Presentation on theme: "Alan C. Wong, MD, MPH Cynthia W. Ko, MD, MS"— Presentation transcript:
1Alan C. Wong, MD, MPH Cynthia W. Ko, MD, MS Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During PregnancyAlan C. Wong, MD, MPHCynthia W. Ko, MD, MSDepartment of MedicineDivision of GastroenterologySeattle, Washington
2IntroductionGallstone disease results in >700,000 cholecystectomies each year.Female gender is a risk factor, and pregnancy is a high risk period for gallstone formation.Gallbladder (GB) disease is the most common non-obstetrical cause of maternal rehospitalization in the first 60 days after delivery.Carbohydrate intake has been linked to increased risk of cholecystectomy in women.The effect of carbohydrate consumption on GB disease during pregnancy is unclear.
3Study AimTo determine the effect of dietary carbohydrate intake on the formation of biliary sludge and stones during pregnancy.
4Study Design – General Overview Prospective studyCohort of pregnant womenExposure:Carbohydrate consumption during pregnancy, determined by food frequency questionnaire.Outcome:Formation of new GB sludge/stones, determined by serial GB ultrasound.
5Consecutive women attending 1st obstetrics clinic (n = 8,929) Age <18, poor language comprehension, >20 weeks pregnant, declined to participate (n = 4,032)Eligible and interested (n = 4,897)Gallstones on entry GB ultrasound (n = 208)Had cholecystectomy(n = 33)Fewer than two GB ultrasounds (n = 1,402)Did not complete dietary questionnaire (n = 184)Included in analysis (n = 3,070)
6Serial fasting gallbladder ultrasounds 1st trimester(10-12 weeks)2nd trimester(17-19 weeks)3rd trimester(26-28 weeks)Post-partum(4-6 weeks)Minimum of 2 interpretable ultrasounds per subjectDefinition of incident GB sludge/stones:Progression of baseline sludge to stones orNew sludge orNew stones
7Ultrasonographic Definitions: 1) Sludge: low-level echoes, shift with positional changes, no post-acoustic shadowing.2) Stones: high-amplitude echoes, >2 mm in diameter, post-acoustic shadowing present.Interpretation:Technicians had specific training in GB ultrasoundImages reviewed by 1 of 2 radiologists
8Measurement of Carbohydrate Intake 1st trimester2nd trimester3rd trimester3rd trimesterPost-partumDietary QuestionnaireValidated food frequency questionnaireDaily consumption (g/day) of total carbohydrate, starch, sucrose, galactose, fructose, lactose, and maltose.
9Statistical MethodsRisk of incident GB sludge/stones determined for each quartile of intake of total carbohydrate and individual carbohydrates (starch, sucrose, galactose, fructose, lactose, and maltose)Multivariate logistic regression adjusting for:agepre-pregnancy body mass indexweight gain during pregnancyparityHispanic originsmokinghistory of diabetesintake of alcohol, caffeine, total calories, protein, fat, fiber, cholesterol, fatty acids
11Results Incidence of GB disease = 10.2% New sludge = 5.1% New stones = 2.8%Baseline sludge to stones = 2.3%
12Characteristics of Study Subjects ResultsCharacteristics of Study SubjectsNo new sludge/stonesNew sludge/stonesP - valuen = 2756n = 314Hispanic origin (%)10.417.80.001BMI pre-pregnancy (kg/m2)2427<0.0001Weight gain during pregnancy (kg)14.612.6Caffeine intake (mg/day)40500.018Alcohol intake (g/day)0.10.50.038No significant difference between groups:history of diabetesgestational diabetesintake of calories, fat, fiber
13ResultsCarbohydrate consumption and the risk of incident gallstone diseaseNutrientAdjusted Odds Ratio95% Confidence IntervalTotal carbohydrate2.295Starch*1.812Fructose*2.054Galactose*0.664- Highest quartile of intake compared to lowest quartile- Adjusted for: age, pre-pregnancy BMI, weight gain, parity, Hispanic origin, smoking, history of diabetes, intake of alcohol, caffeine, calories, protein, fat, fiber, cholesterol, fatty acids* With additional adjustment for total carbohydrate intake
14Carbohydrate consumption and the risk of incident gallstone disease * P < 0.05, compared to Quartile 1
28Limitations Only one dietary time point GB ultrasounds were done at varying stages of pregnancyNo serum insulin/leptin levels
29ConclusionHigh intake of total carbohydrate, starch, and fructose is associated with increased risk of developing biliary sludge/stones during pregnancy.Dietary modification during pregnancy may reduce this risk.
30ReferencesAmerican Gastroenterological Association. The burden of gastrointestinal diseases. Bethesda, MD: The American Gastroenterological Association, 2001.Lydon-Rochelle M et al. Association between method of delivery and maternal rehospitalization. JAMA May 10;283(18):Tsai CJ et al. Glycemic load, glycemic index, and carbohydrate intake in relation to risk of cholecystectomy in women. Gastroenterology Jul;129(1):Nakeeb A et al. Insulin resistance causes human gallbladder dysmotility. J Gastrointest Surg Jul-Aug;10(7):940-8; discussionGielkens HA et al. Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans. J Hepatol Apr;28(4):Dubrac S et al. Insulin injections enhance cholesterol gallstone incidence by changing the biliary cholesterol saturation index and apo A-I concentration in hamsters fed a lithogenic diet. J Hepatol Nov;35(5):550-7.Biddinger SB et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med Jul;14(7): Epub 2008 Jun 29.Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr May;71(5 Suppl):1256S-61S.Wang HH et al. New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta Nov;1791(11):Wu Z et al. Progesterone inhibits L-type calcium currents in gallbladder smooth muscle cells. J Gastroenterol Hepatol Dec;25(12):Miller A et al. Dietary fructose and the metabolic syndrome. Curr Opin Gastroenterol Mar;24(2):204-9.Ko CW et al. Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology Feb;41(2):This study is supported by National Institutes of Health (NIH) grant DK 46890