Why Surgical Treatment of Diabetes May Not be a

Good OptionMcGill First Canadian Summit on

Surgery for Type 2 DiabetesMontréal, Québec

May 7, 2010

David C.W. Lau, MD, PhD, FRCPCProfessor of Medicine and Biochemistry

Julia McFarlane Diabetes Research CentreUniversity of Calgary

Email: dcwlau@ucalgary.ca

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, Boehringer-Ingelheim, GSK, Eli Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Roche, sanofi-aventis, Sepracor

• Speaker bureau:CDA, HSFC, AstraZeneca, Abbott, Bayer, Boehringer-Ingelheim, 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?

6 - 9 yr follow-up

MacDonald et al J Gastrointest Surg 1997;1:213-220

Bariatric Surgery Decreases Type 2 Diabetes

100%

80%

60%

40%

20%

0%

87.0%

8.6%

Controls

Gastricbypass

% T

ype

2 D

iabe

tes

Dixon, JB et al. JAMA 2008;299:316-323

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

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)

Medication use (N) 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

Dixon, JB et al. JAMA 2008;299:316-323

Weight Loss and Diabetes at 2 Years

Dixon, JB et al. JAMA 2008;299:316-323

• Remission occurred > 6 months post-surgery

• 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

Weight Loss and Diabetes Remission

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

Systematic Analysis of 621 studies, N=135,246Mean age 40.2 years; BMI 47.9 kg/m2; 80% women

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 1-2 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• 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

Disadvantages• Surgical complications

(short- and long-term)• Remission not achieved in

all patients who achieved > 10% wt loss

• Long surgical wait list• Requires long-term follow-

up• 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

Frachetti KL, et al. Curr Opin Endocrinol Diabetes Obes. 2009;16:119-124

Obesity Surgery

Obesity DiabetesCo-Morbidities

Operative Risks

Benefits:- Weight loss- Metabolic improvements- Mortality benefit

Complications:

- Nutrient deficiency

- Dumping syndrome

- Hypoglycemia

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?