The female gender and multiparity are the two most important positive correlates of cholesterol gallstone disease. Pregnancy represents the period of time when the 'lithogenic' pressure on a woman is the highest. Biliary sludge is a precursor stage of gallstones. We studied the etiological factors associated with the development of sludge and stones during pregnancy, and our early results suggest that it is inversely related to physical activity. We also found that being overweight, a known risk factor for gallstone disease, is associated with high blood leptin levels. In addition, the risk associated with high leptin levels is partially mitigated by physical activity. In order to disentangle the effects of physical activity, leptin and gestational diabetes on gallbladder disease risk, and to understand the mechanisms behind the observed associations, we propose to conduct a randomized controlled trial. This interventional study is a logical extension of our previous observational investigation.
Our Specific Aims are: 1. To evaluate whether an endurance exercise program is associated with lower risk of gallbladder disease in overweight pregnant women.2. To evaluate whether an endurance exercise intervention program changes leptin levels in pregnancy among overweight women.3. To examine the associations between gallbladder disease incidence and potential causal variables in this prospective trial. These variables include leptin levels, HDL, insulin levels, BMI (as it varies within women classified as overweight), as well as changes in these variables. Gallstone disease affects 15-20% of adult Americans. Cholecystectomy is one of the most commonly performed operations. The morbidity, and the burden of cost, incurred by gallstones are staggering. Yet there is a dearth of understanding in the epidemiology and the cause of this disease. The results of this investigation should generate new, important and useful insights into the pathogenesis, and provide a rational strategy for the prevention, of this common and costly disease.
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