Treatment of obesity (and diabetes) Prof. Francesco Rubino Chair of Bariatric and Metabolic Surgery King's College London Consultant (Hon) Surgeon King’s College Hospital
Treatment of obesity (and diabetes)
Prof. Francesco Rubino
Chair of Bariatric and Metabolic SurgeryKing's College London
Consultant (Hon) SurgeonKing’s College Hospital
Obesity Diabetes
How Big is the Problem ?
We think we know
We do not know what
causes obesity or diabetes
How Big is the Problem?
MisconceptionsStigma, discrimination
Failure to prevent and treat
MISCONCEPTIONS
Lifestyle vs BiologyConventional Wisdom vs Science
Body Weight Regulation
Non-surgical treatments of ObesityWhy is it so hard to lose weight ?
OBESITY:
RISK FACTOR, CONDITION OR DISEASE?
Cultural Barriers/ Misperceptions
Risk Factor Disease
Lifestyle Modification Is complementary
Surgery, Radiotherapy,Chemotherapy
Treatments Considered Rationale
Smoking Cancer
>
Physiologic Alterations or Mild Dysfunction;
“Pre-disease”Disease state
Physiology, Pre-disease, Disease State
“Point of No Return”
Severe Obesity (i.e. BMI >40kgm2)
Depressed Mood
Increased Body Weight (mild/temporary)
Clinical Depression
Mild Hyperthermia Fever
Bronchitis/Inflammation Lung Cancer
• Lifestyle Modifications• Mechanical/Physical Remedies• ‘Over the counter drugs”
Medical Interventions(drugs, surgery, radiotherapy etc)
How we Define “Disease State” in
Obesity
(and so, when should it be treated)?
Hazard ratios for all-cause mortality based on different levels of body mass index (BMI) at baseline and during follow-up among black and white patients with type 2 diabetes mellitus.
Wenhui Zhao et al. Circulation. 2014;130:2143-2151
Copyright © American Heart Association, Inc. All rights reserved.
A significantly increased risk of all-cause mortality was observed among blacks with BMI <30 kg/m2 and ≥35 and among whites with BMI <25 kg/m2 and ≥40 kg/m2 compared with patients with BMI of 30 to 34.9 kg/m2
Physiologic Alterations or Mild Dysfunction;
“Pre-disease”Disease state
Physiology, Pre-disease, Disease State
“Point of No Return”
Severe Impairment of QoLObesity (i.e. BMI >40kgm2)
Increased Body Weight (mild/temporary)
Pre-diabetes Diabetes
Insulin resistance Metabolic Syndrome/ Cardiometabolic disease
• Lifestyle Modifications• Mechanical/Physical Remedies• ‘Over the counter drugs”
Medical Interventions(drugs, surgery, radiotherapy etc)
PREVENTION VS TREATMENT
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Misperception of bariatric surgery
Obesity
The Missing Link between Obesity and Diabetes
Diabetes
The XX century model of Diabetes Pathophysiology
Increases in BMI greatly affect the relative risk of developing Type 2 diabetes
Astrup, 2001 (Public Health Nutrition)
Association vs Causation
A
B
1. A B
2. B A
A3. C
B
t2dm
BMI
1. Obesity T2DM
2. t2dm Obesity
Obesity
3. X (IR?) Diabetes
Clinical Observations• Although the vast majority of
patients with T2DM are obese or overweight, the vast majority of overweight and obese patients are not diabetic
• 25-30-% of (severe) morbidly obese patients are diabetic
• Diabetes Prevalence in super obese patients (BMI >50) is lower than in pts with BMI 30-50 – UK National registry of bariatric surgery
BMI
t2dm
3025 50
?
Signs and Symptoms of Disease
Infection
Fever Coughing
Pneumonia
Signs and Symptoms of Disease
Metabolic Dysfunction
Increased Adiposity/Weight Gain
Hyperglycemia
T2DM
Criteria Ex-Juvantibus
Liposuction
Omentectomy
GI Surgery
No remission of T2DM
Durable Remission of T2DM
No remission of T2DM
…a square peg in a round hole”
“Obesity causes diabetes” ?
Obesity
Bariatric Surgery vs
Metabolic (Diabetes) Surgery
Diabetes
Benefits of Surgery in Patients with T2DM
Improvement of Glycemia
Chance of Disease Remission
Reduction of CVD and Mortality Risk
Reduction of Complexity of Medical Rx
Improvement QoL Cost-Effectivenes
s
F. Rubino. Nature 533, 459-–461 (2016).
RCT comparing surgery vs medical therapy not acceptable by IRBs
1999
F. Rubino Nature 533, 459-–461 (2016).
Diabetes-focused studies
RCTs
BBC
0.3 to 1% of suitable candidates have access to surgical treatment for diabetes
35
Obesity/Weight Problem
Diabetes
Obesity Rx
Diabetes Rx
2nd DIABETES SURGERY SUMMIT (DSS-II)London, Sept 2015
2nd Diabetes Surgery Summit (DSS-II) International Guidelines Endorsed by 47 worldwide organizations
June 2016
GI Surgery Becomes a Standard Treatment Option for Type 2 Diabetes
All Available Randomized Clinical Trials (11) Show Superiority of Surgery compared to Conventional Treatment for Type 2
Diabetes
Rubino et al. Diabetes Care 2016
RYGB induces system-wide physiological changes
Insulin sensitivity
Bile Acids
Intestinal Glucose Metabolism
Glucose TransportersNutrient Sensing
Gut Hormones
Gut Microbiota
Insulin secretionInsulin sensitivity
Energy expenditure Gut hormone secretion Microbiota composition
GI Mechanisms of Metabolic Regulation
Insulin sensitivity in Liver
Insulin sensitivity Lowering Blood Sugar Levels
Other unknown mechanisms?
45 ENDORSING SOCIETIES(currently 49!!)
The largest endorsement for New guidelines by scientific societies in medical history
42
In 2016, metabolic surgery was incorporated into clinical guidelines endorsed by major diabetes and surgical societies across the world
American Diabetes AssociationAmerican Assoc. of Clinical EndocrinologistsAmerican Gastroenterological Assoc.American College of SurgeonsAmerican Society for Metabolic and Bariatric SurgerySociety of American Gastro and Endoscopic SurgeonsSociety for Surgery of the Alimentary TractThe Obesity Society
Czech Society for the Study of Obesity
Chinese Diabetes Society
Argentine Society of DiabetesArg Soc for Bariatric and Metab Surg
Australian Diabetes Society
Diabetes UKAssoc of British Clin DiabetologistsSociety for Endocrinology
Brazilian Soc of DiabetesBrazilian Soc of Bariatric and Metab Surg
Chilean Soc for End and DiabetesChilean Soc for Bar and Metab Surg
Global:
• International Diabetes Federation• International Federation for the Surgery
of Obesity and Metabolic Disorders• European Assoc for the Study of Obesity
Saudi Diabetes & Endocrine Assoc
Qatar Diabetes Assoc
Mexican College of Bariatric SurgeonsMexican Soc of Nutrition and Endocrinology
Belgian Diabetes Assoc
French Soc of DiabetesFrench Soc of Bariatric and Metab Surgery
Israel Diabetes Assoc
Italian Soc of Bar and Metab SurgItalian Soc of Diabetology
South African Soc for SurgeryObesity and Metabolism
Japan Diabetes SocietySpanish Soc for Bar and Metab SurgerySpanish Soc of Diabetes
Diabetes India
German Diabetes SocietyGerman Soc for Obesity Surgery
Hellenic Diabetes Assoc
Asia Pacific Bariatric & Metab Surgery Society
Latin America Assoc of Diabetes
January 2017:The American Diabetes Association (ADA) introduces surgery in the Standards of Medical Care for Diabetes
“One of the most radical changes in the treatment of diabetes in almost a century” -
“One of the most significant changes in treating diabetes since the discovery of insulin in 1921”
“The conclusion that Surgery should be considered a mainstream response is unavoidable”