1. Department of Internal Medicine
Short-term and longer-term metabolic effects of biliopancreatic diversion (BPD) in non-morbidly obese patients with type 2 diabetes (T2DM)
Brenno D Astiarraga, Stefania Camastra, Monica Nannipieri, Andrea Mari1, Simona Baldi, Francesco Papadia2, Franco Adami2, Nicola Scopinaro2, Ele Ferrannini.
Department of Internal Medicine, University of Pisa, 1C N R Institute of Biomedical Engineering, Padova and 2 Department of Surgery, University of Genova, Italy
University of Pisa
School of Medicine
Department of Internal Medicine

2. Marked improvement or resolution of diabetes has been reported after bariatric surgery in morbidly obese patients (BMI ≥35 kg/m2). Preliminary evidence shows that bariatric surgery can improve glycaemic control also in patients with BMI ≤35 kg/m2.
In morbidly obese subjects, biliopancreatic diversion (BPD) induces an early improvement of insulin sensitivity and ß-cell function. These effects persists in the long term, after significant weight loss has occurred.
Recent studies suggest that diabetes control by bariatric surgery is the direct effect of the anatomical rearrangement of the small bowel, independently of weight loss.
BACKGROUND

3. AIMS
To assess diabetes remission and its mechanisms in T2DM patients with BMI ≤ 35 kg/m2 early and late after BPD by:
testing oral glucose tolerance
measuring ß-cell function in response to a mixed meal
measuring insulin sensitivity

4. STUDY PROTOCOL BPD Subjects: 15 T2DM (9 men/6 women)
Age: 56 ± 4 years (mean ± SD)
T2DM duration: 15 ± 6 years
BMI: 28.3 ± 2.1 kg/m2 ( )
Inclusion criteria:
HbA1c >8.0%, poor metabolic control, presence of comorbidities
Pharmacological treatment:
oral hypoglycaemic agents (n=6)
oral hypoglycaemic agents plus variable insulin doses (n=9)
The protocol was approved by the Ethics Committee
1 week
BPD
55±24 days
1 year
Pre-op
Post 1
Post 2
OGTT: Oral Glucose Tolerance test
MTT: Meal Tolerance Test
EHC: Euglycaemic Hyperinsulinaemic Clamp

5. STUDY PROTOCOL Standard OGTT - (75-gram oral glucose load)
MTT - (54% carboydrate, 30% lipid, 16% protein)
C-peptide deconvolution was used to reconstruct insulin secretion rates
ß-cell function was evaluated by mathematical modelling
Insulin clamp (240 pmol.m2.min-1) - Whole body glucose uptake, M value (mol.kgffm-1.min-1) was normalised to fat-free mass (FFM)

6. Biliopancreatic diversionml
300 cm
75 cm

7. RESULTS: Anthropometric and metabolic changes
0.0007
Pre-op
Post 1
Post 2
HbA1c (%)
0.01
BMI (kg/m2)
0.03
≤ 0.001
FPG (mmol/l)
0.06
FPI (pmol/l)
≤ 0.003
0.05

8. RESULTS: Changes in glucose tolerance (OGTT)
mean ± SE
T2DM remission
Pre-op
Post 1
Post 2
T2DM 15 11 9
Remission*
---- 4 6
Glucose (mmol/l)
Time (min)
Pre-op
Post 1
Post 2
* HbA1c<6.5% off Tx + FPG <7.0 mmol/l + 2-h PG <11.1 mmol/l

9. RESULTS: Changes in insulin sensitivity (M)
Pre-op
Post 1
Post 2 HC
HC = historical controls (210 BMI- and age-matched nondiabetic subjects). M
(µmol.min-1kgffm-1)
p =

10. RESULTS: Mixed Meal Test Insulin secretion (pmol.min.m2)
Glucose (mmol/l)
Insulin secretion (pmol.min.m2)
Time (min)
Pre-op
Post 1
Post 2

11. RESULTS: Insulin secretion vs glucose dose-response
(pmol.min-1.m2)
Glucose (mmol/l)
100
150
200
250
300
350
400 6 4 8 10 12 14 16 18 20 22
pre-surgery
2-month post
1-year post 50
450

12. RESULTS: Changes in ß-cell function (MTT)*
Total Insulin output
(nmol.m-2)
-cell glucose sensitivity
(pmol.min-1.m-2.mM-1)
0.01
0.04
0.05
Pre-op
Post 1
Post 2 HC

13. CONCLUSIONS
In non-morbidly obese patients with long-standing, poorly controlled T2DM, BPD is followed by a substantial amelioration in glycaemic control due to major improvements in both insulin sensitivity and ß-cell function despite relatively small weight loss. The improvement is evident early after surgery and is maintained in the longer term. Defects in both insulin sensitivity and ß-cell function, however, persist at one year.

14. RESULTS: Anthropometric and metabolic changes
Pre-op
Post 1
Post 2 p p1 p2
Weight (kg)
78 ± 11
68 ± 9
64 ± 10
0.0007
0.02
Mean glucose MTT (mmol/l)
18.2 ± 1.8
11.2 ± 2.3
10.4 ± 2.7
0.001 ns
Mean insulin MTT (pmol/l)
236 ± 127
129 ± 34
150 ± 75
0.002
0.01
Triglycerides (mmol/l)
1.94 ± 0.64
1.92 ± 0.71
1.90 ± 0.97
Total Cholesterol (mmol/l)
5.30 ± 1.56
3.47 ± 0.64
3.53 ± 0.44
0.007
0.009
HDL cholesterol (mmol/l)
1.18 ± 0.26
0.97 ± 0.18
1.06 ± 0.28
LDL cholesterol (mmol/l)
3.28 ± 1.41
1.53 ± 0.35
1.80 ± 0.30
0.03
data: mean ± SD
p = Post 1 vs Pre-op, p1 = Post 2 vs Pre-Op, and p2 Post 2 vs Post 1 by Wilcoxon signed rank test.

15. RESULTS: Changes in ß-cell function (MTT)*
Fast ISR
(pmol.min-1.m2)
0.03 ns
0.02
RESULTS: Changes in ß-cell function (MTT)*