Korean Diabetes J.  2009 Apr;33(2):77-82. 10.4093/kdj.2009.33.2.77.

Insulin Resistance During Pregnancy

• Ahn KJ

• KMID: 2298063
• DOI: http://doi.org/10.4093/kdj.2009.33.2.77

Abstract

Pregnancy is a complex metabolic state involving dramatic alterations in the hormonal or cytokine environments (increases in estrogen, progesterone, prolactin, cortisol, human chorionic gonadotropin, placental growth hormone and human placental lactogen, TNF-alpha, resistin, leptin, and a decrease in adiponectin) as well as an increasing burden of fuel utilization by the conceptus. Metabolically, the first trimester is characterized by increased insulin sensitivity and lipogenesis. The second and third trimesters, in contrast, are characterized by insulin resistance and increased lipolysis.

Keyword

Cytokines; Insulin resistance; Placental hormones; Pregnancy

MeSH Terms

Chorionic Gonadotropin
Cytokines
Estrogens
Female
Growth Hormone
Humans
Hydrocortisone
Insulin
Insulin Resistance
Leptin
Lipogenesis
Lipolysis
Placental Hormones
Placental Lactogen
Pregnancy
Pregnancy Trimester, First
Pregnancy Trimester, Third
Progesterone
Prolactin
Resistin
Tumor Necrosis Factor-alpha
Chorionic Gonadotropin
Cytokines
Estrogens
Growth Hormone
Hydrocortisone
Insulin
Leptin
Placental Hormones
Placental Lactogen
Progesterone
Prolactin
Resistin
Tumor Necrosis Factor-alpha

Reference

1. Akerman F, Lei ZM, Rao CV. Human umbilical cord and fetal membranes co-express leptin and its receptor genes. Gynecol Endocrinol. 2002. 16:299–306.

2. Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased p85/55/50 expression and decreased phosphotidylinositol 3-kinase activity in insulin-resistant human skeletal muscle. Diabetes. 2005. 54:2351–2359.

3. Barbour LA, Mizanoor Rahman S, Gurevich I, Leitner JW, Fischer SJ, Roper MD, Knotts TA, Vo Y, McCurdy CE, Yakar S, Leroith D, Kahn CR, Cantley LC, Friedman JE, Draznin B. Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess. J Biol Chem. 2005. 280:37489–37494.

4. Barbour LA, Shao J, Qiao L, Pulawa LK, Jensen DR, Bartke A, Garrity M, Draznin B, Friedman JE. Human placental growth hormone causes severe insulin resistance in transgenic mice. Am J Obstet Gynecol. 2002. 186:512–517.

5. Beck P, Daughaday WH. Human placental lactogen: studies of its acute metabolic effects and disposition in normal man. J Clin Invest. 1967. 46:103–110.

6. Brelje TC, Scharp DW, Lacy PE, Ogren L, Talamantes F, Robertson M, Friesen HG, Sorenson RL. Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology. 1993. 132:879–887.

7. Caminos JE, Nogueiras R, Gallego R, Bravo S, Tovar S, Garcia-Caballero T, Casanueva FF, Dieguez C. Expression and regulation of adiponectin and receptor in human and rat placenta. J Clin Endocrinol Metab. 2005. 90:4276–4286.

8. Catalano P. The Diabetogenic State of Maternal Metabolism in Pregnancy. NeoReviews. 2002. 3:8.

9. Catalano PM, Hoegh M, Minium J, Huston-Presley L, Bernard S, Kalhan S, Hauguel-De Mouzon S. Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism. Diabetologia. 2006. 49:1677–1685.

10. Catalano PM, Huston L, Amini SB, Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol. 1999. 180:903–916.

11. Challier J, Galtier M, Bintein T, Cortez A, Lepercq J, Hauguel-de Mouzon S. Placental leptin receptor isoforms in normal and pathological pregnancies. Placenta. 2003. 24:92–99.

12. Chen J, Tan B, Karteris E, Zervou S, Digby J, Hillhouse EW, Vatish M, Randeva HS. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia. 2006. 49:1292–1302.

13. Combs TP, Pajvani UB, Berg AH, Lin Y, Jelicks LA, Laplante M, Nawrocki AR, Rajala MW, Parlow AF, Cheeseboro L, Ding YY, Russell RG, Lindemann D, Hartley A, Baker GR, Obici S, Deshaies Y, Ludgate M, Rossetti L, Scherer PE. A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocrinology. 2004. 145:367–383.

14. Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 2001. 60:349–356.

15. Cortelazzi D, Corbetta S, Ronzoni S, Pelle F, Marconi A, Cozzi V, Cetin I, Cortelazzi R, Beck-Peccoz P, Spada A. Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies. Clin Endocrinol (Oxf). 2007. 66:447–453.

16. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002. 290:1084–1089.

17. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2003. 301:1045–1050.

18. Gavrila A, Peng CK, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS. Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab. 2003. 88:2838–2843.

19. Handwerger S, Freemark M. The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development. J Pediatr Endocrinol Metab. 2000. 13:343–356.

20. Kinalski M, Telejko B, Kuzmicki M, Kretowski A, Kinalska I. Tumor necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes. Horm Metab Res. 2005. 37:450–454.

21. Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM. TNF-alpha is a predictor of insulin resistance in human pregnancy. Diabetes. 2002. 51:2207–2213.

22. Kirwan JP, Varastehpour A, Jing M, Presley L, Shao J, Friedman JE, Catalano PM. Reversal of insulin resistance postpartum is linked to enhanced skeletal muscle insulin signaling. J Clin Endocrinol Metab. 2004. 89:4678–4684.

23. Kuhl C. Etiology and pathogenesis of gestational diabetes. Diabetes Care. 1998. 21:Suppl 2. B19–B26.

24. Lepercq J, Challier JC, Guerre-Millo M, Cauzac M, Vidal H, Hauguel-de Mouzon S. Prenatal leptin production: evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab. 2001. 86:2409–2413.

25. Lord E, Ledoux S, Murphy BD, Beaudry D, Palin MF. Expression of adiponectin and its receptors in swine. J Anim Sci. 2005. 83:565–578.

26. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002. 8:731–737.

27. Malek A, Sager R, Schneider H. Effect of hypoxia, oxidative stress and lipopolysaccharides on the release of prostaglandins and cytokines from human term placental explants. Placenta. 2001. 22:Suppl A. S45–S50.

28. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med. 1997. 3:1029–1033.

29. Nogueiras R, Gualillo O, Caminos JE, Casanueva FF, Dieguez C. Regulation of resistin by gonadal, thyroid hormone, and nutritional status. Obes Res. 2003. 11:408–414.

30. Ramos MP, Crespo-Solans MD, del Campo S, Cacho J, Herrera E. Fat accumulation in the rat during early pregnancy is modulated by enhanced insulin responsiveness. Am J Physiol Endocrinol Metab. 2003. 285:E318–E328.

31. Ranheim T, Haugen F, Staff AC, Braekke K, Harsem NK, Drevon CA. Adiponectin is reduced in gestational diabetes mellitus in normal weight women. Acta Obstet Gynecol Scand. 2004. 83:341–347.

32. Ryan EA, Enns L. Role of gestational hormones in the induction of insulin resistance. J Clin Endocrinol Metab. 1988. 67:341–347.

33. Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol. 2000. 143:293–311.

34. Wolf M, Sauk J, Shah A, Vossen Smirnakis K, Jimenez-Kimble R, Ecker JL, Thadhani R. Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus. Diabetes Care. 2004. 27:21–27.