Insulin Resistance and Incident Gallbladder Disease in Pregnancy

Background & Aims: Insulin resistance is associated with prevalent gallstones, but its effect on initial gallstone formation is not well-understood. Methods: We conducted a nested case-control study to examine whether insulin resistance is a risk factor for initial gallbladder sludge and stone formation during pregnancy. Cases were 205 women with new gallbladder sludge and stones during pregnancy and the early postpartum. Controls were 443 randomly selected women without sludge or stones during pregnancy. Gallbladder ultrasounds were obtained during each trimester and at 4–6 weeks post partum. Fasting serum glucose, lipids, and insulin were measured at 26–28 weeks gestation. Insulin resistance was measured by the homeostasis model. Logistic regression was used to identify independent risk factors for gallstone formation. Results: Insulin resistance was significantly greater in cases than in controls on univariate analysis (P < .001). Pre-pregnancy body mass index was strongly associated with gallstone formation on univariate analysis (P < .001), but this association was diminished after adjusting for insulin resistance (P = .01). On multivariate analysis, insulin resistance was significantly associated with gallstone formation (P = .004), even after adjustment for pre-pregnancy body mass index and other confounding factors including high-density lipoprotein cholesterol and physical activity. This association was strongest in women with pre-pregnancy body mass index <30 kg/m2. Conclusions: Insulin resistance is a risk factor for incident gallbladder sludge and stones during pregnancy, even after adjustment for body mass index. Insulin resistance might represent a causal link between obesity and overweight and gallstones.