Post on 18-Feb-2019
University of PisaUniversity of Pisa
School of MedicineSchool of Medicine
Dipartimento di Medicina Clinica e SperimentaleDipartimento di Medicina Clinica e Sperimentale
UniversitUniversitàà degli Studi di Pisadegli Studi di Pisa
Effetti endocrino-metabolici della chirurgia bariatrica:non solo calo
ponderaleMonica Nannipieri
Buchwald H et al, Am J Med, 2009
Weight and type 2 diabetes after bariatric surgery:systematic review and meta-analysis
Results: weight loss, surgical procedure, and diabetes resolution
Total Gastric Gastroplasty Gastric BPD/DSbanding bypass
% excess bw loss 55.9 46.2 55.5 59.7 63.6
% resolved overall 78.1 56.7 79.7 80.3 95.1
2 <years 80.3 55.0 81.4 81.6 94.0
2 >years 74.6 58.3 77.5 70.9 95.9
BPD/DS = bilio-pancreatic diversion/duodenal switch
Buse JB et al. Diab Care 2009
HbA1c < 6.5 %
Glycemia 100-125 mg/dl
HbA1c < 6.0 %
Glycemia < 100 mg/dl
↑ insulin sensitivity
and
↑ β-Cell Function
Cure
remission of the disease
(correction of disease mechanisms)
Metabolic EffectsMetabolic Effects
Insulin sensitivity and/or insulin Insulin sensitivity and/or insulin
secretion?secretion?
From Restrictive to Malabsorbitive From Restrictive to Malabsorbitive
SurgerySurgery
00
1010
2020
3030
4040
5050
6060
7070
8080
1515 2020 2525 3030 3535 4040 4545 5050 5555 60601515 2020 2525 3030 3535 4040 4545 5050 5555 6060
controls
gastric bypass
biliopancreatic diversion
Body mass index (kg.m-2)
Insu
lin s
ensi
tivity
(µm
ol. m
in-1
. kg-
1 )
Muscelli et al. Am J Med 2005;118:51-7
Insulin sensitivity after BPD vs RYGB
ββββ-cell Function in RYGB and DBP
Nannipieri M. Diabetes Care Submitted
Astiarraga B. JCEM 2013
ISR
(p
mo
l. min
-1.m
-2)
Plasma glucose (mmol/L)
0
100
200
300
400
500
600
700
5 7 9 11 13 15 17 19 21 23
Controls
T2D
before2 mos
12 mos
4 5 6 7 8 9 10 11 120
100
200
300
400
500
600
glucose (mM)
secr
etio
n (p
mol
/min
/m2 )
Sleeve Gastrectomy
post
pre
y1
4 5 6 7 8 9 10 11 120
100
200
300
400
500
600
glucose (mM)
secr
etio
n (p
mol
/min
/m2 )
Gastric by-pass
post
pre
y1
DIABETES DURATION
Clinical outcomes of diabetes according to duration of
T2DM prior to surgery.
Shimizu H, J Obes 2012
%
BMI AND DIABETES DURATION
How Important Is Weight Loss in the Resolution of Diabetes by
Bariatric Surgery?
Lebovitz HE, Obes Surg 2013
Predictive Factors of Type 2 Diabetes Remission 1
Year
After Bariatric Surgery
Robert M, Ob Surg 2013
Predicting the Glycemic Response to
Gastric Bypass Surgery in Patients
With Type 2 Diabetes
Dixon JB, Diabetes Care 2013
Remission of Type 2 Diabetes
When?
Predictors of successful sustained euglycemia
Retnakaran R, Zinman B, Diabetes, Obesity and Metabolism, 2012.
Baseline 45 days 1 year0
20
40
60
80
100
120
ß-c
ell
glu
cose
se
nsi
tivit
y(p
mo
l. min
-1. m
-2 .m
M-1
)
Insu
lin
se
nsi
tivit
y(m
l. min
-1. m
-2)
Early remitters
Late remitters
Non-remitters
0
100
200
300
400
500
600
Baseline 45 days 1 yearNannipieri M. et al, JCEM 2011
β-Cell Function and Insulin Sensitivity in the Remission
of Type 2 Diabetes after RYGB
p<0.0001
p<0.0005
p<0.02
GLP-1 in remitters and no-remitters
Minutes Minutes
(pg
/ml)
(pg
/ml)
Nannipieri M et al Diabetes Care, Submitted
Proposed mechanism of diabetes resolution after RYGB surgery.
Holst J J Diabetes 2011;60:2203-2205
Copyright © 2011 American Diabetes Association, Inc.
Intestinal
Gluconeogenesis
Hepato-portal
sensing
Intestinal
Gluconeogenesis
Hepato-portal
sensing
Ileal Brake
Gut Hormones
Ileal Brake
Gut Hormones
Fat metabolism
Adipokines
Fat metabolism
Adipokines
Bile
metabolism
Bile
metabolism
Gut microbiota
modulation
Gut microbiota
modulation
Metabolite shift
(systemic/local)
Metabolite shift
(systemic/local)
Nerve-mediated
effects
Nerve-mediated
effects
Starvation,
caloric restriction,
Weight loss
Starvation,
caloric restriction,
Weight loss
Mechanisms Facilitating T2DM Improvement/Resolution
Metabolic effects-Pancreas (enteroinsular
axis)
-Liver (hepatic glucose
production)
-Adipose tissue (Lipolysis)
-Muscle (insulin resistance)
Metabolic effects-Pancreas (enteroinsular
axis)
-Liver (hepatic glucose
production)
-Adipose tissue (Lipolysis)
-Muscle (insulin resistance)
Foregut Exclusion
Gut Hormones
Foregut Exclusion
Gut Hormones
GhrelinGhrelin
Effect of Weight Loss by Gastric Bypass Surgery Versus Hypocaloric Diet (10
days) on Glucose and Incretin Levels in Patients with Type 2 Diabetes
Laferrere B, JCEM 2008
OGTT 50 g
Isbell JM. et al Diabetes Care 2010
Laferrere B, JCEM 2008
Effect of Weight Loss by Gastric Bypass Surgery Versus Hypocaloric Diet on
Glucose and Incretin Levels in Patients with Type 2 Diabetes
Evans S, Surg Endosc 2012
Caloric Restriction in the Early Improvements in Insulin Sensitivity After Roux-en-Y
Gastric Bypass Surgery
Isbell JM. et al Diabetes Care 2010
Foregut Exclusion
Gut Hormones
Foregut Exclusion
Gut Hormones
Ileal Brake
Gut Hormones
Ileal Brake
Gut Hormones
GhrelinGhrelin
Diamant M Ob Rev 2011 (modified)
Do nutrient–gut–microbiota interactions play a role in human obesity, insulin
resistance and type 2 diabetes?
Short-Chain FAShort-Chain FA
Bariatric SurgeryBariatric Surgery
conjugationsecretionsecretion
UPPER GI
Fecal lossFecal loss
12 g/day12 g/day
0.5 g/day0.5 g/day
reabsorptionreabsorption
LOWER GI
12 cycles/day12 cycles/day
flora
LIVER
synthesis
deconjug
cholesterol
tau/gly
secondary bile acidssecondary bile acids
Bile acids turnoverBile acids turnover
TGR5 (and PPAR?) TGR5 (and PPAR?) activationactivation by bile acids leads to:by bile acids leads to:
•• Increase in the conversion from TIncrease in the conversion from T44 into Tinto T33 (through DIO2) (through DIO2)
•• Increase in energy expenditureIncrease in energy expenditure
•• Improvement of insulin sensitivityImprovement of insulin sensitivity
•• Increase in release of GLPIncrease in release of GLP--1 and GIP (via c1 and GIP (via c--AMP)AMP)
B= Serum Bile Acids
B= Serum Bile Acids:
Potential contribution to improve glucose metabolism
Patti ME. et al Obesity 2009
SUMMARY
�The effects of bariatric surgery on diabetes are related to improvement or
restoration of:
a.insulin sensitivity (weight loss in restrictive or mixed surgery);
b.insulin secretion (possibly due to modification of GI transit and neuro-
endocrine factors and reduction of glucotoxicity and lipotoxicity).
�Rate of success of bariatric surgery in terms of diabetes remission may
depend on the extent of β-cell dysfunction/loss at time of operation and, hence,
could be lower for:
a.longer diabetes duration;
b.less severe degrees of obesity.
•Bariatric surgery is associated with a significant rate of short term and long
term complications
Role of the foregut in the early improvement in glucose tolerance and insulin
sensitivity following Roux-en-Y gastric bypass surgery
Hansen EN et al Am J Physiol 2011
Hansen EN et al Am J Physiol 2011
Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity
following RYGBP