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Insulin resistance: The possible link between gestational diabetes mellitus and hypertensive disorders of pregnancy

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Abstract

Gestational hypertension, preeclampsia, and diabetes are all associated with increased risks of poor maternal and perinatal outcomes. Pregnant women with gestational diabetes have been shown in population studies to have increased risk of pregnancy-associated hypertension compared with nondiabetic women. Moreover, pregnant patients with hypertension are at increased risk for developing gestational diabetes mellitus. It has been hypothesized that this association could be due, at least in part, to insulin resistance. Although insulin resistance is a physiologic phenomenon in normal pregnancy, in predisposed individuals this could lead to hyperinsulinemia with the development of gestational hypertension, gestational diabetes mellitus, or both.

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References and Recommended Reading

  1. ACOG: diagnosis and management of preeclampsia and eclampsia. acog practice bulletin no. 33. obstet gynecol 2002, 99:159–167.

    Article  Google Scholar 

  2. Sibai BM: Hypertensive disorders of pregnancy: the United States perspective. Curr Opin Obstet Gynecol 2008, 20:102–106.

    Article  PubMed  Google Scholar 

  3. Buchanan TA, Xiang A, Kjos SL, Watanabe R: What is gestational diabetes? Diabetes Care 2007, 30(Suppl 2):S105–S111.

    Article  PubMed  CAS  Google Scholar 

  4. Cheung NW, Byth K: Population health significance of gestational diabetes. Diabetes Care 2003, 26:2005–2009.

    Article  PubMed  Google Scholar 

  5. Bryson CL, Ioannou GN, Rulyak SJ, Critchlow C: Association between gestational diabetes and pregnancy-induced hypertension. Am J Epidemiol 2003, 158:1148–1153.

    Article  PubMed  Google Scholar 

  6. Cousins L: Obstetric complications in diabetic pregnancies. In Diabetes in Women: Adolescence, Pregnancy, and Menopause. Edited by Albert EA, Coustan DR, and Gabbe SG. Philadelphia: Lippincot Williams and Wilkins; 2004:351–362.

    Google Scholar 

  7. Hedderson MM, Ferrara A: High blood pressure before and during early pregnancy is associated with an increased risk of gestational diabetes mellitus. Diabetes Care 2008, 31:2362–2367.

    Article  PubMed  Google Scholar 

  8. Yang XL, Lau JT: Undue increase in insulin resistance during pregnancy may manifest pregnancy-induced hypertension and gestational diabetes. Horm Metab Res 2004, 36:655–661.

    Article  PubMed  CAS  Google Scholar 

  9. Montoro MN, Kjos SL, Chandler M, et al.: Insulin resistance and preeclampsia in gestational diabetes mellitus. Diabetes Care 2005, 28:1995–2000.

    Article  PubMed  CAS  Google Scholar 

  10. Sermer M, Naylor CD, Gare DJ, et al.: Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes: The Toronto trihospital gestational diabetes project. Am J Obstet Gynecol 1995, 173:146–156.

    Article  PubMed  CAS  Google Scholar 

  11. Stanley K, Fraser R, Bruce C: Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique. Br J Obstet Gynaecol 1998, 105:756–759.

    PubMed  CAS  Google Scholar 

  12. Catalano PM, Tyzbir ED, Roman NM, et al.: Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol 1991, 165(6 Pt 1):1667–1672.

    PubMed  CAS  Google Scholar 

  13. Catalano PM, Tyzbir ED, Wolfe RR, et al.: Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol 1993, 264(1 Pt 1):E60–E67.

    PubMed  CAS  Google Scholar 

  14. Reaven GM: Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 1993, 44:121–131.

    Article  PubMed  CAS  Google Scholar 

  15. Ehrmann DA, Liljenquist DR, Kasza K, et al.: Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006, 91:48–53.

    Article  PubMed  CAS  Google Scholar 

  16. Hod JB: Hypertensive disorders and diabetic pregnancy. In Textbook of Diabetes and Pregnancy. Edited by Moshe Hod LJ, Di Renzo GC, de Leiva A, Langer O. London: Informa UK Ltd; 2008:308–317.

    Google Scholar 

  17. Reaven GM: Role of insulin resistance in the pathophysiology of non-insulin dependent diabetes mellitus. Diabetes Metab Rev 1993, 9(Suppl 1):5S–12S.

    PubMed  Google Scholar 

  18. Barker D: Commentary: birthweight and coronary heart disease in a historical cohort. Int J Epidemiol 2006, 35:886–887.

    Article  PubMed  Google Scholar 

  19. Leon DA, Lithell HO, Vagero D, et al.: Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15,000 Swedish men and women born 1915–29. BMJ 1998, 317:241–245.

    PubMed  CAS  Google Scholar 

  20. Stein CE, Fall CH, Kumaran K, et al.: Fetal growth and coronary heart disease in south India. Lancet 1996, 348:1269–1273.

    Article  PubMed  CAS  Google Scholar 

  21. Frankel S, Elwood P, Sweetnam P, et al.: Birthweight, adult risk factors and incident coronary heart disease: the Caerphilly Study. Public Health 1996, 110:139–143.

    Article  PubMed  CAS  Google Scholar 

  22. Negrato CA, Jovanovic L, Tambascia MA, et al.: Association between insulin resistance, glucose intolerance, and hypertension in pregnancy. Metab Syndr Relat Disord 2008 Oct 11(Epub ahead of print).

  23. Barker DJ, Osmond C: Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986, 1:1077–1081.

    Article  PubMed  CAS  Google Scholar 

  24. Eriksson JG, Forsen T, Tuomilehto J, et al.: Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 1999, 318:427–431.

    PubMed  CAS  Google Scholar 

  25. Barker DJ, Martyn CN, Osmond C, Wield GA: Abnormal liver growth in utero and death from coronary heart disease. BMJ 1995, 310:703–704.

    PubMed  CAS  Google Scholar 

  26. Barker DJ: Fetal origins of coronary heart disease. BMJ 1995, 311:171–174.

    PubMed  CAS  Google Scholar 

  27. Meyer NL, Mercer BM, Friedman SA, Sibai BM: Urinary dipstick protein: a poor predictor of absent or severe proteinuria. Am J Obstet Gynecol 1994, 170(1 Pt 1):137–141.

    PubMed  CAS  Google Scholar 

  28. Yen SS: Endocrine regulation of metabolic homeostasis during pregnancy. Clin Obstet Gynecol 1973, 16:130–147.

    Article  PubMed  CAS  Google Scholar 

  29. Solomon CG, Seely EW: Brief review: hypertension in pregnancy: a manifestation of the insulin resistance syndrome? Hypertension 2001, 37:232–239.

    PubMed  CAS  Google Scholar 

  30. Kuhl C: Insulin secretion and insulin resistance in pregnancy and GDM. Implications for diagnosis and management. Diabetes 1991, 40(Suppl 2):18–24.

    PubMed  Google Scholar 

  31. Dunaif A, Segal KR, Futterweit W, Dobrjansky A, et al.: Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989, 38:1165–1174.

    Article  PubMed  CAS  Google Scholar 

  32. Solomon CG, Graves SW, Greene MF, Seely EW, et al.: Glucose intolerance as a predictor of hypertension in pregnancy. Hypertension 1994, 23(6 Pt 1):717–721.

    PubMed  CAS  Google Scholar 

  33. Sowers JR, Saleh AA, Sokol RJ: Hyperinsulinemia and insulin resistance are associated with preeclampsia in African-Americans. Am J Hypertens 1995, 8:1–4.

    Article  PubMed  CAS  Google Scholar 

  34. Yasuhi I, Hogan JW, Canick J, et al.: Midpregnancy serum C-peptide concentration and subsequent pregnancy-induced hypertension. Diabetes Care, 2001, 24:743–747.

    Article  PubMed  CAS  Google Scholar 

  35. Parretti E, Lapolla A, Dalfra M, et al.: Preeclampsia in lean normotensive normotolerant pregnant women can be predicted by simple insulin sensitivity indexes. Hypertension 2006, 47:449–453.

    Article  PubMed  CAS  Google Scholar 

  36. Girouard J, Giguere Y, Moutquin JM, Forest JC, et al.: Previous hypertensive disease of pregnancy is associated with alterations of markers of insulin resistance. Hypertension 2007, 49:1056–1062.

    Article  PubMed  CAS  Google Scholar 

  37. Thadhani R, Ecker JL, Mutter WP, et al.: Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia. Hypertension 2004, 43:988–992.

    Article  PubMed  CAS  Google Scholar 

  38. Lanzone A, Caruso A, Di Simone N, et al.: Polycystic ovary disease. A risk factor for gestational diabetes? J Reprod Med 1995, 40:312–316.

    PubMed  CAS  Google Scholar 

  39. Urman B, Sarac E, Dogan L, Gurgan T: Pregnancy in infertile PCOD patients. Complications and outcome. J Reprod Med 1997, 42:501–505.

    PubMed  CAS  Google Scholar 

  40. Abbasi F, McLaughlin T, Lamendola C, et al.: Comparison of plasminogen activator inhibitor-1 concentration in insulin-resistant versus insulin-sensitive healthy women. Arterioscler Thromb Vasc Biol 1999, 19:2818–2821.

    PubMed  CAS  Google Scholar 

  41. Segal KR, Landt M, Klein S: Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 1996, 45:988–991.

    Article  PubMed  CAS  Google Scholar 

  42. Vitoratos N, Chrystodoulacos G, Kouskouni E, et al.: Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy. Eur J Obstet Gynecol Reprod Biol 2001, 96:59–62.

    Article  PubMed  CAS  Google Scholar 

  43. Fernandez-Real JM, Broch M, Ricart W, et al.: Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance. Diabetes 1998, 47:1757–1762.

    Article  PubMed  CAS  Google Scholar 

  44. Meigs JB, Mittleman MA, Nathan DM, et al.: Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 2000, 283:221–228.

    Article  PubMed  CAS  Google Scholar 

  45. McCarthy JF, Misra DN, Roberts JM: Maternal plasma leptin is increased in preeclampsia and positively correlates with fetal cord concentration. Am J Obstet Gynecol 1999, 180(3 Pt 1):731–736.

    Article  PubMed  CAS  Google Scholar 

  46. Williams MA, Farrand A, Mittendorf R, et al.: Maternal second trimester serum tumor necrosis factor-alpha-soluble receptor p55 (sTNFp55) and subsequent risk of preeclampsia. Am J Epidemiol 1999, 149:323–329.

    PubMed  CAS  Google Scholar 

  47. Buchanan TA, Metzger BE, Freinkel N, Bergman RN: Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes. Am J Obstet Gynecol 1990, 162:1008–1114.

    PubMed  CAS  Google Scholar 

  48. Bowes SB, Hennessy TR, Umpleby AM, et al.: Measurement of glucose metabolism and insulin secretion during normal pregnancy and pregnancy complicated by gestational diabetes. Diabetologia 1996, 39:976–983.

    Article  PubMed  CAS  Google Scholar 

  49. Persson B, Edwall L, Hanson U, et al.: Insulin sensitivity and insulin response in women with gestational diabetes mellitus. Horm Metab Res 1997, 29:393–397.

    Article  PubMed  CAS  Google Scholar 

  50. 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.

    Article  PubMed  CAS  Google Scholar 

  51. DeFronzo RA, Ferrannini E: Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14:173–194.

    Article  PubMed  CAS  Google Scholar 

  52. Metzger BE, Lowe LP, Dyer AR, et al.: Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008, 358:1991–2002.

    Article  PubMed  Google Scholar 

  53. Garner P, et al.: A randomized controlled trial of strict glycemic control and tertiary level obstetric care versus routine obstetric care in the management of gestational diabetes: a pilot study. Am J Obstet Gynecol 1997, 177:190–195.

    Article  PubMed  CAS  Google Scholar 

  54. Yogev Y, Xenakis EM, Langer O: The association between preeclampsia and the severity of gestational diabetes: the impact of glycemic control. Am J Obstet Gynecol 2004, 191:1655–1660.

    Article  PubMed  Google Scholar 

  55. Glueck CJ, Wang P, Kobayashi S, et al.: Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002, 77:520–525.

    Article  PubMed  CAS  Google Scholar 

  56. Combs CA, et al.: Early-pregnancy proteinuria in diabetes related to preeclampsia. Obstet Gynecol 1993, 82:802–807.

    PubMed  CAS  Google Scholar 

  57. Hanson U, Persson B: Outcome of pregnancies complicated by type 1 insulin-dependent diabetes in Sweden: acute pregnancy complications, neonatal mortality and morbidity. Am J Perinatol 1993, 10:330–333.

    Article  PubMed  CAS  Google Scholar 

  58. Page NM, Kemp CF, Butlin DJ, Lowry PJ: Placental peptides as markers of gestational disease. Reproduction 2002, 123:487–495.

    Article  PubMed  CAS  Google Scholar 

  59. Scioscia M, Gumaa K, Kunjara S, et al.: Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate-1 and -2. J Clin Endocrinol Metab 2006, 91:709–717.

    Article  PubMed  CAS  Google Scholar 

  60. Cohen A, Lim K-H, Lee Y, et al.: Circulating levels of the antiangiogenic marker soluble FMS-like tyrosine kinase 1 are elevated in women with pregestational diabetes and preeclampsia. Diabetes Care 2007, 30:375–377.

    Article  PubMed  CAS  Google Scholar 

  61. Rademacher TW, Gumaa K, Scioscia M: Preeclampsia, insulin signalling and immunological dysfunction: a fetal, maternal or placental disorder? J Reprod Immunol 2007, 76:78–84.

    Article  PubMed  CAS  Google Scholar 

  62. Albareda M, Caballero A, Badell G, et al.: Diabetes and abnormal glucose tolerance in women with previous gestational diabetes. Diabetes Care 2003, 26:1199–1205.

    Article  PubMed  Google Scholar 

  63. Aberg AE, Jonsson EK, Eskilsson I, et al.: Predictive factors of developing diabetes mellitus in women with gestational diabetes. Acta Obstet Gynecol Scand 2002, 81:11–16.

    Article  PubMed  Google Scholar 

  64. Hanson U, Persson B, Hartling SG, Binder C: Increased molar proinsulin-to-insulin ratio in women with previous gestational diabetes does not predict later impairment of glucose tolerance. Diabetes Care 1996, 19:17–20.

    Article  PubMed  CAS  Google Scholar 

  65. Sattar N, Ramsay J, Crawford L, et al.: Classic and novel risk factor parameters in women with a history of preeclampsia. Hypertension 2003, 42:39–42.

    Article  PubMed  CAS  Google Scholar 

  66. Kestenbaum B, Seliger SL, Easterling TR, et al.: Cardiovascular and thromboembolic events following hypertensive pregnancy. Am J Kidney Dis 2003, 42:982–989.

    Article  PubMed  Google Scholar 

  67. Irgens HU, Reisaeter L, Irgens LM, Lie RT, et al.: Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001, 323:1213–1217.

    Article  PubMed  CAS  Google Scholar 

  68. Marcoux S, Brisson J, Fabia J: The effect of leisure time physical activity on the risk of pre-eclampsia and gestational hypertension. J Epidemiol Community Health 1989, 43:147–152.

    Article  PubMed  CAS  Google Scholar 

  69. Bar J, Chen R, Schoenfeld A, et al.: Pregnancy outcome in patients with insulin dependent diabetes mellitus and diabetic nephropathy treated with ACE inhibitors before pregnancy. J Pediatr Endocrinol Metab 1999, 12:659–665.

    PubMed  CAS  Google Scholar 

  70. Bar J, Hod M, Erman A, et al.: Microalbuminuria as an early predictor of hypertensive complications in pregnant women at high risk. Am J Kidney Dis 1996, 28:220–225.

    Article  PubMed  CAS  Google Scholar 

  71. Caritis S, Sibai B, Hauth J, et al.: Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 1998, 338:701–705.

    CAS  Google Scholar 

  72. Stella CL, O’Brien JM, Forrester KJ, et al.: The coexistence of gestational hypertension and diabetes: influence on pregnancy outcome. Am J Perinatol 2008, 25:325–329.

    Article  PubMed  Google Scholar 

  73. Hinton AC: Hypertensive disorders in pregnancy. In Diabetes in Women: Adolescence, Pregnancy, and Menaupause. Edited by Albert EA, Coustan DR, Gabbe SG. Philadelphia: Lippincot Williams and Wilkins; 2004:363–369.

    Google Scholar 

  74. Hawkins JS, Casey BM: Labor and delivery management for women with diabetes. Obstet Gynecol Clin North Am 2007, 34:323–334.

    Article  PubMed  Google Scholar 

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  1. Obstetrics, Gynecology, and Reproductive Sciences, Temple University Medical School, 3401 N. Broad Street, Philadelphia, PA, 19140, USA

    Dimitrios S. Mastrogiannis

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  1. Dimitrios S. Mastrogiannis
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  2. Michail Spiliopoulos
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  3. Wadia Mulla
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  4. Carol J. Homko
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Correspondence to Dimitrios S. Mastrogiannis.

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Mastrogiannis, D.S., Spiliopoulos, M., Mulla, W. et al. Insulin resistance: The possible link between gestational diabetes mellitus and hypertensive disorders of pregnancy. Curr Diab Rep 9, 296–302 (2009). https://doi.org/10.1007/s11892-009-0046-1

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