friday general session fatty liver disease: a practical ... go better with coke coca cola 12 oz....

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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.

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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

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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?

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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

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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.


Men: no significant trend between education and obesity Women: obesity increases as education decreases.


Between 1988–1994 and 2007–2008 the prevalence of obesity among adults increased at all income levels


Between 1988–1994 and 2007–2008 the prevalence of obesity increased at all education levels


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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

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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

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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


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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

friday general session fatty liver disease: a practical ... go better with coke coca cola 12 oz....

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