Internal Medicine

1. Obesity Update 2014
Susan S. Beland, M.D.
Associate Professor
General Internal Medicine

2. The Case
 35-year-old woman
 5’4” tall, weight 190 lbs (BMI = 32.6 kg/m2)
 BP 150/100
 FBS 240, HbA1C 8.5%
 LDL 180
 Strong family history of diabetes, HTN, and CHD
 Referred to dietician, started on lisinopril, metformin,
and statin; also instructed to begin a walking program.
 We can treat these problems, but how successful will we
be on changing her underlying problem of obesity?

3. History of Obesity
 Term “obesity” does not appear in English language
until the 17th century.
 Prior to modern times, corpulence was associated
with power and influence.
 Art in Middle Ages and Renaissance portrays
statuesque women (Michelangelo and Rubens).
 In literature, the corpulent were portrayed as jolly
and lovable.
 Not until the latter half of the 20th century did obesity
become stigmatized.

4. History of Obesity (Cont.)
 Burden of disease was that of pestilence and famine for
early hunter-gatherers in prehistoric times.
 Natural selection rewarded the “thrifty” genotypes of
those who could store the greatest amount of fat.
 Discovery of agriculture and domestication of animals
gradually reduced the precarious food supply.
 Hunger remained and the Bible is filled with food
imagery (promise of a land of milk and honey, etc.).

5. Obesity in Art and Literature
“Let me have men about me
that are fat, sleek-headed men
and such as sleep a nights.
Yon Cassius has a lean and
hungry look. He thinks too
much.”
Julius Caesar, Shakespeare
“Falstaff sweats to
death, and lards the lean
earth as he walks along”
Henry IV, Shakespeare

6. Obesity in Art and Literature
“But wait a bit,” the Oysters
cried, “before we have our chat.
For some of us are out of breath,
and all of us are fat!”
“Through the Looking Glass”, Lewis Carroll
“No woman can
ever be too rich or
too thin.”
Duchess of Windsor

7. NY Times 1894

8. Definition of Obesity
Body Mass Index (BMI; kg/m2) is the most helpful
measure:
 Underweight = <18.5
 Normal BMI = 20.0 - 24.9
 Overweight = 25.0 - 29.9
 Class I = 30.0 - 34.9
 Class II = 35.0 - 39.9
 Class III = >40.0

9. Complications of Obesity
 Hypertension
 Hyperlipidemia
 Metabolic syndrome
 Coronary heart disease
 Type II diabetes
 Respiratory disease (OSA)
 Gastrointestinal disease (NAFLD and NASH)
 Cancer
 Rheumatologic disease (osteoarthritis, gout)
 Psychiatric
 Increased risk of mortality

10. Geographic Distribution of Obesity

11. Geographic Distribution of Smokers

12. Demographics of Obesity
 Results from 2011-12 National Health and Nutrition
Examination Survey (NHANES).
 9100 participants in cross-sectional national surveys.
 Last survey completed in 2003-04.
Odgen et al., JAMA 311:806-814 (2014)

13. Demographics of Obesity
Overweight or obese Obese
White men 72.7% 33.4%
Black men 69.1% 37.0%
Hispanic men 77.9% 40.1%
White women 64.6% 33.7 %
Black women 82.1% 56.7%
Hispanic women 76.2%
43.3%
Overall 33.7% of men and 36.5% of women were obese,
and 6.4% overall had class III obesity.
No significant increase since the last survey in 2003-04.

14. Body-Mass Index and Cause-Specific
Mortality in 900,000 Adults: Collaborative
Analyses of 57 Prospective Studies
 900,000 participants, primarily from Western Europe
and North America.
 Mean age 46.
 Analysis adjusted for age, sex and smoking status.
 Mortality lowest at BMI of 22.5 - 25.0.
 BMI 30 - 35, median survival reduced by 2 - 4 years.
 BMI 40 - 45, median survival reduced by 8 - 10 years.
 BMI < 22.5, excess mortality mainly due to smoking.
Prospective Studies Collaboration, Lancet 373:1083-1096 (2009)

15. Body-Mass Index and Cause-Specific
Mortality in 900,000 Adults: Collaborative
Analyses of 57 Prospective Studies (Cont.)
 Overall mortality for each 5 kg/m2 increase was 30%.
 40% for mortality due to vascular disease.
 60-120% for diabetic, renal and hepatic mortality.
 10% for neoplastic mortality.
 Obesity is approaching cigarette smoking as a
leading avoidable cause of premature death.
Prospective Studies Collaboration, Lancet 373:1083-1096 (2009)

16. Body-Mass Index and Cause-Specific
Mortality in 900,000 Adults: Collaborative
Analyses of 57 Prospective Studies (Cont.)
Cause-Specific Mortality Hazard ratio
(BMI 25-50)
Ischemic heart disease 1.39
Stroke 1.39
Diabetes 2.16
Kidney disease 1.59
Liver disease 1.82
Respiratory disease 1.20
All causes 1.29
Prospective Studies Collaboration, Lancet 373:1083-1096 (2009)

17. Obesity and Mortality
 In adult life, it may be easier to avoid substantial
weight gain than to lose weight.
 By avoiding a further increase from 28 kg/m2 to 32
kg/m2, a typical person in early middle age would
gain ~2 years of life expectancy, and avoiding an
increase from 24 kg/m2 to 32 kg/m2, a young adult
would on average gain ~3 extra years of life.

18. Childhood Obesity

19. Childhood Obesity
 Weight >85th percentile defines overweight, and
>95th percentile defines obesity in children (based
on standard CDC thresholds).
 2011-12 NHANES data:
 Overall, 31.8% of children between 2-19 years
old are overweight.
 16.9% are obese, with Hispanic (22.4%) and
black (20.2%) at greater risk.
Odgen et al., JAMA 311:806-814 (2014)

20. Childhood Obesity
 Data from the Early Childhood Longitudinal Study,
Kindergarten Class 1998-99.
 >700 participants followed through 8th grade.
 At entry (mean age 5.6 yrs) 12.4% were obese and
14.9% were overweight.
 By 8th grade (mean age 14.1 yrs) 20.8% were obese
and 17.0% were overweight.
 Overweight 5-year-olds were 4x as likely as normal
weight children to become obese.
Cunningham et al., NEJM 370:403-411 (2014)

21. Economic Costs of Obesity
 Data from US Medical Expenditure Panel Survey
 Impact on annual medical costs estimated to
be $3,613 for women and $1,152 for men.
 Estimate of costs of obesity-related illness is
$209.7 billion (in 2008 dollars).
 20.6% of US national health expenditures are
spent in treating obesity-related illness.
Cawley & Meyerhoefer, J Health Econ 31:219-230 (2012)

22. Leptin
 Control of body weight is complex, involving hormones
and neurotransmitters.
 Leptin and the OB gene were discovered in 1994.
 Secreted by adipocytes - signals brain to reduce food
intake.
 Mouse model.
 Not found to be of use clinically, as obese people have
increased leptin levels but are resistant to its effects.

23. There is No Magic Pill
FTC Cracks Down on Fad Weight-Loss Products

24. FDA-Approved Diet Pills
 Phentermine: Amphetamine-like action.
 Xenical (Orlistat).
 Contrave (Bupropion/Naltrexone).
 Qsymia (Phentermine/Topiramate).
 Belviq (Lorcacerin): 5HT receptor agonist.
 Concern over cardiovascular events with Qsymia and
Belviq. Post-marketing trials are not to be completed
until 2017.
 Meridia (Sibutramine) was one of the most popular pills
but was taken off the market due to cardiovascular risks.
 Fenfluramine/Phentermine (Fen-Phen) also banned due to
risk of pulmonary HTN and valvular heart disease.

25. FDA Approved Diet Pills (Cont.)
 None is approved for long-term use.
 Weight loss benefits modest at best.
 FDA approval only for BMI >30 (or BMI >27,
with a weight-related illness).

26. Diets and Weight Loss
 Many diet fads have come and gone over the years.
 General agreement that if dieting is going to work
long-term, weight loss must be accomplished slowly
and consistently.
 Diets only work if people adhere to them.
 “Miracle diets” that cause acute weight loss
invariably fail.
 Long-term success rates are low for many reasons:
 Set-point theory of weight control.
 Failure to make behavioral modifications.
 Adherence to restrictive regimens diminishes with
time.

27. Comparative Effectiveness of Weight-
Loss Interventions in Clinical Practice
 415 obese patients with at least one cardiovascular
risk factor recruited from primary care practices.
 Two behavioral interventions:
 Remote support through telephone, web site,
and email.
 In-person support with group and individual
sessions + the three remote means.
 Control group weight loss was self-directed.
 PCP’s had a supportive role and received regular
progress reports.
Appel et al., NEJM 365:1959-1968 (2011)

28. Comparative Effectiveness of Weight-
Loss Interventions in Clinical Practice
(Cont.)
Appel et al., NEJM 365:1959-1968 (2011)

29. Effects of Low-Carbohydrate and Low-
Fat Diets: A Randomized Trial
 147 adults with BMI 30 - 45.
 73 randomized to low fat diet (< 30% of intake).
 75 randomized to low carbohydrate diet (< 40
g/day).
 Total caloric intake was similar in each group.
 At 12 months, low carb group had significantly
greater weight loss (5.3 kg vs. 1.8 kg), increase
in HDL, and decrease in Framingham 10-year
CHD risk score.
Bazzano et al., Ann Intern Med 161:309-318 (2014)

30. Effects of Dietary Composition on
Energy Expenditure During Weight-Loss
Maintenance
 Maintaining significant weight loss over the long
term is problematic.
 Hypothesis is that weight loss leads to decline in
energy expenditure and an increase in hunger,
resulting in weight gain.
 Examined effects of 3 diets on energy expenditure
after weight loss.
 21 young adults with BMI >27.
 Run-in diets achieved 10-15% weight loss.
Ebbeling et al., JAMA 307:2627-2634 (2012)

31. Effects of Dietary Composition on
Energy Expenditure During Weight-Loss
Maintenance (Cont.)
 3 diets:
 Isocaloric low-fat (60% carbs, 20% fat, & 20% protein).
 Low-glycemic index (40% carbs, 40% fat, & 20%
protein).
 Very low carbohydrate (10% carbs, 60% fat, & 30%
protein).
 All participants were fed each diet in random order
for 4 weeks each.
 Resting energy expenditure (REE) measured by
indirect calorimetry.
Ebbeling et al., JAMA 307:2627-2634 (2012)

32. Effects of Dietary Composition on
Energy Expenditure During Weight-Loss
Maintenance (Cont.)
 Decrease from baseline REE was greatest in the low-fat
diet (-205 kcal/d).
 Low glycemic index diet decrease was -166 kcal/d.
 Very low carbohydrate decrease was -138 kcal/d.
 Total energy expenditure showed a similar pattern.
 Authors maintain that this study challenges the notion
that a calorie is a calorie from a metabolic perspective.
 Very low carbohydrate diets are likely not to work in
practice due to adherence issues.
 Moderate carbohydrate restriction seems to be of benefit.

33. Long-Term Persistence of Hormonal
Adaptations to Weight Loss
Caloric restriction results in reduction of
circulating leptin as well as other neuropeptides
that control appetite.
One year after initial weight reduction, levels of
these mediators of appetite that encourage
weight regain do not revert to the levels
recorded before weight loss.
Sumithran et al., NEJM 365:1597-1604 (2011)

34. Exercise and Weight Loss
 Exercise alone does not result in significant
weight loss.
 Increased activity should, however, be a part of
any weight loss strategy.
 NHANES data show that about 50% of all
Americans do not have any significant physical
activity.
 Even in the overweight and obese, exercise can
lower risks, especially for CHD.

35. The Sugar Connection
O
O
OH
OH
HO
OH
OH
OH
OH
O
HO
Glucose + Fructose
Sucrose

36. Sugar Intake and Obesity
Lustig et al., Nature 482:27-29 (2012)

37. Sugar Intake and Obesity (Cont.)
 Sugar consumption has tripled worldwide over the
past 50 years, primarily due to added sugars
 Sugar is added to nearly all processed foods, often in
the form of high fructose corn syrup.
 High fructose corn syrup is composed of 55%
fructose, which is not vastly different from sucrose.
 There is growing evidence that fructose intake is
linked to several chronic diseases:
 Metabolic syndrome
 Obesity
 Hypertension
 Dyslipidemia
 Hepatic dysfunction (NASH)

38. Metabolism of Glucose and Fructose
Glucose
Insulin
Liver
Glucose-6-phosphate
Glycogen
80% Brain and muscle
2% Pyruvate Acetyl CoA
FFA’s
VLDL
Glucokinase

39. Metabolism of Glucose and Fructose
(Cont.)
Fructose (Nearly all ingested
fructose goes to the
liver)
Liver
(Only a small amount of
fructose is converted to
glycogen under normal
circumstances)
Fructose-1-phosphate
Pyruvate Acetyl CoA de novo
lipogenesis
Fructokinase

40. Fructose: It’s “Alcohol Without the Buzz”
 Ethanol enters the liver through osmosis, and is
metabolized to acetaldehyde
 This can generate reactive oxygen species
 Large doses of ethanol result in metabolism to
acetyl CoA and the generation of FFA’s
 “The dose determines the “poison”of either
ethanol or fructose, since both uniquely drive de
novo lipogenesis, leading to fatty liver,
inflammation, and insulin resistance.”
Lustig, Adv Nutr 4:226-235 (2013)

41. The Toxic Truth About Sugar
 Sugar consumption is linked to a rise in non-communicable
disease.
 Sugar’s effects on the body can be similar to
those of alcohol.
 Regulation could include tax, limiting sales
during school hours, and/or placing age limit
on purchases.
Lustig et al., Nature 482:27-29 (2012)

42. Nation’s First Soda Tax Is Passed
 Berkeley, Calif., became the first U.S. city to pass a
law taxing sugary drinks including sodas.
 More than three-quarters of the votes cast were in
favor of Measure D, according to the Alameda
County Registrar of Voters. The measure will place a
1-cent-an-ounce tax on soft drinks.
 In nearby San Francisco, city voters rejected a
similar measure to tax sugary drinks.
USA Today 5 Nov 14

43. F Stands for Fructose and Fat
 In overweight humans, diet high in fructose (25%
of total caloric intake) promotes development of
the metabolic syndrome.
 Mice lacking the enzyme fructokinase are
incapable of processing fructose.
 Wild type mice fed a Western diet (high in fat and
sucrose) developed severe non-alcoholic
steatohepatitis, while the mice lacking
fructokinase did not.
Lyssiotis & Cantley, Nature 502:181-183 (2013)

44. Storm Brewing Over WHO Sugar
Proposal
Industry Backlash Expected Over Suggested Cut
12-ounce serving of Coke
contains 38 grams of sugar
and 140 calories
1 g ≈ 4 cal
1 teaspoon ≈ 4 g = 16 cal
Owens, Nature 507:150 (2014)
in Intake

45. WHO Sugar Proposal (Cont.)
 In 2003, proposed guideline that no more than 10%
of daily calories should come from sugar.
 Current proposal cuts this in half to 5%, citing the
need to fight obesity.
 Sugar in the average person should only account
for 100 cal/day which translates to ~26 grams or 6
teaspoons
 Opposed by the food industry – “If people follow
this advice, that would be very bad for business”.
Owens, Nature 507:150 (2014)

46. WHO Sugar Proposal (Cont.)
Owens, Nature 507:150 (2014)

47. Summary
 One-third of Americans are obese.
 Obesity has a significant impact on morbidity and
mortality, approaching that of cigarette smoking.
 Diets work only if adhered to and lifestyle is
modified.
 Long-term maintenance of weight loss remains
problematic.
 Obesity in children is increasing and fat children
tend to become fat adults.
 Sugar consumption is a major factor in obesity and
related diseases due to increased caloric intake and
the effects of fructose metabolism.
 There is no magic bullet - “We are what we eat.”

48. Comments or questions?