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New Realities on Obesity & Weight Management

Christine Kessler ANP. CNS, BC-ADM, CDTC, FAANP ckessler@maranatha.net

Disclosures

Novo Nordisk – Consultant, Speaker (obesity)

Astra Zeneca – Consultant on T2DM

Medtronic - Consultant on insulin pumps

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Objectives

At the conclusion of this talk, the attendee

will be able to: 1. List at least 5 major epidemiologic factors

influencing the rise of obesity in this country

2. Describe various interconnections between fat, gut &

brain in relation to appetite, calorie utilization and mood

3. Relate the physiologic impact of various weight loss

intervention & prevention strategies as well as way to

reduce weight regain

One simple suggestion….

Call obesity…..

Fast Facts on Obesity (aka “Adiposity”)

• Obesity is a chronic disease, NOT a character flaw – Thus, chronic treatment is necessary

• The cause of obesity is multifactorial – Yep---it is your hormones! – Treatment should be multifaceted

• Obesity is associated with many co-morbidities and soaring medical costs – Intervention can help reduce these

• Obesity continues to rise in this country – Prevention and intervention is imperative

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More Ponderings on Obesity

• You CAN lose wait (keeping it off is hard but…)

• There is HOPE for your patients--and us

• Consider obesity as the common denominator in the waiting room…..

We know the physiologic cause for weight regain.

Obesity Among U.S. Adults • The prevalence of obesity began its meteoric rise in late 1970s

• Currently, no state has an obesity rate < 20%.

• 19 states have adult obesity rates between 30% and <35%. – 1 in 6 children now with obesity

• Only 5 states and the District of Columbia had a prevalence of obesity between 20% and <25%.

• Arkansas, West Virginia and Mississippi (that order) have highest obesity prevalence of 35% or greater.

• Obesity affects 1 in 6 children

• Greater prevalence in Blacks and Latinos—twice as much in women!!

• For obesity rates per state check out this interactive site: http://stateofobesity.org/rates

http:/www.cdc.gov/obesity/data/prevalence-maps.html (Accessed 2/14/2016)

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The Obesity Epidemic

“If this trend continues, almost every single American will be obese by 2040”

- John Foreyt, Director of Behavioral Medicine at Baylor.

We haven’t gotten the obesity epidemic under control.

WHY?

FOOD INTAKE

ENERGY OUTPUT

The Old Obesity Paradigm

Old SHAME Notion: You simply eat too much and move too little

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Recalling fat facts

Obesity is a Complex Multi-factorial Chronic Disease

Obesogenic environment Psychobiologic input Highly palatable, calorie dense food (fast or processed food) Food marketing Reduced physical activity Endocrine disrupting chemicals (EDC) Weight-inducing drugs Less sleep

Food-induced pleasure Stress Smoking cessation Psychology Societal-cultural impact

The Appetite & Satiety Centers Hypothalamus

Genetics Gut Fat

Stanley S et al. Physiol Rev. 2005;85:1131‒1158. 2. Dietrich MO & Horvath TL. Nat Rev Drug Discov. 2012;11:675‒691.

Genetic Impact on Obesity Risk

• Approx. 50 genetic loci associated with BMI, waist-hip ratio, percentage body fat & morbid obesity.

• But only explains a fraction of the inter-individual variation in BMI (low predictive value!) – Extreme rise in prevalence indicates strong environmental

influences (modify genes?)

• Some genetic alterations impact hunger and satiety (and cravings)

• Physical activity attenuates the BMI-increasing effect of some of the genes.

Frayling TM, Ong K. Piecing together the FTO jigsaw. Genome Biol. 2011. 12(2):104 Day FR, Loos RJ. Developments in obesity genetics in the era of genome-wide association studies. J Nutrigenet Nutrigenomics. 2011. 4(4):222-38.

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Most common “Obesity Genes”

• FTO gene most commonly cited obesity gene (regulates ghrelin, an appetite hormone, impacting eating behavior)

• Variant of melanocortin receptor gene (MC4R )

Frayling TM, Ong K. Piecing together the FTO jigsaw. Genome Biol. 2011. 12(2):104

Biologic Pathways for Appetite Regulation & Weight Control

GLP-1 / PYY/ CCK INSULIN LEPTIN

Suppresses appetite

Stimulates appetite

Courtesy: Scott Urquhart PA-C, DFAAPA

Adapted by C. Kessler

Hypothalamus and Appetite

Hypothalamus –neuropeptides- appetite Impact on hypothalamus by insulin, fat & gut incretins

Orexigenic neuropeptides

AgRP NPY

Insulin [inhibited by leptin and insulin]

Anorexigenic neuropeptides

CART POMC

[stimulated by leptin and

insulin]

Eat more

Reduced metabolism

Eat less

Increase metabolism

Suzuki K et al. Exp Diabetes Res. 2012;2012:824305. Created by c. kessler

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Satiety = reward Food addictions &

Carb craving?

Dopamine receptors (D1)

& opioid receptors

activates reward system

https://commons.wikimedia.org/w/index.php?curid=213970

Binge Eating Disorder (BED)

-Once you start—can’t stop

-37% of those with obesity

-Women and men nearly equal

-Unlike bulemia—no corrective

actions

www.mybingeeatingdisorder.com

•i •1

•

■ •

Sumithran P et al. NEJM 2011; 365(17):1597-1604.

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Dementia

The Problem With Fat

• Hypertrophy (or hyperplasia) of fat cells

• Visceral fat releases adipokines that are: – pro-inflammatory (CRP, IL-1, IL-6, TNFa, etc)

– Pro-thrombotic

– pro-growth (more fat!)

• Results is endothelial dysfunction, chronic inflammation

• Associated with numerous co-morbidities

http://www.jisponline.com/searchresult.asp?search=&author=Sunitha+Jagannathachary&journal=Y&but_searc

h=Search&entries=10&pg=1&s=0 (accessed 2/21/2016

Types of FAT (Adipose Tissue AT)

WAT – white

BAT -brown

SAT –SC

VAT- visceral

MAT - muscle

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Most abundant in babies—loss it as we age

Generates non-shivering heat (via TGs)

Same precursors as skeletal muscle

Can mess up PET scans

Counters pro-obesity white fat?

“Turned” on by lowered ambient temp (<64 degrees F)

Less in Asians?

Possible Rx for obesity?

More points on Brown Fat

Irisin: The “Exercise” Hormone

http://www.nature.com/scitable/blog/student-

voices/the_messenger_goddess_of_exercise; accessed 7/2/2014

Skeletal

muslce White

fat Brown fat

EXERCISE Irisin

Weight loss

Improved glucose tolerance

Increased heat generation

Created by c.kessler

How Does Food Make us Fat? • Genetics (nutrigenetics)

• Change in our food*

– Quality & quantity

• GI responses to various nutrients

– Altered microbiome & incretins*

• Neuropeptides—hunger/satiety/mood*

• Brain responses to nutrients*

* Where we can intervene

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So What Can We Do About Obesity?

What works and what doesn’t?

BTW--The quicker you can loose a pound the better the

compliance

Points about Obesity Management

– PCPs must engage in weight management as a pathway to better health for their patients.

– Screen with BMI at every visit. But BMI is only a screening tool.

– Waist circumference is a risk factor. Use the cut points >35 inches for women & >40 inches for men

– Overweight and obese patients should be screened for CVD risk factors and comorbidities.

Jensen MD, Ryan DH et al. Circulation. 2013. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee.citation

CMS Will Reimburse…

• For patients with obesity (BMI >30) who are competent and alert

• For 14 visits in first 6 months:

– One face-to-face visit every week for the first month

– One face-to-face visit every other week for months 2–6

• If 3 kg loss is achieved in 6 months:

– One face-to-face visit every month for months 7–12

• The challenge:

– Must be in primary care setting

– Must be delivered by PC physician or practitioner

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• Intensive behavioral intervention should be consistent with the 5-A Framework highlighted by the U.S. Preventive Services Task Force (USPSTF) • Assess

• Advise

• Agree

• Assist

• Arrange

CMS would like IBT for obesity to be the

following…

What do you need to know before developing a weight loss plan?

• Degree of interest in weight loss…satisfied with weight?

• How much weight loss is desired? Realistic?

• What are the health goals—abilities?

• Has there been dieting in the past?

• What has worked (or not) in the past?

• What has triggered the initial weight gain?.

• Dietary preferences and cultural influences.

Variety of Obesity Management Guidelines

• 2015 Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline.

• 2014 VA/DoD Clinical Practice Guideline for Screening and Management of Overweight and Obesity

• 2013 AHA/ACC/TOS Guidelines for the Management of Overweight and Obesity in Adults

• 2013 American Society of Bariatric Physicians Obesity Algorithm

• 2013 Institute for Clinical Systems Improvement Health Care Guideline on Prevention and Management of Obesity for Adults

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Reality-based Interventions • Behavioral: Changing the thinking paradigm

– Life coaching

– Psych/addiction counseling

• Food/dietary intervention (decrease calorie)

• Exercise/activity (start small)

• Pharmacologic interventions

– Prescription

– OTC

• Surgical bariatric interventions

Ryan D, Kessler C. Exploring Trends in the Multimodal Management of Overweight/Obesity. Clinician

Reviews (CME). 2014; november supplement

Assessment data?

• Height, weight, BMI

• Waist circumference

• Existing comorbidities

• Blood pressure

• Lipid profile (esp. TGs)

• Glycemic status (HbA1c, FPG)

• How is this patient feeling and functioning?

Waist-to-Height Ratio Plus BMI Identifies Obese at Highest CVD Risk. Medscape. Jun 02, 2014.

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Fast Dietary Tips

• Can lose weight quicker with caloric restriction

• Important to understand why they eat and what they eat before prescribing an intensive dietary regimen

– Stress eaters? Binge eaters? Carb addicts?

• Consider cultural and genetic (taste) influences

• Food diaries are of enormous help

• Most diets work—just need to stick with it

• Use diet apps where applicable

• Cut sweetened beverages first!

Dietary Interventions • Two general diet categories

– Balanced, low-calorie (reduced portion) diets • Jenny Craig, Nutrisystems, meal replacements, Weight Watchers ,etc

– Diets with different macronutrient (fat, carbohydrate, protein) compositions.

• The above diets are useful for short-term wgt-loss; NOT for sustained weight loss

• Dietary counseling with a nutritionist is optimal, but not often available—

• BTW: Low-carb vs Low-fat: – Both lose weight – Low-carb—less hunger and cravings – Low-fat—lose more fat stores

Tobias d. et al. Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis. The Lancet Diabetes & Endocrinology, 2015 DOI: 10.1016/S2213-8587(15)00367-8 (accessed 2/12/2016) Foster GD et al., Rosenbaum DL, Brill C, et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med. 2010 Aug 3. 153(3):147-57

A word about Very Low Calorie Diets (VLCD)

– Best used in an established , comprehensive

wgt-loss program

– Intake of 800 kcal/day or less (can lose 3.3-5.5 lb/wk)

• Benefit of less than 800 kcal/day not found

– Associated with profound initial (and short-term) wgt-loss

– Weight regain can occur

– Avoid in pregnancy

Very low calorie diets. Drug Ther Bull. 2012 May. 50(5):54-7

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A good dietary intervention

Kessler’s Tips For Weight Loss • Avoid mindless eating—and don’t skip meals

• Portion control—bring portioned food to table to eat – Portion control plates help: MyPlate, toddler plates

etc

• Fiber, fiber, fiber

• Drink before or after meal…reduce during

• Slooowww it down, approx 24 chews

• Avoid eating out so much

• Eat protein & fat first…delay carbs—eat around the plate (curious incretin effects)

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Weight Loss Exercise Pointers • Best to use the word, “activity” vs “exercise

• Exercise alone usually not enough for weight loss

• Focus on on-going health benefits of exercise (not simply a weight-loss tool)

• Determine pain levels, mobility concerns, and motivation

• Screen patient for CV and respiratory adequacy (adjust intensity)

• Diet-alone weight loss reduces muscle mass –have as much if add exercise by 27%;

Villareal DT, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011 Mar 31. 364(13):1218-29

Exercise Pointers

• Again: exercise WITH dietary modification is more effective for weight loss (overall health benefits)

• What to suggest: – Endurance training (adjust intensity as needed)

• Aerobic exercise 3-5 days per week

• Continuous or intermittent aerobic activity for 20-60 minutes (OKAY—5 to 10min bouts throughout the day)

– Resistance training (isometric, weights)

– Flexibility training (stretching, modified yoga)

– Go low and slow and give rewards

– Just move!

http://emedicine.medscape.com/article/324583-overview#a8 (accessed 2/14/2016)

Tracking Exercise (& Diet)

• Many apps for smart phones—selected free apps for one or both: – MyFitnessPal

– 7 Minute Workout

– Calorie Counter PRO MyNetDiary

– Diet Assistance

– Amwell (links to providers)

– Diet Assistance (offers diet suggestions too)

– Fooducate

– Endomondo (exercise tracker—highly rated)

– Jawbone UP

– Instant Heart Rate

– Weight Watchers Mobile

– Fitbit (but you have to by the device)

http://www.healthline.com/health/diet-and-weight-loss/top-iphone-android-apps (accessed 2/13/2016)

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So Exercise (for Irisin) !!! or

Just MOVE

150 minutes a week

Okay, now what? • Move to medications

– if BT fails

– Pt has BMI of 27 with 1 co-morbidity

– Pt has BMI > 30

Ryan D, Kessler C. Exploring Trends in the Multimodal Management of Overweight/Obesity. Clinician

Reviews (CME). 2014; november supplement

How Drugs Help

• Stimulants

• Nutrient blockers

• Satiety (appetite suppressant) agents (the new frontier)

–Peripheral

–Central

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What drugs do we have currently?

• phentermine (Adipex-P, Suprenza)

• orlistat (Xenical)

• lorcaserin (Belviq)

• phentermine-topiramate (Qsymia)

• naltrexone-bupropion (Contrave)

• liraglutide (Saxenda)

• FYI---if drug not showing 4-5% weight loss in 12 to 16 weeks—stop it

Ryan D, Kessler C. Exploring Trends in the Multimodal Management of Overweight/Obesity. Clinician

Reviews (CME). 2014; November supplement

Incretin impact Appetite Regulation & Weight Control

GLP-1 / PYY/ CCK INSULIN LEPTIN

Suppresses appetite

Stimulates appetite

Courtesy: Scott Urquhart PA-C, DFAAP

Adapted by C. Kessler

GLP-1 sensitizers/agonists

Gastric bypass Gastric Sleeve

Satiety = reward Food addictions &

Carb craving?

Dopamine receptors (D1)

& opioid receptors

activates reward system

https://commons.wikimedia.org/w/index.php?curid=213970

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Lorcaserin (Belvic) • Action: exact mechanism unknown, activates 5-HT2C

receptors, promoting satiety (selective serotonin agonist) • Dosing: 10 mg bid • DEA Schedule: IV • Pregnancy: X • Monitoring: sx of depression/suicide, glucose at baseline,

CBC • Side effects: HA, fatigue, Serotonin syndrome or

neuroleptic malignant syndrome; valvular heart disease (possible);, depression, suicidal ideation; hypoglycemia with glucose-lowering medications; priapism

• Contraindications:, CKD 3B, CHF, valvular heart disease, pregnancy, depression, DM, bradycardia

• Ave wt. loss 5%

©2013-2014 American Society of Bariatric Physicians and Epocrates

Additional information is available on resource slides at the end

phentermine-topiramate (Qsymia)

• Action: phentermine – short acting sympathomimetic; topiramate – long acting neurostabilizer

• Dosing: 3.75/23 starting dose, titrate to 7.5mg/46mg, 11.25mg/69mg, top dose 15mg/92mg

• DEA Schedule: IV • Pregnancy: X • Monitoring: depression, CV evaluation at baseline,

hypokalemia • Side effects: paresthesias, insomnia, HA , dry mouth, acute

myopia/glaucoma; cognitive impairment; metabolic acidosis; elevated creatinine; hypoglycemia

• Ave wt. loss ranged from 6.7 - to 8.9 % • REMS program

©2013-2014 American Society of Bariatric Physicians and Epocrates

naltrexone-bupropion (Contrave) • Action: an opioid antagonist, and bupropion,

an antidepressant – might help with cravings • Dosing: 8/90mg, 1 tab po qam titrating to max

of 2 tabs po q am and 1 tab po q pm • Pregnancy: X • Monitoring: BP, HR, depression/suicide • Adv. effects: nausea, headache, insomnia • Contraindications: seizure disorders, eating

disorders, chronic opioid use • Ave wt. loss ranged from 5 -10% • Black Box Warning: Suicidal Thoughts and

Behaviors; and Neuropsychiatric Reactions

Medication Insert and Epocrates

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Liraglutide (Saxenda)

• Class: Obesity • Action: glucagon-like peptide-1 receptor agonist • Dosing: Initiate at 0.6 mg per day SQ for one week. In

weekly intervals, increase the dose until a dose of 3 mg is reached.

• Pregnancy: X • Monitoring: monitor for medullary thyroid carcinoma,

pancreatitis, cholelithiasis or cholecystitis, hypoglycemia (especially if patient on sulfonylurea), HR, renal impairment, and depression or suicidal thoughts.

• Adv. effects: nausea, hypoglycemia, diarrhea, fatigue, dizziness, abdominal pain, and increased lipase.

• Ave wt. loss ranged from 5 -10% • REMS program • Avoid if gastroparesis, thyroid ca risk, pancreatitis, severe IBS

Drug Pointers

• Phentermine 3 months only—but…

• Newer prescription drugs approved for chronic use

• Not recommended in pregnancy

• Consider the contraindications and co-morbidities when deciding on a drug to start with

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Sensory Factors:

•Taste

•Smell

•Texture

•Sight

Effects of: •Variety of foods

•Sensory-specific satiety

•Palatability

•Food components

•Ease of access

Brain Mechanisms: •satiety signals to

produce appetite &

reward value

Satiety/Hunger Signals: •Fat cell hormones (leptin)

•Gut hormones (incretins)

•Gastric distention

Cognitive Factors: •Beliefs about the food

•Advertising and culture

Eating

Other Influencers of Food Intake

Adapted from: Rolls ET. Obes Rev. 2007;8(suppl1):67-72.

Family & Social

Influences

Selected OTC Pharmacologic Aids • Satiety agents

– Hoodia: (No)

– Grapeseed oil (no)

– Raspberry ketones (NO!

– Pine nuts (yes) like GLP-1

– 5-HTP (ok) feel full

– Fennel tea (yes) evening help

– Garcinia cambogia (yes...no...maybe) 60% HCA

Drugs Don’t Work So Now What…?

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Common Bariatric Surgery Procedures

No Incretin

effects

Adjustable Gastric Banding Sleeve Gastrectomy Gastric Bypass

(Roux n Y)

GLP-1 ↑

PYY ↑ Ghrelin ↓

Weight Loss +++ Weight Loss + Weight Loss ++++

A variety of new surgical approaches as well as space occupying devices

Questions?

ckessler@maranatha.net