A high carbohydrate intake in pregnancy raises the risk of developing gallstones, according to investigators at the University of Washington, Seattle, who presented their findings here at Digestive Disease Week (DDW) 2011.
The study involved 3070 women in their first trimester of pregnancy. Results showed that the risk for gallbladder disease was significantly higher among women in the highest quartile of total carbohydrate consumption compared with those in the lowest quartile, even after accounting for dietary intake of fat and protein. High fructose consumption also indicated a higher risk.
“Women in the highest quartiles of carbohydrate consumption had more than double the risk for gallbladder disease compared to women in the lowest quartile. Although further clinical studies are now needed, our results suggest that decreasing intake of carbohydrates, starches, and fructose during pregnancy may decrease the risk of forming gallstones,” said senior investigator Cynthia Ko, MD, speaking at a press briefing here.
She noted that gallstones are diagnosed in approximately 15% of pregnant women and that gallstone-related disease is the most common nonobstetric cause of hospitalization in the first 2 months after delivery.
The women were followed-up from their first trimester of pregnancy until 4 to 6 weeks postpartum. Participants underwent 3 ultrasounds during pregnancy and 1 test postpartum to evaluate for gallstones and biliary sludge, and they also completed a validated food frequency questionnaire early in the third trimester.
The definition of incident gallbladder sludge/stones was the progression of baseline sludge to stones, the development of new sludge, or the development of new stones.
The cumulative incidence of gallbladder disease (sludge and/or stones) was 10.2% overall, including new sludge in 5.1%, new stones in 2.8%, and progression from baseline sludge to stones in 2.3% of participants, reported coinvestigator Alan C. Wong, MD, who presented the findings at an oral session here.
Sludge/stones were significantly more likely among Hispanic women (P = .0001), those with greater body mass index prepregnancy (P < .0001), those with less weight gain during pregnancy (P < .0001), and those with high caffeine (P = .018) and alcohol (P = .038) intake, Dr. Wong reported.
“There was no significant difference between the groups who developed gallstones vs those who did not in history of diabetes, development of gestational diabetes, or intake of calories, fat, or fiber,” he noted.
In a multivariate logistic regression analysis, Dr. Wong and colleagues adjusted for all these factors, as well as age, parity, and smoking history, and compared women in the highest quartile of carbohydrate intake with those in the lowest quartile.
Dr. Wong reported that gallbladder disease was related to total carbohydrate consumption (adjusted odds ratio [OR], 2.3; 95% confidence interval [CI], 1.130 – 4.661), starch intake (OR, 1.8; 95% CI, 1.002 – 3.277), and fructose intake (OR, 2.0; 95% CI, 1.183 – 3.568). In contrast, high consumption of galactose was protective (OR, 0.7; 95% CI, 0.441 – 0.999).
The investigators could not explain why galactose intake would be protective. “It is a small constituent of the diet. No one has reported this inverse relationship before,” Dr. Ko noted.
The carbohydrate connection, in contrast, is understandable, the authors said. The hormonal milieu of pregnancy leads to hyperinsulinemia and insulin resistance, which can be exacerbated by carbohydrates. The consequence can be increased bile cholesterol secretion, reduced bile acid synthesis, and increased bile cholesterol saturation, which can result in bile cholesterol “super saturation.” The other effect of this scenario is gallbladder status, which is also necessary for the development of gallstones, Dr. Wong explained.
“In addition, not all carbohydrates are handled in the same way,” he added. “Fructose has many unique properties. For example, it does not require insulin for uptake into the cells, it stimulates less insulin release than glucose, and it is largely metabolized in the liver.”
Dr. Ko elaborated: “We hypothesize that fructose is metabolized differently from other carbohydrates, and its high intake leads to insulin resistance that predisposes to gallstone formation.”
Dr. Ko recommended that pregnant women should pay attention to their carbohydrate intake and “potentially lower it,” and should decrease consumption of refined carbohydrates in favor of more complex carbohydrates such as whole grains.
Lawrence Friedman, MD, chair of medicine at Newton Wellesley Hospital in Newton, Massachusetts, and professor of medicine at Harvard Medical and Tufts University School of Medicine, Boston, Massachusetts, commented on the study for Medscape Medical News.
“Certainly, we would need to do a prospective study, randomizing pregnant women to a low-carbohydrate diet vs standard diet to see if there is a difference in outcomes. This study is presumptive, and we need to test the hypothesis in a controlled trial,” he said. “But there are populations of women who have a particularly high risk for gallstones, and for them a dietary intervention might be worthwhile.”
Dr. Wong, Dr. Ko, and Dr. Friedman have disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2011: Abstract 322. Presented May 8, 2011.
— Caroline Helwick
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