bariatric surgery in diabetes mellitus type 2 josephine carlos- raboca m.d. weight wellness center
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Bariatric Surgery in diabetes mellitus type 2
Josephine Carlos- Raboca M.D.
Weight Wellness Center
Bariatric Surgery
1995 the number of bariatric surgeries performed was well over 20000
2003 - 103,000
2004 - 144,000
Average age of patient – 30 years old
Length of Hospital Stay – 3.9 days
Bariatric surgeons – increased by 500%
Complication rate – 10%
Deaths <1% CDC, 2006
Long-term Effect of Gastric Bypass Surgery on Body Weight
Poiries et al. Ann Surg 1995;222:339.
BMI (kg/m2): 50 34 35 35
We
igh
t Los
s(%
of E
xces
s W
eig
ht)
Years After Surgery
0
20
40
60
80
1000 2 4 6 8 10 12 14
-30
-25
-20
-15
-10
-5
0
Obrien et al. Ann Intern Med. 2006;144:625-33
Wei
ght L
oss,
%
Baseline
Surgical
Nonsurgical
*(VLCD, behavioral modification, and pharmacotherapy)
6 mo 12 mo 18 mo 24 mo
LLaparoscopic aparoscopic AAdjustable djustable GGastric astric BBanding anding Produces Produces Greater Weight Loss than CGreater Weight Loss than Comprehensive omprehensive MMedical edical TTherapyherapy** in in PPatients with Class I Obesity (BMI 30-35 kg/matients with Class I Obesity (BMI 30-35 kg/m22))
ApproximateLoss of Excess
Procedure Weight (%)
Laparoscopic gastric banding 45–65
Gastric bypass procedure 55–65
Biliopancreatic diversion 60–75
with duodenal switch
Effect of Different Bariatric Surgical Procedures on Weight Loss
Klein et al. Gastroenterology. 2002;123:882-932
BARIATRIC SURGERY IN ST LUKE’S
PATIENT PROFILE*MALE FEMALE TOTAL
Number (%) 18 (36%) 32 (64%) 50
Age group
14-18 1 (6%) 1(3%) 2 (4%)
19-59 15 (83%) 30 (94%) 45 (90%)
>60 2 (11%) 1 (3%) 3 (6%)
BMI (mean)
14-18 57 46.8 51.9
19-59 47.07 46.15 46.5
>60 39.45 39 39.3
Obesity Types
Obese (30-40)
7 (39%) 10 (31%) 17 (34%)
Morbidly obese (40-50)
4 (22%) 12 (38%) 16 (32%)
Super obese
7(39) 10(21%) 17 (34%)*Dineros, Obesity Surgery, 2007
COMPLICATIONS
• Early Complications• Wound infection 2/50• Pneumonia 1/50• Dehydration 1/50• Gastritis 1/50• Leakage 1/50
COMPLICATIONS
• Late Complications• Band Slippage 2/20 (10%)• Stomal Stenosis 1/20 (5%)• Ventral Hernia 1/5 (20%)
0
25
50
75
100
Patents with Type 2 Diabetes
Patients with IGT
Pa
tie
nts
wit
h N
orm
al F
asti
ng
B
loo
d G
luc
os
e a
nd
Hb
A1
c A
fte
r S
urg
ery
(%)
Gastric Bypass Surgery Improves Glycemic Control in Impaired Glucose Tolerance or Type 2
Diabetes
Pories et al. Ann Surg 1995;222:339.
4.7
18.5
0.0
3.6
0.0
4.0
8.0
12.0
16.0
20.0
2 8Follow-up After Surgery (y)
Inci
denc
e of
Typ
e 2
Dia
bete
s(%
Pat
ient
s)
Control Bariatric surgery
Prevention of Type 2 Diabetes at 8 Years After Bariatric Surgery (94% Restrictive)
Sjostrom et al. Hypertension 2000;36:20.
Control Surgery Initial BMI (kg/m2) 41 5 41 4Weight change at year 8: 1 11% -16 12%
0
20
40
60
80
100
2 yr 10 yr 2 yr 10 yr 2 yr 10 yr
Effect of Bariatric Surgery on Obesity-related Metabolic Complications
Sjöström: N Engl J Med 2004;351:2683.
Rat
io o
f Rec
over
y (%
of s
ubje
cts)
21
72
Diabetes Hypertension Hypertriglyceridemia
13
36
21
34
11
19 22
62
24
46
Control Surgery
Adams et al., NEJM 2007
• 15850 gastric bypass patients and matched controls (Utah)
• 7.1 year mean follow-up
• Gastric bypass group exhibited overall 40% reduction in mortality
• Specific-cause mortality after gastric bypass
– 56% reduction from CAD
– 92% reduction from Type 2 diabetes
– 60% reduction from Cancer
0
1
2
3
4
5
6
7
Control Bariatric Surgery
Long-term Survival: Canada
Rel. Risk = 0.11 (.04-.27)
89% reduction in risk ofdeath over 5 years
Christou et al. Ann Surg 2004;240:416-424
% M
ort
alit
y
Gastric Banding in morbid obese DM2
• 905 consecutive patients followed up for a median of 12.5mos
• 78 DM2• 64 IGT• 100 MS• patients on OHA: 81% remission• patients on OHA+insulin:• 43% ceased or reduced OHA• 93% ceased or reduced insulin• Patients on insulin: only 75% reduced or ceased insulin
• 88% of MS remission or improved
• 100% IGT did not progress to DM
Meta-analysis of Bariatric Surgeries
• 1990-2006
• 621 studies
• 145,246 patients
• Mean age 40.2 years
• BMI 47.9 kg/m2
• 80% female
• weight loss was 38.5kg (55.9%)
• 78.1% of diabetic patients had complete resolution
• Diabetes improved or resolved in 86.6%• Resolution rate: biliopancreatic
diversion/duodenal switch>gastric bypass> gastric banding
• More pronounced with greater weight loss and maintained for 2 years or more
• Am J Med 2009
Major Obesity-related Comorbidities That Have Been Improved by Bariatric Surgery
• Type 2 diabetes• Hypertension• Obstructive sleep apnea• Obesity hypoventilation• GERD• NALD, NASH• Pseudotumor cerebri• Depression
• Dyslipidemias• Coronary artery disease• Cardiac dysfunction• Venous stasis disease• Polycystic ovary syndrome• Infertility• Cancers• Degenerative joint disease• Quality of life
Results of Different Types of Results of Different Types of Bariatric SurgeryBariatric Surgery
ResultResult MalabsorptiveMalabsorptive
(BPD)(BPD)
RestrictiveRestrictive
(LAGB. VBG)(LAGB. VBG)
CombinedCombined
(RYGB)(RYGB)
Excess weight Excess weight loss, %loss, %
7272 48-6848-68 6262
Resolution of Resolution of Comorbid Comorbid Conditions. %Conditions. %
Type 2 DMType 2 DM 9898 48-7248-72 8484
HypertensionHypertension 8181 28-7328-73 7575
Dyslipidemia, Dyslipidemia, improved improved
100100 71-8171-81 9494
Operative Mortality Operative Mortality rate, %rate, %
1.101.10 0.10.1 0.50.5
Marion L. Vetter, MD, RD; Serena Cardillo, MD; Michael R. Rickels, MD, MS; and Nayyar Iqbal, MD, MSCE, Effect of Bariatric Surgery on Type 2 Diabetes Mellitus. Ann Intern Med. 2009;150:94-103. www.annals.org
PROPOSED MECHANISMS FOR IMPROVED GLYCEMIC CONTROL AFTER BARIATRIC SURGERY
Effects of Decreased Caloric Intake on Fasting Glycemia
• Decreased caloric intake affects glucose metabolism
• Rate of diabetes remission are not the same – Complete remission within days of intestinal
bypass procedures (Porries, 1995)– Takes months to occur in LAGB (Dixon, 2008)
GLP-1 and GIP Are the Two Major Incretins
GLP-1 GIP• Produced by L cells mainly located
in the distal gut (ileum and colon) • Stimulates glucose-dependent
insulin release
• Produced by K cells in the proximal gut (duodenum)
• Stimulates glucose-dependent insulin release
Other effects• Suppresses hepatic glucose output
by inhibiting glucagon secretion in a glucose-dependent manner
• Inhibition of gastric emptying; reduction of food intake and body weight
• Enhances beta-cell proliferation and survival in animal models and isolated human islets
• Minimal effects on gastric emptying; no significant effects on satiety or body weight
• Potentially enhances beta-cell proliferation and survival in islet cell lines
GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide.
Drucker DJ. Diabetes Care. 2003;26:2929–2940; Ahrén B. Curr Diab Rep. 2003;3:365–372; Drucker DJ. Gastroenterology. 2002;122:531–544; Farilla L et al. Endocrinology. 2003;144:5149–5158; Trümper A et al. Mol Endocrinol. 2001;15:1559–1570; Trümper A et al. J Endocrinol. 2002;174:233–246; Wideman RD et al. Horm Metab Res. 2004;36:782–786.
Nonincretin Gut Peptides
• GHRELIN– Secreted by gastric fundus and proximal small intestine
and acts on the hypothalamus to regulate appetite
– Inhibits insulin secretion by a paracrine mechanism
– Systemic ghrelin levels increase before a meal and decrease afterward
– Ghrelin stimulates appetite and food intake and suppresses energy expenditure and fat catabolism
– Inversely proportional to body weight
– Weight loss increases ghrelin levels suggests that ghrelin affects long term regulation of body weight
Nonincretin Gut Peptides
• Peptide YY (PYY)– Secreted by the L cells of the distal intestine– Present in 2 molecular forms: PYY(1-36) and
PYY (3-36), a cleavage product– PYY increases satiety and delays gastric
emptying through neuropeptide Y-receptor subtypes in the central and peripheral nervous system
– IV PYY(3-36) increases satiety and decreases food intake in humans
FOREGUT EXCLUSION THEORY ( Hypothesis of the Proximal Bowel)
• Exclusion of the duodenum and jejunum prevents the secretion of a “putative signal” that promotes insulin resistance and Type 2 DM
• Bypass of proximal gut prevents secretion of “Anti-incretin factor” or “decretin”
• May be implicated in the pathogenesis of diabetes
HINDGUT HYPOTHESIS (HYPOTHESIS of distal bowel)
• Intestinal rearrangement speeds the delivery of nutrients to the distal intestines
• Causes exaggerated GLP-1 and PYY levels and improves glucose tolerance and insulin secretion
Cummings, et al, 2007
Rat Experiments
• Simple gastrojejunostosmy without bypassing proximal intestine did not improve diabetes
• GJB + proximal intestinal bypass improved diabetes
• Supports Proximal Bowel Hypothesis
Gut Peptide Response to Different Bariatric Surgical Procedures*
HORMONE
Cell Type (Location)
Effect on Insulin Secretion
BPD RYGB LAGB
Ghrelin X/A cells Stomach
Decrease Increase Increase/Decrease
Increase/No Change
GIP K cells duodenum
Increase Decrease Decrease No change
GLP-1 L cellsDistal ileum
Increase Increase Increase No change
Peptide YY L cellsDistal ileum
Decrease Increase Increase No change
*Folli, 2007
Markers for remission
• Post op dietary behaviour
• Beta cell dysfunction
• Insulin resistance
• More recent onset <5years
• Satisfactory control on diet or oral hypoglycemic agents
• Greater weight loss
CLINICAL PRACTICE RECOMMENDATIONS, 2009 ADA
• Bariatric surgery should be considered for
adults with BMI 35 kg/m2 and type 2 diabetes, especially if the diabetes is difficult to control with lifestyle and pharmacologic therapy. (B)
• Patients with type 2 diabetes who have undergone bariatric surgery need life-long lifestyle support and medical monitoring. (E)
Surgery for nonobese DM2
• 24 week interventional prospective trial
• BMI 25-29.9 kg/m2
• DM<15 years
• Insulin treated
• No history of major complications
• Preserved beta cell function
• Absence of autoimmunity
12 open duodenal-jejunal exclusion surgery vs 12 standard medical care
• Results reductions in • FBS 14% vs 7%• A1c 8.78 to 7.84 p<0.01• vs 8.93 to 8.71 p<0.05 between groups• Insulin requirements 93% vs 29% p<0.01• 10 patients stopped insulin but continued oral
medications in surgical patients.
• Conclusion: duodenal jejunal exclusion was an effective treatment for nonobese T2DM patients and superior to medical treatment in achieving better glycemic control along with reduction in insulin requirements.
Clinical improvement after duodenojejunal bypass for nonobese type 2 diabetes despite minimal
improvement in glycemic homeostasis
• 7 patients T2DM with BMI<35 - LDJB
• 12 month prospective study
Results: At 12 months after surgery, all subjects consistently felt relief from fatigue pain and/or numbmess in the extremeties, polyuria and polydipsia
Conclusion
• Although this is a small series data showed that at 12 months after surgery, clinical improvement was obvious, LDJG may not be effective at inducing remission of T2DM and the Metabolic Syndrome in certain patients . This suggests that larger patient studies should be conducted before conlcuding that surgery may offer clinical and biochemical resolution to a disease once treated medically. Longer follow up is required for better evaluation.
• Until better approaches become available, bariatric surgery is the therapy of choice for patients with severe obesity
• Pories WJ JCEM 2008 Nov; 93(11 Supp 1) S89-96.
• While indiscriminate use of bariatric surgery to treat diabetes is potentially harmful, ignoring an opportunity offered by surgery is not an option either at a time when medical cure is not available.