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 T2DM

Although glucose tolerance returns to normal levels after delivery in the majority of women with GDM, this condition represents an early stage in the natural history of T2DM to many clinicians.[15,16] The strength of the association between GDM and T2DM, and the knowledge that both conditions have many of the same risk factors (e.g., family history for diabetes, overweight, increased age and ethnic group), suggest a common genetic background for GDM and T2DM. In accordance with this hypothesis, it has been reported that women with pGDM more frequently display some alleles associated with the high risk of T2DM.[17,18]

The transition time from GDM to overt T2DM can be shortened as a function of the number of pregnancies. According to Peters et al., a second pregnancy is associated with a threefold increase in the risk of developing T2DM in women with a pGDM,[19] suggesting that recurrence of insulin-resistant states can accelerate the decline of β-cell function. Several factors are known to contribute to evolution toward overt T2DM. Indeed, this is more frequent in women for whom (Box 1):[20,21]

  • GDM is diagnosed before the 24th week of pregnancy (5-year risk: 80%);

  • Fasting glucose levels before pregnancy are higher;

  • A defect in insulin secretion is apparent;

  • Insulin therapy is indicated during pregnancy;

  • Obesity precedes pregnancy (risk: 50–75%);

  • A positive family history of diabetes mellitus exists;

  • Bodyweight increases excessively in the postpartum;

  • Ethnicity is non-Caucasian.

The differences of diagnostic tests, of criteria for GDM, of the ethnic groups and of the length of follow-up, do not allow one to assess the true prevalence of T2DM in women with pGDM, nor the rate of conversion from GDM to T2DM.

In the classic studies by O'Sullivan performed 30 years ago, diabetes was diagnosed in 36% of women 22–28 years after pregnancy with GDM.[22] In 2002, Kim and colleagues conducted a systematic literature review of articles published between 1965 and 2001.[23] A total of 28 follow-up studies, performed between 6 weeks to 28 years postpartum were examined, and the cumulative incidence of diabetes ranged from 2.6% to over 70%. The authors reported that after adjustment for various lengths of follow-up and testing rates, the cumulative incidence of T2DM increased in the first 5 years after delivery and reached a plateau after 10 years.

More recently, in a meta-analysis performed by Cheung and colleagues from six controlled follow-up studies, the overall relative risk for developing diabetes after GDM was calculated to be 6.0.[24] The authors, estimating that 10–31% of parous women with diabetes have had GDM, underlined the population health significance of GDM.

Our population, including 160 women with pGDM, underwent an OGTT 1–3 years after delivery; five (3.81%) had diabetes and 31 (19.37%) had impaired glucose regulation (i.e., impaired glucose tolerance and/or impaired fasting glucose).[25] Prepregnancy BMI, fasting and 120-min glucose levels were independent contributors of postpartum diabetes or impaired glucose regulation. Notably, at postpartum follow-up, all women with normal pregnancy were normotolerant and all pGDM women who were found to be normotolerant had significantly higher fasting and post-challenge plasma glucose levels compared with control women.

More recently, Bellamy and colleagues performed a new meta-analysis of cohort studies in which women who had developed T2DM after GDM were followed-up between 1965 and 2009.[26] Their analysis, including 20 studies of 675,455 women and 10,859 cases of T2DM, reported that women with pGDM have at least a 7.5-times increased risk of developing T2DM in the future compared with those with normoglycemic pregnancy. Moreover, the authors reported that within 5 years of a pregnancy complicated by gestational diabetes, women had a relative risk of 4.69, which more than doubled to 9.34 in those who were examined more than 5 years postpartum.

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