Gestational Diabetes Mellitus: an Opportunity to Prevent Type 2 Diabetes and Cardiovascular Disease in Young Women

Graziano Di Cianni; Alessandra Ghio; Veronica Resi; Laura Volpe

Disclosures

Women's Health. 2010;6(1):97-105. 

In This Article

GDM: A Risk for Cardiovascular Disease

In addition to T2DM, women with pGDM also tend to display features of the MS, such as hypertension, dyslipidemia and microalbuminuria,[6] and they may present an increased cardiovascular risk factor profile (Figure 2).[27,28] In this context they show elevated total cholesterol, LDL-cholesterol and triglyceride concentrations and low HDL-cholesterol.[29,30]

Figure 2.

Gestational diabetes mellitus: a risk for Type 2 diabetes and for cardiovascular disease later in life.
pGDM: Previous gestational diabetes mellitus.

Moreover, other nontraditional cardiometabolic risk factors, such as higher levels of plasminogen activator type 1, acute-phase inflammatory biomarkers (e.g., leukocyte count, fibrinogen, C-reactive protein and sialic acid) and low circulating levels of adiponectin have been found in women with pGDM.[31–34] As a consequence, MS prevalence after a GDM-complicated pregnancy is significantly higher than in women with normal pregnancy, in just the first 10 years following the index pregnancy (Figure 3).[35–37] In a previous study, we have demonstrated that the rate of MS was 9% in women with pGDM and 1% in the control group in a cohort of women with pGDM 16 months after delivery.[34] Based on this observation, it appears rational to propose that pGDM should be considered a manifestation of this syndrome.

Figure 3.

Follow-up program for the prevention of T2DM in women with previous gestational diabetes mellitus.
IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; NGT: Normal glucose tolerance; OGTT: Oral glucose tolerance test; T2DM: Type 2 diabetes mellitus.

The observation that the association between subclinical inflammation and MS occurs more frequently in women with pGDM than in women with normal pregnancy makes plausible the theory that these women may be exposed to a more atherogenic insult.[38] In fact, studies performed in these women have demonstrated increased vascular dysfunction, including impaired endothelium-dependent vasodilatation, increased vessel stiffness, early abnormalities in diastolic function and impaired cardiac autonomic function.[33,39–41] In this context, we observed that relatively young women, just 2 years after index pregnancy, are at risk for the early onset of subclinical atherosclerosis, as indicated by increased carotid artery intima-media thickness (Table 2).[42] Therefore, pregnancy offers an important opportunity for assessing the risk of cardiovascular and metabolic disease, and it could be considered as an event with the potential to unveil a pre-existing susceptibility that is higher in women who previously developed GDM.

Recently, this anticipated association between pGDM and subsequent CVD has been confirmed by Shah et al..[43] Their study included 8191 women with GDM and 81,262 women without GDM in matched cohorts, with mean ages of 31 years at entry and median follow-up of 11.5 years. The hazard ratio for CVD events was 1.71. They concluded that the increased risk was attributable to subsequent development of T2DM. The importance of these data is that cardiovascular events have been registered in young women. This study confirms the previous observation of Carr et al. who, in a retrospective study of premenopausal women with a family history of T2DM, found that women with pGDM had a higher prevalence of CVD risk factors, including MS and T2DM, but also of CVD events at a younger age compared with those without GDM.[44]

The potential role of overt T2DM in determining the vascular risk associated with pGDM remains unclear. However, considering the low period of time generally required for the development of CVD in T2DM, it seems unlikely that diabetes precedes the onset of CVD in women with pGDM. T2DM and CVD probably develop in parallel in this patient group.

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