gemma frühbeck-lo último en obesidad
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Gema Frühbeck Dept. Endocrinology & NutritionMetabolic Research Laboratory
Pamplona, Spain
Outcomes of bariatric surgery on obesity and its complications
Critical analysis: Need for a paradigm shift
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
Procedures
Restrictive
Malabsorptive
Mixed
GastroplastiesGastric bandingSleeve gastrectomy
Gastric bypassBiliopancreatic div.Duodenal switch
Types of bariatric surgery
Comorbidities. .
Low self-esteem;psychosocial problems
Stroke
Sleep apnoe;hypoventilationHypertension;
coronary heart disease
Steatohepatitis
Gallbladder disease
DyslipidaemiaInfertility
Osteoarthritis
Diabetes mellitus
Atherosclerosis;thromboembolism
Gout
Gastro-oesophagic reflux
Urinary incontinence
Hiatus hernia
Cancer
Life expectancyMortality{
Sjöström, J Intern Med 2013
Percentage weight change in SOS trial
Sjöström, J Intern Med 2013
Cumulative diabetes incidence in SOS trial
Control NO profControl prof
VBGBandingGBP
P<0.001
Sjöström, JAMA 2012
Fatal cardiovascular events Total cardiovascular events
CVD first cause of mortality in both groupsDecreased after bariatric surgery
Cumulative mortality in SOS trial
Effect on cancer incidence in SOS study
Sjöström et al. Lancet Oncol 2009
Decreased cancer incidence following bariatric surgery,but only significant in women
Increased incidence in comparison to the one observed after 2 yearsMaintenance 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
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 yearsbetween control and bariatric surgery groups
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
AGB
RYGB
BPDDS
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 improvementAbsolute HbA1c resol.
30-40%Mean weight loss
3.8%
Excess weight loss
T2D resolution T2D improvementAbsolute HbA1c resol.
Mean weight loss 25-35%
2.1-2.9%
Excess weight loss
T2D resolution T2D improvementAbsolute HbA1c resol.
Mean weight loss 15-30%
Excess weight loss
T2D resolution T2D improvementAbsolute 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 parallelwith weight loss
Quick, prior tobody weight loss
Quick, prior tobody weight loss
Intermediate,rel. to weight loss
Mechanism beyond body weight loss
Ann Surg 2004Bariatric surgery therapeutic alternative to T2D ttm
Diabetes Surgery SummitConsensus Conference
Recomnendations for the evaluation and use of gastrointestinal surgery to
treatType 2 Diabetes Mellitus
Rubino et al on behalf of DSS Delegates Ann Surg 2010
Frühbeck, Nat Rev Endocrinol 2015
Clinical characteristics of patients relative to surgery
Lancet September 5, 2015
RCT comparison conv. vs RYGB vs BPD treatment over 5 y
Mingrone et al. Lancet 2015
Mingrone et al. Lancet 2015
RCT comparison conv. vs RYGB vs BPD treatment over 5 y
“BRAVE effects”Bile flow alterationReduction of gastric sizeAnatomical rearrangement - altered flow of nutrientsVagal manipulationEnteric hormone modul.
Ashrafian et al. Obesity Rev 2010
Foregut hypothesis Hindgut hypothesisMidgut hypothesis
Mechanisms of action underlying the resolution of type 2 diabetes
Hypothesis
Rubino et al. Annal Surg 2006
T2DM
?
Foregut hypothesis
Mechanisms of action underlying the resolution of type 2 diabetes
Gastric Inhibitory
Peptide(GIP)
“Anti-incretin” factor
Foregut hypothesis
Increasedtransit
Mechanisms of action underlying the resolution of type 2 diabetes
Non obesediabetic
rat
DiabetesResolution
Reappearance of diabetes
Effects of intraluminal devices
EndobarrierEndobarrierperforated
Midgut hypothesis
“Hepato-portal sensing”
Mechanisms of action underlying the resolution of type 2 diabetes
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 gluconeogenesisIncreased 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
Hindgut hypothesis
GLP-1 PYY
Mechanisms of action underlying the resolution of type 2 diabetes
GLP-1 Gastric Bypass >> Gastric Banding
Le Roux. Ann Surg 2006
Rodieux. Obesity 2008
GBPG banding
LeanObese
GBP
G banding
GBP
G banding
GBPG banding
Wilson-Perez et al. Diabetes 2013
GLP-1
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
* anatomical
* hormonal
* neural
* secretory * absorptive
* microbiological
Underlying mechanisms of action
Fasting, caloric restriction
Bile acidsmetabolism
Gastrointestinalhormones
Other signalshepatoportal Changes in
microbiota
Weight loss
Inflammation
Adiposity
Vagalstimulacion
Intestinalgluconeogenesis
Insulinresistance
Frühbeck (in preparation)
Integrated Medical/SurgicalDiabetes Care Algorithm
DSS-II Consensus
• Perspectives
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 fatIncrease in adiposity after 2 years of performing the gastric bypass
METABOLICSurgery
BARIATRICSurgery
BMI 30-35 kg/m2 BMI > 35-40 kg/m2BMI 35 kg/m2
Frühbeck, Nat Rev Endocrinol 2015
Eligibility criteria separation based on BMI
BMI 30-35 kg/m2 BMI > 35-40 kg/m2BMI 35 kg/m2
Dysfunctional adiposity
METABOLICSurgery
BARIATRICSurgery
Frühbeck, Nat Rev Endocrinol 2015
Eligibility criteria separation based on BMI blurred by adiposity
Bariatric surgery eligibility according to body fat
HbA1c
Gómez-Ambrosi et al. Obes Surg 2015
Lean
BMI<35 H
F
BMI35-40
com
BMI>400
50
100
150
200
250
300
350m
g/dL
Lean
BMI<35 H
F
BMI35-40
com
BMI>400
50
100
150
200
250
300
350
mg/
dL
**** ***
†
*** ******
Triglycerides Triglycerides
CRP CRP
Lean
BMI<35 H
F
BMI35-40
com
BMI>40
-0.5
0.0
0.5
1.0
1.5
2.0
Lean
BMI<35 H
F
BMI35-40
com
BMI>40-0.5
0.0
0.5
1.0
1.5
2.0*********
¶¶
*******
†††¶¶
Bariatric surgery eligibility according to body fat
Frühbeck et al. Diabetes 2014
Habegger et al. Diabetes 2014
Response to GLP1 receptor agonistpredicts glycemic control after RYGB
Calculation of DiaRem score for prediction of T2D remission
Still et al. Lancet Diabetes Endocrinol 2014
CUN – Compl. Hosp. Nav.
Javier SalvadorCamilo SilvaPatricia IbañezNeus VilaMª Ang. MargallSonia Romero
Metabolic Research Laboratory Javier Gómez AmbrosiAmaia RodríguezVictoria CatalánLeire Méndez
Sara BecerrilBeatriz RamírezAndoni LanchaSilvia Ezquerro
AcknowledgmentsMultidisciplinary Obesity Team
Víctor ValentíFernando Rotellar
Rafael MoncadaJavier A.
CienfuegosMª Jesús Gil
Ana ZugastiEstrella Petrina
Amelia Marí
Changes in bile acid & cholesterol physiology in ileal interposition
Kohli R et al. Am J Physiol Gastrointest Liver Physiol 2010
GLOBAL WEIGHT
LOSS
HORMONAL CHANGES
FAT MASS
DECREASE
Weight loss-dependent
Weight loss-independent Adiposity-dependent
Respiratory functionObstructive sleep apneaGastroesophageal reflux
Psycho-social alterationsHealth-related quality of life
Osteoarthritis and joint problems
Type 2 diabetesDyslipidemia
Non-alcoholic fatty liver diseaseCardiovascular diseasesLow-grade inflammation
HypertensionCancer