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Glucose Intolerance and Insulin Resistance: Relevance in Preeclampsia

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Book cover Preeclampsia

Part of the book series: Comprehensive Gynecology and Obstetrics ((CGO))

Abstract

The major symptoms of preeclampsia are de novo hypertension and proteinuria during pregnancy, and the clinical diagnosis of preeclampsia has classically been based on these symptoms. However, glucose tolerance defects and insulin resistance are prominent features of preeclampsia but have not been considered significant phenotypes, particularly when establishing animal models of preeclampsia. This review seeks to evaluate the pathomechanical significance of glucose tolerance defects and insulin resistance in the biology of preeclampsia.

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References

  1. Shenoy V, Kanasaki K, Kalluri R. Pre-eclampsia: connecting angiogenic and metabolic pathways. Trends Endocrinol Metab. 2010;21:529–36.

    Article  CAS  PubMed  Google Scholar 

  2. Kanasaki K, Kanasaki M. Angiogenic defects in preeclampsia: what is known, and how are such defects relevant to preeclampsia pathogenesis? Hypertens Res Pregnancy. 2014;1:9.

    Google Scholar 

  3. Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol. 1991;165:1667–72.

    Article  CAS  PubMed  Google Scholar 

  4. Catalano PM, et al. Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant women. Am J Obstet Gynecol. 1992;167:913–9.

    Article  CAS  PubMed  Google Scholar 

  5. Catalano PM, et al. Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol. 1993;264:E60–7.

    CAS  PubMed  Google Scholar 

  6. Rieck S, Kaestner KH. Expansion of beta-cell mass in response to pregnancy. Trends Endocrinol Metab. 2010;21:151–8. https://doi.org/10.1016/j.tem.2009.11.001.

    Article  CAS  PubMed  Google Scholar 

  7. Ryan EA, Enns L. Role of gestational hormones in the induction of insulin resistance. J Clin Endocrinol Metab. 1988;67:341–7. https://doi.org/10.1210/jcem-67-2-341.

    Article  CAS  PubMed  Google Scholar 

  8. Kuhl C. Aetiology of gestational diabetes. Baillieres Clin Obstet Gynaecol. 1991;5:279–92.

    Article  CAS  PubMed  Google Scholar 

  9. Yogev, et al. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol. 2010;202:255.e1–7. https://doi.org/10.1016/j.ajog.2010.01.024.

    Article  CAS  Google Scholar 

  10. Hauguel S, Leturque A, Gilbert M, Girard J. Effects of pregnancy and fasting on muscle glucose utilization in the rabbit. Am J Obstet Gynecol. 1988;158:1215–8.

    Article  CAS  PubMed  Google Scholar 

  11. Hauguel S, Gilbert M, Girard J. Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit. Am J Physiol. 1987;252:E165–9.

    CAS  PubMed  Google Scholar 

  12. Leturque A, et al. Glucose utilization rates and insulin sensitivity in vivo in tissues of virgin and pregnant rats. Diabetes. 1986;35:172–7.

    Article  CAS  PubMed  Google Scholar 

  13. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci U S A. 1994;91:4854–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Xiang AH, et al. Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. Diabetes. 1999;48:848–54.

    Article  CAS  PubMed  Google Scholar 

  15. Kirwan JP, et al. TNF-alpha is a predictor of insulin resistance in human pregnancy. Diabetes. 2002;51:2207–13.

    Article  CAS  PubMed  Google Scholar 

  16. Hotamisligil GS, et al. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.

    Article  CAS  PubMed  Google Scholar 

  17. Saghizadeh M, Ong JM, Garvey WT, Henry RR, Kern PA. The expression of TNF alpha by human muscle. Relationship to insulin resistance. J Clin Invest. 1996;97:1111–6. https://doi.org/10.1172/JCI118504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sermer M, et al. Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project. Am J Obstet Gynecol. 1995;173:146–56.

    Article  CAS  PubMed  Google Scholar 

  19. Sowers JR, Saleh AA, Sokol RJ. Hyperinsulinemia and insulin resistance are associated with preeclampsia in African-Americans. Am J Hypertens. 1995;8:1–4. https://doi.org/10.1016/0895-7061(94)00166-9.

    Article  CAS  PubMed  Google Scholar 

  20. Joffe GM, et al. The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women. Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol. 1998;179:1032–7.

    Article  CAS  PubMed  Google Scholar 

  21. Wolf M, et al. First trimester insulin resistance and subsequent preeclampsia: a prospective study. J Clin Endocrinol Metab. 2002;87:1563–8. https://doi.org/10.1210/jcem.87.4.8405.

    Article  CAS  PubMed  Google Scholar 

  22. Parretti E, et al. Preeclampsia in lean normotensive normotolerant pregnant women can be predicted by simple insulin sensitivity indexes. Hypertension. 2006;47:449–53. https://doi.org/10.1161/01.HYP.0000205122.47333.7f.

    Article  CAS  PubMed  Google Scholar 

  23. Matthews DR, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  24. Kirwan JP, Huston-Presley L, Kalhan SC, Catalano PM. Clinically useful estimates of insulin sensitivity during pregnancy: validation studies in women with normal glucose tolerance and gestational diabetes mellitus. Diabetes Care. 2001;24:1602–7.

    Article  CAS  PubMed  Google Scholar 

  25. Hauth JC, et al. Maternal insulin resistance and preeclampsia. Am J Obstet Gynecol. 2011;204(327):e321–6. https://doi.org/10.1016/j.ajog.2011.02.024.

    Google Scholar 

  26. D’Anna R, et al. Adiponectin and insulin resistance in early- and late-onset pre-eclampsia. BJOG. 2006;113:1264–9. https://doi.org/10.1111/j.1471-0528.2006.01078.x.

    Article  PubMed  Google Scholar 

  27. Montoro MN, et al. Insulin resistance and preeclampsia in gestational diabetes mellitus. Diabetes Care. 2005;28:1995–2000.

    Article  CAS  PubMed  Google Scholar 

  28. Sierra-Laguado J, et al. Determination of insulin resistance using the homeostatic model assessment (HOMA) and its relation with the risk of developing pregnancy-induced hypertension. Am J Hypertens. 2007;20:437–42. https://doi.org/10.1016/j.amjhyper.2006.10.009.

    Article  CAS  PubMed  Google Scholar 

  29. Legro RS. Insulin resistance in women’s health: why it matters and how to identify it. Curr Opin Obstet Gynecol. 2009;21:301–5. https://doi.org/10.1097/GCO.0b013e32832e07d5.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ryan EA, et al. Defects in insulin secretion and action in women with a history of gestational diabetes. Diabetes. 1995;44:506–12.

    Article  CAS  PubMed  Google Scholar 

  31. Fuh MM, et al. Resistance to insulin-mediated glucose uptake and hyperinsulinemia in women who had preeclampsia during pregnancy. Am J Hypertens. 1995;8:768–71.

    Article  CAS  PubMed  Google Scholar 

  32. Soonthornpun K, Soonthornpun S, Wannaro P, Setasuban W, Thamprasit A. Insulin resistance in women with a history of severe pre-eclampsia. J Obstet Gynaecol Res. 2009;35:55–9. https://doi.org/10.1111/j.1447-0756.2008.00865.x.

    Article  CAS  PubMed  Google Scholar 

  33. Sattar N, Ramsay J, Crawford L, Cheyne H, Greer IA. Classic and novel risk factor parameters in women with a history of preeclampsia. Hypertension. 2003;42:39–42. https://doi.org/10.1161/01.HYP.0000074428.11168.EE.

    Article  CAS  PubMed  Google Scholar 

  34. Girouard J, Giguere Y, Moutquin JM, Forest JC. Previous hypertensive disease of pregnancy is associated with alterations of markers of insulin resistance. Hypertension. 2007;49:1056–62. https://doi.org/10.1161/HYPERTENSIONAHA.107.087528.

    Article  CAS  PubMed  Google Scholar 

  35. Smith GN, et al. A history of preeclampsia identifies women who have underlying cardiovascular risk factors. Am J Obstet Gynecol. 2009;200:58.e1–8. https://doi.org/10.1016/j.ajog.2008.06.035.

    Article  Google Scholar 

  36. Agatisa PK, et al. Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk. Am J Physiol Heart Circ Physiol. 2004;286:H1389–93. https://doi.org/10.1152/ajpheart.00298.2003.

    Article  CAS  PubMed  Google Scholar 

  37. Kvehaugen AS, et al. Endothelial function and circulating biomarkers are disturbed in women and children after preeclampsia. Hypertension. 2011;58:63–9. https://doi.org/10.1161/HYPERTENSIONAHA.111.172387.

    Article  CAS  PubMed  Google Scholar 

  38. Hawfield A, Freedman BI. Pre-eclampsia: the pivotal role of the placenta in its pathophysiology and markers for early detection. Ther Adv Cardiovasc Dis. 2009;3:65–73. https://doi.org/10.1177/1753944708097114.

    Article  PubMed  Google Scholar 

  39. Caballero AE. Endothelial dysfunction, inflammation, and insulin resistance: a focus on subjects at risk for type 2 diabetes. Curr Diab Rep. 2004;4:237–46.

    Article  PubMed  Google Scholar 

  40. Callaway LK, et al. Diabetes mellitus in the 21 years after a pregnancy that was complicated by hypertension: findings from a prospective cohort study. Am J Obstet Gynecol. 2007;197(492):e491–7. https://doi.org/10.1016/j.ajog.2007.03.033.

    Google Scholar 

  41. Lykke JA, et al. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension. 2009;53:944–51. https://doi.org/10.1161/HYPERTENSIONAHA.109.130765.

    Article  CAS  PubMed  Google Scholar 

  42. Engeland A, et al. Risk of diabetes after gestational diabetes and preeclampsia. A registry-based study of 230,000 women in Norway. Eur J Epidemiol. 2011;26:157–63. https://doi.org/10.1007/s10654-010-9527-4.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Feig DS, et al. Preeclampsia as a risk factor for diabetes: a population-based cohort study. PLoS Med. 2013;10:e1001425. https://doi.org/10.1371/journal.pmed.1001425.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Facca TA, Kirsztajn GM, Sass N. Preeclampsia (marker of chronic kidney disease): from genesis to future risks. J Bras Nefrol. 2012;34:87–93.

    Article  PubMed  Google Scholar 

  45. Craici I, Wagner S, Garovic VD. Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test? Ther Adv Cardiovasc Dis. 2008;2:249–59. https://doi.org/10.1177/1753944708094227.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Harskamp RE, Zeeman GG. Preeclampsia: at risk for remote cardiovascular disease. Am J Med Sci. 2007;334:291–5. https://doi.org/10.1097/MAJ.0b013e3180a6f094.

    Article  PubMed  Google Scholar 

  47. Kanasaki K, Kalluri R. The biology of preeclampsia. Kidney Int. 2009;76:831–7.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kanasaki K, et al. Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature. 2008;453:1117–21. https://doi.org/10.1038/nature06951.

    Article  CAS  PubMed  Google Scholar 

  49. Tunbridge EM, Harrison PJ, Weinberger DR. Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol Psychiatry. 2006;60:141–51.

    Article  CAS  PubMed  Google Scholar 

  50. Barnea ER, MacLusky NJ, DeCherney AH, Naftolin F. Catechol-o-methyl transferase activity in the human term placenta. Am J Perinatol. 1988;5:121–7.

    Article  CAS  PubMed  Google Scholar 

  51. Yan J, et al. 2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats. Exp Neurol. 2006;202:348–56.

    Article  CAS  PubMed  Google Scholar 

  52. Barchiesi F, et al. 2-Methoxyestradiol, an estradiol metabolite, inhibits neointima formation and smooth muscle cell growth via double blockade of the cell cycle. Circ Res. 2006;99:266–74. https://doi.org/10.1161/01.RES.0000233318.85181.2e.

    Article  CAS  PubMed  Google Scholar 

  53. Dubey RK, Jackson EK, Keller PJ, Imthurn B, Rosselli M. Estradiol metabolites inhibit endothelin synthesis by an estrogen receptor-independent mechanism. Hypertension. 2001;37:640–4.

    Article  CAS  PubMed  Google Scholar 

  54. Dubey RK, Jackson EK. Potential vascular actions of 2-methoxyestradiol. Trends Endocrinol Metab. 2009;20:374–9. https://doi.org/10.1016/j.tem.2009.04.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lee SB, et al. Preeclampsia: 2-methoxyestradiol induces cytotrophoblast invasion and vascular development specifically under hypoxic conditions. Am J Pathol. 2010;176:710–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Takanashi K, Honma T, Kashiwagi T, Honjo H, Yoshizawa I. Detection and measurement of urinary 2-hydroxyestradiol 17-sulfate, a potential placental antioxidant during pregnancy. Clin Chem. 2000;46:373–8.

    CAS  PubMed  Google Scholar 

  57. Annerbrink K, et al. Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men. Metabolism. 2008;57:708–11.

    Article  CAS  PubMed  Google Scholar 

  58. Zhu BT. Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis. Curr Drug Metab. 2002;3:321–49.

    Article  CAS  PubMed  Google Scholar 

  59. Need AC, Ahmadi KR, Spector TD, Goldstein DB. Obesity is associated with genetic variants that alter dopamine availability. Ann Hum Genet. 2006;70:293–303. https://doi.org/10.1111/j.1529-8817.2005.00228.x.

    Article  CAS  PubMed  Google Scholar 

  60. Tworoger SS, et al. The effect of CYP19 and COMT polymorphisms on exercise-induced fat loss in postmenopausal women. Obes Res. 2004;12:972–81.

    Article  CAS  PubMed  Google Scholar 

  61. Hall KT, et al. Catechol-O-methyltransferase association with hemoglobin A1c. Metabolism. 2016;65:961–7. https://doi.org/10.1016/j.metabol.2016.04.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Barchiesi F, et al. Candidate genes and mechanisms for 2-methoxyestradiol-mediated vasoprotection. Hypertension. 2010;56:964–72. https://doi.org/10.1161/HYPERTENSIONAHA.110.152298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Matthews L, et al. Thiazolidinediones are partial agonists for the glucocorticoid receptor. Endocrinology. 2009;150:75–86. https://doi.org/10.1210/en.2008-0196.

    Article  CAS  PubMed  Google Scholar 

  64. Waite LL, et al. Placental peroxisome proliferator-activated receptor-gamma is up-regulated by pregnancy serum. J Clin Endocrinol Metab. 2000;85:3808–14. https://doi.org/10.1210/jcem.85.10.6847.

    CAS  PubMed  Google Scholar 

  65. Waite LL, Louie RE, Taylor RN. Circulating activators of peroxisome proliferator-activated receptors are reduced in preeclamptic pregnancy. J Clin Endocrinol Metab. 2005;90:620–6. https://doi.org/10.1210/jc.2004-0849.

    Article  CAS  PubMed  Google Scholar 

  66. Barroso I, et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402:880–3. https://doi.org/10.1038/47254.

    Article  CAS  PubMed  Google Scholar 

  67. Ueki N, Kanasaki K, Kanasaki M, Takeda S, Koya D. Catechol-O-methyltransferase deficiency leads to hypersensitivity of the pressor response against angiotensin II. Hypertension. 2017;69:1156–64. https://doi.org/10.1161/HYPERTENSIONAHA.117.09247.

    Article  CAS  PubMed  Google Scholar 

  68. Berg D, Sonsalla R, Kuss E. Concentrations of 2-methoxyoestrogens in human serum measured by a heterologous immunoassay with an 125I-labelled ligand. Acta Endocrinol (Copenh). 1983;103:282–8.

    CAS  Google Scholar 

  69. Kanasaki M, et al. Deficiency in catechol-o-methyltransferase is linked to a disruption of glucose homeostasis in mice. Sci Rep. 2017;7:7927.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Coletta DK, et al. Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial. Diabetologia. 2009;52:723–32. https://doi.org/10.1007/s00125-008-1256-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The author declares no conflicts of interests related to this work. This work was partially supported by grants from the Japan Society for the Promotion of Science for KK (23790381, 26460403) and several research grants for KK (the Daiichi-Sankyo Foundation of Life Science, the Ono Medical Research Foundation, the Takeda Science Foundation, Novo Nordisk Insulin Research Foundation, and the Banyu Life Science Foundation International). This work was partially supported by Grant for Promoted Research awarded to KK (S2014-4, S2015-3, S2016-3, S2017-1) from Kanazawa Medical University. This work was also partially supported by the Medical Research Encouragement Prize of the Japan Medical Association for KK. Boehringer Ingelheim (Japan), Mitsubishi Tanabe Pharma, and Ono Pharmaceutical contributed to establishing the Division of Anticipatory Molecular Food Science and Technology. KK is under a consultancy agreement with Boehringer Ingelheim.

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Correspondence to Keizo Kanasaki M.D., Ph.D. .

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Kanasaki, K. (2018). Glucose Intolerance and Insulin Resistance: Relevance in Preeclampsia. In: Saito, S. (eds) Preeclampsia. Comprehensive Gynecology and Obstetrics. Springer, Singapore. https://doi.org/10.1007/978-981-10-5891-2_5

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  • DOI: https://doi.org/10.1007/978-981-10-5891-2_5

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