1. Surgery: Considerations and Research
First Annual Minnesota Pediatric Obesity Conference Practical Approaches for Managing and Preventing Pediatric Obesity
Surgery: Considerations and Research
Sayeed Ikramuddin, MD

2. Aldolescent obesity

3. Disclosures Fellowship support: Ethicon, Covidien
Research grant support: Covidien
Proctorship: Ethicon
I will discuss off label use of the gastric band system

4. Retrospective analysis
600 gastric bypass patients, of which approx 300 had T2DM
Examined role of gastric bypass in treating T2DM and followed patients for as long as 14 years
At that time, approx 80% were taking no medication and 99% of those with abnormal fasting glucose became euglycemic
Pories, W.J., et al., Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg, (3): p ; discussion

5. Bariatric surgery procedures
Roux En Y Gastric Bypass (RNYGP)
50% of procedures in 2008
Laparoscopic Adjustable Gastric Banding (LAGB)
40% of procedures in 2008
Biliopancriatic Diversion w/ Duodenal Switch (Switch)
3-5% of procedures in 2008
Laparoscopic Sleeve Gastrectomy (LSG)
5-7% of procedures in 2008

6. Diabetes resolved = discontinued treatment, Diabetes improved = reduced treatment.
Buchwald H. Estok R. Fahrbach K. Bantle D. Jensen MD. Pories WJ. Bantle JP. Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. American Journal of Medicine. 122(3): e5, 2009 Mar.

7. Glycemia as an Endpoint
Year
Author N
Level
Therapy
Control
Outcome
2008
Dixon J 60 A
LAGB (BMI kg/m2)
Medical management
72% Resolution of Type 2 DM
2007
Sjostrom L
4047
Surgery (GBP, GB, VBG)
24% reduction in mortality with surgery
2006
O’Brien PE 79
LAGB (BMI kg/m2)
Reduction in metabolic syndrome
93%- surgery vs.
46%- medical management
2004
Buchwald H
22,094 B
Bariatric Surgery
Meta Analysis
77% Resolution of Type 2 DM
Adams TD
15,850
RYGBP
Conventional treatment
92% reduction in diabetes related death
le Roux CW 39
/LAGB
Lean and obese patients
improved insulin, GLP-1 response after RYGBP
Lee WJ
158 C
RYGBP < 35 kg/m2
RYGBP >35 kg/m2
76.5% success in BMI<35 kg/m2; 88.9% success in BMI 35–45 kg/m2,
Cohen R 37
97% Resolution of Type 2 DM
2005
Torquati A
107
Wickremesekera K 31
Insulin resistance decrease at 6 days post surgery maintained after 12 months;
This Slide shows a selected evidence list graded in line with ADA guidelines and shows that surgery is very effective at treating diabetes. All of these papers cited in this presentation, as well as those cited in our public comment from Dr. Denman, are included in the CD we have distributed
This includes three randomized prospective trials and one meta-analysis. Dixon and Sjostrom were the subject of international media attention given there robust design and long term follow-up respectively.
While scientific rigor declined as we move down the table, we see consistent findings from study to study and center to center that surgery is highly effective in achieving resolution of t2dm – resolution being normal a1c, normal fasting glucose and no requirement for medications; The studies have endpoints ranging from 1 to 14 years.
Data is also included for patients with a BMI below 35kilogram per meter squared. While these studies lack sufficient power or follow-up, Cohen and Lee, both showed high success in the treatment of diabetic patients with gastric bypass.
Two studies show a decrease in deaths in the surgery cohort compared a non-surgery cohort. Adams, published last year in the New England Journal of Medicine, showed an 92% reduction is diabetes associated deaths.
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8. In which remission is defined as: No antihyperglycemic meds AND either A1c<6% or Glu<100, except in the case of both labs being available, in which case BOTH conditions must be met.
When multiple lab values are available for one AV, the one closest to the midpoint (ie: 12, 24, 36 months, etc) is used.
%Weight Loss (%WL) = [ (Weight Preop – Weight Postop) / Weight Preop ] *100

9. Gastric bypass Small divided gastric pouch (30 cc)
Roux limb 75cm-150cm Biliopancreatic limb 20cm-100cm
antecolic or retrocolic roux
“Gold Standard”

10. Bypass considerations
Longest followup
moderate malabsorption (Iron, B12, Thiamine)
hypoglycemia
marginal ulcers
excluded stomach
internal hernia
Higher perioperative complications

11. adjustable band Restrictive procecure Low volume high pressure band
Pars Flaccida Approach
adjust to produce wt loss of kg/week

12. Band considerations Not FDA approved for < 18
very low short term morbidity and mortality
poor results in the superobese
explantation 10%
long-term risk of slippage
long-term risk of erosion
need for adjustments

13. Procedures
Band
Sleeve
Gastric bypass
Duodenal switch

14. Sleeve considerations
little long term data
potential for leak
insurance coverage an issue
Increased incidence of GERD
No nutritional complications
ease of conversion to DS or to RNY

15. Duodenal switch Malabsorbtive and restrictive procedure
most durable weight loss
4% incidence of revision for nutritional problems
42F sleeve (32-60)
100 cm common channel (50-125)

16. Effectiveness of Weight Management Programs in Children and Adolescents

17. Effectiveness of Weight Management Programs in Children and Adolescents

18. Introduction Weight Loss Surgery in Adolescents
The treatment of the morbidly obese adolescent patient is controversial.
No clear consensus on best treatment of the morbidly obese adolescent.
Contention between bariatric surgeons and pediatricians.

19. Adolescent Obesity and Diabetes What is Known
A steep rise in the prevalence of T2DM parallels the rise in obesity .
Young patients with T2DM have rapidly progressive disease.
5 fold increase in the incidence of obesity since 1970’s
Progressive retinopathy and ASHD noted within 5yrs of diagnosis of T2DM in young adults.
Health-related QOL 5.5x more likely to be impaired compared to healthy kids. similar to those diagnosed as having cancer.
# Kohn M and Booth M. Adol Med 2003
*Schwimmer JB, Burwinkle TM, Varni JW. JAMA 2003

20. Adolescent Obesity What is Unknown
When is the best time in the course of development (physical and emotional) for surgical intervention?
How is compliance in this patient population?
What are the long-term nutritional sequelae?
What are the multi-generational sequelae?
What are the long-term outcomes and recidivism rates?

21. Bariatric surgery Outcomes
Author (year) N
Procedure (n)
Age
range
Mean
follow- up
%EWL
Compl.
rate
Deaths
Lawson ML
et al. (3 centers;
2006) 39
LRYGB (34)
ORYGB (5)
13 to 21
1 year
(n=30)
63%
39%
(n=15) 1
(9 mos.)
Sugerman, et al. (2003) 33
LRYGB (2)
ORYGB (28)
Open gastroplasty (3)
12 to 17
Up to
14 years
58%
40% (n=13)
2 (late)
Stanford et al.
(2003) 4
LRYGB (4)
17 to 19
17 mos.
87% 0%
Strauss et al.
(2001) 10
ORYGB (10)
15 to 17
> 1 year
55%
50% late
(n=5)
Rand et al.
(1994) 34
ORYGB (30)
Open gastroplasty (4)
11 to 19
6 years
66% NR
Barnett et al.
(2005) 15
Open gastroplasty (7)
JIB (3)
13 to 17
(>9 mos.)
(n=9)
64%
33%

22. Lap Band Outcomes Author (year) N Procedure (n) Age range Mean follow-up
%EWL
Compl.
rate
Deaths
Silberhumer
(2006) 50
LAGB (50)
9 to 19
35 mos.
61% 2%
Dolan et al.
(2003) 17
LAGB (17)
12 to 19
2 years
59%
12%
(n=2)
Agrisani (2005) 58
LAGB(58)
15-19 7
56%
10% band removal

23. Current Management of the Morbidly Obese Adolescent at the University of Minnesota
Evaluation by multidisciplinary team(statewide).
Pediatric gastroenterologist / weight loss specialist
Pediatric psychologist
Bariatric surgeon with > 50 cases adolescent
Dietician: minimum of 6 months
Intensive medical weight loss program
Outpatient / inpatient treatment
Bariatric surgery candidate
Demonstrated compliance with medical weight loss
Serious medical comorbidities

24. Demographics: LRYGB (n=30) Laparoscopic Weight Loss Surgery in Adolescents
Mean age 17.0 (range 12-19)
8 patients ≤ 15 years
Mean BMI 55 kg/m2 (range )
Mean weight 156 kg (range kg)
All > 95th percentile for BMI
Two patients with BMI > 90 kg/m2 were hospitalized ≥ 1 month preoperatively for intensive medical management.

25. Comorbid Diseases (Total 66)N
Musculoskeletal
Painful joints (10)
Low back pain (6)
Arthritis (2) 18
Pulmonary
Obstructive sleep apnea (5)
Asthma (4)
Bronchitis (1) 10
Depression / Anxiety
Cardiovascular
Hypertension (4)
Dyslipidemia (9) 13
GERD 5
Metabolic / Endocrine
Type 2 diabetes mellitus (2)
Polycystic ovary syndrome (3)
Genitourinary
Urinary stress incontinence (2)
Renal stones (1) 3
Pseudotumor cerebri 2

26. Follow-Up Laparoscopic Weight Loss Surgery in Adolescents
Range 0 to 45 months, mean 15.8 months.
14 patients had ≥ 12 month follow-up.
Poor overall compliance with follow-up.
28.1% (n=9) lost to follow-up.
Letters sent, phone calls made.
Of those who didn't follow-up
55.6% (n=5) lost within first year
44.4% (n=4) lost after 18 months

27. Adolescent Outcomes

28. Results: LRYGB Weight Loss Weight Loss Surgery in Adolescents
12 y/o Pseudotumor cerebri BMI 47
33 months post op BMI 25.5 = 90% EWL
Normal growth exceeding mid-parental height

29. Weight Loss Surgery in Adolescents
Summary of Findings
Weight Loss Surgery in Adolescents
Adolescent bariatric surgery appears to be similar to adult bariatric surgery in terms of weight loss and complications.
surgery safe in short term followup across the age spectrum
followup can be more difficult than the adult population
Absolute commitment to post-operative follow-up schedules need to be made pre-operatively with adolescent patients and their parents.
evidence for choice of operation mixed

30. Band Lower BMI(30-40)
it is the amount of weight loss not the method that determines the remission of type 2 diabetes
Dixon et al JAMA January 23rd 2008

31. Glucagon-Like Peptide-1 or GLP-1 (“Enteroglucagon”)
The Effects of Bariatric Surgery on Type 2 Diabetes The Entero-insular Axis
Glucagon-Like Peptide-1 or GLP-1 (“Enteroglucagon”)
Secreted by ileal “L-cells” in (rapid) response to a meal
Actions
Potent stimulator of insulin / supresses glucagon
Slows gastric emptying
Reduces appetite
Increases beta cell mass
Increased after gastric bypass (??)
Peptide YY (PYY)
Gastric Inhibitory Polypeptide (GIP)
Wynne K. J Clin Endo Met, 2004

32. Select “known” peptides with various effects
The Effects of Bariatric Surgery on Type 2 Diabetes The Entero-insular Axis
Enteral glucose ingestion yields a greater insulin release than does parenteral glucose infusion *
Secreted gut hormones effect insulin production, secretion and usage = “incretins” / “anti-incretins”
Select “known” peptides with various effects
* Elrick H. J Clin Endocrinol Metab. 1964

33. The Effects of Bariatric Surgery on Type 2 Diabetes The Entero-insular Axis
1967 – Gastric Bypass
Rehfeld J, 2004

34. Peptides in T2DM
GLP-1 response to mixed meal is blunted compared to non diabetics
GIP response is blunted
After weight loss GLP-1 response improves

35. Exaggerated GLP-1 and Blunted GIP Secretion are Associated with Gastric Bypass but not Gastric Banding
Korner J, Bessler M, Inabnet WB et al. Surg Obes Relat Dis Oct 10; [Epub ahead of print] .

36. Insulin response with OGTT RNY
LaFerre et al JCEM 2008

37. Ghrelin
Cummings et al NEJM

38. Bariatric Surgery: Effects on Weight Loss and Mortality14
Control
29% 12
Control 10
-10
Band 8
Change in Weight (%)
Cumulative Mortality (%)
Surgery
-20
VBG 6 4
p = 0.04
Gastric Bypass
-30 2
Sjostrom, in the landmark Swedish Obesity Study, the SOS study, also published last year in the New England Journal of Medicine, showed a mortality reduction of 24% in the bariatric surgery arm at 15 years. They also showed a significant long term weight reduction in the surgical arm, with gastric bypass showing greater weight loss than gastric banding or vertical banded gastroplasty. Interestingly, this study included significant numbers of VBG patients which likely compromised the potential benefit when compared with a gastric bypass dominant population
One of the largest differences in outcomes was the lower number of myocardial infarctions in the surgery group, 13 compared to 25, p = (chi- square dichotomous comparison 2 4 6 8 10 15 4 8 12 16
Years
Years
Sjostrom, L, et.al.; N Engl J Med. 2007;357:741-52
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39. Case Matched Mortality (Mean Follow up of 7.1 years; out to 18 years
All Subjects
Matched Subjects
Surgery Group
(N = 9949)
Control Group
(N = 9628)
(N = 7925) No
./10,000
person-yr
/10,000
n/10,000
All causes of death
288
37.2
425
61.1
213
37.6
321
57.1
All deaths caused by disease
198
25.6
380
54.7
150
26.5
285
50.7
Cardiovascular disease 66
8.5
134
19.3 55
9.7
104
18.5
Coronary artery disease 17
2.2 46
6.6 15
2.6 33
5.9
Heart failure 2
0.3 7
1.0
0.4 6
1.1
Stroke 9
1.2 14
2.0 11
Other cardiovascular disease 38
4.9 67
9.6 31
5.5 54
Diabetes 24
3.5 19
3.4
Cancer 42
5.4
102
15.0 73
13.3
Other diseases 88
11.4
120
17.0 62
11.0 89
15.5
All nondisease causes 90
11.6 45
6.5 63
11.1 36
6.4
Accident unrelated to drugs 29
3.7
2.7 21
3.0
Poisoning of undetermined intent
1.9 4
0.6
1.6
0.7
Suicide 8 5
0.9
Other nondisease cause 25
3.2 18 10
1.8

40. Conclusion Type 2 DM is a complex disease
It is most strongly associated with obesity
Patient and physicians struggle to meet therapeutic goals
Bariatric surgery is established as a treatment of obesity
The effect on diabetes is profound
Clinical trials will allow for treatment of lower BMI individuals
Adolescents want to look like their peers but they also want to eat like their peers