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

19

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”