Current Diabetes Reports

, Volume 12, Issue 1, pp 43–52 | Cite as

Gestational Diabetes: Implications for Cardiovascular Health

  • Shannon D. Sullivan
  • Jason G. Umans
  • Robert RatnerEmail author
Diabetes and Pregnancy (CJ Homko, Section Editor)


Gestational diabetes mellitus (GDM) is a pregnancy complication that is becoming more prevalent with recent population trends in obesity and advancing maternal age. A diagnosis of GDM not only increases risk for maternal and fetal complications during pregnancy, but also significantly increases a woman’s risk of both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in the postpartum. Even women with milder forms of abnormal glucose homeostasis during pregnancy, specifically gestational impaired glucose tolerance, are at increased risk, justifying the recent recommendation to tighten the diagnostic criteria for GDM, thus implicating many more women. Risk factors that increase risk for future CVD among women with a history of GDM include postpartum progression to T2DM; metabolic syndrome; obesity; hypertension; and altered levels of circulating inflammatory markers, specifically, adiponectin, C-reactive protein, and tumor necrosis factor-α. Medical therapies such as metformin that prevent progression to T2DM may prove to be our primary defense against earlier CVD among women with GDM.


Gestational diabetes Gestational impaired glucose tolerance Cardiovascular disease Metabolic syndrome Type 2 diabetes mellitus Obesity Inflammation 

Clinical Trial Acronyms


Diabetes Prevention Program


Hyperglycemia and Adverse Pregnancy Outcomes


International Association of Diabetes in Pregnancy Study Group


Kidney Early Evaluation Program


Pioglitazone in Prevention of Diabetes


Troglitazone in Prevention of Diabetes.



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ. 2002;325:157–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Rich-Edwards JW, McElrath TF, Karumanchi SA, et al. Breathing life into the lifecourse approach: pregnancy history and cardiovascular disease in women. Hypertension. 2010;56:331–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes. Diab Care. 2002;25:1862–68.CrossRefGoogle Scholar
  4. 4.
    Sullivan SD, Umans JG, Ratner R. Hypertension complicating diabetic pregnancies: pathophysiology, management, and controversies. J Clin Hypert. 2011;13:275–84.CrossRefGoogle Scholar
  5. 5.
    Joffe GM, Esterlitz JR, Levine RJ, et al. The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women. Am J Ob Gyn. 1998;174:1032–7.CrossRefGoogle Scholar
  6. 6.
    Roberts R. Hypertension in women with gestational diabetes. Diabetes Care. 1998;21 Suppl 2:B27–32.PubMedGoogle Scholar
  7. 7.
    Metzger BE, Buchanan TA, Coustand DR, et al. Summary and recommendations of the Fifth International Workshop Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007;30:s251–60.PubMedCrossRefGoogle Scholar
  8. 8.
    ADA. Gestational diabetes mellitus. Diab Care. 2000;23 Suppl 1:S77–9.Google Scholar
  9. 9.
    Lauenborg J, Mathiesen E, Hansen T, et al. The prevalence of the metabolic syndrome in a Danish population of women with previous gestational diabetes mellitus is three-fold higher than in the general population. JCEM. 2005;90:4004–10.PubMedGoogle Scholar
  10. 10.
    Shah BR, Retnakaran R, Booth GL. 2008. Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care 31:1668–9. In this Canadian, population-based retrospective cohort study of more than 8000 young women with a history of GDM and more than 80,000 matched control women without GDM, risk of CVD events (including acute myocardial infarction, stroke, coronary bypass or angioplasty, and carotid endarterectomy) over 11.5 years of follow-up was significantly greater among the GDM cohort (HR, 1.7; 95% CI, 1.1–6.9), although this risk was attenuated after adjusting for subsequent T2DM (HR, 1.1; 95% CI, 0.7–1.9). Google Scholar
  11. 11.
    Heitritter SM, Solomon CG, Mitchell GF, et al. Subclinical inflammation and vascular dysfunction in women with previous gestational diabetes mellitus. JCEM. 2005;90:3983–88.PubMedGoogle Scholar
  12. 12.
    HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. NEJM. 2008;358:1991–2002.CrossRefGoogle Scholar
  13. 13.
    Leary J, Pettitt DJ, Jovanovic L. Gestational diabetes guidelines in a HAPO world. Best Pract Res Clin Endocrinol Metab. 2010;24:673–85.PubMedCrossRefGoogle Scholar
  14. 14.
    Freire CM, Nunes MC, Barbosa MM, et al. Gestational diabetes: a condition of early diastolic abnormalities in young women. J Am Soc Echocardiogr. 2006;19:1251–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Tarim E, Yigit F, Kilicdag E, et al. Early onset of subclinical atherosclerosis in women with gestational diabetes mellitus. Utrasound Obstet Gynecol. 2006;27:177–82.CrossRefGoogle Scholar
  16. 16.
    Welch GN, Loscalzo J. Homocysteine and atherothrombosis. NEJM. 1998;338:1042–50.PubMedCrossRefGoogle Scholar
  17. 17.
    Bo S, Balpreda S, Menato G, et al. Should we consider gestational diabetes a vascular risk factor? Atherosclerosis. 2007;194:72–9.CrossRefGoogle Scholar
  18. 18.
    Kautzky-Willer A, Fasching P, Jilma B, et al. Persistent elevation and metabolic dependence of circulating E-selectin after delivery in women with gestational diabetes mellitus. JCEM. 1997;82:4117–21.PubMedGoogle Scholar
  19. 19.
    Fasching P, Veitl M, Rohac M, et al. Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus. JCEM. 1996;81:4313–7.PubMedGoogle Scholar
  20. 20.
    Carr DB, Utzschneider KM, Hull RL, et al. Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diab Care. 2006;29:2078–83.CrossRefGoogle Scholar
  21. 21.
    Retnakaran R, Shah BR. 2009. Mild glucose intolerance in pregnancy and risk of cardiovascular disease: a population-based cohort study. CMAJ 181:371–6. This retrospective population-based cohort study of Canadian women with at least one live birth demonstrated that compared to women who remained normoglycemic during pregnancy, women with either GDM or a milder form of glucose intolerance during pregnancy (defined as an abnormal glucose challenge test and a normal diagnostic OGTT) had significantly increased risk of an acute cardiovascular event over a median of 12 years of follow-up after the index pregnancy. Google Scholar
  22. 22.
    Xiang AH, Peters RK, Kjos SL, et al. Effect of thiazolidinedione treatment on progression of subclinical atherosclerosis in premenopausal women at high risk for type 2 diabetes. JCEM. 2005;90:1986–91.PubMedGoogle Scholar
  23. 23.
    Kvehaugen AS, Andersen LF, Staff AC. Anthropometry and cardiovascular risk factors in women and offspring after pregnancies complicated by preeclampsia or diabetes mellitus. Acta Obstet Gynecol. 2010;89:1478–85.CrossRefGoogle Scholar
  24. 24.
    Retnakaran R, Qi Y, Connelly PW, et al. 2010. Glucose intolerance in pregnancy and postpartum risk of metabolic syndrome in young women. JCEM 95:670–7. This prospective study compared rates of metabolic syndrome at 3 months postpartum among women with GDM, GIGT, and normal glucose tolerance during pregnancy. Investigators demonstrate that prevalence of metabolic syndrome progressively increases with increasing severity of gestational dysglycemia (NGT, 9%; GIGT, 15%; GDM, 17% using American Heart Association/National Heart, Lung, and Blood Institute criteria), supporting the notion that even mild forms of glucose intolerance in pregnancy predict increased future CVD risk. Google Scholar
  25. 25.
    Verma A, Boney CM, Tucker R, et al. Insulin resistance syndrome in women with prior history of gestational diabetes mellitus. JCEM. 2002;87:3227–35.PubMedGoogle Scholar
  26. 26.
    Pallardo LF, Harranz L, Martin-Vaquero P, et al. Impaired fasting glucose and impaired glucose tolerance in women with prior gestational diabetes are associated with a different cardiovascular profile. Diab Care. 2003;26:2318–22.CrossRefGoogle Scholar
  27. 27.
    Meyers-Seifer CH, Vohr BR. Lipid levels in former gestational diabetic mothers. Diabetes Care. 1996;19:1351–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Retnakarn R, Qi Y, Connelly PW, et al. The graded relationship between glucose tolerance status in pregnancy and postpartum levels of low density lipoprotein cholesterol and apolipoprotein B in young women: implications for future cardiovascular risk. JCEM. 2010;95:4345–53.Google Scholar
  29. 29.
    Bergholm R, Tiikkainen M, Vehkavaara S, et al. Lowering of LDL cholesterol rather than moderate weight loss improves endothelium-dependent vasodilatation in obese women with previous gestational diabetes. Diabetes Care. 2003;26:1667–72.PubMedCrossRefGoogle Scholar
  30. 30.
    Carpenter MW. Gestational diabetes, pregnancy, hypertension, and late vascular disease. Diabetes Care. 2007;30:S246–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. NEJM. 2005;352:2477–86.PubMedCrossRefGoogle Scholar
  32. 32.
    Steinberg HO, Chaker H, Leaming R, et al. Obesity/insulin resistance is associated with endothelial dysfunction: implications for the syndrome of insulin resistance. J Clin Invest. 1996;97:2601–10.PubMedCrossRefGoogle Scholar
  33. 33.
    Petrie JR, Ueda S, Webb S, et al. Endothelial nitric oxide production and insulin sensitivity: a physiological link with implications for pathogenesis of cardiovascular disease. Circulation. 1996;93:1331–3.PubMedGoogle Scholar
  34. 34.
    Anastasiou E, Lekakis JP, Alevizaki M, et al. Impaired endothelial-dependent vasodilatation in women with previous gestational diabetes. Diabetes Care. 1998;21:2111–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Retnakaran R, Hanley AJ, Raif N, et al. C-Reactive protein and gestational diabetes: the central role of maternal obesity. JCEM. 2003;88:3507–12.PubMedGoogle Scholar
  36. 36.
    Xiang AH, Kawakubo M, Trigo E, et al. Declining B-cell compensation for insulin resistance in Hispanic women with recent gestational diabetes mellitus. Diabetes Care. 2010;33:396–401.PubMedCrossRefGoogle Scholar
  37. 37.
    McLachlan KA, O’Neal D, Jenkins A, et al. Do adiponectin, TNF-alpha, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with and without gestational diabetes, during and after pregnancy. Diabet Metab Res Rev. 2006;22:131–8.CrossRefGoogle Scholar
  38. 38.
    Szarka A, Rigo J, Lazar L, et al. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol. 2010;11:59–67.PubMedCrossRefGoogle Scholar
  39. 39.
    Kocyigit Y, Atamer Y, Atamer A, et al. Changes in serum levels of leptin, cytokines and lipoprotein in pre-eclamptic and normotensive pregnant women. Gynecol Endocrinol. 2004;19:267–73.PubMedCrossRefGoogle Scholar
  40. 40.
    Alexander BT, Cockrell KL, Massey MD, et al. Tumor necrosis factor-alpha-induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression. Am J Hypertens. 2002;15:170–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Retnakaran R, Qi Y, Connelly PW, et al. Low adiponectin concentration in pregnancy predicts postpartum insulin resistance, beta-cell dysfunction, and fasting glycaemia. Diabetologia. 2010;53:268–76.PubMedCrossRefGoogle Scholar
  42. 42.
    DiBenedetto A, Russo GT, Corrado F, et al. Inflammatory markers in women with a recent history of gestational diabetes mellitus. J Endocrinol Invest. 2005;28:34–8.Google Scholar
  43. 43.
    Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51:2796–803.PubMedCrossRefGoogle Scholar
  44. 44.
    Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese and type 2 diabetic subjects. Diabetes. 2002;51:2968–74.PubMedCrossRefGoogle Scholar
  45. 45.
    Kim C, Cheng YJ, Beckles GL. Cardiovascular disease risk profiles in women with histories of gestational diabetes but without current diabetes. Obstet Gynecol. 2008;112:875–83.PubMedCrossRefGoogle Scholar
  46. 46.
    Rarikh NI, Hwang SJ, Larson MG, et al. Chronic kidney disease as a predictor of cardiovascular disease (from the Framingham Heart Study). Am J Cardiol. 2008;102:47–53.CrossRefGoogle Scholar
  47. 47.
    Jensen JS, Feldt-Rasmussen B, Borch-Johnsen K, et al. 1997. Microalbuminuria and its relation to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals. J Hum Hypertens. 11(11):727–32.Google Scholar
  48. 48.
    Klausen K, Borch-Johnsen, Feldt-Rasmussen B, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation. 2004;110:32–5.PubMedCrossRefGoogle Scholar
  49. 49.
    • Bomback AS, Rekhtman Y, Whaley-Connell AT, et al. 2010. Gestational diabetes mellitus alone in the absence of subsequent diabetes is associated with microalbuminuria: results from the Kidney Early Evaluation Program (KEEP). Diabetes Care 33(12):2586–91. In this secondary analysis of the KEEP trial, women with a history of GDM were compared to women with overt T2DM and nondiabetic women in prevalence of micro-/macroalbuminuria and CKD. Women with GDM had a significantly higher rate of microalbuminuria compared with nondiabetic patients (10% vs 8%), both less than the prevalence seen in T2DM women (14%). Further, risk of CKD stage 1 to 2 in women with GDM was higher than the risk in nondiabetic patients and similar to the risk seen in women with T2DM, suggesting GDM may be an independent risk factor for future renal disease and CVD. Google Scholar
  50. 50.
    Friedman S, Rabinerson D, Bar J, et al. Microalbuminuria following gestational diabetes. Acta Obstet Gynceol Scand. 1995;74:356–60.CrossRefGoogle Scholar
  51. 51.
    • Ratner RE, Christophi CA, Metzger BE, et al. 2008. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrin Metab. 93:4774–9. Women enrolled in the DPP trial reporting a history of GDM were 71% more likely to progress to T2DM compared to women without GDM despite have similar degrees of impaired glucose tolerance (IGT) at baseline. Lifestyle modification (diet and exercise) reduced progression to T2DM equally in women with and without GDM histories (~ 50% risk reduction), whereas metformin was significantly more effective in reducing progression to T2DM among women with GDM (50% vs 14% reduction). Thus, both lifestyle modification and metformin help prevent or delay progression to T2DM with equal effectiveness in women with a history of GDM who have IGT and/or impaired fasting glucose postpartum. Google Scholar
  52. 52.
    Xiang AH, Hodis HN, Kawakubo M, et al. Effect of pioglitazone on progression of subclinical atherosclerosis in non-diabetic premenopausal Hispanic women with prior gestational diabetes. Atherosclerosis. 2008;199:207–14.PubMedCrossRefGoogle Scholar
  53. 53.
    DiCianni G, Seghieri G, Lencioni C, et al. Normal glucose tolerance and gestational diabetes mellitus: what is in between? Diabetes Care. 2007;30:1783–8.CrossRefGoogle Scholar
  54. 54.
    Lowe LP, Metzger BE, Lowe WL, et al. 2010. Inflammatory mediators and glucose in pregnancy: results from a subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Diabetes Care 95:5427–34. This secondary analysis of a subset of patients enrolled in the HAPO study examined the association between inflammatory mediators known to be elevated in T2DM with maternal glucose levels and neonatal size. Among women who did not meet criteria for GDM, adiponectin levels were lower, and plasminogen activator inhibitor type 1 and CRP levels were higher, across increasing levels of maternal fasting glucose, C-peptide, and BMI. Further, maternal adiponectin and CRP levels were inversely associated with birth weight. This study underscores that the pathophysiologic process of increased systemic inflammation is exacerbated by even mild degrees of glucose intolerance in pregnancy. Google Scholar
  55. 55.
    Retnakaran R, Qi Y, Connelly PW, et al. Risk of early progression to prediabetes or diabetes in women with recent gestational hyperglycemia but normal glucose tolerance at 3-month postpartum. Clin Endocrinol (Oxf). 2010;73:476–83.Google Scholar
  56. 56.
    Xiang AH, Peters RK, Kjos SL, et al. Effect of pioglitazone on pancreatic B-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes. 2006;55:517–22.PubMedCrossRefGoogle Scholar
  57. 57.
    Berkowitz K, Peters R, Kjos SL, et al. Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM. Diabetes. 1996;45(11):1572–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Pallardo F, Herranz L, Garcia-Ingelmo T, et al. Early postpartum metabolic assessment in women with prior gestational diabetes. Diab Care. 1999;22:1053–8.CrossRefGoogle Scholar
  59. 59.
    Pettitt DJ, Nelson RG, Saad MF, et al. Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care. 1993;16:310–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Shannon D. Sullivan
    • 1
  • Jason G. Umans
    • 2
    • 3
  • Robert Ratner
    • 2
    • 3
    Email author
  1. 1.Department of EndocrinologyWashington Hospital CenterWashingtonUSA
  2. 2.Medstar Health Research InstituteHyattesvilleUSA
  3. 3.Georgetown-Howard Universities Center for Clinical and Translational ScienceWashingtonUSA

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