1. Diabetes surgery for the non-obese
Dr John B Dixon, MBBS PhD
Associate Professor
Head of Obesity Research
School of Primary Health Care
Monash University, Melbourne, Australia
NHMRC Senior research fellow
Hypertension and Vascular – Obesity Research
Baker Heart Research Institute
Melbourne, Australia

2. Disclosures: Associate Professor John B Dixon
Abbott Speakers Bureau & Educational Material
Allergan Inc Consultant, Research Support
Bariatric Advantage Consultant, Speakers Bureau
Eli Lilly Speakers Bureau
Merck Sharp and Dohme Speakers Bureau
Nestle Australia Medical Advisory Board, Speakers Bureau, Research Support
Novartis Australia Educational material
ResMed Research Support
Scientific Intake Consultant & Research Support
SP Health Co Consultant
Weight Watchers Speaker and Educational Material
Valeant Pharmaceuticals Speaker and Educational Material

3. Diabetes surgery for BMI < 30
Why?
Efficacy?
Safety?
How does it compare with medical therapy?

4. Why?

5. Relationship Between BMI and Risk of Type 2 Diabetes
Age-Adjusted Relative Risk
Body Mass Index (kg/m2)
<23
24–24.9
25–26.9
27–28.9
33–34.9 25 50 75
100
1.0
2.9
4.3
5.0
8.1
15.8
27.6
40.3
54.0
93.2
<22
23–23.9
29–30.9
31–32.9
35+
1.5
2.2
4.4
6.7
11.6
21.3
42.1
Men
Women
The risk of diabetes increases with increasing BMI values in men and women [1,2]. Moreover, the age-adjusted relative risk for diabetes begins to increase at BMI values that are considered normal for men (24 kg/m2) and women (22 kg/m2) based on mortality risk. The marked increase in the prevalence of obesity is an important contributor to the 25% increase in the prevalence of diabetes in the United States over the last 20 years [3]. Increases in abdominal fat mass, weight gain since young adulthood, and a sedentary lifestyle are additional obesity-related risk factors for diabetes [1,4,5].
1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:
2. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:
3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, Diabetes Care 1998;21:
4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985;34:
5. Helmrich SP, Ragland DR, Leung RW, Paffenbarger Jr RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;325:
Chan J et al. Diabetes Care 1994;17:961.
Colditz G et al. Ann Intern Med 1995;122:481.

6. Where is the increase in diabetes occurring?
Gregg EW, Cheng YJ, Narayan KM, et al. Prev Med. 2007;45:

7. There is a burden of diabetes – But also real competition!
43% of those with diabetes are in this weight range
There are a range of interventions
Weight loss can produce important benefits in an intensive lifestyle program Look AHEAD
Dietary interventions
Metformin, SU, GLP-1 agonists, and DPP IV inhibitors and even insulin
Quenexa ?

8. Efficacy

9. 403 gastric cancer patients with T2DM underwent gastrectomy between May 2003 and September 2009.
Information from medical records
T2DM: resolution, improvement, same, and worse.

10. Results – mean 10% weigh loss

11. Factors influencing diabetes course

12. Factors influencing diabetes course

13. Multivariate analysis:
Improvement was influenced most greatly by weight loss and weight gain
Little happened with less than 10% weight loss

14. Authors conclusions

15. Studies of “Metabolic Surgery” BMI <35
Fried, M., G. Ribaric, et al. (2010). Obes Surg 20(6):

16. Procedures Total 29 studies LII LDJB LRYGB LMGB Data on 675 patients
BPD
LAGB
Total 29 studies
Brazil 12
Italy 5
USA 2
Taiwan 2
Korea 2
Chile 2
Australia 1
Venezuela 1
Data on 675 patients
Mean BMI change
29.95 – 24.83
17%

18. BMI < 35 – the whole review Remission HbA1c < 7% no medications

19. Prospective Study of RYGB for Type 2 DM in Asian Indians With BMI < 35 kg/m2
“Overweight” to “Obese” by Indian-specific
WHO criteria
Type 2 DM
Confirmed with Abs, C-peptide, FHx
Severe diabetes
Mean duration: 9 years
80% on insulin (all others or oral DM meds)
HbA1c: 10.1%
Other features
Dyslipidemia: 93%
Hypertension: 60%
Shah, S. S., J. S. Todkar, et al. (2009). Surg Obes Relat Dis.

20. RYGB in Asian Indians with body mass index <35: baseline and 9 months (n=15)
Shah, S. S., J. S. Todkar, et al. (2009). Surg Obes Relat Dis.

21. RYGB in Asian Indians with body mass index <35 (n=15)
There was significant and sustained reduction in HbA1c throughout the 9 months following RYGB (* after surgery).
Shah, S. S., J. S. Todkar, et al. (2009). Surg Obes Relat Dis.

22. RYGB in Asian Indians with body mass index <35 (n=15)
There was significant and sustained reduction in FBG throughout the 9 months following RYGB (* after surgery).
Shah, S. S., J. S. Todkar, et al. (2009). Surg Obes Relat Dis.
Source: Surgery for Obesity and Related Diseases (DOI: /j.soard )
Copyright © American Society for Metabolic and Bariatric Surgery Terms and Conditions

23. Did you calculate the weight loss?
20%

24. Gastric bypass – Taiwan A comparison of BMI <35 & >35
BMI< n=44
BMI > n=157
Weight loss at 1–year 32% for all
HbA1c <7% 76.5% of BMI<35 kg/m2 92.4% of BMI>35 (p=0.06)
While there was a lower response rate in those with BMI <35 results still acceptable
Lee, W. J., W. Wang, et al. (2008). J Gastrointest Surg 12(5):

25. Mini-gastric bypass – Taiwan A comparison of BMI <35 & >35
BMI<30 Remission 62.5% cw 78% for >30

27. 20 patients mini DS Duodenal part jejunal exclusion
BMI 20-30
Excluded very poor control
Selected only patients taking metformin, sulponylurea and glitizones included
Ramos, A. C., M. P. Galvao Neto, et al. (2009). Obes Surg 19(3):

28. Type 2 diabetes (n=20)
Ramos, A. C., M. P. Galvao Neto, et al. (2009). Obes Surg 19(3):

29. Laparoscopic Duodenal - jejunal bypass
20 diabetic patients underwent laparoscopic duodenal-jejunal exclusion.
There was significant weight loss Mean 10%
Only two patients were on oral medication after the sixth months - Only included those on oral hypoglycaemics
There were no comments on complications in particular gastric emptying issues
Studies with longer follow-up and a larger number of patients are necessary to better define the role of this new and promising procedure.
Ramos AC, et al. Obes Surg. Mar 2009;19(3):

30. Lap Duodenal-Jejunal Bypass (n=7)
12 month prospective observational study
Remission 1:7
Most reduced medications for diabetes
HbA1c 9.4% to 8.5%
FPG 209 to 154 mg/dl
BMI 27.5 – 27.3
Authors recommend caution
Ferzli, G. S., E. Dominique, et al. (2009). "Clinical improvement after duodenojejunal bypass for nonobese type 2 diabetes despite minimal improvement in glycemic homeostasis." World J Surg 33(5):

31. Prospective randomized controlled trial of two versions of laparoscopic ileal interposition with sleeve gastrectomy
Type 2 diabetic patients with BMI 21 – 34
Mean follow-up of 25 months
HbA1c < 7 without medication in 90.9% of patients

32. Diverted Sleeve Gastrectomy
Ileal Interposition –
Sleeve Gastrectomy
Ileal Interposition –
Diverted Sleeve Gastrectomy
ileum
ileum

33. Weight Change = 26%
Group comparisons with baseline - p<0.001

34. HbA1c before and after surgery*
8.6%
6.1%
* p<0.001 vs corresponding group before surgery
82% of patients achieved optimal glycemic control, considered as HbA1c < 6.5%, without antidiabetic treatment
DePaula AL, Vencio S, Mari A, Muscelli E, Ferranninni E. – Diabetologia 2009;52

35. Ileal interposition with sleeve gastrectomy
At a 3-year follow-up there was a significant improvement in insulin sensitivity, insulin secretion and in the disposition index, as measured by a 3-hour OGTT study in type 2 diabetic patients who underwent laparoscopic ileal interposition with sleeve gastrectomy.

36. Biliopancreatic diversion BMI 25 -35 (n=30)
Remission in 30% at 12 months
Diabetes remission correlated positively with BMI at 12 months
Initial BMI R2 = 0.25; P = 0.02
All patients with BMI ≥30 kg/m2 were in control at 12 months,
5 patients with BMI HbA1c >7%
Mean HbA1c 6.5% - Triglycerides went up
Scopinaro, N., G. F. Adami, et al. (2011). Ann Surg 253(4):

37. Biliopancreatic diversion BMI 25 -30 (n=15) 30-35 (n=15)
1 year changes
BMI HbA1c reduced from 9.5 – 5.9
Triglycerides fell and HDL-C unchanged
BMI HbA1c reduced from 9.1 – 6.9
Triglycerides were higher
HDL-C lower
It seem BMI may be quite important!
Scopinaro, N., G. F. Adami, et al. (2011). Obes Surg 21(7):

38. Beta cell defect V Insulin Resistance Hypothesis
Age-Adjusted Relative Risk
Body Mass Index (kg/m2)
<23
24–24.9
25–26.9
27–28.9
33–34.9 25 50 75
100
1.0
2.9
4.3
5.0
8.1
15.8
27.6
40.3
54.0
93.2
<22
23–23.9
29–30.9
31–32.9
35+
1.5
2.2
4.4
6.7
11.6
21.3
42.1
The risk of diabetes increases with increasing BMI values in men and women [1,2]. Moreover, the age-adjusted relative risk for diabetes begins to increase at BMI values that are considered normal for men (24 kg/m2) and women (22 kg/m2) based on mortality risk. The marked increase in the prevalence of obesity is an important contributor to the 25% increase in the prevalence of diabetes in the United States over the last 20 years [3]. Increases in abdominal fat mass, weight gain since young adulthood, and a sedentary lifestyle are additional obesity-related risk factors for diabetes [1,4,5].
1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:
2. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:
3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, Diabetes Care 1998;21:
4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985;34:
5. Helmrich SP, Ragland DR, Leung RW, Paffenbarger Jr RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;325:

39. Safety Safety data is limited and mixed
It appears related to the complexity of the procedures
Surgery is NOT likely to be safer than in class 1 obese patients
No data on nutrition, quality of life, functional capacity, body composition, depression and psychological wellbeing

40. Gaede et al., NEJM, 2008;358:580-91

41. Steno multifactorial intervention 2 groups of 80 with type 2 diabetes and microalbuminuria
Gaede et al., NEJM, 2008;358:580-91

42. Treatment of T2 diabetes
Blood pressure
Cholesterol, triglyceride
Smoking
Inactivity

43. Treatment of T2 diabetes
Blood pressure
Cholesterol, triglyceride
Smoking
Inactivity
& Glycemic control

44. My Conclusions Evidence for surgery is very limited
The best results come with the best weight loss
Surgery is less effective at lower levels of BMI
We will need properly conducted RCTs and benefits likely to be less substantial than in the severely obese
Surgery specifically designed for GI effects without generating significant weight loss should proceed cautiously
The competition at level is considerable and evidence WILL need to be of high quality and compelling