Surgery for T2DM in BMIs < 35. Novel Procedures

• The Center of Excelence for the Surgical Treatment of Obesity and Metabolic Disorders

Hospital Oswaldo Cruz, São Paulo, Brasil

Ricardo Cohen MD FACS

•Why operate? Evidences in the obese population:

• Decreased long term mortality, CV, all cause and T2DM related (Sjostrom,2004; Christou,2004; Flum, 2004;Adams, 2007)

• Evidences of resolution without direct relation to weight loss in some bariatric operations (Laferrere,2008;Lee,2008;Patou 2008)

Surgery over the GI tract can improve T2DM controlSurgery over the GI tract can improve T2DM control

Surgery over the GI tract can improve T2DM controlSurgery over the GI tract can improve T2DM control

If it seems that there is a surgical induced antidiabetic effect, and most diabetics in the world are NOT morbidly obese, most of them are NOT under control, why not offer this option to some selected patients???

45 % with BMI BELOW 30

• 10 to 15% of T2DM are normal weight (Mokad, in JAMA,2000)

• 70% of morbidly obese patients have NO T2DM!!

Duodenal-Jejunal Bypass

with sleeve gastrectom

y

Ileal interposition

Sleeve gastrectomyNovel procedures

T2DM & THE METABOLIC EFFECTS OF BARIATRIC SURGERYT2DM & THE METABOLIC EFFECTS OF BARIATRIC SURGERY

Novel Surgical OptionsNovel Surgical Options

• Ileal Interposition +/- Sleeve GastrectomyIleal Interposition +/- Sleeve Gastrectomy• Physiologic Basis = Enteroinsular AxisPhysiologic Basis = Enteroinsular Axis

• HighlightsHighlights• Complex MIS procedureComplex MIS procedure

• 3 GI anastomosis3 GI anastomosis

• Scant worldwide experienceScant worldwide experience

T2DM & THE METABOLIC EFFECTS OF BARIATRIC SURGERYT2DM & THE METABOLIC EFFECTS OF BARIATRIC SURGERY

Novel Surgical OptionsNovel Surgical Options• “ “First in Man” Ileal interposition & Sleeve First in Man” Ileal interposition & Sleeve GastrectomyGastrectomy

• 19 patients19 patients• Mean 37 years oldMean 37 years old• Mean BMI 40 (range 35-44)Mean BMI 40 (range 35-44)

• Select co-morbiditySelect co-morbidity• n=5 T2DM - n=5 T2DM - At 3 weeks, 5/5 T2DM patients off meds with normal FPGAt 3 weeks, 5/5 T2DM patients off meds with normal FPG• n=8 HTNn=8 HTN• n=2 OSAn=2 OSA• n=11 hyperlipidemin=11 hyperlipidemiaa

A dePaula et.al. SOARD, 2006

Ileal interposition- De Paula, 2008

– Conclusions: Laparoscopic II-SG and II-DSG seem to be promising procedures for the control of the metabolic syndrome and type 2 diabetes mellitus. Excluding the duodenum may improve results. A longer follow-up period is needed.

Surg Endosc Surg Endosc

De Paula II/SGII

• RCT- IT with and without duodenal exclusion

Adding a duodenal exclusion improves results (ASMBS,2009)

IT + Duodenal Exclusion improves(DSG)T2DM more than without excluding the duodenum

SOARD, in press

Ileal Interposition- De Paula

• It’s effective, although complex a procedure :

• ~ 10% of pts with BMI 20-22 were operated(may be criticized)

• 3.5% mortality

• Revisions (unpublished data) described for several reasons

• major operation, tough patients, ~ 7.5% of major complications

Sleeve gastrectomy in lower BMIs

There were only 3 T2DM pts, with 2 resolutions and 1 improvement, related to weight loss

4

9

8

7

6

5

0 1 2 3 4 5 6 7 8 9Hb

A1

c (%

)

Time Post Surgery (month)

26

30

29

28

27

0 1 2 3 4 5 6 7 8 9

BM

I (kg

/m2)

Time Post Surgery (month) R Cohen et.al SOARD, 2007

1st Protocol - Original Intact Stomach DJB1st Protocol - Original Intact Stomach DJB

• 46 pts46 pts- April 2007-March 2008April 2007-March 2008- 27 men27 men- Hx of T2DM – 2 to 10 yearsHx of T2DM – 2 to 10 years- BMI 22-34.9BMI 22-34.9- Fasting C peptide>1Fasting C peptide>1- LADA ruled out LADA ruled out

( (negative antibodies)negative antibodies)

• Analysis of 46 patients withAnalysis of 46 patients with @ 12 mo follow-up@ 12 mo follow-up

Surgical treatment of T2DM

Outcomes Classification Outcomes Classification

• ResolutionResolution - - No meds/insulin, HbA1c<7No meds/insulin, HbA1c<7

• ControlControl - - Less meds/no insulin, HbA1c<7Less meds/no insulin, HbA1c<7

• ImprovementImprovement- - Less meds/no insulin, Less meds/no insulin, HbA1c< baselineHbA1c< baseline

• Non responseNon response - - Same or worst than Same or worst than baselinebaseline

Outcomes Classification

Resolution Control ImprovementNo

response

10 cases 4 cases 3 cases 7 cases

Between resolution and Improvement = 70%41 % of pts are OFF MEDS

All insulin users, including non responders are OFF insulin

Delta BMI Delta BMI x A1c and FPGx A1c and FPG

Delta BMI HAS NO IMPACT in the negative variation of A1c AND FPG from preop to 12 months

FPG

No relation between weight

loss/gain and DM resolution

We have learned and moved forward, seeking for better

results

• The role of Ghrelin

• The role of the biliary limb lenght

Results w

ere less dramatic

than

those in th

e obese population

GHRELIN

↑ GH

↑ ACTH & Cortisol

↑ Epinephrine

↑ Glucagon?

↓ Adiponectin

↓ Insulin Action

↓ Insulin Secretion

↑ Food Intake

↑ GLUCOSEC

ounter-regulatory

Courtesy of DE Cummings

Ghrelin

is D

iabetogenic

Moving Forward• Increased the biliary limb lenght

Data suggests that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB with longer biliary limbs.

ADA

Sleeved DJB orShort DS

100 cm150 cm

BIG TRIALS• it’s not all about sugar !!!!

2008;358:580-91.

Sleeved DJB orShort DS

• Endpoints in 24 mo

• A) Primary• Glycemic control - fasting and post prandial

• A1c<7

• B) Secondary• Blood pressure

• Lipids

• Carothideal Inthima Thickness(CIT)

2nd Protocol - Sleeved DJB orShort DS

• May 2008 - Jul 2009• 78 operated cases

• Mean BMI = 28.6 ( 25.6-30.4)

• Mean time of Hx of T2DM - 13.3 y( 4-20 y)

• Mean preop A1c= 8.2+- 0.9

• 46 insulin users ( 59%)

• Ruled out LADA ( negative GAD/ICA)

• Fasting C peptide over 1, with corrected fasting glycemia below 120 mg/dl

• Increase of C peptide after a mixed meal challenge

Sleeved DJB orShort DS

• RESULTS

• First 30 pts @ 12mo Follow up

• TBWL 9.7% +- 2.6%

• 22 insulin users

Follow-up Mean A1c Insulin Unchanged Control,A1c<7

Less medsResolution No meds,A1c<7

12 mo 6.3+-0.4* NONE 3%( 1 pt) 24%(10 pts)

63%(19 pts)

* 11 ( 37%) pts with A1c less than 6

97% between Control &Resolution

Is there weight loss relation to T2DM resolution?

• Although there is some weight loss, there is no direct cause-effect relation !

Why the more WL, worst outcome?

Can anybody tell me why?

Delta BMI

A1c<7, NO MEDS

Change in body composition?

• Hb A1c preop to 12 months - * p<0,05

8..9+-0.9

7.1+-0.46.9+-0.6

6.3+-0.4*

FPG preop to 12 months - * p<0,05

176+-19

123+-9

101 +-13*

142+-23

120 min Mixed meal challenge preop to 12 months - * p<0,05

242+-23

196+-11

140+-13

161+-14

Preop 3 mo 6 mo 12 mo

CIT

• n= 30, in mm, * p<0.05

preop 3 mo 12 mo

0,71±0,16 0,69±0,11 0,60±0,14*

*p<0.05 vs. preop

BP(mmHg)n= 30, *p<0,05

preop 6 mo 12 mo

PAS 131,1±14,5 123±11,* 120 ±13,8*

PAD 88,7±7.4 80±12,* 71 ±12,7*

Lipid Profile

Preop 6 mo 12 mo

HDL 41 ±9,5 44 ±6,7 48,7 ±9,8

LDL 181 ±23,7 127±13,5 101 ±12,7*

Tryglycerides 337 ±54,3 210 ±31,9 111 ±14,3*

* p<0.05

Short DS and low BMI T2DMPredictors of Success(A1c<7)

• There is NO significance, comparing preop to 3,6, 9 & 12 mo ( **p<0.05)

• Gender

• Time of Hx of T2DM ( 2- 20 years)

• Previous use of insulin

• Weight loss

• Homa IR decrease

• Homa B increase

• Preop fasting and stimulated C peptide

• ** p value of Chi-Square test, Exact Fisher test or Mann-Whitney test

Delta WC x Success

• If pts lost > 7% of WC @ 6 mo they tend to succeed (P=0,05, Non parametric Mann-Whitney test)

GI Surgery for T2DM

• Sleeved DJB /Short DS is more effective that “Classic DJB”

• The only predictor is the loss of more than 7% of WC until the 6th month

• T2DM history and previous use of insulin(after proper screening)has no effect on success

• No straight relation between WL and success

• Why the more WL, less chance for success???? Change of paradigm !

DJB-literature

DJB-literature

Remission Improvement remission and improved

LRYGB 100% 100%

LSG 67% 33% 100%

LAGB 50% 25% 75%

LSG+DJB 93% 7% 100%

DJB-literature

Modest decrease in BMI, withdecrease in A1c @ 6 mo

T2DM surgery in lower BMIs

• BMI 30-35, growing support for surgery in uncontrolled T2DM patients.

• RYGB and BPD seems to have a good role

Treatment AlgorithmWe want to be “an arrow”!!!

BMI > 30

Psychologic stability12 month history of uncontrolled DM/Metabolic Syndrome

Metabolic Surgery

T2DM surgery in lower BMIs

• BMIs below 30 : “Different” patient• Ileal interposition may be a good option, but

carries a higher mortality and morbidity rates, as is a complex procedure in a complex patient. MORE DATA NEEDED.

• In De Paula’s randomized trial between II+SG versus II+SG+duodenal diversion,bypassing the duodenum improves results!!

• Sleeved duodenal exclusion, seems so far a good procedure, BUT WE NEED MORE DATA!!

T2DM surgery in lower BMIs

• Although we believe that we have several SILENT EVIDENCES, that point us that surgery may benefit T2DM in lower BMIs, we need to start speaking NATIVE CONTEMPORARY DIABETOLESE!

RANDOMIZED CONTROLLED TRIALS!!!

RYGB x Sleeved DJBxBest Med treatment in BMIs 26-35

Work in Progress !!

45

Increased Insulin Resistance

Plasmatic Insulin

Blood sugar

Beta cell failure

Beta cell failure

T2DM symptoms

T2DM symptoms

Timing for SurgeryTiming for Surgery

Time

T2DM Surgery

Climbing the EverestClimbing the Everest

We’re here!

Need to get to the top!!

Serious studies demanded!