Women who are obese, have type 2 diabetes or a family history of type 2 diabetes could one day have more successful pregnancies because of a study at Washington University School of Medicine in St. Louis.

This study, performed in mice, suggests that Metformin, the most commonly prescribed anti diabetes drug, could potentially improve pregnancy outcomes in women with insulin resistance.

"We found that embryos of insulin-resistant mice also have some degree of insulin resistance, and if we correct the insulin resistance in the embryo with this drug, we improve the quality of the embryo," says Kelle Moley, M.D., lead author and professor of obstetrics and gynecology.

The finding, published online in Diabetes, suggests that Metformin could benefit women with type 2 diabetes or polycystic ovary syndrome (PCOS). About 8 percent of women trying to conceive have insulin resistance, Moley says, and even more are suspected to be borderline. In some cases, a family history of type 2 diabetes or being overweight may be the only indication that the patient may be prone to insulin resistance.

Metformin is often given to women with PCOS, an endocrine disorder that affects insulin and results in higher rates of miscarriage. These women often share the same pregnancy complications as women with type 2 diabetes and obesity.

Recent studies have shown that metformin not only aids conception in women with PCOS but also reduces the high miscarriage rates; however, how the drug does this has been unclear.

Using early-stage mouse embryos, Moley and her colleagues showed for the first time that metformin improves insulin action in insulin-resistant embryos. That allowed the embryos to absorb glucose, an important energy source, and prevented the death of cells in the embryos. As a result, the embryos were more likely to successfully implant in the uterus and to continue growing.

Moley's group also identified the molecular mechanism that accounts for metformin's positive effects. They found the drug triggers an important sensor of the energy level of cells, which sets off a chain of reactions that help insulin do its job. Previously it was not known that this sensor molecule was active in early embryos.

Moley hypothesizes that in insulin-resistant women, high levels of insulin and related factors cause their embryos to compensate by shutting down insulin signaling mechanisms. That impairs the early embryo's ability to take in glucose at a critical stage of development and can lead to pregnancy failure.

"We found that Metformin improves glucose uptake and improves the survival of the early embryo as a result," Moley says. "Mouse embryos in a high-insulin environment that were not exposed to Metformin did not survive."

Most miscarriages are due to chromosomal abnormalities. But Moley says this study provides new scientific evidence that miscarriages related to insulin resistance possibly could be avoided through the use of metformin.

"This will help physicians know better how to treat these women and reassure them that they're being correctly treated for their medical problems and that their babies will benefit from that treatment," she says.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

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