Medical Treatment Options for Obesity

Jennifer DeBruler, M.D.

Medical Director

Advocate Weight Management

Board Certified Internal Medicine

October 2012

Goals for this presentation…

Discuss low fat diet, Mediterranean diet, Paleo diet

Discuss exercise recommendations for weight loss and mantainence

Discuss medication options for treatment of obesity

Provide an office tool to help patients loss weight

– Dietary Guideline for Americans 2010• US Department of Agriculture• www.dietaryguidelines.gov

– Decrease saturated fat– Consume >45% from carbohydrate

– Once size fits all approach only fits a minority of the population

Jeff S. Volek, PhD, RD

Re-Examining the Role of Carbohydrate

The Low Fat Era

The increase in calories during the obesity epidemic was largely due to carbohydrate intake.

Jeff S. Volek, PhD, RD

Saturated Fat & the Diet Heart Hypothesis

We know decreased SFA intake leads to increased carb intake which can lead to metabolic syndrome then diabetes and ultimately heart disease

Is it true that increased SFA intake causes increased plasma LDL and heart disease?

Jeff S. Volek, PhD, RD

What happens to a carbohydrate?

Eat Carbohydrate, it goes into blood glucose and is broken down to glycogen and oxidized

Too much carbohydrate leads to glycogen and excess carbohydrate fuels lipogenesis (fat synthesis)

Plasma Saturated Fat

Predicts Heart disease– Br Med J 1982;285993-6– Am J Epidemiolo. 1995;142: 469-76– Nut Metab Crdiovasc Dis 2003;13:256-66– Am Heart J 2008; 156:965-74

Predicts Diabetes– AJCN. 2003; 78:91-8– Diabetologia. 2005; 48:1999-2005– AJCN. 2007; 86:189-97– AJCN. 2010; 92:1214-22

Dietary Saturated Fat and Heart Disease3 Recent Meta-Analyses

Study Pooled Cohort Studies

Baseline Cohort (n)

Follow-Up (yr)

Interpretation

Skeaff & Miller. Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomized controlled trials Ann Nutr Metab, 2009. 55(1-3): p. 173-201.

28 280,000 4-25 No association between SFA intake & CHD events/death

Jakobsen, et al., Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr, 2009. 89(5): p. 1425-32.

11 344,696 4-10 Increased SFA intake not associated w/CHD events

Siri-Tarino et al., Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr, 2010. 91 (3): p. 535-46.

21 347,747 5-23 No association b/t SFA intake & CVD, CHD or stroke

If you decrease SF, it matters what you replace it with.

Replacing 5% of SFA with carbohydrates increase coronary events.

It increases your relative risk of CAD

Jakobsen et al. AJCN , Feb 2011

Conclusion

When it comes of SFA, you are not what you eat Consumption of carbohydrate at levels that exceed a

persons ability to directly oxidize them contributes to increased circulation SFA

Instead of telling everyone to restrict dietary saturated fat a more rational and effective strategy would be to focus on ways to help people find their “right” level of carbohydrate

For people with insulin resistance, a low carb lifestyle can have a profoundly beneficial effect on a metabolic risk factors including SFA

Jeff S. Volek, PhD, RD

Mediterranean Diet

Large quantities of minimally processed, fresh, plant-based foods (fruit, vegetables, whole grains, seeds and nuts)

Olive oil is principal source of dietary fat Low consumption of red meat and dairy Red Wine in low to moderate amounts with

meals 45% Carbohydrate Low glycemic load

Minich DM, et al. Nutr Rev Vol 66(8): 429-444.

Mediterranean DietLyon Diet Heart Study

Prospective secondary prevention in 605 subjects for 5 years

Subjects randomized to – Mediterranean diet with 40% fat, 45% carbs– ADA Step 1 Diet with 25% fat, 60% carbs

– De Lorgeril M. Circulation. 1999; 99: 779-785.

Mediterranean DietLyon Diet Heart Study

Study halted after 27 months due to excess mortality in the AHA Step 1 Diet

– Total mortality (cardiac + non-cardiac) 72% (p<0.0001)

– Cardiovascular events (MI, CHF, PE) 47% (p<0.0001)

– De Lorgeril M. Circulation. 1999; 99: 779-785.

Mediterranean DietLyon Diet Heart Study

The Mediterranean diet dramatically reduced heart attack and overall mortality compared to the AHA diet

No change in serum lipids, BP, BMI

Key difference: Mediterranean diet modifies inflammation

De Lorgeril M. Circulation. 1999; 99: 779-785.

Mediterranean DietLyon Diet Heart Study

Mediterranean diet includes nutrients known to decrease inflammatory mediators (crp, IL-6, WBC)– Omega 3- EFA, DHA-EPA– Gamma Tocopherol– Flavenoids, coumarins anthyrocyanin

Med. Diet excludes nutrients that increase inflammatory mediators– Omega 6-EFA, linoleate and arachidonate– Iron– Trans fat: increase CRP– Alpha tocopherol: reduces gamma tocopherol (Vit E)

Mediterranean Diet

Great for moderately obese, 20-30 pounds overweight

Not concerned with rapid weight loss

For patients who want to use diet to prevent or treat co-morbids, – e.g. Metabolic syndrome, diabetes, CAD

The Paleo Diet

Typical food in the Western Diet were virtually unknown in ancestral human diets– Breads, cereals, rice, and pasta– Dairy Products– Added Salt– Refined vegetable oil– Refined sugars, except honey– Processed Meats– Alcohol

– Cordain et al. Am J Clin Nutr 2001;71:682-92

The Paleo Diet

Eat like the cavemen eat– Fresh Veggies– Nuts/Seeds– Healthful Oils– Fresh fruits– Fish/seafood– Grass produced meats

The Paleo Diet

Typical Hunter-Gatherer Diet– Animal food energy 55%

• Hunted animal 27.5%• Fished animal 27.5%• No processed meats• No dairy food

– Plant food energy 45%• No cereal grains• Minimally processed fresh fruits, veggies, seeds & nuts

– No Processed Foods

– Cordain et al. Am J Clin Nutr 2001;71:682-92

The Paleo Diet

Nutrient differences between: – wild vs. cultivated plant food

• Smaller• More fiber• Less sugar• Slightly greater minerals• Vitamin content similar

The Paleo Diet

Seems like a lot of cholesterol in this diet? Dietary cholesterol has a minimal influence

on serum cholesterol.– Lowering dietary cholesterol from 491 mg (paleo) to

300mg (recommended) drops serum cholesterol by 4.5 mg/dl

– Lowering dietary cholesterol from 491 mg (paleo) to 219 mg (food pyramid) drops serum cholesterol by 6 mg/dl

– Cutting dietary cholesterol from 491mg to 219 mg would reduce a high cholesterol 240 to 234 or 2.5%

– Schonfeld G et al. J Clin Invest 1982;69:1072-80

The Paleo Diet

High protein diet is more effective than high carbohydrate diet in causing weight loss– After 6 mo – high protein/low fat group had lost

average of 19.6 lbs– After 6 mo – high carb/low fat group had lost an

average of 11.2 lbs

Similar studies have replicated results– Baba NH et al. 1999– Torbay N et al. 2002– Johnston CS et al. 2002– Parker B et al., 2002– Weigle DS et al, Am J Clin Nutr 2005

Exercise Recommendations

General Health Benefit– Moderate aerobic exercise 150 min/wk (about 30

minutes 5x/wk) + strength training Prevention of Weight Gain

– 150-250 minutes per week– 150-300 minutes per week

Prevention of Weight Regain– 200-300 minutes per week– 300-420 minutes per week

– Donnelly JE. Med Sci Sports Exerc. 2009– USDHHS. PA Guidelines for Americans. 2008

Medical Clearance for Physical Activity

ACSM Guidelines for Risk Stratification– Men>45, women>55 w/2 or more risk factors– Risk factors include:

• FHx of MI in 1st degree relative M<55, F<65• Smoking in last 6 mo• Hypertension• Abnormal lipids• Impaired Fasting Glucose• BMI ≥ 30• Sedentary Lifestyle

– Plan to exercise at >60% of max, vigorous– Consider Stress testing

– Thompson WR, Ed. ACSM’s Guidelines for Exercise Testing & Prescription, 2010

Medications for Weight Loss

Phenylethylamines Sympathomimetic effect Works at the hypothalamus and limbic system Appetite suppressant effect

Meta-analysis of phentermine and diethylproprion– 3.6 kg additional weight loss at 6 mo for phentermine– 3 kg additional weight loss at 6 mo for diethylpropion

– Li, A. Ann Intern Med. 2005.

Medication for Weight Loss

Phenylethylamines Short term adjunct in a regimen of weight

reduction involving lifestyle changes in management of adult obesity

BMI ≥ 30 or ≥ 27 with comorbid condition Contraindication – advanced arteriosclerosis,

CAD, mod/severe HTN, hyperthyroid, glaucoma, agitated states, history of known drug abuse, pregnancy

Medication for Weight Loss

Phenylethylamines Adverse Effects

– CV: palpitations, tachycardia, primary pulm HTN

– CNS: restlessness, dizziness, insomnia, HA– GI: dry mouth, diarrhea, constipation– Endocrine: impotence, change in libido

Medication for Weight Loss

Orlistat

Gastric and pancreatic lipase inhibitor Inhibits uptake of up to 1/3 ingested fat Needs to be used in accordance with low-fat,

calorie controlled diet.

Medication for Weight Loss

Orlistat May be used long-term up 4 yrs for weight loss or for

weight loss maintenance in adult obese patients Pediatric indication: 12-16 y/o obese adolescents Should be accompanied by vitamin supplementation Common SE: fecal soiling, dyspepsia, flatulence,

vitamin malabsorbtion, elevated liver enzymes Rare SE: severe liver injury Contraindication: cholestasis, malabsorbtion syndrome,

liver disease

Medication for Weight Loss

Metformin Biguanide: reduces hepatic glucose

production and improves insulin sensitivity Induces modest weight loss initially Improves fertility in PCOS patient Lost 8 kg more weight over 24 wks than

placebo Lee A. Obes Res. 1998

Medication for Weight loss

GLP-1 Agonists Exenatide, liraglutide Enhances glucose dependent insulin release Suppress inappropriate glucagon release Delays gastric emptying Reduction in food intake directly acting on

hypothalamus

Medication for Weight Loss

GLP-1 Agonist

Great medication for DM treatment and weight loss

Works synergistically with carbohydrate controlled diet

Nausea common, usually self-limited Watch out for pancreatitis

Medication for Weight Loss

Bupropion Dopamine and norepinephrine reuptake

inhibitor Tx major depression, smoking cessation,

ADHD Do not use in bulimic patients, may lower

seizure threshold

Medication for Weight Loss

Bupropion Works centrally as an appetite suppressant Only anti-depressant with consistent weight

loss effect May blunt weight regain in smoking cessation

Medication for Weight Loss

Phentermine & topiramate ER (Qsymia)– BMI ≥ 30 or ≥ 27 with comorbid– Synergistic with Phentermine

• Increased satiety through reduced GI motility• Increased taste aversion• Reduced calorie intake

– SE: increased HR, paresthesias, metabolic acidosis

– TBD when released

Medication for Weight Loss

Phentermine & topiramate ER (Qsymia)– Caution: women of reproductive age

• Cleft palate in 1st trimester• Women must be on OCP• Avoid with glaucoma• Hyperthyroidism• MAOI’s

Studies show 5-10 kg weight loss

Medication for Weight Loss

Lorcaserin (Belviq) – Activates the seratonin 2C receptor– Works at centrally acting satiety receptors– Caution:

• Valvular HD, CHF, HTN• Men with predisposition to erection more than

4 hrs (sickle cell, MM, Leukemia) or deformed penis

– 3.7% weight loss, 7kg.

Office Tool

Thank you