Kapustin R.V., Arzhanova O.N., Selkov S.A., Pakin V.S.

The role of key adipokines (leptin, adiponectin, resistin, visfatin, apelin, omentin) had been assessed as important factors for perinatal complications in mother with disorders of carbohydrate metabolism. The survey based on the analysis of literature data. Hyperglycemia and obesity during pregnancy were shown to give rise in the deterioration of both synthesis and functions of cytokines in adipose tissue. Dysregulation of the production of studied adipokines causes the dysfunction of β-cells of the pancreas and insulin receptors, which leads to the development of insulin resistance and the subsequent formation of gestational diabetes. Under conditions of concomitant sub-clinical inflammation and oxidative stress there is developed the more pronounced disturbance of adipocyte function and adipose tissue macrophages, production of pro-inflammatory cytokines, which leads to the formation of processes of endothelial dysfunction and disorders of the transport of fatty and amino acids to the fetus. Mentioned pathogenic mechanisms underlie in the appearance of pre-eclampsia and fetal macrosomia. The dysregulation of studied adipokines production was shown to occur just at the early stages of pregnancy. In this regard, the detection of concentrations of these adipokines can be used in routine practice for early diagnosis and prediction of disorders of carbohydrate metabolism and hypertensive disorders during pregnancy.
adipokines, leptin, adiponectin, resistin, visfatin

Список литературы: 
  1. Bergmann K., Sypniewska G. Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers? Clin. Chem. Lab. Med. 2013; 51: 177–85.
  2. Rasouli N., Kern P. Adipocytokines and the metabolic complications of obesity. J. Clin. Endocrinol. Metab. 2008; 93: 64–73.
  3. Galic S., Oakhill J., Steinberg G. Adipose tissue as an endocrine organ. Mol. Cell. Endocrinol. 2010; 316: 129–39.
  4. Denison F., Roberts K., Barr S., Norman J. Obesity, pregnancy, inflammation, and vascular function. Reproduction. 2010; 140: 373–85.
  5. Henry BA, Clarke IJ. Adipose tissue hormones and the regulation of food intake. J. of Neuroendocrinology. 2008; 20: 842–9.
  6. Shi H., Kokoeva M.V., Inouye K., Tzameli I., Yin H., Flier J.S. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Investig. 2006; 116: 3015–25.
  7. Surkan P., Hsieh C., Johansson A., Dickman P., Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstetrics and Gynecology. 2004; 104: 720–6.
  8. Ahlsson F., Gustafsson J., Tuvemo T., Lundgren M. Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants. Acta Paediatrica. 2007; 96: 358–62.
  9. Briana D., Malamitsi-Puchner A. Reviews: Adipocytokines in normal and complicated pregnancies. Reprod. Sci. 2009; 16: 921–37.
  10. Miehle K., Stepan H., Fasshauer M. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin. Endocrinol. 2012; 76: 2–11.
  11. Fasshauer M., Bluher M., Stumvoll M. Adipokines in gestational diabetes. Lancet Diabetes Endocrinol. 2014; 2: 488–99.
  12. Grattan D., Ladyman S., Augustine RA. Hormonal induction of leptin resis- tance during pregnancy. Physiology and Behavior. 2007; 91: 366–74.
  13. Highman T., Friedman J., Huston L., Wong W., Catalano P. Longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate in pregnancy. American Journal of Obstetrics and Gynecology. 1998; 178: 1010–5.
  14. Lopez-Tinoco C., Roca M., Fernandez-Deudero A., Garcia-Valero A., Bugatto F., Aguilar-Diosdado M., Bartha J. Cytokine profile, metabolic syndrome and cardiovascular disease risk in women with late-onset gestational diabetes mellitus. Cytokine. 2012; 58: 14–9.
  15. Atègbo J.M., Grissa O., Yessoufou A., Hichami A., Dramane K.L., Moutairou K., Miled A, Grissa A., Jerbi M., Tabka Z. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J. Clin. Endocrinol. Metab. 2006; 91: 4137–43.
  16. Kautzky-Willer A.P.G., Tura A., Bieglmayer C., Schneider B., Ludvik, B., Prager R., Waldhausl W. Increased plasma leptin in gestational diabetes. Diabetologia. 2001; 44: 164–72.
  17. Xu J., Zhao Y.H., Chen Y.P., Yuan X.L, Wang J., Zhu H., Lu C.M. Maternal circulating concentrations of tumor necrosis factor-α, leptin, and adiponectin in gestational diabetes mellitus: A systematic review and meta-analysis. Sci. World J. 2014; 926–32.
  18. Georgiou H.M., Lappas M., Georgiou G.M., Marita A., Bryant V.J., Hiscock R., Permezel M., Khalil Z., Rice G.E. Screening for biomarkers predictive of gestational diabetes mellitus. Acta Diabetol. 2008; 45: 157–65.
  19. Qiu C., Williams M.A., Vadachkoria S., Frederick I.O., Luthy D.A. Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus. Obstet. Gynecol. 2004; 103: 519–25.
  20. Kirwan J.P., Hauguel-De Mouzon S., Lepercq J., Challier J.C., Huston-Presley L, Friedman J.E., Kalhan S.C., Catalano P.M. TNF-α is a predictor of insulin resistance in human pregnancy. Diabetes. 2002; 51: 2207–13.
  21. Bao W., Baecker A., Song Y., Kiely M., Liu S., Zhang C. Adipokine levels during the first or early second trimester of pregnancy and subsequent risk of gestational diabetes mellitus: A systematic review. Metab. Clin. Exp. 2015; 64: 756–64.
  22. Meller M., Qiu C., Vadachkoria S., Abetew D., Luthy D., Williams M. Changes in placental adipocytokine gene expresion associated with gestational diabetes mellitus. Physiol Res. 2006; 55: 501–12.
  23. Scvarca A., Tomazic M., Blagus M., Krhin B., Janez A. Adiponektin/leptin ratio and insulin resistence in pregnancy. J. Int. Med. Res. 2013; 41: 123–8.
  24. Lappas M., Yee K., Permezel M., Rice GE. Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies. J. Endocrinol. 2005; 186 (3): 457–65.
  25. Christou H., Connors J.M., Ziotopoulou M., Hatzidakis V., Papathanassoglou E. Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J. Clin. Endocrinol. Metab. 2001; 86: 935–8.
  26. Schubring C., Siebler T., Kratzsch J., Englaro P., Blum WF. Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight. Clin. Endocrinol. 1999; 51: 199–204.
  27. Tennekoon K.H., Poopalapillai J., Karunanayake A.G., Jayasinghe H.D., Kumarasiri J.M. Association of cord blood leptin, soluble leptin receptor, insulin-like growth factor-I and insulin-like growth factor-binding protein-1 on birth indices in healthy full-term newborns. Horm Res Pediatr. 2014; 81: 232–8.
  28. Tsai P.J., Yu C.H., Hsu S.P., Lee Y.H., Chiou C.H. Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal adiposity. Clin. Endocrinol. 2004; 61: 88–93.
  29. Mazaki-Tovi S., Kanety H., Pariente C., Hemi R., Schiff E. Cord blood adiponectin in large-for-gestational age newborns. Am. J. Obstet Gynecol. 2005; 193: 1238–42.
  30. Palei A.C., Spradley F.T., Granger J.P. Chronic hyperleptinemia results in the development of hypertension in pregnant rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2015; 308 (10): 855–61.
  31. Kalinderis M., Papanikolaou A., Kalinderi K., Vyzantiadis TA., Ioakimidou A., Tarlatzis BC. Serum levels of leptin and IP-10 in preeclampsia compared to controls. Arch. Gynecol. Obstet. 2015; 292 (2): 343–7.
  32. Ouyang Y., Chen H., Chen H. Reduced plasma adiponectin and elevated leptin in pre-eclampsia. Int. J. Gynaecol. Obstet. 2007; 98 (2): 110–4.
  33. Mumtaz F., Memon A.R., Yousfani S., Tahir S.M., Khushk I., Memon M., Memon A. Role of serum leptin level as a marker of severity of pre eclampsia. J. Ayub. Med. Coll. Abbottabad. 2008; 20 (1): 13–5.
  34. Salimi S., Farajian–Mashhadi F., Naghavi A., Mokhtari M., Shahrakipour M., Saravani M., Yaghmaei M. Different profile of serum leptin between early onset and late onset preeclampsia. Dis Markers. 2014; 628476.
  35. Stefan N., Stumvoll M., Vozarova B., Weyer C., Funahashi T., Matsuzawa Y., Bogardus C., Tataranni P.A. Plasma adiponectin and endogenous glucose production in humans. Diabetes Care. 2003; 26: 3315–9.
  36. Kishida K., Funahashi T., Shimomura I. Molecular mechanisms of diabetes and atherosclerosis: Role of adiponectin. Endocr. Metab. Immune Disord. Drug Targets. 2012; 12: 118–31.
  37. Wojcik M., Chmielewska–Kassassir M., Grzywnowicz K., Wozniak L., Cypryk K. The relationship between adipose tissue-derived hormones and gestational diabetes mellitus (GDM). Endokrynol. Polska. 2014; 65: 134–42.
  38. Silha J.V., Nyomba B.L., Leslie W.D., Murphy L.J. Ethnicity, insulin resistance, and inflammatory adipokines in women at high and low risk for vascular disease. Diabetes Care. 2007; 30: 286–91.
  39. Fuglsang J., Skjaerbaek C., Frystyk J., Flyvbjerg A., Ovesen P. A longitudinal study of serum adiponectin during normal pregnancy. British J. of Obstetrics and Gynaecology. 2006; 113: 110–3.
  40. Eriksson B., Lof M., Olausson H., Forsum E. Body fat, insulin resistance, energy expenditure and serum concentrations of leptin, adiponectin and resistin before, during and after pregnancy in healthy Swedish women. British J. of Nutrition. 2010; 103: 50–7.
  41. Ballesteros M., Simón I., Vendrell J., Ceperuelo–Mallafré V., Miralles R. Maternal and cord blood adiponectin multimeric forms in gestational diabetes mellitus: a prospective analysis. Diabetes Care. 2011; 34: 2418–23.
  42. Retnakaran R., Hanley A., Raif N., Connelly P., Sermer M., Zinman, B. Reduced adiponectin concentration in women with gestational diabetes: a potential factor in progression to type 2 diabetes. Diabetes Care. 2004; 27: 799–800.
  43. Doruk M., Ugur M., Oruç A., Demirel N., Yildiz Y. Serum adiponectin in gestational diabetes and its relation to pregnancy outcome. J. Obstet. Gynaecol. 2014; 34: 471–5.
  44. Lain K.Y., Daftary A.R., Ness R.B., Roberts J.M. First trimester adipocytokine concentrations and risk of developing gestational diabetes later in pregnancy. Clin. Endocrinol. (Oxf.) 2008; 69: 407–11.
  45. Williams M.A., Qiu C., Muy–Rivera M., Vadachkoria S., Song T., Luthy D.A. Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetes mellitus. J. Clin. Endocrinol. Metab. 2004; 89: 2306–11.
  46. Ianniello F., Quagliozzi L., Caruso A., Paradisi G. Low adiponectin in overweight/obese women: Association with diabetes during pregnancy. Eur. Rev. Med. Pharmacol. Sci. 2013; 17: 3197–205.
  47. Lowe L.P., Metzger B.E., Lowe W.L., Dyer A.R., McDade T.W., McIntyre H.D. Inflammatory mediators and glucose in pregnancy: Results from a subset of the hyperglycemia and adverse pregnancy outcome (HAPO) study. J. Clin. Endocrinol. Metab. 2010; 95: 5427–34.
  48. Lacroix M., Battista M.C., Doyon M., Menard J., Ardilouze J.L., Perron P., Hivert M.F. Lower adiponectin levels at first trimester of pregnancy are associated with increased insulin resistance and higher risk of developing gestational diabetes mellitus. Diabetes Care. 2013; 36: 1577–83.
  49. Nanda S., Akolekar R., Sarquis R., Mosconi A.P., Nicolaides K.H. Maternal serum adiponectin at 11 to 13 weeks of gestation in the prediction of macrosomia. Prenat. Diagn. 2011; 31: 479–83.
  50. McManus R., Summers K., de Vrijer B., Cohen N., Thompson A., Giroux I. Maternal, umbilical arterial and umbilical venous 25-hydroxyvitamin d and adipocytokine concentrations in pregnancies with and without gestational diabetes. Clin. Endocrinol. (Oxf.). 2014; 80: 635–41.
  51. 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: 258–63.
  52. Lobo T.F., Torloni M.R., Gueuvoghlanian–Silva B.Y., Mattar R., Daher S. Resistin concentration and gestational diabetes: A systematic review of the literature. J. Reprod. Immunol. 2013; 97: 120–7.
  53. Christiansen M., Hedley P.L., Placing S., Wøjdemann K.R., Carlsen A.L., Jørgensen J.M., Gjerris A.C., Shalmi A.C., Rode L., Sundberg K., Tabor A. Maternal Serum Resistin Is Reduced in First Trimester Preeclampsia Pregnancies and Is a Marker of Clinical Severity. Hypertens Pregnancy. 2015; 34 (4): 422–33.
  54. Seol H.J., Oh M.J., Yeo M.K., Kim A., Lee E.S., Kim H.J. Comparison of serum levels and the placental expression of resistin between patients with preeclampsia and normal pregnant women. Hypertens Pregnancy. 2010; 29 (3): 310–7.
  55. Challis J.R., Lockwood C.J., Myatt L., Norman J.E., Strauss J.F., Petraglia F. Inflammation and pregnancy. Reprod. Sci. 2009; 16: 206–15.
  56. Moschen A.R., Kaser A., Enrich B., Mosheimer B., Theurl M., Niederegger H., Tilg H. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J. Immunol. 2007; 178: 1748–58.
  57. Krzyzanowska K., Krugluger W., Mittermayer F., Rahman R., Haider D., Shnawa N., Schernthaner G. Increased visfatin concentrations in women with gestational diabetes mellitus. Clin. Sci. 2006; 110: 605–9.
  58. Ferreira A.F., Rezende J.C., Vaikousi E., Akolekar R., Nicolaides K.H. Maternal serum visfatin at 11–13 weeks of gestation in gestational diabetes mellitus. Clin. Chem. 2011; 57: 609–13.
  59. Gkiomisi A., Makedou K.G., Anastasilakis A.D., Polyzos S.A., Kourtis A., Gerou S., Gavana E., Dagklis T., Rousso D., Giannoulis C. Serum vaspin levels in women with and without gestational diabetes mellitus during pregnancy and postpartum. Cytokine. 2013; 61: 127–32.
  60. Jia X., Wang S., Ma N., Li X., Guo L., Liu X., Dong T., Liu Y., Lu Q. Comparative analysis of vaspin in pregnant women with and without gestational diabetes mellitus and healthy non-pregnant women. Endocrine. 2015; 48: 533–40.
  61. Stepan H., Kralisch S., Klostermann K., Schrey S., Reisenbuchler C., Verlohren M., Verlohren H.J., Drynda K., Bluher M., Stumvoll M. Preliminary report: Circulating levels of the adipokine vaspin in gestational diabetes mellitus and preeclampsia. Metab. Clin. Exp. 2010; 59: 1054–6.
  62. Giomisi A., Kourtis A., Toulis K.A., Anastasilakis A.D., Makedou K.G., Mouzaki M., Gerou S., Gavana E., Agorastos T., Giannoulis C. Serum vaspin levels in normal pregnancy in comparison with non-pregnant women. Eur. J. Endocrinol. 2011; 164: 579–83.
  63. Barker G., Lim R., Georgiou H.M., Lappas M. Omentin-1 is decreased in maternal plasma, placenta and adipose tissue of women with pre-existing obesity. PLoS ONE. 2012; 7: e42943.
  64. Weerakiet S., Lertnarkorn K., Panburana P., Pitakitronakorn S., Vesathada K., Wansumrith S. Can adiponectin predict gestational diabetes? Gynecol. Endocrinol. 2006; 22: 362–8.