carbohydrate intake: a risk factor for biliary sludge and stones during pregnancy
DESCRIPTION
Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy. Alan C. Wong, MD, MPH Cynthia W. Ko , MD, MS. Department of Medicine Division of Gastroenterology Seattle, Washington. Introduction. Gallstone disease results in >700,000 cholecystectomies each year . - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/1.jpg)
Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy
Alan C. Wong, MD, MPHCynthia W. Ko, MD, MS
Department of MedicineDivision of Gastroenterology
Seattle, Washington
![Page 2: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/2.jpg)
Introduction
• Gallstone 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.
![Page 3: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/3.jpg)
Study Aim
To determine the effect of dietary carbohydrate intake on the formation of biliary sludge and stones during pregnancy.
![Page 4: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/4.jpg)
- Prospective study
- Cohort of pregnant women
- Exposure:Carbohydrate consumption during pregnancy, determined by food frequency questionnaire.
- Outcome:Formation of new GB sludge/stones, determined by serial GB ultrasound.
Study Design – General Overview
![Page 5: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/5.jpg)
Consecutive women attending 1st obstetrics clinic (n = 8,929)
Eligible and interested (n = 4,897)
Gallstones on entry GB ultrasound (n = 208)
Had cholecystectomy (n = 33)
Did not complete dietary questionnaire (n = 184)
Fewer than two GB ultrasounds (n = 1,402)
Included in analysis (n = 3,070)
Age <18, poor language comprehension, >20 weeks pregnant, declined to participate (n = 4,032)
![Page 6: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/6.jpg)
1st trimester(10-12 weeks)
2nd trimester(17-19 weeks)
Post-partum(4-6 weeks)
3rd trimester(26-28 weeks)
Serial fasting gallbladder ultrasounds
• Definition of incident GB sludge/stones:- Progression of baseline sludge to stones or- New sludge or- New stones
• Minimum of 2 interpretable ultrasounds per subject
![Page 7: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/7.jpg)
Ultrasonographic 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 ultrasound- Images reviewed by 1 of 2 radiologists
![Page 8: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/8.jpg)
Measurement of Carbohydrate Intake
1st trimester 2nd trimester Post-partum3rd trimester
Dietary Questionnaire
- Validated food frequency questionnaire
- Daily consumption (g/day) of total carbohydrate, starch, sucrose, galactose, fructose, lactose, and maltose.
3rd trimester
![Page 9: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/9.jpg)
Statistical Methods
- Risk 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: - age - pre-pregnancy body mass index- weight gain during pregnancy- parity - Hispanic origin - smoking- history of diabetes - intake of alcohol, caffeine, total calories, protein, fat, fiber, cholesterol,
fatty acids
![Page 10: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/10.jpg)
Results
![Page 11: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/11.jpg)
Results
Incidence of GB disease = 10.2%
• New sludge = 5.1%
• New stones = 2.8%
• Baseline sludge to stones = 2.3%
![Page 12: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/12.jpg)
Characteristics of Study Subjects
Results
No new sludge/stones New sludge/stones P - value
n = 2756 n = 314
Hispanic origin (%) 10.4 17.8 0.001
BMI pre-pregnancy (kg/m2) 24 27 <0.0001
Weight gain during pregnancy (kg) 14.6 12.6 <0.0001
Caffeine intake (mg/day) 40 50 0.018
Alcohol intake (g/day) 0.1 0.5 0.038
No significant difference between groups:- history of diabetes- gestational diabetes- intake of calories, fat, fiber
![Page 13: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/13.jpg)
Nutrient Adjusted Odds Ratio 95% Confidence Interval
Total carbohydrate 2.295 1.130 - 4.661
Starch* 1.812 1.002 - 3.277
Fructose* 2.054 1.183 - 3.568
Galactose* 0.664 0.441 - 0.999
Results
Carbohydrate consumption and the risk of incident gallstone disease
* With additional adjustment for total carbohydrate intake
- 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
- Highest quartile of intake compared to lowest quartile
![Page 14: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/14.jpg)
Quartile 1 Quartile 2 Quartile 3 Quartile 40
0.5
1
1.5
2
2.5
Total carbohydrate Starch Fructose Galactose
Odd
s Rati
o
*
*
*
*
**
Carbohydrate consumption and the risk of incident gallstone disease
* P < 0.05, compared to Quartile 1
![Page 15: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/15.jpg)
Discussion
![Page 16: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/16.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
![Page 17: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/17.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Hyperinsulinemia+
Insulin resistance
![Page 18: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/18.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Hyperinsulinemia+
Insulin resistance
Postprandial insulin ↑ 3-fold
Basal insulin↑ 2-fold
Insulin sensitivity↓ 50-70%
![Page 19: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/19.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Bile cholesterol super-saturation
↑ bile cholesterol saturation
↑ bile cholesterol secretion
↓ bile acid synthesis
Hyperinsulinemia+
Insulin resistance
![Page 20: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/20.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Bile cholesterol super-saturation
GB stasis
↑ bile cholesterol saturation
↑ bile cholesterol secretion
↓ bile acid synthesis
↓ GB ejection fraction
↓ GB emptying response to CCK
Hyperinsulinemia+
Insulin resistance
![Page 21: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/21.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Bile cholesterol super-saturation
GB stasis
↑ bile cholesterol saturation
↑ bile cholesterol secretion
↓ bile acid synthesis
↓ GB ejection fraction
↓ GB emptying response to CCK
Hyperinsulinemia+
Insulin resistance
Carbohydrates
![Page 22: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/22.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Bile cholesterol super-saturation
GB stasisCarbohydrates
↑ bile cholesterol saturation
↑ bile cholesterol secretion
↓ bile acid synthesis
↓ GB ejection fraction
↓ GB emptying response to CCK
Hyperinsulinemia+
Insulin resistance
![Page 23: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/23.jpg)
↑ cortisol↑ estrogen
↑ progesterone↑ human placental lactogen
Pregnancy
Bile cholesterol super-saturation
GB stasis
↑ bile cholesterol saturation
↑ bile cholesterol secretion
↓ bile acid synthesis
↓ GB ejection fraction
↓ GB emptying response to CCK
Hyperinsulinemia+
Insulin resistance
Carbohydrates
![Page 24: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/24.jpg)
Fructose
![Page 25: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/25.jpg)
Fructose
– does not require insulin for uptake into cells
– stimulates less insulin release than glucose
– largely metabolized in the liver
![Page 26: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/26.jpg)
Fructose
leptin resistance↑ leptin level
hepatic lipogenesis↑ triglyceride
hepatic insulin resistance
![Page 27: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/27.jpg)
Fructose
leptin resistance↑ leptin level
hepatic lipogenesis↑ triglyceride
hepatic insulin resistance
Gallstone disease
![Page 28: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/28.jpg)
Limitations
1) Only one dietary time point
2) GB ultrasounds were done at varying stages of pregnancy
3) No serum insulin/leptin levels
![Page 29: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/29.jpg)
• High 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.
Conclusion
![Page 30: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/30.jpg)
References• American 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. 2000 May
10;283(18):2411-6.• Tsai CJ et al. Glycemic load, glycemic index, and carbohydrate intake in relation to risk of cholecystectomy in
women. Gastroenterology. 2005 Jul;129(1):105-12.• Nakeeb A et al. Insulin resistance causes human gallbladder dysmotility. J Gastrointest Surg. 2006 Jul-
Aug;10(7):940-8; discussion 948-9.• Gielkens HA et al. Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans. J
Hepatol. 1998 Apr;28(4):595-602.• 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. 2001 Nov;35(5):550-7.• Biddinger SB et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med. 2008
Jul;14(7):778-82. Epub 2008 Jun 29.• Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus.
Am J Clin Nutr. 2000 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. 2009 Nov;1791(11):1037-47.• Wu Z et al. Progesterone inhibits L-type calcium currents in gallbladder smooth muscle cells. J Gastroenterol
Hepatol. 2010 Dec;25(12):1838-43. • Miller A et al. Dietary fructose and the metabolic syndrome. Curr Opin Gastroenterol. 2008 Mar;24(2):204-9.• Ko CW et al. Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology.
2005 Feb;41(2):359-65.
This study is supported by National Institutes of Health (NIH) grant DK 46890
![Page 31: Carbohydrate Intake: A Risk Factor for Biliary Sludge and Stones During Pregnancy](https://reader035.vdocument.in/reader035/viewer/2022062310/56815c56550346895dca54ae/html5/thumbnails/31.jpg)
Thank You