Evolving Treatment Strategies:
The Complexity of Energy Homeostasis
Artificial sweetners lead
to weight gain?
Energy Balance and Body Weight:
What is Metabolism?
Energy In
(Caloric Intake)
Body Weight
Energy Out
(Metabolism)
Energy Homeostasis:
The Quick Fix?
The Diet Strategy
Failure Rate of Diet Alone 90-98%
New Set Point
Baseline
Weight
↓ 5-10%
Counter-Regulation
Weight Management
Counter-Regulation and the Failure of the “Diet” – HCG Diet
Weight Loss
Counter-Regulation and the Failure of the “Diet” –
Ideal Protein
308
295
Ideal Protein Diet
↓ 28%
211
Fatigue, Depression, Fibromyalgia,
Sleep Disorder,
“Must be something hormonal”
Energy Balance and Body Weight:
What is Metabolism?
Energy In
(Caloric Intake)
Body Weight
Energy Out
(Metabolism)
Low Metabolism
How Do I Fix It? – “Get Your Ducks in a Row”
• Sleep Problems – Sleep Apnea
• Vitamin D Deficiency
• Thyroid
• Vitamin B12
• Low Testosterone (male)
• Medications (centrally acting)
Energy Homeostasis:
The Miracle Pill?
Hormones
Energy Homeostasis:
The Search for the Magic Pill?
Mechanical
Weight
Loss Pills
Substrates
Qsymia
Belviq
Glucose
N=8,000
N=3,700 52-104
52-104weeks
weeks
Aminoacids
Free Fatty Acids
Contrave
Weight Loss:
Weight
Loss:(bupropionLipids
+
6.7-8.9%
overplacebo
placebo
naltrexone)
3-3.7%
over
70%loss
loss>5%
>5%
47%
Sibutramine
Gastric Distension
Empatic
Insulin
Leptin
Ghrelin
PYY
CCK
Adiponectin
Psychological
Pleasure
Reward
Visual
Olfactory
Taste
Rimonobant
(bupropion +
zonisamide)
Neural
Vagal Afferents
Dopamine, Cannabanoids
(Meridia)
Dosing:10mg
3.75/23mg,
Dosing:
BID 7.5/46mg, 11.25/69mg,
Norepinephrine, NPY
15/92mg
Serotonin, POMC,
GABA etc…
Phentermine
Tesofensine
Qsymia
4-8% Total body weight loss
(NS2330)
(phentermine +
topiramate)
Not sustainable
Topiramate
20-30% Non-response rate
(Topomax)
Belviq
Hypothalmus
Energy Balance Center
Lorcaserin (5HT2C)
The Ominous Octet – Treatment
Strategies
Islet b-cell
Decreased
Incretin Effect
Impaired
Insulin Secretion
Increased
Lipolysis
Islet a-cell
Surgery?
Increased Glucose
Reabsorption
Increased
Glucagon Secretion
Increased
HGP
Neurotransmitter
Dysfunction
Decreased Glucose
Uptake
ADA Clinical Practice Recommendations 2011:
Changing Treatment Paradigms
Energy Homeostasis:
A Role for Surgery?
X
Lap Band
Restriction of caloric intake
Gastric Bypass (Roux-En-Y)
Restriction of caloric intake
Malabsorption of nutrients
Gastric Bypass: Five Operations
CONFIDENTIAL
Gastric Bypass: Five Operations
1. Isolation of
gastric cardia
CONFIDENTIAL
Gastric Bypass: Five Operations
2. Exclusion of distal
stomach
CONFIDENTIAL
Gastric Bypass: Five Operations
3. Exclusion of
duodenum and
proximal jejunum
CONFIDENTIAL
Gastric Bypass: Five Operations
4. Exposure of distal
jejunum to
undigested
nutrients
CONFIDENTIAL
Gastric Bypass: Five Operations
5. Partial vagotomy
CONFIDENTIAL
Energy Homeostasis:
A Role for Surgery?
Sleeve Gastrectomy
Stomach becomes a “sleeve”
Alters signaling mechanisms
Independent glycemic effect
Metabolic Surgery: The STAMPEDE Trial
Type 2 DM, A1c > 7.0%, BMI 27 - 43
N = 150, single center, one surgeon
Intensive Medical Therapy
No
Surgery
Sleeve
Gastrectomy
Gastric
Bypass
Primary Outcome: Proportion with A1c < 6.0% at 12 months
Metabolic Surgery: The STAMPEDE Trial
Metabolic Surgery: The STAMPEDE Trial
THE END