peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin, insulin, glucagon and somatostatin. ⢠Obes Surg. 2010;20(11):1530-5. ⢠Peptides. 2016;77:28-37 ...
How MGB works? Abdulzahra Hussain FRCSEng,FRCSI,FRCS(G.S) FEBS(G.S) Consultant Bariatric surgeon Doncaster Teaching Hospital Honorary Senior Lecturer,Sheffield University ,UK
DISCLOSURE
• Nothing to declare
MGB is a GASTRIC BYPASS • (MGB/OAGB) is a gastric bypass with no Roux limb, just Bilio-Pancreatic and Common Limbs (BPL, CL).
• As such, some of its mechanisms of action are by logic, are similar to that of Roux En Y
Gastric Bypass (RYGBP).
MGB is NOT Mini operation! • It’s a TSUNAMI that affect a dormant digestiveneuroendocrine system to • Reactivate, • Re-programme and • Re-arrange • its current diseased setting . Curr Diab Rep. 2016;16(6):50.
Updates Surg. 2011;63(4):239-42.
Non obstructive Restriction
MGB EFFCET Modification of Gut absorptive function
Metabolic
1.Non Obstructive Restriction(NOR) •
•
Circle circumference=2πr
Volume =π r2h
•
=3.14x(1.4)2x14
•
=89.94 mls
•
What does that mean?
The stoma size& pouch capacity in relation to the cartridge size(pouch length is 14 cm) Cartridge size in mm
Stoma Volume of the size(diameter) in pouch(capacity) cm in mls
% Increase in pouch volume for each 15mm increment in cartridge size
30
1.9
35
0%
45
2.8
89.94
250%
60
3.8
158.69
450%
Smooth ,Slow food flow and Satiety producing MGB Anatomy • The Oesophagus has an internal diameter of 2cm. • The MGB pouch diameter is 2.8 cm [if 45 mm cartridge is used in the first firing]
•
The Jejunum is wider, its diameter being about 4 cm.
• Therefore ,there is a PROGRESSIVE increment in the
diameter of the NEW GI pathway after MGB. •
Henry Gray (1821–1865). Anatomy of the Human Body. 1918
•
http://www.bartleby.com
•
www.ecaware.org
• New MGB anatomy is less likey to produce obstruction
Where to anastomose f •
If GJ is created @B
•
shortening the pouch! And
capacity & the crucial MGB’s 3S & increase bile A
•
bile reflux [GJ becomes closer to B
GOJ]
Types of MGB G-J anastomosis
Functional Pouch length
MGB and Dumping • Early &late DS after RYGBP could reach 18.8% and 11.7% respectively.
• MGB is expected to produce less degree of DS compared to RNY due to the slow emptying.
• The slow the emptying the less the dumping.
• Surg Obes Relat Dis.2017: 28. pii: S1550-7289(17)30215-0 • Gastroenterol Res Pract. 2016;2016:2570237
MGB is less likely to fail because of pouch dilation.Tension=PR/2
http://hyperphysics.phy-astr.gsu.edu/hbase/ptens.html
2.Metabolic Effects
F Rubino.www.slideshare.net
Courtesy Professor Holts [Denmark]
GLP-1&GIP
• J Diabetes Investig. 2010 Apr 22; 1(1-2): 8–23.
ANTI-INCRETIN THEORY • An excess of anti-incretin signals, possibly
stimulated by specific macronutrient composition of modern diet or chemical
additives, could cause insulin resistance, reduced insulin secretion, and β-cell depletion, leading to
T2DM. • Horm Metab Res 2015; 47(01): 84-87
BPL/Duodenal sensing • In diabetes and obesity, intestinal nutrient-sensing mechanisms fail to lower food intake and glucose
production. • This indicate OTHER
mechanisms collectively known as ANTI-INCRETIN • Diabetes Met ResRev.2011:27:113-119 • Diabetes.2013 Sep;62(9):3005-13
Anti-incretin effect
• Rubino et al recent study suggested down regulation of insulin sensitivity following UGI surgery[BPD]. The oral glucose load has induced normal insulin sensitivity
in surgery group. • CONCLUSION: Foodborne factor can affect insulin resistance. • How do we know whether the changes are purely due to oral glucose or due to
metabolic/hormonal/enzymatic/neuronal GI-Brain signalling?? • Diabetes.2017 :29. pii: db170234. doi: 10.2337/db17-0234
Jejunal sensing mechanisms
• Diabetes.2013 Sep;62(9):3005-13
MGB Hormones changes Ghrelin •
GLP-I,GLP-2,GIP ,PYY
• Obes Surg.2016 ;26(11):2622-2628 • Asian Journal of Surgery:2014;37 (3) 130-137
What happens after MGB? • •
Enhancement of incretins effects Reduction of anti-incretin effects
• How? We don’t know all the fine details!
Why there is anti-incretin effect? • Genetic v epigenetic? 1.Deleterious cellular effects of nutrient excess can cause 1.Impaired inflammatory signaling,
2.Endoplasmic reticulum stress, 3.Excess production of reactive oxygen species[peroxides,etc], 4.Mitochondrial dysfunction,
2.Underlying CORRECTABLE abnormality of Beta cell ? Therefore MGB should change /modify the cellular function/metabolism to produce its metabolic effect.
• Nature 2006;444:840–846
Neuroendocrine pathways: • The discovery of Leptin and the neuronal
circuitry involved in mediating its effects, as well as the identification of Gut hormones are the two major advancement to understand the complex bypass mechanism. • Am J Physiol Regul Integr Comp Physiol. 2006;290(6):R1544-9
GI signals &vagus nerve • Activation of vagal afferents by gastrointestinal
(GI)signals during ongoing meals informs the brain of the quantity and quality of food being consumed and these signals contribute to meal termination . • What happens after MGB? • Physiol Behav. 2004;81(2):249-73.
Upper GI signaling and interaction • Brain
• Small bowel
• Adipose tissue Stomach
Liver
Pancreas
Biliary system
• Colon
GI anorectic signals PYY Oxyntom odulin
GLP-1
Anorectic pathway
Amylin
stimulation
Leptin
Cholecys tokinin
Ghrelin
Bile salts/acids:
• Bile salts are playing crucial role in lipid metabolism through farnesoid X receptor (FXR) .
• The decreased postprandial bile acid response in obese subjects compared with normal weight
subjects may partly explain the suboptimal GLP-1 and PYY responses and could affect appetite, glycaemic control and energy expenditure . • Curr Opin Lipidol. 2016;27(3):295-301 • Clin Biochem. 2010;47(Pt 5):482-4.
Bile salts • Bile salts changes after Bypass surgery: they may be partly responsible for the: • Intestinal hypertrophy, • Anorexigenic hormone secretion and • Alterations in gut microbiota.
• Furet JP, Kong LC, Tap J, et al. Diabetes. 2010;59:3049–3057.
Microbiota: • 1000-1200 gut microbiota CELL TYPES. • Prominent role for the gut microbiota in the gut-brain interaction through vagus nerve. • RCT has shown that alteration of microbiota by probiotics could be translated into a clinical benefit of weight loss .
• The gastric bypass is inducing changes in the microbiota of the alimentary limb and the common channel resembling those seen after prebiotic treatment or weight loss by dieting . • Human Microbiology.2013:3-24,J Clin Invest. 2015;125(3):926-38.
• Front Integr Neurosci. 2013;7:70., Gastroenterology. 2017. 153(3):711722.,Physiol Behav. 2013;119:92-6.
Changes in gut microbiota: Transfer of the gut microbiota from GBP-treated mice to non-operated, germ-free mice resulted in weight loss and reduced fat mass in the recipient animals. • The altered microbial production of short-chain fatty acids that increases may partly be an explanation . •
Sci Transl Med 2013; 5:178ra41.
Bile acids-Microbiota relation • Close relationship • Microbiota-bile acid interactions play a role in the mechanisms underlying the effects of
metabolic surgery .
• J Diabetes Investig. 2017. 23. doi: 10.1111/jdi.12687
Bile acids-microbiota interaction
• Pharmacol Rev.2014 Oct; 66(4): 948–983.
Bile acids metabolic complications following bariatric surgery • The findings of systematic review support the effects of BAs on: •
Satiety,
• Lipid and cholesterol metabolism, • Incretins and glucose homoeostasis, •
Energy metabolism,
• Gut microbiota •
Endoplasmic reticulum stress.
•
Int J Obes (Lond). 2015;39(11):1565-74
Effect of Gastric Bypass at tissue level: • Gastric:
Altering physiology of the secretion pathways but also the enzymatic and hormonal regulatory
mechanisms[Ghrelin] •
Surg Obes Relat Dis. 2005;1(2):155-60
•
Am J Surg. 1976;131(2):162-8
Effect of Gastric Bypass at tissue level
• Duodenum:
Enzymatic secretion plus Ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic hormone (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin, insulin, glucagon and somatostatin. •
Obes Surg. 2010;20(11):1530-5
• Peptides. 2016;77:28-37
Effect of Gastric Bypass at tissue level • Jejunum:
Proteins, carbohydrates are absorbed at duodenum and jejunum . Patients who
underwent MGB/OAGB with long BPL are at high risk of developing protein malnutrition and
diarrhea. •
EXS. 2016;107:23-43.
Effect of Gastric Bypass at tissue level
• Pnacreas:
The gastric and intestinal phases are dependent upon food entering in the stomach and the
duodenum and therefore the pancreatic secretion is affected by gastric bypass. •
Physiol Behav. 2003;79(4-5):713-7
Effect of Gastric Bypass at tissue level • Liver: The secretory processes are highly regulated both at transcriptional and posttranscriptional levels with the latter
involving complex receptor mediated signal transduction pathways . • The overall mechanism of bile secretion is governed by different UGI hormones , including VIP, Gastrin ,Secretin, CCK. These hormones are all affected by altering UGI anatomy, specifically by gastric bypass. •
Obes Surg. 2012;22(5):740-8.
•
Compr Physiol. 2013;3(3):1035-78.
Other possible MGB mechanisms: • Neuro-psychiatric: • Taste-like cells at tongue ,pancreas,bowel
• Non GI hormone ; Leptin, others unknown?
• Nat Rev Gastroenterol Hepatol. 2013;10(8):473-86. • Auton Neurosci. 2000;85(1-3):1-17 , Physiol Behav. 2014;136:155-69. , Acta
Physiol (Oxf). 2011;201(3):313-21
Biliopancreatic limb is the MONSTER! • MGB main ARM of action is the BPL. • Research shown NO effect of CLL on EWL after Gastric bypass. • Therefore the BPL is the main effector [MGB has no Roux limb]
• The Roux limb in the RYGBP is mainly a conduit as no significant food absorption takes place before JJ. •
Obes Surg.2016(26):1705-9
Absence of Roux limb? Is it important? • The Roux limb in the RYGB is mainly a conduit as no significant food absorption take place before JJ. • We don’t know the effect of presence or absence of Roux limb in RYGB&MGB
respectivly
Common Limb Length doesn’t affect T2DM resolution
• J Minim Access Surg. 2016 Jan-Mar; 12(1): 54–57.
CLL doesn’t affect EWL[Fixed BPL&ALL] Variable
Mean+-SD
Range
CLL(CM)
358.2+-94.5
155-590
JIL(CM)
585+-94.6
380-815
• Obes Surg. 2016 ;26(8):1705-9
Alimentary Limb Length doesn’t play important role either! • ALL does not play a significant role in • weight loss after gastric bypass in the non-superobese population (BMI 50. •
Obes Surg. 2011;21(1):119–24
•
mexicobariatriccenter.com
BPL action/Major mediators in Jejunal sensing mechanisms • Peptide YY,
• GLP-1 , • CCK , • Gut-brain-liver neuronal axis
• Metabolism.2012:61:1312-20
3.Modification of Gut absorptive function 1.Metabolic effect: Enhanced production in the lower intestine of a substance which opens an alternative insulin-independent pathway for glucose
transport. GI signalling ,hormonal,enzymatic,satiety changes, unknowns?. 2.Weight loss:
Due to NOR ,overall hormonal/metabolic changes and bypassing proximal gut(at least 150-200 cms). • Theor Biol Med Model.2013 Jul 13;10:45. doi: 10.1186/1742-468210-45
Final stage of MGB effect • “Higher-level” brain systems and mental processes (i.e., attention, cognition, and free will);
• The fetal environment and •
Lifelong programming;
• Parenting and other familial influences; • Social, •
Commercial, and
• Cultural food environment all can impact food choice and modulate how the brain guides behavior at any given point in time. •
Mini Rev Med Chem. 2007;7(1):47-53., Proc Natl Acad Sci U S A. 2012;109(31):12294-301.
Thank you
• QUESTIONS?
