Physicians' Academy for Cardiovascular Education

History of gestational diabetes risk factor for early subclinical atherosclerosis

Literature - Gunderson EP et al., J Am Heart Assoc. 2014 - J Am Heart Assoc. 2014 Mar 12;3(2):e000490

 

History of Gestational Diabetes Mellitus and Future Risk of Atherosclerosis in Mid-life: The Coronary Artery Risk Development in Young Adults Study

 
Gunderson EP, Chiang V, Pletcher MJ et al.
J Am Heart Assoc. 2014 Mar 12;3(2):e000490
 

Background

Diabetes mellitus that is first recognised during pregnancy (Gestational DM: GDM) is associated with maternal obesity and confers a 4- to 7-fold greater risk of incident type 2 diabetes (DM)[1,2], as well as an increased risk of developing the metabolic syndrome (MetS) in midlife [3,4]. A history of GDM among nondiabetic women is furthermore characterised by higher fasting glucose and insulin concentrations [5], dyslipidemia and greater inflammation in the absence of the MetS [6-8].
In addition to a higher risk of future metabolic disease, history of GDM has also been linked to excess heart disease [9], although the precise relationship is unclear because previous studies did not take into account metabolic disease before and after pregnancy.
Cross-sectional studies have measured carotid artery intima media thickness (ccIMT) during GDM and non-GDM pregnancies. ccIMT was not measured after post-delivery. The temporal relationship between type 2 diabetes or cardiometabolic disease and endothelial changes after GDM pregnancy are unclear.
Using the CARDIA Study cohort of black and white women (1986-2006), a longitudinal analysis was performed in women without prior heart disease or DM before pregnancies, to investigate whether GDM pregnancy leads to greater carotid artery IMT in midlife (38-50 years). Data of 898 women (47% black, average age: 24 years, range 18-30) were used, who had ccIMT measured 20 years later, and who had delivered at least one birth in this period. 119 (13%) reported a history of GDM.
 

Main results

  • Women who reported GDM were heavier  (BMI: 24.8 vs. 23.3, P=0.001), and had higher mean fasting glucose (81.0 vs. 79.1 mg/dL, P=0.02) and HOMA-IR (2.4 vs. 2.0, P=0.02) at baseline than the non-GDM group.
  • At follow-up, the GDM group had higher mean fasting serum triglycerides (100.3 vs. 89.5 mg/dL, P=0.04), mean fasting glucose (104.2 vs. 92.4 mg/dL, P<0.001), diastolic blood pressure (72.5 vs. 70.1 mmHg, P=0.03) and BMI (31.3 vs 28.9 kg/m2, P<0.001) than the non-GDM group. Women with GDM were more likely to have developed DM (25% vs. 6%, P<0.001) and the MetS (13% vs. 7%, P=0.03) over the 20 years follow-up period.
  • Racial differences were observed in that black women had higher unadjusted mean [SD] ccIMT than white women (0.800 [0.115] vs. 0.729 [0.091], P<0.001), but this difference was largely explained by pre-pregnancy BMI and weight gain.
  • Linear regression models showed a higher mean ccIMT for GDM than non-GDM groups (0.785, 95%CI: 0.767-0.803 vs. 0.762, 95%CI: 0.755-0.769, P=0.020, adjusted for age, race, parity). The statistically significant mean difference in ccIMT was not maintained with further correction for pre-pregnancy BMI. Additional correction for pre-pregnancy HOMA-IR did not affect mean ccIMT.
  • Among 777 women who did not develop DM or MetS during follow-up, mean net difference in ccIMT was 0.023 mm higher for GDM than in non-GDM groups (P=0.039, adjusted for age, race, parity, pre-pregnancy BMI). Pre-pregnancy HOMA-IR had minimal impact on adjusted mean ccIMT, while weight gain during the 20-year follow-up attenuated the difference in ccIMT to 0.019 (P=0.089).
  • Among 121 women who developed DM or MetS during follow-up, no differences were seen in ccIMT according to GDM history.
 

Conclusion

These data show that women with a history of GDM are at greater risk of early subclinical atherosclerosis (as measured by ccIMT), before the onset of diabetes and the metabolic syndrome, irrespective of pre-pregnancy obesity, race, parity and age.
Since these data suggest that a history of GDM influences early atherosclerosis risk before progression to overt diabetes or the metabolic syndrome, they support postpartum screening for CVD risk factors among women with a history of GDM. Body size, blood pressure control and insulin resistance appear to be important modifiable risk factors that can influence progression of atherosclerosis during midlife in women with a history of GDM.
 
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References

1. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373:1773–1779.
2. Gunderson EP, Lewis CE, Tsai AL, et al. A 20-year prospective study of childbearing and incidence of diabetes mellitus in young women controlling for glycemia before conception: the Coronary Artery Risk Development in Young Adults study. Diabetes. 2007;56:2990–2996.
3. Gunderson EP, Jacobs DR Jr, Chiang V, et al. Childbearing is associated with higher incidence of the metabolic syndrome among women of reproductive age controlling for measurements before pregnancy: the CARDIA study. Am J Obstet Gynecol. 2009;201:e1–e9.
4. Noussitou P, Monbaron D, Vial Y, et al. Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland. Diabetes Metab. 2005;31:361–369.
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6. Retnakaran R, Shah BR. Mild glucose intolerance in pregnancy and risk of cardiovascular disease: a population-based cohort study. CMAJ. 2009;181:371–376.
7. Rivero K, Portal VL, Vieira M, Behle I. Prevalence of the impaired glucose metabolism and its association with risk factors for coronary artery disease in women with gestational diabetes. Diabetes Res Clin Pract. 2008;79:433–437.
8. Albareda M, Caballero A, Badell G, et al. Metabolic syndrome at follow-up in women with and
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9. Bentley-Lewis R. Late cardiovascular consequences of gestational diabetes mellitus. Semin Reprod Med. 2009;27:322–329.
 

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