Pregnancy Loss Is Strongly Associated With Development of Type 2 Diabetes, Study Finds

Research shows a strong and consistent association between pregnancy loss and type 2 diabetes (T2D), and the risk of developing T2D increases with a higher number of pregnancy losses, according to a study published in Diabetologia.

About 1 in 4 wanted pregnancies in the United States end in a loss, the study's authors said, with pregnancy loss defined as “the spontaneous demise of a pregnancy prior to 22 weeks of gestation.” This rate corresponds to approximately 1 million lost pregnancies in the United States every year.

According to the researchers, around 60% of pregnancy losses are due to fetal aneuploidy while the remaining 40% of euploid losses may be caused by point mutations, structural abnormalities, or other factors. Previous studies demonstrated pregnancy loss is a predictor of atherosclerotic disease and ischemic heart failure in later life.

In a nationwide case-control study, Danish researchers matched 24,774 women with T2D born between 1957 and 1997 to 247,740 controls. For each case of T2D, “10 female birth year- and education-matched controls without T2D were randomly selected from the Danish general population using an exact matching algorithm, where cases could not be used as controls.”

Although 74.5% of the case participants and 78.7% of controls never experienced a pregnancy loss, women with 1, 2, and at least 3 pregnancy losses constituted 19.1%, 4.3%, and 2.1% of the case population and 16.8%, 3.2%, and 1.3% of the controlsl.

Data revealed:

• Women with 1, 2, and at least 3 pregnancy losses had T2D odds ratios (ORs) of 1.18 (95% CI, 1.13-1.23), 1.38 (95% CI, 1.27-1.49), and 1.71 (95% CI, 1.53-1.92) compared with ever-pregnant women with no losses, respectively
• In the case cohort, 7847 (31.7%) never became pregnant compared with 62,214 (25.1%) of controls
• Women who never achieved a pregnancy had a T2D OR of 1.56 (95% CI, 1.51-1.61) compared with ever-pregnant women with any number of losses
• Women with recurrent pregnancy loss (at least 3 consecutive pregnancy losses) had a T2D OR of 1.65 (95% CI, 1.44-1.90)
• Women with recurrent pregnancy loss after a complicated delivery had a T2D OR of 2.01 (95% CI, 1.26-3.20)

After adjusting for obesity, a case sample of 3064 was compared with 42,276 controls. Data showed women who lost pregnancies still had significantly increased ORs for T2D. “Likewise, pregnancy loss remained a significant risk factor after adjustment for gestational diabetes,” the authors said.

The study also found women never achieving pregnancy and women with pregnancy losses with a high probability of euploid losses and losses with an immunological background both exhibited an increased risk of T2D.

“The association between these predefined groups and T2D supports the theory that the association could be influenced by immunological factors (eg, low-grade inflammation or metabolic disturbances with an immune component),” the authors said. However, psychological distress related to pregnancy loss, potentially altering lifestyle habits, and increasing body mass index could also increase the risk of T2D.

“Whether metabolic conditions at the time of pregnancy loss explain the association with T2D or the association is caused by a shared aetiology need to be explored in future studies,” the authors concluded.

Reference

Egerup P, Mikkelsen AP, Kolte AM, et al. Pregnancy loss is associated with type 2 diabetes: a nationwide case-control study. Diabetologia. Published online May 20, 2020. doi:10.1007/s00125-020-05154-z