Dr John B Dixon, MBBS PhDAssociate ProfessorHead of Obesity ResearchSchool of Primary Health CareMonash University, Melbourne, Australia

NHMRC Senior research fellowHypertension and Vascular – Obesity ResearchBaker Heart Research InstituteMelbourne, Australia

Diabetes surgery for the non-obese

Disclosures: Associate Professor John B Dixon

Abbott Speakers Bureau & Educational Material

Allergan Inc Consultant, Research Support

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Novartis Australia Educational material

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Diabetes surgery for BMI < 30

Why? Efficacy? Safety? How does it compare with medical therapy?

Why?

Relationship Between BMI and Risk of Type 2 Diabetes

Chan J et al. Diabetes Care 1994;17:961. Colditz G et al. Ann Intern Med 1995;122:481.

Ag

e-A

dju

sted

Re

lativ

e R

isk

Body Mass Index (kg/m2)

<23 24–24.9 25–26.9 27–28.9 33–34.90

25

50

75

100

1.02.9 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+

1.0 1.52.2 4.4

6.711.6

21.3

42.1

1.0

Men

Women

Where is the increase in diabetes occurring?

Gregg EW, Cheng YJ, Narayan KM, et al. Prev Med. 2007;45:348-52.

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 ?

Efficacy

403 gastric cancer patients with T2DM underwent gastrectomy between May 2003 and September 2009.

Information from medical records

T2DM: resolution, improvement, same, and worse.

Results – mean 10% weigh loss

Factors influencing diabetes course

Factors influencing diabetes course

Multivariate analysis:

Improvement was

influenced most greatly by weight loss and weight gain

Little happened with less than 10% weight loss

Authors conclusions

Total 29 studiesBrazil 12Italy 5USA 2Taiwan 2Korea 2Chile 2Australia 1Venezuela 1

Data on 675 patients

ProceduresLIILDJBLRYGBLMGBBPDLAGB

Mean BMI change29.95 – 24.83

17%

BMI < 35 – the whole reviewRemission HbA1c < 7% no medications

Prospective Study of RYGB for Type 2 DM in

Asian Indians With BMI < 35 kg/m2

BMI 22-35 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.

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.

Shah, S. S., J. S. Todkar, et al. (2009). Surg Obes Relat Dis.

RYGB in Asian Indians with body mass index <35 (n=15)

Source: Surgery for Obesity and Related Diseases (DOI:10.1016/j.soard.2009.08.009 )

Copyright © American Society for Metabolic and Bariatric Surgery Terms and Conditions

Shah, S. S., J. S. Todkar, et al. (2009). Surg Obes Relat Dis.

RYGB in Asian Indians with body mass index <35 (n=15)

Did you calculate the weight loss?

20%

Gastric bypass – TaiwanA comparison of BMI <35 & >35

BMI<35 n=44 BMI > 35 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): 945-952.

Mini-gastric bypass – TaiwanA comparison of BMI <35 & >35

BMI<30 Remission 62.5% cw 78% for >30

20 patients mini DSDuodenal 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): 307-312.

Type 2 diabetes (n=20)

Ramos, A. C., M. P. Galvao Neto, et al. (2009). Obes Surg 19(3): 307-312.

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):307-312.

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): 972-979.

• 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

Ileal Interposition – Sleeve Gastrectomy

Ileal Interposition – Diverted Sleeve Gastrectomy

ileum

ileum

Weight Change = 26%

Group comparisons with baseline - p<0.001

Pre (A) 0-12 (B) 13-24 (C ) 25-38 (D)05

101520253035

30.1

24 22.9 23.8

BMI

Months

Kg/m

2

0

2

4

6

8

10

pre post

Hb

A1

c

-%

lean OW OB

* * *

* p<0.001 vs corresponding group before surgery

82% of patients achieved optimal glycemic control, considered as HbA1c < 6.5%, without antidiabetic treatment

8.6%6.1%

DePaula AL, Vencio S, Mari A, Muscelli E, Ferranninni E. – Diabetologia 2009;52

HbA1c before and after surgery

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.

Ileal interposition with sleeve gastrectomy

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 25-30 HbA1c >7% Mean HbA1c 6.5% - Triglycerides went up

Scopinaro, N., G. F. Adami, et al. (2011). Ann Surg 253(4): 699-703.

Biliopancreatic diversion BMI 25 -30 (n=15) 30-35 (n=15)

BMI 30-35 HbA1c reduced from 9.5 – 5.9– Triglycerides fell and HDL-C unchanged

BMI 25-30 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): 880-888.

1 year changes

Beta cell defect V Insulin Resistance Hypothesis

0

10

20

30

40

50

60

70

80

20-25 25-30 30-35 40+

Insulin resistance

Beta cell defect

Age

-Adj

uste

d R

elat

ive

Ris

k

Body Mass Index (kg/m2)

<23 24–24.9 25–26.9 27–28.9 33–34.90

25

50

75

100

1.02.9 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+

1.0 1.52.2 4.4

6.711.6

21.3

42.1

1.0

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

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

Steno multifactorial intervention2 groups of 80 with type 2 diabetes and

microalbuminuria

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

Treatment of T2 diabetes

Blood pressure

Cholesterol, triglyceride

Smoking

Inactivity

Treatment of T2 diabetes

Blood pressure

Cholesterol, triglyceride

Smoking

Inactivity

& Glycemic control

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