sohn, C.; Steinborn, A. The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus. Clin. Exp. Immunol., 2014, 177, 76-85.
Lund, F.E. Cytokine-producing B lymphocytes - key regulators of immunity. Curr. Opin. Immunol., 2008, 20(3), 332-338.
DeFuria, J.; Belkina, A.C.; Jagannathan-Bogdan, M.; Snyder-Cappione, J.; Carr, J.D.; Nersesova, Y.R.; Markham, D.; Strissel, K.J.; Watkins, A.A.; Zhu, M.; Allen, J.; Bouchard, J.; Toraldo, G.; Jasuja, R.; Obin, M.S.; McDonnell, M.E.; Apovian, C.; Denis, G.V.; Nykolajczyk, B. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc. Natl. Acad. Sci. USA, 2013, 110, 5133-5138.
Jagannathan, M.; McDonnell, M.; Liang, Y.; Hasturk, H.; Hetzel, J.; Rubin, D.; Kantarci, A.; Van Dyke, T.E.; Ganley-Leal, L.M.; Nykolajczyk, B.S. Toll-like receptors regulate B cell cytokine production in patients with diabetes. Diabetologia, 2010, 53, 1461-1471.
Hong, E.G.; Ko, H.J.; Cho, Y.R.; Kim, H.J.; Ma, Z.; Yu, T.Y.; Friedlien, R.H.; Kurt-Jones, E.; Finberg, R.; Fischer, M.A.; Granger, E.L.; Norbury, C.C.; Hauschka, S.D.; Philbrick, W.M.; Lee, C.G.; Elias, J.K.; Kim, J.K. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes, 2009, 58, 2525-2535.

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Article Details

Year: 2019
Published on: 15 April, 2019
Page: [358 - 366]
Pages: 9
DOI: 10.2174/1871530319666190101130300

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