520184
research-article2014
PENXXX10.1177/0148607113520184Journal of Parenteral and Enteral NutritionMathew and Ko
Brief Communication
Dietary Fat and Protein Intake Are Not Associated With Incident Biliary Sludge and Stones During Pregnancy Lisa K. Mathew, MD, MSPH1; and Cynthia Ko, MD, MS1
Journal of Parenteral and Enteral Nutrition Volume 39 Number 1 January 2015 124–128 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607113520184 jpen.sagepub.com hosted at online.sagepub.com
Abstract Background: Dietary composition can cause insulin resistance, elevated serum lipid levels, and obesity, all of which predispose to gallstone formation. The effects of dietary fat (including individual fatty acids) and protein on gallstone formation are controversial. The aim of this study was to examine the effects of dietary fat and protein intake on incident gallstone disease during pregnancy, a high-risk time for stone formation. Methods: We prospectively studied 3070 pregnant women who underwent serial gallbladder ultrasound examinations during pregnancy and at 4–6 weeks postpartum. All women had at least 2 study ultrasounds for comparison. A semi-quantitative food frequency questionnaire was completed by subjects in the early third trimester. Multivariate logistic regression was performed to assess the risk of incident gallbladder disease across quartiles of intake of total fat, individual fatty acids (polyunsaturated, monounsaturated, saturated, and total trans-fatty acids, as well as cholesterol), protein, and protein subtype (animal or vegetable based). Results: The cumulative incidence of new biliary sludge/stones or progression of baseline sludge to stones was 10.2% by 4–6 weeks postpartum. There was no association between total dietary fat (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.64–2.18 comparing lowest and highest quartiles) or protein intake (OR, 0.83; 95% CI, 0.44–1.22 comparing lowest and highest quartiles) and incident gallbladder disease. There was also no association between individual fatty acids or protein subtype and gallbladder disease. Conclusions: Neither total nor subtype of dietary fat or protein was associated with incident biliary stone or sludge formation in this cohort of pregnant women. (JPEN J Parenter Enteral Nutr. 2015;39:124-128)
Keywords gallstones; pregnancy; dietary fat; dietary protein
Clinical Relevancy Statement Pregnancy is a high-risk time for gallstone formation and can increase lifetime risk of gallstone disease in women. Dietary factors have been implicated as possible modifiable risk factors in gallstone formation. We show that dietary fat and protein intake are not associated with gallstone formation in this high-risk period. These findings are clinically relevant for providers who care for women and patients with gallstone disease.
Introduction Pregnancy is a high-risk period for gallstone formation in women and is a significant cause of peripartum morbidity.1 Biliary stones and sludge form in up to 2% and 31% of pregnancies, respectively.2,3 Acute cholecystitis occurs in between 1 and 8 per 10,000 pregnancies, and gallstone disease represents the leading nonobstetrical cause of postpartum hospitalization.4 Furthermore, incident gallstone formation during pregnancy likely increases lifetime risk of gallbladder disease. Gallstones affect 7% of nulliparous and 20% of multiparous women.2,5 Strategies to prevent gallstone formation during pregnancy may help reduce the burden and cost of gallbladder disease in women.
The pathogenesis of cholesterol gallstone formation is multifactorial and includes cholesterol supersaturation of bile, decreased biliary motility, and nucleation and growth of cholesterol stones.6-9 Insulin resistance and resultant hyperinsulinemia are thought to contribute to gallstone formation through a variety of mechanisms.6 Dietary composition can affect insulin resistance and potentially affect gallstone incidence. We have previously shown that total carbohydrate and fructose intake increase the risk of gallstone formation during pregnancy, perhaps mediated through hyperinsulinemia.10 Diets high in saturated fats have been shown to increase insulin resistance while diets high in polyunsaturated fats may reverse From the 1Department of Medicine, University of Washington, Seattle. Financial disclosure: This study was funded by grant DK046890 from the National Institutes of Health. Received for publication September 3, 2013; accepted for publication December 20, 2013. This article originally appeared online on January 17, 2014. Corresponding Author: Cynthia Ko, MD, MS, Division of Gastroenterology, University of Washington, 1959 NE Pacific St, Box 356424, Seattle, WA 98195, USA. Email: [email protected]
Downloaded from pen.sagepub.com at GEORGIAN COURT UNIV on May 8, 2015
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this effect.6,11 The results of studies correlating total dietary fat with gallstone formation are variable,6-8,11,12 suggesting that the quantity of fat in our diet may not be as important as the type of fat. Previous studies have suggested a protective effect of vegetarian diets on gallstone formation.13 This could, in part, be mediated by dietary protein intake and protein subtype (animal vs vegetable protein sources). Data supporting the effect of protein and protein subtypes on gallstone formation are limited. Several studies suggest that dietary protein does not affect postprandial insulin concentrations.14,15 In this study, we prospectively evaluated the effect of dietary fat and protein and their subtypes on incident gallbladder stone or sludge formation during pregnancy. We hypothesized that women with diets high in saturated fats and animal protein would be at higher risk of sludge/stone formation during pregnancy, while diets high in polyunsaturated fats and vegetable protein would be at lower risk.
Methods Pregnant women attending their first obstetrics clinic at Madigan Army Medical Center (Tacoma, WA) were approached consecutively (n = 8929). Women were excluded if they were younger than 18 years, had poor English-language comprehension, were more than 20 weeks pregnant, or had plans to move away within 3 months. Those who were eligible and interested in enrollment (n = 4897) gave written informed consent. Enrolled participants were offered serial fasting gallbladder ultrasound examination during each trimester of pregnancy (10–12 weeks’ gestation, 17–19 weeks’ gestation, and 26–30 weeks’ gestation) and at 4–6 weeks postpartum. The study was approved by the Institutional Review Boards of the University of Washington and Madigan Army Medical Center. At study entry, participants completed a questionnaire documenting their medical, obstetrical, family, and social histories. Nutrient data were collected using a food frequency questionnaire (version WHX, 1992) developed by the Nutrition Assessment Shared Resource (NASR) of the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA).16 This validated questionnaire was administered in the early third trimester of pregnancy and inquired about the nutrition habits of the participants from the time of conception to the time the questionnaire was given, therefore reflecting dietary intake over the first 2 trimesters of pregnancy. Nutrient analysis was performed using the Nutrition Data Systems for Research software (NDSR) developed by the Nutrition Coordinating Center (NCC) at the University of Minnesota (Minneapolis). Prepregnancy body mass index (BMI) was calculated from self-reported height and weight immediately before pregnancy. Weight gain during pregnancy was calculated as the difference between predelivery weight and prepregnancy weight. Fasting serum samples were obtained at 26–28 weeks’ gestation and tested for glucose and lipid values by the clinical laboratory at the Madigan Army Medical Center. Gallbladder ultrasonography was performed with a standard imaging protocol using a 3.5- to 7.0-MHz rotatory sector
scanning transducer (ATL, Inc, Bothell, WA, or Acuson Corp, Mountain View, CA). All study ultrasounds were performed by sonographers with specialized training in gallbladder ultrasound and with women fasting or having drunk only sips of water. Findings were recorded by the sonographers, and images and findings were reviewed by 1 of 2 designated study radiologists with expertise in gallbladder ultrasound. Sludge was defined as the presence of low-level echoes that shift with position changes and without postacoustic shadowing. Stones were defined as high-amplitude echoes greater than 2 mm in diameter with postacoustic shadowing. In 10,887 scans, there were discrepancies between the radiologist’s and the sonographer’s readings in 70 regarding the diagnosis of sludge (κ = 0.93) and in 25 regarding the diagnosis of stones (κ = 0.98). In case of discrepancy, the radiologist’s reading was accepted as correct. Gallbladder volume and contraction were not measured. The cumulative incidence of gallbladder sludge and stones was determined from the serial gallbladder ultrasounds. Women with new sludge, new stones, or progression of baseline sludge on entry ultrasound to stones on a subsequent ultrasound were defined as having incident gallbladder disease. Women were excluded from the final data analyses if they did not complete a dietary questionnaire (n = 184) or had fewer than 2 interpretable gallbladder ultrasounds (n = 1402), gallstones on entry ultrasound (n = 208), or prior cholecystectomy (n = 33). This resulted in 3070 participants included in the analysis. On univariate analysis, we used t tests to compare continuous variables and χ2 tests for categorical variables. Multivariate logistic regression analysis was performed (STATA 12.1; Stata Corporation, College Station, TX)17 to assess the risk of incident gallbladder disease across quartiles of intake of total dietary fat and individual fats (polyunsaturated, monounsaturated, saturated, and cholesterol) as well as protein and protein subtype (animal or vegetable) after adjustment for other variables such as age, race, prepregnancy BMI, and parity. Twosided P values less than .05 were considered statistically significant. We conducted power calculation, which indicated that with our sample size, we had 90% power to detect a clinically relevant difference of 10 g in mean intake of total dietary protein or fat between women with or without incident gallbladder sludge or stones. Results
Results At 4–6 weeks postpartum, the cumulative incidence of new biliary stones, sludge, or progression from baseline sludge to stones was 10.2%. In univariate analysis, several factors were associated with higher rates of biliary stone or sludge formation (Table 1). These include Hispanic ethnicity, self-reported previous history of gallstones, and higher prepregnancy BMI. Interestingly, women who formed new gallstones or sludge gained less weight during pregnancy compared with those who did not form incident stones or sludge. Lower serum high-density lipoprotein (HDL) and higher serum triglyceride levels were also associated with increased risk of gallstones or sludge
Downloaded from pen.sagepub.com at GEORGIAN COURT UNIV on May 8, 2015
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Journal of Parenteral and Enteral Nutrition 39(1)
Table 1. Selected Characteristics of Study Participants. Characteristic Age, y Hispanic ethnicity, No. (%) Parity, n > 1, (%) Waist hip ratio, in. Self-reported history of gallstones, No. (%) BMI prepregnancy, kg/m2 History of diabetes, No. (%) Diabetes this pregnancy, No. (%) Weight gain during pregnancy, kg Any smoking during pregnancy, No. (%) Caloric intake, kcal/d Total carbohydrate, g/d Protein intake, g/d Fat intake, g/d Cholesterol intake, g/d Saturated fat intake, g/d Monounsaturated fat intake, g/d Polyunsaturated fat intake, g/d Total cholesterol, mg/dLb HDL cholesterol, mg/dLb LDL cholesterol, mg/dLb Triglycerides, mg/dLb
No New Sludge/Stones (n = 2756)
New Sludge/Stones (n = 314)
25.2 ± 4.9 232 (8.45) 956 (35.1) 0.84 ± 0.7 8 (0.29) 26.0 ± 4.9 49 (1.8) 49 (1.9) 14.6 ± 6.2 551 (20.2) 2135 ± 1070 258 ± 128 89 ± 47 87 ± 49 315 ± 210 33 ± 19 31 ± 18 17 ± 10 239 ± 43 66 ± 16 131 ± 41 209 ± 78
25.4 ± 4.8 46 (14.7) 112 (35.8) 0.84 ± 0.7 6 (1.92) 28.3 ± 6.4 3 (1.0) 5 (1.65) 12.6 ± 7.1 58 (18.8) 2106 ± 992 259 ± 113 87 ± 46 84 ± 46 308 ± 256 31 ± 17 30 ± 18 16 ± 10 239 ± 43 63 ± 16 132 ± 39 220 ± 76
P Valuea .51 .005 .24 .71
research-article2014
PENXXX10.1177/0148607113520184Journal of Parenteral and Enteral NutritionMathew and Ko
Brief Communication
Dietary Fat and Protein Intake Are Not Associated With Incident Biliary Sludge and Stones During Pregnancy Lisa K. Mathew, MD, MSPH1; and Cynthia Ko, MD, MS1
Journal of Parenteral and Enteral Nutrition Volume 39 Number 1 January 2015 124–128 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607113520184 jpen.sagepub.com hosted at online.sagepub.com
Abstract Background: Dietary composition can cause insulin resistance, elevated serum lipid levels, and obesity, all of which predispose to gallstone formation. The effects of dietary fat (including individual fatty acids) and protein on gallstone formation are controversial. The aim of this study was to examine the effects of dietary fat and protein intake on incident gallstone disease during pregnancy, a high-risk time for stone formation. Methods: We prospectively studied 3070 pregnant women who underwent serial gallbladder ultrasound examinations during pregnancy and at 4–6 weeks postpartum. All women had at least 2 study ultrasounds for comparison. A semi-quantitative food frequency questionnaire was completed by subjects in the early third trimester. Multivariate logistic regression was performed to assess the risk of incident gallbladder disease across quartiles of intake of total fat, individual fatty acids (polyunsaturated, monounsaturated, saturated, and total trans-fatty acids, as well as cholesterol), protein, and protein subtype (animal or vegetable based). Results: The cumulative incidence of new biliary sludge/stones or progression of baseline sludge to stones was 10.2% by 4–6 weeks postpartum. There was no association between total dietary fat (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.64–2.18 comparing lowest and highest quartiles) or protein intake (OR, 0.83; 95% CI, 0.44–1.22 comparing lowest and highest quartiles) and incident gallbladder disease. There was also no association between individual fatty acids or protein subtype and gallbladder disease. Conclusions: Neither total nor subtype of dietary fat or protein was associated with incident biliary stone or sludge formation in this cohort of pregnant women. (JPEN J Parenter Enteral Nutr. 2015;39:124-128)
Keywords gallstones; pregnancy; dietary fat; dietary protein
Clinical Relevancy Statement Pregnancy is a high-risk time for gallstone formation and can increase lifetime risk of gallstone disease in women. Dietary factors have been implicated as possible modifiable risk factors in gallstone formation. We show that dietary fat and protein intake are not associated with gallstone formation in this high-risk period. These findings are clinically relevant for providers who care for women and patients with gallstone disease.
Introduction Pregnancy is a high-risk period for gallstone formation in women and is a significant cause of peripartum morbidity.1 Biliary stones and sludge form in up to 2% and 31% of pregnancies, respectively.2,3 Acute cholecystitis occurs in between 1 and 8 per 10,000 pregnancies, and gallstone disease represents the leading nonobstetrical cause of postpartum hospitalization.4 Furthermore, incident gallstone formation during pregnancy likely increases lifetime risk of gallbladder disease. Gallstones affect 7% of nulliparous and 20% of multiparous women.2,5 Strategies to prevent gallstone formation during pregnancy may help reduce the burden and cost of gallbladder disease in women.
The pathogenesis of cholesterol gallstone formation is multifactorial and includes cholesterol supersaturation of bile, decreased biliary motility, and nucleation and growth of cholesterol stones.6-9 Insulin resistance and resultant hyperinsulinemia are thought to contribute to gallstone formation through a variety of mechanisms.6 Dietary composition can affect insulin resistance and potentially affect gallstone incidence. We have previously shown that total carbohydrate and fructose intake increase the risk of gallstone formation during pregnancy, perhaps mediated through hyperinsulinemia.10 Diets high in saturated fats have been shown to increase insulin resistance while diets high in polyunsaturated fats may reverse From the 1Department of Medicine, University of Washington, Seattle. Financial disclosure: This study was funded by grant DK046890 from the National Institutes of Health. Received for publication September 3, 2013; accepted for publication December 20, 2013. This article originally appeared online on January 17, 2014. Corresponding Author: Cynthia Ko, MD, MS, Division of Gastroenterology, University of Washington, 1959 NE Pacific St, Box 356424, Seattle, WA 98195, USA. Email: [email protected]
Downloaded from pen.sagepub.com at GEORGIAN COURT UNIV on May 8, 2015
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this effect.6,11 The results of studies correlating total dietary fat with gallstone formation are variable,6-8,11,12 suggesting that the quantity of fat in our diet may not be as important as the type of fat. Previous studies have suggested a protective effect of vegetarian diets on gallstone formation.13 This could, in part, be mediated by dietary protein intake and protein subtype (animal vs vegetable protein sources). Data supporting the effect of protein and protein subtypes on gallstone formation are limited. Several studies suggest that dietary protein does not affect postprandial insulin concentrations.14,15 In this study, we prospectively evaluated the effect of dietary fat and protein and their subtypes on incident gallbladder stone or sludge formation during pregnancy. We hypothesized that women with diets high in saturated fats and animal protein would be at higher risk of sludge/stone formation during pregnancy, while diets high in polyunsaturated fats and vegetable protein would be at lower risk.
Methods Pregnant women attending their first obstetrics clinic at Madigan Army Medical Center (Tacoma, WA) were approached consecutively (n = 8929). Women were excluded if they were younger than 18 years, had poor English-language comprehension, were more than 20 weeks pregnant, or had plans to move away within 3 months. Those who were eligible and interested in enrollment (n = 4897) gave written informed consent. Enrolled participants were offered serial fasting gallbladder ultrasound examination during each trimester of pregnancy (10–12 weeks’ gestation, 17–19 weeks’ gestation, and 26–30 weeks’ gestation) and at 4–6 weeks postpartum. The study was approved by the Institutional Review Boards of the University of Washington and Madigan Army Medical Center. At study entry, participants completed a questionnaire documenting their medical, obstetrical, family, and social histories. Nutrient data were collected using a food frequency questionnaire (version WHX, 1992) developed by the Nutrition Assessment Shared Resource (NASR) of the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA).16 This validated questionnaire was administered in the early third trimester of pregnancy and inquired about the nutrition habits of the participants from the time of conception to the time the questionnaire was given, therefore reflecting dietary intake over the first 2 trimesters of pregnancy. Nutrient analysis was performed using the Nutrition Data Systems for Research software (NDSR) developed by the Nutrition Coordinating Center (NCC) at the University of Minnesota (Minneapolis). Prepregnancy body mass index (BMI) was calculated from self-reported height and weight immediately before pregnancy. Weight gain during pregnancy was calculated as the difference between predelivery weight and prepregnancy weight. Fasting serum samples were obtained at 26–28 weeks’ gestation and tested for glucose and lipid values by the clinical laboratory at the Madigan Army Medical Center. Gallbladder ultrasonography was performed with a standard imaging protocol using a 3.5- to 7.0-MHz rotatory sector
scanning transducer (ATL, Inc, Bothell, WA, or Acuson Corp, Mountain View, CA). All study ultrasounds were performed by sonographers with specialized training in gallbladder ultrasound and with women fasting or having drunk only sips of water. Findings were recorded by the sonographers, and images and findings were reviewed by 1 of 2 designated study radiologists with expertise in gallbladder ultrasound. Sludge was defined as the presence of low-level echoes that shift with position changes and without postacoustic shadowing. Stones were defined as high-amplitude echoes greater than 2 mm in diameter with postacoustic shadowing. In 10,887 scans, there were discrepancies between the radiologist’s and the sonographer’s readings in 70 regarding the diagnosis of sludge (κ = 0.93) and in 25 regarding the diagnosis of stones (κ = 0.98). In case of discrepancy, the radiologist’s reading was accepted as correct. Gallbladder volume and contraction were not measured. The cumulative incidence of gallbladder sludge and stones was determined from the serial gallbladder ultrasounds. Women with new sludge, new stones, or progression of baseline sludge on entry ultrasound to stones on a subsequent ultrasound were defined as having incident gallbladder disease. Women were excluded from the final data analyses if they did not complete a dietary questionnaire (n = 184) or had fewer than 2 interpretable gallbladder ultrasounds (n = 1402), gallstones on entry ultrasound (n = 208), or prior cholecystectomy (n = 33). This resulted in 3070 participants included in the analysis. On univariate analysis, we used t tests to compare continuous variables and χ2 tests for categorical variables. Multivariate logistic regression analysis was performed (STATA 12.1; Stata Corporation, College Station, TX)17 to assess the risk of incident gallbladder disease across quartiles of intake of total dietary fat and individual fats (polyunsaturated, monounsaturated, saturated, and cholesterol) as well as protein and protein subtype (animal or vegetable) after adjustment for other variables such as age, race, prepregnancy BMI, and parity. Twosided P values less than .05 were considered statistically significant. We conducted power calculation, which indicated that with our sample size, we had 90% power to detect a clinically relevant difference of 10 g in mean intake of total dietary protein or fat between women with or without incident gallbladder sludge or stones. Results
Results At 4–6 weeks postpartum, the cumulative incidence of new biliary stones, sludge, or progression from baseline sludge to stones was 10.2%. In univariate analysis, several factors were associated with higher rates of biliary stone or sludge formation (Table 1). These include Hispanic ethnicity, self-reported previous history of gallstones, and higher prepregnancy BMI. Interestingly, women who formed new gallstones or sludge gained less weight during pregnancy compared with those who did not form incident stones or sludge. Lower serum high-density lipoprotein (HDL) and higher serum triglyceride levels were also associated with increased risk of gallstones or sludge
Downloaded from pen.sagepub.com at GEORGIAN COURT UNIV on May 8, 2015
126
Journal of Parenteral and Enteral Nutrition 39(1)
Table 1. Selected Characteristics of Study Participants. Characteristic Age, y Hispanic ethnicity, No. (%) Parity, n > 1, (%) Waist hip ratio, in. Self-reported history of gallstones, No. (%) BMI prepregnancy, kg/m2 History of diabetes, No. (%) Diabetes this pregnancy, No. (%) Weight gain during pregnancy, kg Any smoking during pregnancy, No. (%) Caloric intake, kcal/d Total carbohydrate, g/d Protein intake, g/d Fat intake, g/d Cholesterol intake, g/d Saturated fat intake, g/d Monounsaturated fat intake, g/d Polyunsaturated fat intake, g/d Total cholesterol, mg/dLb HDL cholesterol, mg/dLb LDL cholesterol, mg/dLb Triglycerides, mg/dLb
No New Sludge/Stones (n = 2756)
New Sludge/Stones (n = 314)
25.2 ± 4.9 232 (8.45) 956 (35.1) 0.84 ± 0.7 8 (0.29) 26.0 ± 4.9 49 (1.8) 49 (1.9) 14.6 ± 6.2 551 (20.2) 2135 ± 1070 258 ± 128 89 ± 47 87 ± 49 315 ± 210 33 ± 19 31 ± 18 17 ± 10 239 ± 43 66 ± 16 131 ± 41 209 ± 78
25.4 ± 4.8 46 (14.7) 112 (35.8) 0.84 ± 0.7 6 (1.92) 28.3 ± 6.4 3 (1.0) 5 (1.65) 12.6 ± 7.1 58 (18.8) 2106 ± 992 259 ± 113 87 ± 46 84 ± 46 308 ± 256 31 ± 17 30 ± 18 16 ± 10 239 ± 43 63 ± 16 132 ± 39 220 ± 76
P Valuea .51 .005 .24 .71
