Gestational diabetes boosts risk of liver issue during pregnancy: Study
ICP can increase risk of major health problems for mother and developing fetus
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A genetic susceptibility to gestational diabetes mellitus (GDM), a common pregnancy complication marked by intolerance to blood sugar due to low levels of the insulin hormone, raises the risk of intrahepatic cholestasis of pregnancy (ICP), a new study reports.
“These findings provide genetic evidence supporting a causal effect of GDM on ICP risk and suggest that women with GDM may benefit from closer monitoring of liver function,” researchers wrote.
The study, “Association of gestational diabetes mellitus with intrahepatic cholestasis of pregnancy: A 2-sample Mendelian randomization analysis utilizing FinnGen consortium data,” was published in the journal Medicine.
ICP the most common pregnancy-specific liver disease
ICP, the most common pregnancy-specific liver disease, is a form of cholestasis, a condition in which the flow of bile, a digestive fluid, from the liver to the intestines is slowed or stopped. This causes bile to build up in the liver, leading to damage. Bile can also leak into the bloodstream, driving symptoms such as pruritus (itching).
Mounting data show ICP can increase the risk of major health problems for both the mother and the developing fetus. These include GDM and preeclampsia (sudden maternal high blood pressure and organ dysfunction), along with preterm birth (before 37 weeks of gestation) and stillbirth.
GDM is another pregnancy-related condition associated with complications including preeclampsia, abnormally large birth weight, and low blood sugar in the newborn. Previous studies have also suggested that GDM may increase the risk of ICP in the same gestational period.
However, despite research suggesting a possible link between the two conditions, no study has established whether this is a cause-and-effect relationship, in which one condition increases the chances of the other.
To learn more, a team of researchers in China applied Mendelian randomization (MR), a statistical method that leverages genetic variation to identify potential cause-and-effect relationships between an exposure and an outcome — in this case, genetically determined GDM and ICP, respectively.
Results indicate positive link between genetic liability to GDM, ICP risk
The MR framework drew on data from genome-wide association studies. These large-scale studies scan a person’s entire DNA to identify individual DNA changes, called single-nucleotide polymorphisms (SNPs), strongly associated with GDM. Data were sourced from the FinnGen consortium, a large Finnish biobank research project.
The team found that women carrying more SNPs associated with GDM had significantly higher odds, by 30%, of developing ICP. A second MR method also found higher odds of 36%. Both results were statistically significant, meaning they were unlikely to have occurred by chance.
While three other MR methods all pointed in the same direction, the results weren’t statistically significant, meaning they could be due to chance.
“These results indicate a positive association between genetic liability to GDM and ICP risk,” the researchers wrote.
A sensitivity analysis, in which each SNP was removed one at a time, found that no single SNP was disproportionately driving the result, supporting a model in which the combined effects of several SNPs are influencing the link between GDM and ICP.
This MR study provides genetic evidence supporting an increased risk of ICP associated with GDM. Early identification and close monitoring of women with GDM, including assessment of [blood] bile acids and liver function, may contribute to reducing adverse perinatal outcomes.
Lastly, the team ruled out reverse causation, meaning that genetically predetermined GDM increases the chance of ICP rather than the other way around.
To explain these findings, researchers proposed that metabolic and hormonal changes accompanying GDM, including abnormally high insulin levels and an imbalance of blood fats, may impair the liver’s ability to maintain proper bile balance. They also suggested that GDM-associated inflammation may interfere with bile transport.
“This MR study provides genetic evidence supporting an increased risk of ICP associated with GDM,” the researchers concluded. “Early identification and close monitoring of women with GDM, including assessment of [blood] bile acids and liver function, may contribute to reducing adverse perinatal outcomes.” Bile acids are the main components of bile, and perinatal refers to the period shortly before, during, and shortly after birth.
The team noted that future studies in diverse populations are needed to confirm these findings.
