Nav: Home

Common diabetes drug may help prevent preterm birth

July 25, 2016

CINCINNATI -- Metformin, a medication routinely used by millions of people with type 2 diabetes, may also play an unexpected role in blocking a significant cause of preterm birth, according to research findings published July 25.

The early-stage study, based on results from mice bred to be prone to premature birth, was led by a team of scientists at Cincinnati Children's along with colleagues in France and Japan. Their findings were posted online in JCI: The Journal of Clinical Investigation.

The study is important for two reasons. First, it details a little-understood molecular pathway that can lead to premature birth by disrupting the function of the decidua - a thick membrane that lines the uterus and supports the continued growth of developing fetuses. Second, the researchers demonstrate - in mice -- two successful methods for restoring the lining's function and achieving healthy, full-term births.

"This proof-of-concept study illuminates a potential mechanism behind preterm birth," says Sudhansu K. Dey, PhD, director of the Division of Reproductive Sciences at Cincinnati Children's and senior author of the new study. "It also demonstrates possible remedies that are already approved for human use."

New clues in the mystery of preterm birth

The study involved analyzing mice bred to lack the p53 gene in the uterus, a condition known to make pregnancies more likely to end in premature birth. The new study adds new detail to why this occurs.

Without the gene, decidual cells show increased activity of a protein complex called mammalian target of rapamycin complex 1 (mTORC1). They also show reduced activity of a signaling protein called AMP-activated protein kinase (AMPK).

Combined, these two changes can lead to premature cellular aging in the decidua, which in turn, can trick the mother's body into going into labor. The sooner this occurs, the higher the risk of a miscarriage or premature birth.

Digging deeper, the research team learned that another protein, called sestrin 2, plays a critical role in coordinating the relationship between AMPK and mTORC1 signaling. Levels of sestrin 2 also decline in mice missing the p53 gene.

Discovery leads to intriguing potential solution

The researchers found that treating the mice with metformin reversed the early aging cycle, causing sestrin 2 levels and AMPK activity to increase and mTORC1 signaling to decrease. The mice treated with metformin went on to have full-term births.

The team also reported similar - but less effective - results when treating mice with resveratrol, an anti-oxidant and anti-aging dietary supplement made from grape seed extract.

The latest findings continue a line of research that Dey has pursued for several years. In previous studies, Dey and colleagues discovered that rapamycin, an immune suppressing agent, showed promise in mice at preventing preterm birth. However, that medication may be risky for use in pregnant women.

Metformin appears to be a potentially safer alternative that works along the same molecular pathway, Dey says.

Next steps

Preterm birth can be caused by many factors. It remains unclear how many preterm births are triggered by early decidual aging, but Dey says it could be a significant number.

Advancing these mice-based findings into a treatment available for would-be mothers at risk for preterm birth will require extensive work. The process of preparing and conducting human clinical trials to further test the medications could take several years.

Currently, other investigators are studying metformin and resveratrol for their potential to act as anti-aging drugs. However, Dey says his team has not found any human clinical trials investigating the medications for use in preventing preterm birth.

Experts working to reduce stubbornly high premature birth rates in Cincinnati and other cities say the new findings merit further investigation - especially to establish the safety of metformin use during pregnancy.

"I think the study has interesting implications. It forms the first step in a potential new intervention that would have to be carefully evaluated in human clinical trials. Metformin has been widely used, but only to a limited extent in pregnancy. Future studies will be needed," says Louis Muglia, MD, PhD, director of the Center for Prevention of Preterm Birth at Cincinnati Children's.

A collaborative achievement

The research team at Cincinnati Children's included Wenbo Deng, PhD, Jeeyeon Cha, MD, PhD, Jia Yuan, PhD, and other colleagues led by Dey in the Division of Reproductive Sciences. Collaborators also included Yasushi Hirota, University of Tokyo, Benoit Viollet at INSERM in France, and Heather Bradshaw from Indiana University Bloomington.

This work was supported in part by grants from the March of Dimes and the March of Dimes Prematurity Research Center Ohio Collaborative as well as NIH grants to S.K. Dey. Jeeyeon Cha was a National Research Service Awardee.
About Cincinnati Children's

Cincinnati Children's, a non-profit, pediatric, academic medical center established in 1883, is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. It is one of the top three recipients of pediatric research grants from the National Institutes of Health, ranked third in the nation among all Honor Roll hospitals in U.S. News and World Report's Best Children's Hospitals, and a research and teaching affiliate of the University of Cincinnati's College of Medicine. Its patient population includes the eight-county primary service area covering parts of Ohio, Kentucky and Indiana. A destination for children with complex medical conditions, it also served patients from all 50 states and nearly 70 countries during the past year. Additional information can be found on the Cincinnati Children's website. Connect on the Cincinnati Children's blog, via Facebook and on Twitter.

Cincinnati Children's Hospital Medical Center

Related Diabetes Articles:

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at