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
Weight Loss
(% of Excess Weight)
0
20
40
60
80
100
0
2
BMI (kg/m2): 50
Poiries et al. Ann Surg 1995;222:339.
4
6
8
10
Years After Surgery
34
35
12
14
35
Laparoscopic Adjustable Gastric Banding Produces
Greater Weight Loss than Comprehensive Medical Therapy*
in Patients with Class I Obesity (BMI 30-35 kg/m2)
0
Weight Loss, %
-5
-10
-15
-20
Surgical
-25
-30
Nonsurgical
Baseline
6 mo
12 mo
*(VLCD, behavioral modification, and pharmacotherapy)
Obrien et al. Ann Intern Med. 2006;144:625-33
18 mo
24 mo
Effect of Different Bariatric Surgical
Procedures on Weight Loss
Procedure
Approximate
Loss of Excess
Weight (%)
Laparoscopic gastric banding
45–65
Gastric bypass procedure
55–65
Biliopancreatic diversion
with duodenal switch
60–75
Klein et al. Gastroenterology. 2002;123:882-932
BARIATRIC SURGERY IN ST
LUKE’S
PATIENT PROFILE*
MALE
FEMALE
TOTAL
18 (36%)
32 (64%)
50
14-18
1 (6%)
1(3%)
2 (4%)
19-59
15 (83%)
30 (94%)
45 (90%)
>60
2 (11%)
1 (3%)
3 (6%)
14-18
57
46.8
51.9
19-59
47.07
46.15
46.5
>60
39.45
39
39.3
7 (39%)
10 (31%)
17 (34%)
4 (22%)
12 (38%)
16 (32%)
10(21%)
17 (34%)
Number (%)
Age group
BMI (mean)
Obesity Types
Obese (3040)
Morbidly
obese (40-50)
Super
7(39)
obese*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%)
Patients with Normal Fasting
Blood Glucose and HbA1c
After Surgery (%)
Gastric Bypass Surgery Improves Glycemic
Control in Impaired Glucose Tolerance or Type 2
Diabetes
100
75
50
25
0
Patents with
Type 2 Diabetes
Pories et al. Ann Surg 1995;222:339.
Patients with
IGT
Incidence of Type 2 Diabetes
(% Patients)
Prevention of Type 2 Diabetes at 8 Years
After Bariatric Surgery (94% Restrictive)
20.0
16.0
18.5
Control
Bariatric surgery
12.0
8.0
4.7
3.6
4.0
0.0
0.0
2
8
Follow-up After Surgery (y)
Control
Initial BMI (kg/m2)
41  5
Weight change at year 8: 1  11%
Sjostrom et al. Hypertension 2000;36:20.
Surgery
41  4
-16  12%
Ratio of Recovery (% of subjects)
Effect of Bariatric Surgery on Obesity-related
Metabolic Complications
100
Control
Surgery
72
80
62
60
46
36
34
40
21
13
21
19
22
24
11
20
0
2 yr
10 yr
Diabetes
Sjöström: N Engl J Med 2004;351:2683.
2 yr
10 yr
Hypertension
2 yr
10 yr
Hypertriglyceridemia
•
•
•
•
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
% Mortality
Long-term Survival: Canada
7
Rel. Risk = 0.11 (.04-.27)
6
89% reduction in risk of
death over 5 years
5
4
3
2
1
0
Control
Christou et al. Ann Surg 2004;240:416-424
Bariatric Surgery
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
Bariatric Surgery
Result
Malabsorptive
(BPD)
Restrictive
(LAGB. VBG)
Combined
(RYGB)
72
48-68
62
Type 2 DM
98
48-72
84
Hypertension
81
28-73
75
Dyslipidemia,
improved
100
71-81
94
Operative Mortality
rate, %
1.10
0.1
0.5
Excess weight
loss, %
Resolution of
Comorbid
Conditions. %
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
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
• Produced by K cells in the proximal
gut (duodenum)
• Stimulates glucose-dependent
insulin release
• 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*
HORMON
E
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 cells
Increase
Distal ileum
Increase
Increase
No change
Peptide YY
L cells
Decrease
Distal ileum
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.