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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