friday general session fatty liver disease: a practical ... go better with coke coca cola 12 oz....
TRANSCRIPT
4
Friday General Session
Fatty Liver Disease: A Practical Approach to Management
Norman Sussman, MD Associate Professor of Surgery Baylor College of Medicine Medical Director, Project ECHO Baylor St. Luke’s Medical Center Houston, Texas
Educational Objectives By the end of this activity, the participant should be better able to:
1. Discuss the mechanisms by which fat accumulates in hepatocytes. 2. Recognize the role of carbohydrates in weight gain. 3. Comprehend secular trends in food intake in America. 4. Distinguish that not all carbohydrates are created equal.
Speaker Disclosure Dr. Sussman has disclosed that he has received grant support from Tobira and Wilson Pharmaceuticals; he is a consultant for AbbVie and Genfit; he is on the speaker’s bureau for AbbVie, Gilead, Merck & Company, and Intercept Pharmaceuticals; and he is on the advisory board for Merck & Company.
1
Fatty Liver DiseaseA Practical Approach to Management
Texas Academy of Family Physicians2nd June, 2017
Norman L. Sussman, MD
Associate Professor, Surgery
Director, Project ECHO®
__________
Baylor College of Medicine
& BSLMC
Houston, TX
Disclosures
Clinical Event Committee
Genfit
Research Funding
TaiwanJ, NGM, Tobira
Speaking & Honoraria
AbbVie, Gilead, Merck, Intercept
Consulting and advisory
AbbVie, Merck
No off‐label use will be discussed
Learning ObjectivesAfter this lecture you will better able to:
Discuss the mechanisms by which fat accumulates in hepatocytes.
Recognize the role of carbohydrates in weight gain.
Comprehend secular trends in food intake in America.
Distinguish that not all carbohydrates are created equal.
Fatty Liver Disease ASH & NASH look the same
Which of the following is not associated with fatty liver disease?
1. TPN
2. High carbohydrate diet
3. Bariatric surgery
4. Methotrexate
5. Erythromycin
NAFLDTriglycerides in the Liver
Angulo, P. NEJM (2002) 346:1221‐1231
Impaired VLDL synthesis and secretion • Apo B• Protein malnutrition• Choline deficiency
Microsomal triglyceride transfer protein (MTTP) • Defect decreased lipidation of Apo B• Drug‐induced NAFLD (amiodarone, TCN)
Increased Production• Rapid breakdown of fat (weight loss)• Overfeeding (TPN)
Orphan Nuclear Receptor Small heterodimer partner (SHP)Orphan Nuclear Receptor Small heterodimer partner (SHP)Orphan Nuclear Receptor Small heterodimer partner (SHP)
Decreased oxidation• B5 depletion• Alcohol• Co‐A Deficiency
• Valproate, ASA
2
Obesity began to increase in the 1980s ‐ rate flattened in the 2000s, leading to hopes of improved obesity
Calorie intake dropped for children and adults
Soda consumption has declined by 25% since 1990s
But 17% of Americans ages 2 to 19 are obese, the same as in 2003 and 2004
Obesity rates did not rise for youth
NHANES 2011‐2014
Black women 57% White women 36%
Hispanic women 46% White men 34%
Hispanic men 39%
Do I Look Fat? Men Ask This Question, TooWSJ, March 8, 2016
“Psychology of Men and Masculinity”
111,958 heterosexual and 4,398 gay men who responded to a series of five surveys posted on MSNBC.com, NBCNews.com and Today.com between 2003 and 2012. The respondents ranged from 18 to 65 years old.
29% of heterosexual men and 37% of gay men said they had gone on a weight‐loss diet in the past year. More than half of both had exercised to lose weight in the past year
21% of heterosexual men and 29% of gay men were dissatisfied, compared with 27% of heterosexual women and 30% of lesbians
Asked if they avoided having sex during the past month because they felt bad about their body, 5% of heterosexual men said they did, compared with 20% of gay men
Will we pay a price?
“Because of the increasing rates of obesity, unhealthy eating habits and physical inactivity, we may see the first generation that will be less healthy and have a shorter life expectancy than their parents.
Fat vs. Carb9 kcal vs. 4 kcal
Ancel Keys, 1961• BMI• Unsaturated fat• Mediterranean diet
Uffe Ravskov, 1961• Alb/creat clearance ratio• Unsaturated fat is bunk
Diabetes in New YorkSugar as a risk factor
Increasing incidence
1900 = 3/100,000
1920s = 30/100,000
Wealthy
Over age 45
Men and post‐menopausal women
Food industry workers
Merchants and food handler
Sugar intake
Haven Emerson, Arch Int Med 1924
Haven Emerson (1874‐1957)NYC Health Commissioner
Is it Really this Simple?
3
Pitfalls in Self‐Reported Diet & Exercise
Amount and type of activity
Amount and type of food
Inaccurate reporting for both
A 5’ 3” woman weighing 135 lbs. jogs for 30 minutes. She will burn approximately ___ calories?
1. 115 kcal
2. 215 kcal
3. 315 kcal
4. 415 kcal
5. 515 kcal
Poverty income ratio (PIR): The ratio of household income to the poverty threshold after accounting for inflation and family size. Data for 2008
350 % PIR: $77,000 for a family of four
130% PIR: $29,000 for a family of four
Median household income: $50,000
13.2% of the population lived below the poverty level
The cut point for participation in the Supplemental Nutrition Assistance Program (SNAP) is 130% of the poverty level
http://www.census.gov/newsroom/releases/archives/income_wealth/cb09‐141.html
4
Most obese adults are not low income (below 130% of the poverty level)
Ogden et al. NCHS Data Brief 50, Dec 2010
Poverty and lack of education are associated with obesity in which of the following?
1. Similar in men and women
2. Men, but not women
3. Women, but not men
4. Neither – poverty is associated with lower BMI
Men: obesity is similar at all income levels, with a tendency to be slightly higher at higher income levels.
Ogden et al. NCHS Data Brief 50, Dec 2010
Men: no significant trend between education and obesity Women: obesity increases as education decreases.
Ogden et al. NCHS Data Brief 50, Dec 2010
Between 1988–1994 and 2007–2008 the prevalence of obesity among adults increased at all income levels
Ogden et al. NCHS Data Brief 50, Dec 2010
Between 1988–1994 and 2007–2008 the prevalence of obesity increased at all education levels
Ogden et al. NCHS Data Brief 50, Dec 2010
5
Trends in Food Intake; 1971‐2006 (NHANES)
The prevalence of obesity increased
11.9% 33.4% in men
16.6% 36.5% in women
% of energy from carbohydrates: 44.0% 48.7%
% of energy from fat 36.6% 33.7%
% of energy from protein 16.5% 15.7%
Trends were identical across all weight groups
Energy intake increased in all 3 BMI groups
GL Austin, LG Ogen, JO Hill. Am J Clin Nutr. 2011;93:836–43
Trends in Food Intake; 1971‐2006 (NHANES)
GL Austin, LG Ogen, JO Hill. Am J Clin Nutr. 2011;93:836–43
Corn Refiners Association: “no scientific support for the hypothesis that high fructose corn syrup is causally linked to obesity in the United States . . . any more or less than
other caloric sweeteners”
Health concernsabout animalproducts
Health concernsAbout carbohydrates
Things go better with Coke
Coca Cola 12 oz. (355 ml) CanSugars, total: 39gCalories, total: 140 Calories from sugar: 140
20 oz. (590 ml) BottleSugars, total: 65gCalories, total: 240 Calories from sugar: 240
1 Liter (34 oz.) BottleSugars, total: 108gCalories, total: 400 Calories from sugar: 400Sugarstacks.com
But even better with Mountain Dew
Mountain Dew 20 oz. (590 ml) BottleSugars, total: 77gCalories, total: 290 Calories from sugar: 290
1 L (34 oz.) BottleSugars, total: 124gCalories, total: 440 Calories from sugar: 440
Sugarstacks.com
6
O.J. can kill you
Orange Juice 8 oz. (240 ml) ServingSugars, total: 24gCalories, total: 110 Calories from sugar: 96
16 oz. BottleSugars, total: 48gCalories, total: 220 Calories from sugar: 192
Sugarstacks.com
Fruit
Watermelon1 slice (280g ‐ 50% waste)Sugars, total: 18gCalories, total: 86Calories from sugar: 72
Red Seedless Grapes 1 serving (126g ‐ 4% waste)Sugars, total: 20gCalories, total: 88Calories from sugar: 80
Banana1 large (140g)Sugars, total: 17gCalories, total: 125Calories from sugar: 68 Sugarstacks.com
And the winner is ….
Cinnabon Cinnamon Roll 1 pastry Sugars, total: 55gCalories, total: 813Calories from sugar: 220
Sugarstacks.com
Ancient and Modern Wheat
Wild grains
Einkorn – wild grain (semi‐nomadic)
Emmer – Egyptians credited with baking bread
Introduced into the New World
C. Columbus – Puerto Rico – 1493
Bartholomew Gosnold and Pilgrims (circ. 1602)
Triticum aestivum – 4 ft “amber waves of grain”
Triticum durum – pasta
Triticum compactum – very fine flour (cupcakes)
Norman Ernest Borlaug25th Mar 1914 – 12th Sept 2009
Nobel Prize – 1970 PhD at age 27 Known for the Green RevolutionMade Mexico wheat‐sufficient by 1956 India and Pakistan in mid‐1960s
Increased yield – 6x between 1944 & 1964 Semi‐dwarf variety – resist bending Double growing season Naked seeds Disease resistance
Match population with resources
7
Which of the following will cause the greatest production of triglycerides?
1. A four‐egg omelet
2. A croissant with butter
3. A glass of orange juice
4. ¼ cup of olive oil
5. Two cans of diet cola
Disposition of 120 kcal of Carbohydrate
Glucose (2 slices of bread)
20% (24 kcal) enters the liver – 4 kcal to pyruvate
Alcohol (1.5 oz. of 80 proof liquor)
80% (96 kcal) enters the liver – 70 kcal to citrate
Fructose (1 glass orange juice) – 50% fructose
Glut‐5 fructose transported is found only in liver
72 kcal enters the liver – 50 kcal to pyruvate
Lustig, R, The Bariatrition
Not all sugars are created equal
Maltose Sucrose/HFCS
Disposition of 120 kcal of Carbohydrate
Glucose (2 slices of bread)
20% (24 kcal) enters the liver – 4 kcal to pyruvate
Alcohol (1.5 oz. of 80 proof liquor)
80% (96 kcal) enters the liver – 70 kcal to citrate
Fructose (1 glass orange juice) – 50% fructose
Glut‐5 fructose transported is found only in liver
72 kcal enters the liver – 50 kcal to pyruvate
20 oz. Coke = 65 g carbohydrate (35.75 g fructose) = 240 kcal1 can of Coke = 39 g carbohydrate (21.45 g fructose) = 105 kcal
Lustig, R, The Bariatrition
8
Lustig, R, The Bariatrition
Zebrafish: Fructose, Stress, and Rapamycin
V. Sapp et al. Hepatology 2014; 60:1581‐1592
Increased fat caused by:
A. 4% fructose vs. glucose
B. Tunicamycin (ER stress)
C. Vanilomycin (oxidative stress)
All decreased by the mTOR inhibitor, rapamycin
FructoseIsocaloric substitution of starch for sugar
Latino (n=27) and African‐American (n=16) children with obesity and metabolic syndrome
9 day diet with comparable % protein, fat, and carbohydrate, but dietary sugar decreased from 28% to 10% with starch substitution
Dual‐energy X‐ray absorptiometry and OGT on Days 0 and 10.
Reduced diastolic BP (25 mmHg), lactate, TGL and LDL
Glucose tolerance and hyperinsulinemia improved (P<0.001).
Weight reduced by 0.960.2 kg (P<0.001) and fat‐free mass by 0.6 kg (P50.04).
Conclusion: Improved surrogate metabolic parameters irrespective of weight change
Lustig et al. Obesity, e‐pub 2015
The Bottom Line
The effect of cheap calories is at the heart of the obesity epidemic
Sugar is the foundation of our reward system – people are always sabotaging their friends and coworkers
The food industry has learned to create addictive foods that are high in calories, especially carbohydrates
No entity opposes food industry marketing
The Ascent & Descent of Man
Homo SimpsonAustralopithecus Homo erectus Homo sapiens
Summary – NAFLD & NASH
Obesity is the result of behavior – more food and less exercise
Socioeconomic factors are complex, and include poverty, education, and race
Results are unexpected
Weight loss and exercise both improve NAFLD/NASH
Getting patients to take responsibility for their health seems to be the most difficult thing in the world