Placenta's Role in Gestational Diabetes Revealed

A recent study led by the Harvard Pilgrim Health Care Institute has discovered that a deficiency in placental expression of the gene insulin-like growth factor 1 (IGFBP1) and low circulating levels of IGFBP1 are linked to insulin resistance during pregnancy, indicating a potential risk factor for the onset of gestational diabetes.

The research was published in the journal Nature Medicine.

The most common metabolic pregnancy complication, affecting one in seven pregnancies, is gestational diabetes, a disease that can cause multiple complications during pregnancy and delivery. Excessive insulin resistance during pregnancy has been linked to gestational diabetes, according to research that has been done, although the precise causes of this resistance are still unknown.

The placenta – the major driver of changes in insulin physiology in pregnancy – is likely a key source of hormones involved in the development of gestational diabetes. Our goal was to discover novel placental factors that are implicated in gestational diabetes, by studying all proteins expressed in placenta tissues, across the human genome. We identified placental insulin-like growth factor 1 (IGFBP1) as a secreted placental factor that is likely implicated in regulation of glucose in human pregnancy.”

Marie-France Hivert, Associate Professor and Study Lead Author, Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute

The study expands on the substantial research conducted by Dr. Hivert on the genetics, omics, and interactions between lifestyle and environmental factors and determinants of gestational diabetes. The study team measured identified proteins in blood obtained from several pregnancy cohorts with varying backgrounds and performed genome-wide RNA sequencing on maternal-facing placental tissue samples.

The researchers discovered 14 genes whose levels of placental RNA expression were linked to insulin resistance; they discovered that gene IGFBP1 had the strongest correlation.

The measurement of IGFBP1 protein levels in the blood revealed that these levels increase during pregnancy and are five times higher in pregnant individuals than in non-pregnant individuals. These findings support the theory that the placenta is a major source of IGFBP1 protein during pregnancy.

Results additionally demonstrate that reduced levels of circulating IGFBP1 in early pregnancy could serve as an indicator of those at risk of developing gestational diabetes in the late second trimester.

Lastly, the team observed that the trajectory of IGFBP1 levels throughout pregnancy varies among individuals with a subtype of gestational diabetes characterized by insulin resistance, which has previously been associated with a higher likelihood of pregnancy complications.

Identifying a novel protein that characterizes a subtype of gestational diabetes is one additional step towards developing precision medicine for gestational diabetes. It’s possible that measuring IGFBP1 in the first trimester could help identify people at risk of developing gestational diabetes early in pregnancy, potentially offering a window for prevention. We hope to conduct future research to address whether this protein plays a causal role in gestational glycemic regulation.”

Marie-France Hivert, Associate Professor and Study Lead Author, Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute