1. Insulin-resistance in overweight women with breast cancer:
effect of cytokines and body weight,
before and after successful chemotherapy.
E. Chala1, C. Manes2, H. Iliades3, G. Skaragkas2, D. Mouratidou3 and E. Kapantais1
1: Dep.Diabetes-Obesity-Metabolism, Metropolitan Hospital, Athens - Greece
2: Diabetes Center, Papageorgiou Hospital, Thessaloniki - Greece
3: 3rd Dep. Clinical. Oncology, Theagenio Hospital, Thessaloniki - Greece

2. Introduction:
Malignancy is known to be an insulin-resistant state,
possibly attributed to the action of multiple cytokines.
Moreover, insulin resistance (IR) is a well-known condition
in overweight persons, especially those with central obesity.
Aim:
To explore insulin resistance (IR), as well as certain growth factors and cytokine
levels, in women suffering from breast cancer and to possibly prove:
a) their relationship with anthropometric measurements, BMI in particular, and
b) the change in IR when these patients are successfully treated.

3. Methods:
11 not (known) diabetic women, with stage IV breast cancer (hepatic
metastases excluded), age 62.458.43, BMI 28.262.74, and 4 controls (BMI
30.865.51) were subjected to weight and height measurements for calculation
of BMI, and OGTT with 75gr glucose.
Blood glucose levels as well as insulin, leptin, IL-1, IL-6, IL-8, TNF-α,
PDGF, VEGF and IGF-1 were measured before and 120 minutes after glucose
administration. IR and β-cell function were calculated using HOMA method.
Patients were subjected to the same measurements after 6 cycles of
successful chemotherapy.
Statistics included simple and paired t-test, Wilcoxon test, parametric and
non-parametric correlation (r Pearson and r Spearman), multiple regression
analysis and ANOVA for two-way interactions. Calculations were carried out
using SPSS statistical package version 11.5. Results were considered
significant when p<0.05.

4. Results:

5. 12,50
10,00
IR-HOMA
7,50
5,00
2,50
control patient
(p=0.032)
Patients were found to be more insulin resistant than controls:
(7.623.15 vs. 3.162.64, p=0.032)

6. 250
200
150
100
50
insulin 0΄
0 insulin 120΄
control patient
insulin 0΄: p=0.037 - insulin 120΄: p=0.009
Patients had higher insulin levels than controls both before
and after glucose administration
(23.35  8.93 vs. 13.55  10.27, p=0.037 and
160.28  81.30 vs. 36.19  26.50, p=0.009, respectively)

7. OGTT hadhadgreater insulin response
OGTT
a a greater insulin response
in patients than in controls (p=0.016)
in patients than in controls (p=0.016)
180
120
Mean Insulin levels
case
60
control
0 patient
before glucose 120΄ after glucose
OGTT
R square=60.4,F=15.766, sig=0.000
R square=60.4, F=15.766, Sig=0.000
Case: p=0.003, OGTT: p=0.001, case x OGTT: p=0.016 p=0.016
case: p=0.003, OGTT: p=0.001, case x OGTT:

8. 2,4
2,0
1,6
1,2
,8
,4
IL-1, OGTT: 0΄
IL.1
0,0 IL-1, OGTT: 120΄
control patient
(IL-1 0΄ : p=0.056, IL-1 120΄: p=0.031)
case
Patients had higher interleukin-1 levels, than controls
especially after glucose administration

9. 8
6
4
2
interleukin-6 0΄
0 interleukin-6 120΄
control patient
(IL-6 0΄: p=0.047 - IL-6 120΄ : p=0.047)
(IL-6 0΄: p=0.047 IL-6 120΄: p=0.047)
Patients had higher interleukin-6 levels than controls
both before and after glucose administration

10. before OGTT 120 minutes after OGTT
182
150  
100  
105
50  
28
25
0 
 

 
before chemotherapy after 6 months of chemotherapy before chemotherapy after 6 months of chemotherapy
In patients, after 6 months of chemotherapy, insulin levels 120΄ were
statistically lower (111.75  76.19 vs.170.39 78.07mU/ml, p=0.037),
while no difference was noticed in insulin levels 0΄.

11. before OGTT 120 minutes after OGTT
4,00  
3,00  
2,00  
1,00  
0,00  
   
before chemotherapy before chemotherapy
after 6 months of chemotherapy after 6 months of chemotherapy
In patients, neither time 0΄, nor time 120΄ IL-1 levels differed
significantly before and after successful chemotherapy.

12. before OGTT 120 minutes after OGTT
6,00  
4,00  
2,00  
0,00  
   
before chemotherapy before chemotherapy
after 6 months of chemotherapy after 6 months of chemotherapy
In patients, neither time 0΄, nor time 120΄ IL-6 levels differed
significantly before and after successful chemotherapy.

13. be fo re ch e m othe ra p y a fte r 6 m o nths o f ch e m othe ra py
Area under the curve of insulin according to different BMI tertiles,
before and after six months of chemotherapy

14. Insulin response to OGTT and BMI:
a) before and b) after chemotherapy
be fore chemothe ra py af ter 6 months of che mothe rapy

300 
R-Square = 0,27 
(p=0.125) R-Square = 0,50
(p=0.022)



200
Insul in
 

 



 

100  

 




0 
    

    
26 28 30 32 34 26 28 30 32 34
BM I BM I
Multiple regression: Multiple regression:
(R square=69.8, F=5.385, Sig=0.031) (R square=90.2, F=11.44, Sig=0.010)
Beta for BMI=0.364, p=0.180, Beta for BMI=0.578, p=0.011,
Beta for IL-8=1.097, p=0.005, Beta for IL-8=0.567, p=0.017,
Beta for IGF-1=0.757, p=0.039 Beta for age= -0.532, p=0.035,
Beta for TNF-α= -0.611, p=0.016

15. Conclusions:
Successful chemotherapy
a) results in lower post-prandial insulin levels, indicating that
the effect of malignancy to insulin resistance is blunted and
b) at the same time reveals the well-known positive relationship
between BMI and insulin resistance.