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Why Surgical Treatment of
Diabetes May Not be a
Good Option
McGill First Canadian Summit on
Surgery for Type 2 Diabetes
Montréal, Québec
May 7, 2010
David C.W. Lau, MD, PhD, FRCPC
Professor of Medicine and Biochemistry
Julia McFarlane Diabetes Research Centre
University of Calgary
Email: [email protected]
Disclosures
• Research funding:
CIHR, AHFMR, Alberta Cancer Board,
AstraZeneca, BMS, Dainippon, GSK, Eli Lilly, Pfizer
and sanofi-aventis
• Consultant or advisory board member:
Abbott, Allergan, AstraZeneca, Bayer, BoehringerIngelheim, GSK, Eli Lilly, Merck, Novartis, Novo Nordisk,
Pfizer, Roche, sanofi-aventis, Sepracor
• Speaker bureau:
CDA, HSFC, AstraZeneca, Abbott, Bayer, BoehringerIngelheim, Eli Lilly, GSK, Merck, Novo Nordisk, Pfizer
sanofi-aventis and Sepracor
Questions
• How effective is bariatric surgery in treating
diabetes?
• Are all procedures equally effective?
• What is the durability of diabetes remission?
• Is bariatric surgery safe?
• What are the short- and long-term
complications?
• Is bariatric surgery cost effective?
Bariatric Surgery Decreases Type 2 Diabetes
100%
87.0%
Controls
% Type 2 Diabetes
80%
Gastric
bypass
60%
40%
20%
8.6%
0%
6 - 9 yr follow-up
MacDonald et al J Gastrointest Surg 1997;1:213-220
Lap Adjustable Gastric Banding for Diabetes
First randomized controlled
trial comparing surgically
induced weight loss with
conventional therapy
•N=60; 28 men, 32 women
•Mean age ~47 years
•Recently diagnosed Type 2
Diabetes (< 2 years)
•Wt 106 kg, WC 115 cm
•BMI 37.1 kg/m2
•A1C ~7.7%, FPG 8.7 mM
Dixon, JB et al. JAMA 2008;299:316-323
Bariatric Surgery:
Weight Loss and Diabetes Remission
Surgery (N=30)
Control (N=30)
Remission in % (N)
73% (22/30)
13% (4/30)
Achieving A1C < 6.2% in %
80% (N=24)
20% (N=6)
4
28
Weight loss (mean±SD) in
%
20±9.4
1.4±4.9
Excess wt loss (mean±SD)
%
62.5
4.3
Change in BMI (kg/m2)
- 7.4
- 1.5
Medication use (N)
Dixon, JB et al. JAMA 2008;299:316-323
Weight Loss and Diabetes at 2 Years
• Remission occurred > 6 months postsurgery
• 10% body weight loss generally required for
diabetes remission, which was achieved in
22 of surgical patients
• 4/26 patients who lost > 10% body weight
failed to achieved remission
Dixon, JB et al. JAMA 2008;299:316-323
Weight Loss and Diabetes Remission
Systematic Analysis of 621 studies, N=135,246
Mean age 40.2 years; BMI 47.9 kg/m2; 80% women
Total
LAGB
Gastrop
G Bypass
BPD/DS
% EBWL
55.9
46.2
55.5
59.7
63.6
% “Cure”
78.1
56.7
79.7
80.3
95.1
% < 2 yrs
80.3
55.0
81.4
81.6
94.0
% ≥ 2 yrs
74.6
58.3
77.5
70.9
95.9
Buchwald H et al. Am J Med 2009;122:248-256
How effective is bariatric surgery in
treating diabetes?
• Yes, it is effective with a remission rate is
about 84% but no long-term data
• No data on subjects with longer duration of
diabetes
• Results likely vary with less experienced
surgical teams
• No long term data on efficacy of surgery
• Not a cure for diabetes
Hormonal Mechanisms of Weight loss
• Weight dependent effects on glucose homeostasis
• Multiple hypotheses (foregut, hindgut, ghrelin etc.)
on weight independent anti-diabetic effects of RYGB
but detailed mechanisms remain unknown
• Gut hormones (GLP-1, ghrelin, PYY and
oxyntomodulin) likely play an important role
• Increased but usually appropriate GLP-1 response
with Roux-en-Y gastric bypass (RYGB) surgery
• Insulin hypersecretion and insulin resistance are
normalized following malabsorptive bariatric surgery
Hormonal Changes Associated
with Bariatric Surgical Procedures
Frühbeck G et al. N Engl J Med 2004;350:308-309
What are the short- and long-term
complications?
Complications
• Operative risks, morbidity and mortality
• Post-op and short-term mortality
 0.1-0.33% for LAGB
 0.5% for gastric bypass surgery
• Long-term
 Nutrient and vitamin deficiencies
 Malabsorption
 Obstruction
 Dumping syndrome
 Hypoglycemia
Nesidioblastosis and Hypoglycemia
• 5 women and 1 man (median age 47 years; range, 39 to 54)
with postprandial symptoms of neuroglycopenia developed 12 years post-surgery
• Postprandial hyperinsulinemic hypoglycemia and
nesidioblastosis were confirmed in 4 patients and islet cell
tumors in 2 patients; all underwent partial pancreatectomy
• Increased levels of a β-cell trophic polypeptide, such as
glucagon-like peptide 1, may contribute to the hypertrophy of
pancreatic beta cells in these 6 patients
Service GJ, et al N Engl J Med 2005;353:249-254
Bariatric Surgery for Diabetes
Advantages
Disadvantages
• Effective and sustained
long-term weight loss > 10%
• More patients achieve
glycemic and metabolic goal
targets
• Reduction in anti-diabetic
medications
• No hypoglycemia
• May be cost-effective
• Surgical complications
(short- and long-term)
• Remission not achieved in
all patients who achieved >
10% wt loss
• Long surgical wait list
• Requires long-term followup
• Long-term efficacy and
safety data not available
Questions
• How effective is bariatric surgery in treating
diabetes?
• Are all procedures equally effective?
• What is the durability of diabetes remission?
• What are the short- and long-term complications?
• Is bariatric surgery safe?
• Access to surgery is a big barrier with long wait times
• Is bariatric surgery cost effective?
Patient Selection, Benefits and
Complications of Bariatric Surgery
Obesity Diabetes
Co-Morbidities
Operative Risks
Obesity Surgery
Benefits:
- Weight loss
- Metabolic improvements
- Mortality benefit
Complications:
- Nutrient deficiency
- Dumping syndrome
- Hypoglycemia
Frachetti KL, et al. Curr Opin Endocrinol Diabetes Obes. 2009;16:119-124
Is bariatric surgery for the treatment
of type 2 diabetes an option?
• Not quite ready for prime time
• Needs more research and clinical trial data
Thank you
Questions?