Therapy for Adult-Onset Diabetes Mellitus The longer diabetes is present, the more likely one is to. develop a diabetic complication …
The Role of Bariatric Surgery in Morbid Obesity with and without Diabetes
Samer G Mattar, MD, FACS, FRCS Associate Professor of Surgery Indiana University Medical Director, Clarian Bariatrics
Prevalence of Obesity in US Adults - 1995
10
10 to 15
15 to 20
20 to 25
25
Mokdad et al, JAMA, 1999
Prevalence of Obesity in US Adults - 2005
10 to 15 MMWR, 2006; 55:36
15 to 20
20 to 25
25 to 30
30
Disproportional Increase in Severe Obesity
More than 1,000,000 US adults now have a BMI 50
A Global Crisis
Cases of Diabetes Projected for 2030 millions
589
60 50 40 30 20 10 0 US
Yach, Stuckler, Brownell Nature Medicine, 2006
251 134
China
India
Increase in Diabetes, 2000 - 2030
150 125 100 75 50 25 0 Developed Countries
Yach, Stuckler, Brownell Nature Medicine, 2006
124
198
Developing Countries
Obesity Shortens Life Expectancy
Average years of life lost from obesity at age 30
BMI 30 White men White women Black men Black women 1 1 0 0 BMI 40 5 4 5 1 BMI 45 11 8 14 5
Impact of Obesity
Comorbid Diseases Quality of Life Disability
Obesity
Mortality Medical Costs
Effective Obesity Treatment 2006
3 1 1
Lifestyle Medications Surgery Unmet Need
95
Complications of
Obesity
Metabolic Structural Degenerative Neoplastic Psychological
Arthritis Back pain Sleep apnea Eating disorders Depression
Several of these complications exacerbate the underlying obesity, creating a vicious cycle:
Diabetes Therapeutic drugs cause weight gain Limit exercise Disrupted sleep can cause weight gain Can cause further weight gain
50
Medical Complications of Obesity
Pulmonary disease
abnormal function obstructive sleep apnea hypoventilation syndrome
Idiopathic intracranial hypertension Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Cancer
breast, uterus, cervix colon, esophagus, pancreas kidney, prostate
Nonalcoholic fatty liver disease
steatosis steatohepatitis cirrhosis
Gall bladder disease Gynecologic abnormalities
abnormal menses infertility polycystic ovarian syndrome
Osteoarthritis Skin Gout
Phlebitis
venous stasis
Obesity Comorbidity
Starts at the Head
Stroke, Pseudotumor, Diabetic Retinopathy
Goes to the Toes
Diabetic Neuropathy, Infection; Venous Stasis
Gets EVERY ORGAN in Between
Lungs, Heart, Liver, Spleen, Esophagus, Gall Bladder, Colon, Kidneys, Uterus, Breast, Bladder, Prostate,
Pancreas
Proportion of Disease Prevalence Attributable to Obesity
Type 2 diabetes Gallstones Hypertension CHD Osteoarthritis Breast cancer Uterine cancer Colon cancer
0 11 11 11 10 20 30 40 50 60 17 17 14 30 57
Disease Prevalence Attributable to Obesity
Wolf, et al Obes Res 1998;6:97-106
Therapeutic Options
Diet VLCD Diet Exercise Pharmacotherapy Surgery
Adherence and Effectiveness of 4 Popular Diets
Weight Change at 1 Year
Atkins
21 48 kg
Carbohydrate restriction 21 [53] of 40 completed
Ornish Fat restriction
33 73 kg 20 [50] of 40 completed
Weight Watchers Energy restriction
30 49 kg 26 [65] of 40 completed
Zone Macronutrient balance
32 60 kg 26 [65] of 40 completed
Dansinger ML, et al JAMA 2005; 293: 43-53
Pharmacologic Therapy
The Practical Guide, Identification, Evaluation and Treatment of Overweight and Obesity in Adults NIH Publication 00-4084, Oct 2000
Rimonabant, the First CB1 Blocker
CB1 Decrease in food intake Brain Central effects
palatable and non-palatable food
FA Oxidation
Decrease in body weight
Rimonabant
Metabolic peripheral effects
FFA cle ara n ce
Decreased hyperinsulinemia Restoration of insulin sensitivity Decreased TG
CB1
Adipocyte
Adiponectin
Increased HDL-C
RCT of Medical vs Surgical Therapy for Obesity
of Excess Weight Lost
80 70 60 50 40 30 20 10 0 0 mth 6 mth 12 mth 18 mth
EWL
200 /- 78 kg
Surgical Medical
68
50 /- 81 kg
17
24 mth
TIME
Nonsurgical Management of Morbid Obesity NIH 1991 Consensus Conference: Dietary weight reduction with or without behavioral modification or drug therapy had an unacceptably high incidence of weight regain in the morbidly obese within 2 years after maximal weight loss
Growth of Bariatric Surgery: 500
NEJM 2004;350;1075-1079
Bariatric Surgery Increase
Total Number of Roux-en-Y Gastric Bypasses Performed in the USA
1998 1999 2000 2002 2004 2005 25000 23000 38000 40000 140000 170000 National Center for Health Statistics
Operations for Morbid Obesity
Gastric Restriction Combination Malabsorption
VBG
J-I Bypass
RY-Gastric Bypass
Gastric Banding
BPD/DS
Roux-en-Y Gastric Bypass
Advantages
Excellent excess weight loss 60-75 Very good long-term results Solid food well tolerated
Disadvantages
Potential nutrient deficiencies
Surgical Weight Loss Therapy
Why is gastric bypass so effective?
Surgery Is the Un-Diet
Diet
Appetite
Hunger Satiety
Reward-based eating
Surgery
Energy expenditure Stress response
Defending a Body Energy Set Point
kcal / 24 hours
3000
Energy Intake
2500 Energy Balance 2000
Energy Expenditure
Energy Balance
20
25
30
35
Body Mass Index kg/m2
Diminished Appetite After Gastric Bypass
Distention of gastric pouch Nutrients in gastric pouch Afferent signals Rapid passage of undigested nutrients into jejunum
Altering the Set Point with Gastric Surgery
3000
Baseline Energy Intake Post-op Energy Intake Post-op Energy Expenditure Baseline Energy Expenditure
kcal / 24 hours
2500
2000
30
35
40
45
Body Mass Index kg/m2
Lap-Band
Laparoscopic Gastric Banding
FDA approved June 2001 Adapted from open gastric banding Purely a gastric restriction procedure Adjustable silicone band used Band placed around cardia of stomach Significant preliminary experience in Europe
Lap-Band Outcomes
Weight loss Weight loss OR time Hospital stay 40-55 EWL 10-12 BMI 1 hour 1-2 days
Lap-Band Outcomes
Conversion rate Prolapse Er 
osions Infections Tube fractures Re-operation rate Mortality 1 5-8 1-2 1 1-2 10-20 05
Sleeve Gastrectomy
Malabsorption Procedures
Biliopancreatic
Diversion
Duodenal Switch Procedure
Comparison of Bariatric Operations
n 22,094 patients; 2738 citations 1990-2002 Lapband 475 01 478 Gastric bypass 616 05 836 Duodenal switch 701 11 979
Excess weight loss Operative mortality Resolution of diabetes
Buchwald, Avidor, Braunwald, Jensen, Pories, Farbach, Schoelles JAMA 2004;292:1724-1737
Relative Risk of Type 2 Diabetes in US Women According to BMI
Relative risk 100 ageadjusted
80 60 40 20 0
Bars represent 95 220 confidence intervals
220- 230229 239
240- 250- 270249 269 289 BMI kg/m2
290- 310309 329
330- 350 349
Data derived from Colditz et al, Ann Intern Med, 1995
Who Would Have Thought It?
An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus
Walter J Pories MD, Melvin S Swanson PhD, Kenneth G MacDonald MD, Stuart B Long BS, Patricia G Morris BSN, Brenda M Brown MRA, Hisham A Barakat PhD, Richard A deRamon MD, Gay Israel EdD, Jeanette M Dolezal PhD, Lynis Dohm PhD From the Departments of Surgery and Biochemistry of the School of Medicine and the Human Performance Laboratory of East Carolina University, Greenville, NC Presented at the 115th Annual Meeting of the American Surgical
Association, April 6-8, 1995; Chicago, IL
Effect of GBP on Type 2 Diabetes Mellitus
Before operation Glucose impaired Type 2 diabetes
Receiving insulin Oral agent 53 88 20 13
After operation
0 2 10 0
Pories WJ et al Ann Surg 1995;222:339-50
Patient Stratification n191
Duration of T2DM 5 years n119 6-10 years n44 10 years n28 Severity of T2DM IFG n14 Diet controlled T2DM n32 Oral medication only n93 Insulin using n52
Results
1160 patients 240 patients with IFG or T2DM 191 patients for study 80 follow-up
Conclusion
Early surgical intervention is the most effective treatment for T2DM Significant reduction in medication requirement Resolution dependent on preoperative duration and severity of T2DM and on ultimate weight loss
Bariatric Surgery for Type 2 Diabetes
20 studies documenting efficacy The longer one is severely obese, the more likely one is to develop type 2 diabetes The longer diabetes is present, the less likely is a response to surgery The longer diabetes is present, the more likely one is to develop a diabetic complication
Neuropathy Retinopathy Nephropathy Peripheral vascular disease
Surgical Effects on Type 2 Diabetes
90 80 70 60 50
40
30 20 10 0
Gastric banding Gastric Intestinal bypass bypass
Percent resolved
Swedish Obesity Study
Rate of recovery of subjects
80 70 60 50 40 30 20 10 0 2 years 10 years
Sjostrom et al NEJM 2004;351:2683-93
Control Surgery
Effectiveness of Obesity Treatments
0
Percent total weight loss
5 10 15 20 25 30 35 40 45 0 1 2 3 4 5 6 7 8 9 10 Gastric bypass Lifestyle and Medications Gastric banding
Years
How does bariatric surgery help resolve DM2?
GLP-1 Glucagonlike Peptide 1
Produced in the ileum L-cells as a response to the presence of nutrients Stimulates insulin secretion and insulin receptors Stimulates growth of beta cells in pancreas Slows stomach and gut motility following a meal
ileal break hormone
Reduces food intake and provides a sense of fullness
de Graaf C, et al Am J Clin Nutr 2004;79:946-961
Mechanism of Action of Gastric Bypass
Proximal Hypothesis Exclusion of duodenal nutrient passage may offset an existing abnormality
Mechanism of Action of Gastric Bypass
Distal Hypothesis Nutrients reach distal ileum within 5 minutes of food ingestion, stimulating GLP-1 secretion
TEST MEAL
2 toasts 20 gr hamburger 100 gr tomato 140 gr olive oil 10 ml half an egg TOTAL 390
Kcal
74 MBq 99m TC sulfur colloid
Ileal Transposition
Bariatric Surgery
A Systematic Review and Metaanalysis
Excess Weight Loss
All patients Gastric banding Gastric bypass Gastroplasty BPD/DS 612 581-644 475 407-542 616 567-665 682 615-748 701 663-739 01 05 11 768 700 improved not resolved 617 857
Operative Mortality 30 days
Restrictive procedures Gastric bypass BPD/DS
Comorbidity Resolution
Diabetes Hyperlipidemia Hypertension Obstructive sleep apnea
Buchwald et al JAMA 2004;292:1724-1737
Outcomes: Long-Term Mortality Gastric Bypass
9949 post GBP single surgical center 9628 case-matched population-based controls drivers license applicants Mean follow-up: 71 years
Adams et al NEJM 2007 357:753-61
Outcomes: Long-Term Mortality Results mean follow-up: 71 years
GBP reduced mortality by 40 GBP reduced mortality from: - Coronary artery disease by 56 - Diabetes by 92 - Cancer by 60 - Other circulatory diseases by 55 - Other deaths by 36
Adams et al NEJM 2007;357:753-761
Outcomes: Long-Term Mortality Lap-Band
n Surgery MCCS 1468 2119 Follow-up in patient years 5960 25,280 Deaths 5 225
Single surgeon practice
MCCS: Melbourne Collaborative Cohort
Study
Cox regression analysis: surgical patient was 73 less likely to die
Data presented at International Congress of Obesity, Sydney, Australia, September 2006
Outcomes: Long-Term Mortality SOS study
Gastric surgery patients n 2010 Obese control subjects n 2037 Follow-up 109 years Mortality rate reduction in surgery group 246 P 003 Adjusted risk reduction in surgery group 316 P 0008
Data presented at International Congress of Obesity, Sydney, Australia, September 2006
Summary
The prevalence of obesity continues to rise with a concomitant rise in the prevalence of DM2 BMI 35 confers a nearly 100 relative risk of DM2 DM2 prevalence is 57 in obese patients Weight-loss surgery is the most effective and durable therapeutic option for disease resolution Mechanisms of postoperative euglycemia are undefined but probably related to GLP-1 secretion
