Doctor examining pregnant woman with his hands on her stomach
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Scientists at the Harvard Pilgrim Health Care Institute have made a breakthrough in understanding the development of gestational diabetes (GDM), focusing on the placenta’s role in the condition that affects approximately 14 percent of pregnancies worldwide.

The study, titled “Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes,” published in Nature Medicine, examines the relationship between the insulin-like growth factor 1 (IGFBP1) gene in the placenta and its impact on insulin resistance—a key feature of gestational diabetes.

Gestational diabetes not only complicates pregnancy but can also pose long-term health risks for both mother and child, including an increased likelihood of developing type 2 diabetes and cardiovascular diseases. Traditional understanding links excess insulin resistance during pregnancy to the development of GDM, but specific causes remain unknown.

Led by Marie-France Hivert, associate professor of population medicine at Harvard Medical School and Harvard Pilgrim Health Care Institute, the team used genome-wide RNA sequencing on maternal-facing placental tissue samples to map all proteins expressed. The study identified a significant correlation between low placental expression and circulating levels of IGFBP1 and higher insulin resistance.

“Understanding the placental biochemistry is vital because it influences not just the health of the pregnancy, but the long-term health of women and their children,” explained Hivert. “Our findings suggest that IGFBP1 is a critical component in regulating glucose levels during pregnancy.”

This large-scale study analyzed 434 human placentas and measured circulating IGFBP1 protein levels at various stages of pregnancy. The results show a consistent rise in IGFBP1 levels throughout pregnancy, highlighting the placenta as a major source of this protein. Crucially, women with lower IGFBP1 levels in early pregnancy were more likely to be diagnosed with gestational diabetes by the late second trimester.

Moreover, the research identified a subset of gestational diabetes characterized by significant insulin resistance, which is more likely to lead to pregnancy complications. Understanding the trajectory of IGFBP1 levels throughout pregnancy in this subgroup could lead to more targeted interventions.

“The correlation between low IGFBP1 levels and the development of gestational diabetes offers a promising marker for early diagnosis,” Hivert added. “Early detection is key, and measuring IGFBP1 could provide a window for early intervention to prevent the onset of GDM.”

The researchers are optimistic about the implications of their findings for developing precision medicine approaches tailored to manage and prevent gestational diabetes effectively.

As the next step, Hivert and her team plan to explore whether IGFBP1 directly influences glucose regulation in pregnancy or if its levels are indicative of other underlying mechanisms.

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