Horm Metab Res 2008; 40(8): 556-560
DOI: 10.1055/s-2008-1073166
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Circulating Pro- and Anti-inflammatory Cytokines in Polish Women with Gestational Diabetes

M. Kuzmicki 1 , B. Telejko 2 , A. Zonenberg 2 , J. Szamatowicz 3 , A. Kretowski 2 , A. Nikolajuk 2 , P. Laudanski 1 , M. Gorska 2
  • 1Department of Pathophysiology of Pregnancy, Medical University of Bialystok, Poland
  • 2Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Poland
  • 3Department of Gynecology, Medical University of Bialystok, Poland
Further Information

Publication History

received 06.08.2007

accepted 28.01.2008

Publication Date:
30 April 2008 (online)

Abstract

In this study we measured serum concentrations of proinflammatory interleukin-6, interleukin-8, and interleukin-18 as well as anti-inflammatory interleukin-10 in 30 pregnant women with normal glucose tolerance, in 32 women with abnormal results of a 50-g glucose challenge test, and in 57 patients with gestational diabetes mellitus. Patients with gestational diabetes had significantly higher IL-6 (median 1.0 [0.7–1.5] vs. 0.7 [0.4–0.8] pg/ml, p=0.001), IL-8 (2.1 [1.1–4.2] pg/ml vs. 0.7 [0.4–0.9] pg/ml, p<0.0001), and IL-18 (249.3 [188.5–318.7] pg/ml vs. 186.7 [139.9–243.9] pg/ml, p=0.005) as well as lower IL-10 levels than healthy pregnant women (0.6 [0.5–1.5] pg/ml vs. 2.9 [1.8–3.2] pg/ml, p<0.0001). After adjusting for glucose, insulin, and BMI values, the differences in IL-8 and IL-18 became insignificant, whereas the differences in IL-6 and IL-10 levels remained highly significant (p<0.0001). The subjects with abnormal glucose challenge test results had higher IL-6 levels (0.9 [0.7–1.3] pg/ml, p=0.005) and similar levels of other cytokines as compared with the women with normal glucose tolerance. Our results suggest an impaired balance between circulating pro- and anti-inflammatory cytokines in patients with gestational diabetes; however, a significant contribution of maternal obesity to the increased levels of IL-8 and IL-18 should be underlined.

References

  • 1 Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee.  Diabetes Care. 1998;  21 ((Suppl 2)) B161-B167
  • 2 Kautzky-Willer A, Prager R, Waldhausl W, Pacini G, Thomeseth K, Wagner OF, Ulm M, Streli C, Ludvik B. Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy.  Diabetes Care. 1997;  20 1717-1723
  • 3 Ryan EA, Enns L. Role of gestational hormones in the induction of insulin resistance.  J Clin Endocrinol Metab. 1988;  67 341-347
  • 4 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
  • 5 Pickup JC, Chusney GD, Thomas SM, Burt D. Plasma interleukin-6, tumor necrosis factor α and blood cytokine production in type 2 diabetes.  Life Sci. 2000;  67 291-300
  • 6 Yudkin JS. Inflammation, obesity and the metabolic syndrome.  Horm Metab Res. 2007;  39 707-709
  • 7 Konukoglu D, Hatemi H, Bayer H, Bagriacik N. Relationship between serum concentrations of interleukin-6 and tumour necrosis factor alpha in female Turkish subjects with normal and impaired glucose tolerance.  Horm Metab Res. 2006;  38 34-37
  • 8 Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM. TNF-α is a predictor of insulin resistance in human pregnancy.  Diabetes. 2002;  51 2207-2213
  • 9 Kinalski M, Telejko B, Kuzmicki M, Kretowski A, Kinalska I. Tumour necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes.  Horm Metab Res. 2005;  37 450-454
  • 10 Ategbo JM, Grissa O, Yessoufou A, Hichami A, Dramane KL, Moutairou K, Miled A, Grissa A, Jerbi M, Tabka Z, Khan NA. Modulation of adipokines and cytokines in gestational diabetes and macrosomia.  J Clin Endocrinol Metab. 2006;  91 4137-4143
  • 11 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
  • 12 Kristiansen OP, Mandrup-Poulsen T. Intreleukin-6 and diabetes.  The good, the bad, or the indifferent? Diabetes. 2005;  54 ((Suppl 2)) S114-S124
  • 13 Kolb H, Mandrup-Poulsen T. An immune origin of type 2 diabetes.  Diabetologia. 2005;  48 1038-1050
  • 14 Cardellini M, Andreozzi F, Laratta E, Marini MA, Lauro R, Hribal ML, Perticone F, Sesti G. Plasma interleukin-6 levels are increased in subjects with impaired glucose tolerance but not in those with impaired fasting glucose in a cohort of Italian Caucasians.  Diabetes Metab Res Rev. 2007;  23 141-145
  • 15 Müller S, Martin S, Koenig W, Hanifi-Moghaddam P, Rathmann W, Haastert B, Giani G, Illig T, Thorand B, Kolb H. Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors.  Diabetologia. 2002;  45 805-812
  • 16 Winzer C, Wagner O, Festa A, Schneider B, Roden M, Bancher-Todesca D, Pacini G, Funahashi T, Kautzky-Willer A. Plasma adiponectin, insulin sensitivity and subclinical inflammation in women with prior gestational diabetes.  Diabetes Care. 2004;  27 1721-1727
  • 17 Thorand B, Baumert J, Kolb H, Maisinger C, Chambless L, Koenig W, Herder C. Sex differences in the prediction of type 2 diabetes by inflammatory markers. Results from the MONICA/KORA Augsburg case-cohort study, 1984–2002.  Diabetes Care. 2007;  37 854-860
  • 18 Baggiolini M, Loetscher P, Moser B. Interleukin-8 and the chemokine family.  Int Immunopharmacol. 1995;  17 103-108
  • 19 Gerszten RE, Garcia-Zepeda EA, Limm YC, Yoshida M, Ding HA, Gimbrone Jr MA, Luster AD, Luscinskas FW, Rosenzweig A. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions.  Nature. 1999;  398 718-723
  • 20 Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking.  Am J Physiol. 2002;  283 R7-R28
  • 21 Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Cytokine milieu tends toward inflammation in type 2 diabetes.  Diabetes Care. 2003;  26 1647
  • 22 Herder C, Baumert J, Thorand B, Koenig W, Jager W de, Meisinger C, Illig T, Martin S, Kolb H. Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002.  Diabetologia. 2006;  49 921-929
  • 23 Srinivasan S, Bolick DT, Hatley ME, Natarajan R, Reilly KB, Yeh M, Chrestensen C, Sturgil TW, Hedrick CC. Glucose regulates Interleukin-8 production in aortic endothelial cells through activation of the p38 mitogen-activated protein kinase pathway in diabetes.  J Biol Chem. 2004;  279 31930-31936
  • 24 Bruun JM, Pedersen SB, Richelsen B. Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro.  J Clin Endocrinol Metab. 2001;  86 1267-1273
  • 25 Dai SM, Matsuno H, Nakamura H, Nishioka K, Yudoh K. Interleukin-18 enhances monocyte tumor necrosis factor alpha and interleukin-1beta production induced by direct contact with T lymphocytes; implications in rheumatoid arthritis.  Arthritis Rheum. 2004;  50 432-443
  • 26 Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, Sancho J, San Millan JL. Serum Interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity.  J Clin Endocrinol Metab. 2004;  89 806-811
  • 27 Nakamura A, Shikata K, Hiramatsu M, Nakatou T, Kitamura T, Wada J, Itoshima T, Makino H. Serum Interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes.  Diabetes Care. 2005;  28 2890-2895
  • 28 Hung J, MacQuillan BM, Champan CM, Thompson PL, Beilby JP. Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance.  Arterioscler Thromb Vasc Biol. 2005;  25 1268-1273
  • 29 Kim HJ, Higashimori T, Park SY, Choi H, Dong J, Kim YJ, Noh HL, Cho YR, Cline G, Kim YB, Kim JK. Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo.  Diabetes. 2004;  53 1060-1067
  • 30 Blüher M, Fasshauer M, Tonjes A, Kratzsch J, Schon MR, Paschke R. Association of interleukin-6, C-reactive protein, interleukin 10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism.  Exp Clin Endocrinol Diabetes. 2005;  13 534-537
  • 31 Esposito K, Pontillo A, Giugliano F, Giugliano G, Marfella R, Nicoletti G, Giugliano D. Association of low interleukin-10 levels with the metabolic syndrome in obese women.  J Clin Endocrinol Metab. 2003;  88 1055-1058
  • 32 Gezer A, Esen F, Mutlu H, Ozturk E, Ocak V. Prognosis of patients with positive screening but negative diagnostic test for gestational diabetes.  Arch Gynecol Obstet. 2002;  266 201-214
  • 33 Dudhbhai M, Lim L, Bombard A, Juliard K, Meenakshi B, Trachelenberg Y, Weiner Z. Characteristics of patients with abnormal glucose challenge test and normal oral glucose tolerance test results: comparison with normal and gestational diabetic patients.  Am J Obstet Gynecol. 2006;  194 E42-E45

Correspondence

M. KuzmickiMD 

Department of Pathophysiology of Pregnancy

Medical University of Bialystok

M. Curie-Sklodowskiej 24A

15-276 Bialystok

Poland

Phone: +48/8574/76 83 52

Fax: +48/8574/76 86 82

Email: mkuzmicki@op.pl

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