dr john b dixon, mbbs phd associate professor head of obesity research school of primary health care...
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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
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
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