PowerPoint Presentationquestions, and some answers
HENRY VIII
The expanding girth of Henry VIII Age 25: 32” Age 45: 52”
The Seven Deadly Sins Hieronymus Bosch
gluttonygluttony
Socioeconomic Disparity in Obesity Prevalence
Among American Adolescents (NHANES)
Parent high school education or less Parent college education or more
97 loci from >300,000 subjects account for
< 3% of BMI variation
Most obesity SNP variants located in
genes expressed in CNS
Obesity Epidemic
1984 USDA Food Guide Pyramid
Glycemic Index A physiological basis for classifying
carbohydrate
Area under the glycemic curve after consumption of 50 g CHO from test
food divided by area under curve after 50 g CHO from control food
B
Time (hr)
Soy beans
White bread
m m
Time (hr)
Low GI
Med GI
High GI
Time (hr)
GI & Regulation of Food Intake
Ludwig et al. Pediatrics, 103:e261. (1999)
Low GI
Med GI
High GI
(Time hr)
Time (hr)
Ludwig et al. Pediatrics, 103:e261. (1999)
-10
0
10
20
30
40
50
60
E
Time (hr)
Time (hr)
Low GI
Med GI
High GI
Ludwig et al. Pediatrics, 103:e261. (1999)
0
500
1000
e d
Time (hr)
High GI
Med GI
Low GI
Ludwig et al. Pediatrics, 103:e261. (1999)
Low Glycemic Load
Increasing Adiposity: Consequence or Cause of Overeating?
Ludwig et al. JAMA. 311:2167. (2014)
Insulin secretion
Insulin secretion
Treatment
Low Glycemic
Index Diet;
Ebbeling et al. NEJM. 367:1407 (2012)
Hispanics: Greater benefit of low GI Diet, possibly due to higher insulin response?
Common or rare genetic
Modified from O’Rahilly et al. Nat Med, 10:351, 2004
αMSH
Npy
αMSH
Modified from O’Rahilly et al. Nat Med, 10:351, 2004
αMSH
Npy
αMSH
Human LEP Mutation
Metabolism 102: 461–464, 2011
αMSH
Npy
αMSH
Human POMC Mutation
Human MC4R Mutation
Adrenal-MC2R
αMSH
Npy
αMSH
MRAP2?
Asai et al. Science 341, 275, 2013
-3 -2 -1 0 1 2 0
100
200
300
400
500
600
Mutations in MRAP2 in obese humans
Rare (loss of function) mutations important biology
More common mutations important pathophysiology?
Rationale for Metabolic Surgery in Adolescents
• Curative and preventive strategy
available
-(e.g., Type 2 DM, Severe NASH, Pseudotumor, Severe OSA)
• Severe Obesity BMI > 40 + co-morbidities
• Mature, motivated adolescent
• Failed a 6 month organized weight loss program
• Near complete linear growth
• If psychological problem, stable and in treatment
Available Surgical Options
• No definitive data supporting effectiveness and safety in
adolescents
Nicholas Stylopoulos
After Gastric Bypass
Increased Glucose Uptake in the Roux Limb of RYGB
• Pharmaceuticals on market – Orlistat, Xenical (Roche). Pancreatic lipase inhibitor
• Steatorrhea
Serotonin HT2c receptor agonist. 3% weight loss over
placebo.
– Topiramate-phentermine, Qsymia (Vivus). ADULTS
loss over placebo.
Pharmacotherapy for Obesity
Pharmacotherapy for Obesity
Nonselective serotonin receptor agonist-catecholamine
– (Sibutramine, Meridia, 2010). Serotonin reuptake inhibitor.
• Heart attack, stroke
production.
• Concern about cardiovascular toxicity. FDA requires very large outcomes study prior to approval.
– SR01. Leptin sensitizer (ERX, Umut Ozcan, BCH).
• Preclinical. Mice, monkeys
Pharmacotherapy for Obesity
than a lifestyle choice
coverage manual saying obesity was not a disease
(but Medicare Part D denies drug coverage).
• 2013: AMA recognized obesity as a disease.
– Should allow payment for obesity-related care
• Diagnostic evaluations