'Lo último en obesidad'. Este es el título del Simposio Internacional que organizamos en la Fundación Ramón Areces los días 1 y 2 de diciembre de 2015. En colaboración con la Fundación General CSIC, reunió a algunos de los mayores expertos en la materia para analizar cómo reducir este grave problema de salud pública.

1. Gema Frühbeck Dept. Endocrinology & Nutrition
Metabolic Research Laboratory
Pamplona, Spain
Outcomes of bariatric surgery on
obesity and its complications
Critical analysis: Need for a paradigm shift

2. Outline
• Types of surgical procedures
• Impact of bariatric surgery
• Lessons learnt
• Future perspectives
• Classic effects
• Degree of resolution
• Temporal pattern
Metabolic surgery
• Human series
• Experimental models
• Need for a paradigm shift

3.  Procedures
Restrictive
Malabsorptive
Mixed
Gastroplasties
Gastric banding
Sleeve gastrectomy

Gastric bypass
Biliopancreatic div.
Duodenal switch


Types of bariatric surgery

4. Comorbidities
. .
Low self-esteem;
psychosocial problems
Stroke
Sleep apnoe;
hypoventilationHypertension;
coronary heart disease
Steatohepatitis
Gallbladder disease
Dyslipidaemia
Infertility
Osteoarthritis
Diabetes mellitus
Atherosclerosis;
thromboembolism
Gout
Gastro-oesophagic reflux
Urinary incontinence
Hiatus hernia
Cancer
Life expectancy
Mortality{

5. Sjöström, J Intern Med 2013
Percentage weight change in SOS trial

6. Sjöström, J Intern Med 2013
Cumulative diabetes incidence in SOS trial
Control NO prof
Control prof
VBG
Banding
GBP
P<0.001

7. Sjöström, JAMA 2012
Fatal cardiovascular events Total cardiovascular events
CVD first cause of mortality in both groups
Decreased after bariatric surgery
Cumulative mortality in SOS trial

8. Effect on cancer incidence in SOS study
Sjöström et al. Lancet Oncol 2009
Decreased cancer incidence following bariatric surgery,
but only significant in women

9. Increased incidence in comparison to the one observed after 2 years
Maintenance of significant differences after 10 years vs control group
Sjöström et al. N Engl J Med 2004
Follow-up of comorbidity changes in the SOS
CONTROL GROUP BARIATRIC SURGERY

10. Follow-up of comorbidity changes in the SOS
Sjöström et al. N Engl J Med 2004
CONTROL GROUP BARIATRIC SURGERY
Lack of significant differences in incidence at 2 and 10 years
between control and bariatric surgery groups

11. Sjöström et al. N Engl J Med 2004
Long-term maintenance of significant differences between
control and bariatric surgery groups
CONTROL GROUP BARIATRIC SURGERY
Follow-up of comorbidity changes in the SOS

12. AGB
RYGB
BPD
DS
0 10 20 30 40 50 60 80 90 10070Change/Resolution (%)
52.5%
67.5%
75%
83.7%
47.9%
98%
80.8%
93%
77%
Excess weight loss
.
T2D resolution
T2D improvement
Absolute HbA1c resol.
30-40%Mean weight loss
3.8%
Excess weight loss
T2D resolution
T2D improvement
Absolute HbA1c resol.
Mean weight loss 25-35%
2.1-2.9%
Excess weight loss
T2D resolution
T2D improvement
Absolute HbA1c resol.
Mean weight loss 15-30%
Excess weight loss
T2D resolution
T2D improvement
Absolute HbA1c resol.
Mean weight loss
1.8%
55%
47%
75%
20-30%
2.5-2.9%
SG
Effects of type of surgery on body w. & T2D resolution
Frühbeck, Nat Rev Endocrinol 2015
Temporal pattern
Slow, in parallel
with weight loss
Quick, prior to
body weight loss
Quick, prior to
body weight loss
Intermediate,
rel. to weight loss
Mechanism beyond
body weight loss

13. Ann Surg 2004
Bariatric surgery therapeutic alternative to T2D ttm

14. Diabetes Surgery Summit
Consensus Conference
Recomnendations for the evaluation and use
of gastrointestinal surgery to treat
Type 2 Diabetes Mellitus
Rubino et al on behalf of DSS Delegates Ann Surg 2010

15. Frühbeck, Nat Rev Endocrinol 2015
Clinical characteristics of patients relative to surgery

16. Lancet September 5, 2015

17. RCT comparison conv. vs RYGB vs BPD treatment over 5 y
Mingrone et al. Lancet 2015

18. Mingrone et al. Lancet 2015
RCT comparison conv. vs RYGB vs BPD treatment over 5 y

19. “BRAVE effects”
Bile flow alteration
Reduction of gastric size
Anatomical rearrangement
- altered flow of nutrients
Vagal manipulation
Enteric hormone modul.
Ashrafian et al. Obesity Rev 2010

20. Foregut hypothesis Hindgut hypothesisMidgut hypothesis
Mechanisms of action underlying the
resolution of type 2 diabetes
Hypothesis

21. Rubino et al. Annal Surg 2006
T2DM
?
Foregut hypothesis
Mechanisms of action underlying the
resolution of type 2 diabetes

22. Gastric
Inhibitory
Peptide
(GIP)
“Anti-incretin”
factor
Foregut hypothesis
Increased
transit
Mechanisms of action underlying the
resolution of type 2 diabetes

23. Non obese
diabetic
rat
Diabetes
Resolution
Reappearance of
diabetes
Effects of intraluminal devices
Endobarrier
Endobarrier
perforated

24. Midgut hypothesis
“Hepato-portal sensing”
Mechanisms of action underlying the
resolution of type 2 diabetes

25. Midgut hypothesis
Increased expression of the bile acid
transporter BSEP via activation of the
coactivator SRC-2, & subsequent
increase in biliar secretion
AMPK stimulates absorption of lipids
Intestinal gluconeogenesis
Increased activity & protein levels of
neoglucogenic enzymes (G6Pasa &
PEPCK) elevated in EA
Increased production intestinal glucose
Mechanisms of action underlying the
resolution of type 2 diabetes

26. Hindgut hypothesis
GLP-1 PYY
Mechanisms of action underlying the
resolution of type 2 diabetes

27. GLP-1
Gastric Bypass >> Gastric Banding
Le Roux. Ann Surg 2006
Rodieux. Obesity 2008
GBP
G banding
Lean
Obese
GBP
G banding
GBP
G banding
GBP
G banding
Wilson-Perez et al. Diabetes 2013
GLP-1

28. Hindgut hypothesis
Mechanisms of action underlying the
resolution of type 2 diabetes
Ileal
transposition Ahima & Carr, Gastroenterology 2010
Cummings et al, Gastroenterology 2010
• produced in intestinal L cells
• secr. in resp. to calorie intake
• inhib. GI motility & secr. pancr/int.
• produces satiety & dism. intake
• low PYY production in obese indiv.
PYY

29. * anatomical
* hormonal
* neural
* secretory * absorptive
* microbiological
Underlying mechanisms of action

30. Fasting, caloric restriction
Bile acids
metabolism
Gastrointestinal
hormones
Other signals
hepatoportal Changes in
microbiota
Weight loss
Inflammation
Adiposity
Vagal
stimulacion
Intestinal
gluconeogenesis
Insulin
resistance
Frühbeck (in preparation)

31. Integrated Medical/Surgical
Diabetes Care Algorithm
DSS-II Consensus
• Perspectives

32. Evolución comparativa entre IMC y porcentaje de grasa corporal
BMI (kg/m2) % Body fat
Comparison of changes in BMI and body fat
following RYGB in the CUN
More profound changes in BMI than in body fat
Increase in adiposity after 2 years of performing the gastric bypass

33. METABOLIC
Surgery
BARIATRIC
Surgery
BMI 30-35 kg/m2 BMI > 35-40 kg/m2BMI 35 kg/m2
Frühbeck, Nat Rev Endocrinol 2015
Eligibility criteria separation based on BMI

34. BMI 30-35 kg/m2 BMI > 35-40 kg/m2BMI 35 kg/m2
Dysfunctional adiposity
METABOLIC
Surgery
BARIATRIC
Surgery
Frühbeck, Nat Rev Endocrinol 2015
Eligibility criteria separation based on BMI blurred by
adiposity

35. Bariatric surgery eligibility according to body fat
HbA1c
Gómez-Ambrosi et al. Obes Surg 2015

36. Lean
B
M
I<35
H
F
B
M
I35-40com
B
M
I>40
0
50
100
150
200
250
300
350
mg/dL
Lean
B
M
I<35
H
F
B
M
I35-40com
B
M
I>40
0
50
100
150
200
250
300
350
mg/dL
*
***
***
†
***
***
***
Triglycerides Triglycerides
CRP CRP
Lean
B
M
I<35
H
F
B
M
I35-40com
B
M
I>40
-0.5
0.0
0.5
1.0
1.5
2.0
Lean
B
M
I<35
H
F
B
M
I35-40com
B
M
I>40
-0.5
0.0
0.5
1.0
1.5
2.0
***
***
***
¶¶
***
***
*
†††
¶¶
Bariatric surgery eligibility according to body fat

37. Frühbeck et al. Diabetes 2014
Habegger et al. Diabetes 2014
Response to GLP1 receptor agonist
predicts glycemic control after RYGB

38. Calculation of DiaRem score for prediction of T2D remission
Still et al. Lancet Diabetes Endocrinol 2014

39. CUN – Compl. Hosp. Nav.
Javier Salvador
Camilo Silva
Patricia Ibañez
Neus Vila
Mª Ang. Margall
Sonia Romero
Metabolic Research Laboratory
Javier Gómez Ambrosi
Amaia Rodríguez
Victoria Catalán
Leire Méndez
Sara Becerril
Beatriz Ramírez
Andoni Lancha
Silvia Ezquerro
Acknowledgments
Multidisciplinary Obesity Team
Víctor Valentí
Fernando Rotellar
Rafael Moncada
Javier A.
Cienfuegos
Mª Jesús Gil
Ana Zugasti
Estrella Petrina
Amelia Marí

40. Changes in bile acid & cholesterol physiology in ileal interposition
Kohli R et al. Am J Physiol Gastrointest Liver Physiol 2010

41. GLOBAL
WEIGHT
LOSSHORMONAL
CHANGES
Weight loss-dependent
Weight loss-independent Adiposity-dependent
Respiratory function
Obstructive sleep apnea
Gastroesophageal reflux
Psycho-social alterations
Health-related quality of life
Osteoarthritis and joint problems
Type 2 diabetes
Dyslipidemia
Non-alcoholic fatty liver disease
Cardiovascular diseases
Low-grade inflammation
Hypertension
Cancer