Background/Aims: Although the association between inflammation and insulin resistance is well known, the data related to the role of inflammation in gestational diabetes mellitus (GDM) are conflicting. The aim of this study was to investigate the association of several inflammatory mediators with the glycemic status in pregnancy. Methods: Leukocyte count, ferritin, C-reactive protein (CRP), fibrinogen and interleukin-6 levels were measured in 70 patients with normal glucose tolerance, in 57 patients with impaired glucose tolerance and in 35 patients with GDM as determined based on 50-gram oral glucose tolerance test (OGTT) and 100-gram OGTT results. Results: A significant difference among the groups was seen only with regard to CRP and fibrinogen levels; however, no significant differences were observed after adjustment for body mass index (BMI). CRP was found to be strongly associated with current BMI in all three groups. Conclusion: Maternal serum levels of inflammatory mediators are not related to GDM at the time of the glucose challenge test in the late second or early third trimester. The significant difference in the levels of CRP in different strata of glycemic tolerance was not observed after adjustment for BMI. Adiposity may have a central role in GDM, causing an inflammatory response.

Keywords:
Inflammation, Gestational diabetes mellitus, Obesity, C-reactive protein, Fibrinogen
1.
Retnakaran R, Hanley AJ, Raif N, Connelly PW, Sermer M, Zinman B: C-reactive protein and gestational diabetes: the central role of maternal obesity. J Clin Endocrinol Metab 2003;88:3507-3512.
2.
Volpe L, Di Cianni G, Lencioni C, Cuccuru I, Benzi L, Del Prato S: Gestational diabetes, inflammation, and late vascular disease. J Endocrinol Invest 2007;30:873-879.
3.
Radaelli T, Varastehpour A, Catalano P, Hauguel-de Mouzon S: Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 2003;52:2951-2958.
4.
Kjos SL, Buchanan TA: Gestational diabetes mellitus. N Engl J Med 1999;341:1749-1756.
5.
Saucedo R, Zarate A, Basurto L, Hernandez M, Puello E, Campos S, Moreno E: Women with gestational diabetes develop glucose intolerance with high frequency within one year postpartum. Gynecol Obstet Invest 2012;73:58-62.
6.
Ozuguz U, Isik S, Berker D, Arduc A, Tutuncu Y, Akbaba G, Gokay F, Guler S: Gestational diabetes and subclinical inflammation: evaluation of first year postpartum outcomes. Diabetes Res Clin Pract 2011;94:426-433.
7.
Pickup JC, Mattock MB, Chusney GD, Burt D: NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997;40:1286-1292.
8.
Fröhlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W: Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000;23:1835-1839.
9.
Festa A, D'Agostino R Jr, Howard G, Mykkänen L, Tracy RP, Haffner SM: Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000;102:42-47.
10.
Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW: C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999;19:972-978.
11.
Wolf M, Sandler L, Hsu K, Vossen-Smirnakis K, Ecker JL, Thadhani R: First-trimester C-reactive protein and subsequent gestational diabetes. Diabetes Care 2003;26:819-824.
12.
Bo S, Signorile A, Menato G, Gambino R, Bardelli C, Gallo ML, Cassader M, Massobrio M, Pagano GF: C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia. J Endocrinol Invest 2005;28:779-786.
13.
Nicholson W, Wang NY, Baptiste-Roberts K, Chang YT, Powe NR: Association between adiponectin and tumor necrosis factor-alpha levels at eight to fourteen weeks gestation and maternal glucose tolerance: the Parity, Inflammation, and Diabetes Study. J Womens Health (Larchmt) 2013;22:259-266.
14.
Qiu C, Sorensen TK, Luthy DA, Williams MA: A prospective study of maternal serum C-reactive protein (CRP) concentrations and risk of gestational diabetes mellitus. Paediatr Perinat Epidemiol 2004;18:377-384.
15.
D'Anna R, Baviera G, De Vivo A, Facciolà G, Di Benedetto A, Corrado F: C-reactive protein as an early predictor of gestational diabetes mellitus. J Reprod Med 2006;51:55-58.
16.
Carpenter MW, Coustan DR: Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-773.
17.
Walsh SW: Obesity: a risk factor for preeclampsia. Trends Endocrinol Metab 2007;18:365-370.
18.
Madan JC, Davis JM, Craig WY, Collins M, Allan W, Quinn R, Dammann O: Maternal obesity and markers of inflammation in pregnancy. Cytokine 2009;47:61-64.
19.
Wolf M, Kettyle E, Sandler L, Ecker JL, Roberts J, Thadhani R: Obesity and preeclampsia: the potential role of inflammation. Obstet Gynecol 2001;98:757-762.
20.
Greenberg AS, Obin MS: Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:461S-465S.
21.
Schmatz M, Madan J, Marino T, Davis J: Maternal obesity: the interplay between inflammation, mother and fetus. J Perinatol 2010;30:441-446.
22.
Rota S, Yildirim B, Kaleli B, Aybek H, Duman K, Kaptanoğlu B: C-reactive protein levels in non-obese pregnant women with gestational diabetes. Tohoku J Exp Med 2005;206:341-345.
23.
Dalfrà MG, Fedele D, Ragazzi E, Cosma C, Bisson T, Masin M, Lapolla A: Elevations of inflammatory cytokines during and after pregnancy in gestational diabetes. J Endocrinol Invest 2009;32:289-290.
24.
Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW: Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997;82:4196-4200.
25.
Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB: Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999;282:2131-2135.
26.
Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, Hainque B: Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 2000;85:3338-3342.
27.
Morisset AS, Huot C, Légaré D, Tchernof A: Circulating IL-6 concentrations and abdominal adipocyte isoproterenol-stimulated lipolysis in women. Obesity (Silver Spring) 2008;16:1487-1492.
28.
Kim JH, Bachmann RA, Chen J: Interleukin-6 and insulin resistance. Vitam Horm 2009;80:613-633.
29.
Kuzmicki M, Telejko B, Szamatowicz J, Zonenberg A, Nikolajuk A, Kretowski A, Gorska M: High resistin and interleukin-6 levels are associated with gestational diabetes mellitus. Gynecol Endocrinol 2009;25:258-263.
30.
Kuzmicki M, Telejko B, Zonenberg A, Szamatowicz J, Kretowski A, Nikolajuk A, Laudanski P, Gorska M: Circulating pro- and anti-inflammatory cytokines in Polish women with gestational diabetes. Horm Metab Res 2008;40:556-560.
31.
Morisset AS, Dubé MC, Côté JA, Robitaille J, Weisnagel SJ, Tchernof A: Circulating interleukin-6 concentrations during and after gestational diabetes mellitus. Acta Obstet Gynecol Scand 2011;90:524-530.
32.
Lain KY, Daftary AR, Ness RB, Roberts JM: First trimester adipocytokine concentrations and risk of developing gestational diabetes later in pregnancy. Clin Endocrinol (Oxf) 2008;69:407-411.
33.
Lappas M, Permezel M, Rice GE: Release of proinflammatory cytokines and 8-isoprostane from placenta, adipose tissue, and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus. J Clin Endocrinol Metab 2004;89:5627-5633.
34.
Kalantar-Zadeh K, Rodriguez RA, Humphreys MH: Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant 2004;19:141-149.
35.
Lim MK, Lee CK, Ju YS, Cho YS, Lee MS, Yoo B, Moon HB: Serum ferritin as a serologic marker of activity in systemic lupus erythematosus. Rheumatol Int 2001;20:89-93.
36.
Fernández-Real JM, López-Bermejo A, Ricart W: Cross-talk between iron metabolism and diabetes. Diabetes 2002;51:2348-2354.
37.
Tuomainen TP, Nyyssönen K, Salonen R, Tervahauta A, Korpela H, Lakka T, Kaplan GA, Salonen JT: Body iron stores are associated with serum insulin and blood glucose concentrations. Population study in 1,013 eastern Finnish men. Diabetes Care 1997;20:426-428.
38.
Fernández-Real JM, Ricart-Engel W, Arroyo E, Balançá R, Casamitjana-Abella R, Cabrero D, Fernández-Castañer M, Soler J: Serum ferritin as a component of the insulin resistance syndrome. Diabetes Care 1998;21:62-68.
39.
Ford ES, Cogswell ME: Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care 1999;22:1978-1983.
40.
Chen X, Scholl TO, Stein TP: Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: the Camden study. Diabetes Care 2006;29:1077-1082.
41.
Kaygusuz I, Gumus II, Yılmaz S, Simavlı S, Uysal S, Derbent AU, Gözdemir E, Kafalı H: Serum levels of visfatin and possible interaction with iron parameters in gestational diabetes mellitus. Gynecol Obstet Invest 2013;75:203-209.
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2014
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