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Transcript of Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.
![Page 1: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/1.jpg)
Antibiotic resistance evolution among E. coli strains causing
urinary tract infections
Author: Sándor Szabolcs - student
Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor
![Page 2: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/2.jpg)
Urinary tract infections (UTI) are one of the most common type of bacterial infectious diseases. They are most common in infants and people over the age of 70, and predominantly affect women. [1]
Statistically every 2nd adult woman is affected by UTI once in her lifetime. [2]
The #1 cause for UTI is E. coli infection.
Introduction
![Page 3: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/3.jpg)
The aim of this study was to:1. Assess the resistance of E. coli strains
towards certain antibiotics. 2. Evaluate the evolution of antibiotic
resistance over the course of approximately 3 years.
Aim
![Page 4: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/4.jpg)
In this retrospective study we analyzed a sample of 510 bacterial cultures positive for E. coli infection for which antibiotic sensitivity tests (AST) were performed between 1st May 2012- 1st March 2015
Materials and Methods
![Page 5: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/5.jpg)
Samples were considered positive if the culture resulted in > 100.000 CFU/ml. [3]
Cultures having lower values were excluded We excluded ESBL (beta lactamase enzyme)
and Hodge (carbapenemase enzyme) positive strains
Statistical software: Graphpad Statistical test: linear regression
Materials and Methods
![Page 6: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/6.jpg)
We followed:1. resistant cases per month and year,2. evolution of resistance during a year and
its possible connection with both time and seasons,
3. maximum number of resistant strains and their possible connection with both time and/or seasons.
Materials and Methods
![Page 7: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/7.jpg)
The analyzed antimicrobial drugs were:1. Ampicillin (AMP) 2. Amoxicillin (AMC)3. Cephotaxime (CTX)4. Cephtadizime (CAZ)5. Cephuroxim (CXM)6. Cephepime (FEP)7. Gentamycine (GM)8. Nalidixic Acid (NA)9. Trimetophrim/Sulfametoxazole (STX)10. Tetracycline (TE) 11. Levofloxacin (LEV)12. Norfloxacin (NOR)13. Nitrofurantoin (F)
Materials and methods
aminopenicilins
Cephalosporins
fluoroquinolones
Sulphonamid
broad-spectrum bacteriostatic drug
aminoglycoside
nitrofurane
quinolone
![Page 8: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/8.jpg)
AB 2012 2013 2014
AMP 51.11% 53.33% 57.78%
CTX 0.00% 0.00% 5.56%
AMC 6.67% 6.67% 6.11%
CAZ - 0.56% 0.00%
CXM 4.44% 1.82% 3.33%
FEP - 0.56% 0.00%
GN - 3.03% 3.89%
LEV/CIP 11.11% 20.00% 29.44%
NOR 16.67% 20.00% 30.00%
F 1.11% 1.67% 0.56%
NA 18.33% 22.78% 29.44%
SXT 6.86% 22.22% 39.44%
TE 16.00% 32.00% 38.33%
Results I.Antibiotic resistance percentages during the examined
periods
6/13 antibiotics had a resistance value of approx. or greater than 30% by the year 2014
None of the tested antibiotics remained at the value of 0%
![Page 9: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/9.jpg)
Results II.-III.Antibiotic resistance evolution per
year
![Page 10: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/10.jpg)
Should we take into consideration the values of 2015 Jan. and Febr.?◦ Yes, but only IF:• between 2013-2014 the antibiotic resistance
did not peak during January or February AND the AVERAGE (AVG) value of the AB resistance DID NOT EXCEED the AVERAGE of the YEAR, we considered the 2015 values valid.
• Tetracycline(TE) peaked in January, thus it was excluded.
Question
![Page 11: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/11.jpg)
Results II.AMP resistance evolution
AMP
2012 2013 2014 20150.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
AMP is a special case In 2012 it was not
regularly tested, but the 2015 average already exceeded previous resistance rates:
p= 0.0167(0.0404)- significant(S)
Diff = 12.22% (increase of 23.9% in 3+ years)
![Page 12: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/12.jpg)
Results II.LEV/CIP resistance evolution
LEV/CIP
2012 2013 2014 20150.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00% P= 0.046 - S Diff = 18.89%
(increase of +170%) Fastest yearly
increase – 80.01% between 2012-2013
![Page 13: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/13.jpg)
Results II+AMC resistance evolution
AMC
2012 2013 2014 20150.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
7.00%
8.00%
9.00% p=0.035-S (although 2012-2014 p= 0.17 – NS)
Diff = 4.95% (decrease of 59,78%)
![Page 14: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/14.jpg)
Results II+GN resistance evolution
GN
2013 2014 20150.00%
1.00%
2.00%
3.00%
4.00%
5.00%
6.00%
7.00%
8.00% p= 0.18 (NS) although the steady increase is obvious
![Page 15: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/15.jpg)
Results III.NOR resistance evolution
NOR
2012 2013 2014 20150.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00% p= 0.17 (NS) - [2012-2014]
BUT the values of 2015 may increase
![Page 16: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/16.jpg)
Results III.NA resistance evolution
NA
2012 2013 2014 20150.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00% p= 0.0728– Not quite significant
(NQS) [2012-2014]
![Page 17: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/17.jpg)
Results III.SXT resistance evolution
SXT
2012 2013 2014 20150.00%
5.00%
10.00%
15.00%
20.00%
25.00%
30.00%
35.00%
40.00%
45.00% p= 0.26 (NS) - [2012-2014]
![Page 18: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/18.jpg)
Results IV.Assessment of yearly and
comparison of seasonal resistance values
![Page 19: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/19.jpg)
Janu
ary
Febr
uary
Mar
chApr
ilMay
June Ju
ly
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
2
4
6
8
10
12
2012201320142015
Janu
ary
Febr
uary
Mar
chApr
ilMay
June Ju
ly
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
1
2
3
4
5
6
2012201320142015
Results IV.Aminopeniciline comparison of resistance evolution
during 2012-2015 per year and month
AMP AMC
![Page 20: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/20.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 260
2
4
6
8
10
12
AMP
AMC
Results IV Aminopenicillines – linear resistance evolution per month during 2012-2015
![Page 21: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/21.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 340
0.5
1
1.5
2
2.5
3
3.5
4
4.5
CTXCXMCAZ
Results IV. Cephalosporines -linear resistance evolution per month during 2012-2015
![Page 22: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/22.jpg)
Janu
ary
Febr
uary
Mar
chApr
ilMay
June Ju
ly
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
1
2
3
4
5
6
7
8
201220132014
Janu
ary
Febr
uary
Mar
chApr
ilMay
June Ju
ly
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
1
2
3
4
5
6
7
8
2012201320142015
Results IV. Fluorochinolones -seasonal antibiotic resistance values
CIP/LEV NOR
![Page 23: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/23.jpg)
Results IV.Fluoroquinolones linear resistance evolution per month during 2012-2015
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 320
1
2
3
4
5
6
7
8
CIP/LEVNOR
![Page 24: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/24.jpg)
Janu
ary
Febr
uary
March
April
MayJu
ne July
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
1
2
3
4
5
6
7
8
2012201320142015
Results IV.NA- seasonal antibiotic resistance values
![Page 25: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/25.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 340
1
2
3
4
5
6
7
8
Results IV.NA- linear resistance evolution per month during
2012-2015
![Page 26: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/26.jpg)
Janu
ary
Febr
uary
March
April
MayJu
ne July
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
2
4
6
8
10
12
2012201320142015
Results IV.SXT- seasonal antibiotic resistance values
![Page 27: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/27.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 300
2
4
6
8
10
12
SXT
Results IV.SXT- linear resistance evolution per month during
2012-2015
![Page 28: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/28.jpg)
Janu
ary
Febr
uary
March
April
MayJu
ne July
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
2
4
6
8
10
12
2012201320142015
Results IV.TE - seasonal antibiotic resistance values
![Page 29: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/29.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 290
2
4
6
8
10
12
TE
TE
Results IV.TE- linear resistance evolution per month during 2012-
2015
![Page 30: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/30.jpg)
Janu
ary
Febr
uary
March
April
MayJu
ne July
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
0.2
0.4
0.6
0.8
1
1.2
2015201420132012
Results IV.F- seasonal antibiotic resistance values
![Page 31: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/31.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 280
0.2
0.4
0.6
0.8
1
1.2
Results IV.F- linear resistance evolution per month during 2012-
2015
![Page 32: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/32.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240
0.2
0.4
0.6
0.8
1
1.2
Results IV.FEP- linear resistance evolution per month during
2013-2015
![Page 33: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/33.jpg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 250
0.5
1
1.5
2
2.5
Results IV.GN- linear resistance evolution per month during
2013-2015
![Page 34: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/34.jpg)
Janu
ary
Feb
ruar
y
Mar
ch
Apr
il
May
June
July
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
2013
2014
2015
201320142015
Results IV. FEP- seasonal antibiotic resistance values
![Page 35: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/35.jpg)
Janu
ary
Febr
uary
March
April
MayJu
ne July
Augus
t
Sept
embe
r
Octob
er
Novem
ber
Decem
ber
0
0.5
1
1.5
2
2.5
201220142015
Results IV.GN- comparison of resistance evolution during 2012-2015 per year and month
![Page 36: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/36.jpg)
There doesn’t seem to be any cyclicity among individual antibiotic resistances regarding time or season.
Results IV.
![Page 37: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/37.jpg)
Results V.Peak value Summary of the examined periods (2012-2014)
The sum of peaks for each antibiotic shows the following:
antibiotic resistance values seem to peak during the warmer months, while during the cold months the number of cases diminish drastically.
Most peaks: September 9/43.
Least peaks: February and December 0/43.
Jan
Mar
chMay Ju
ly
Sept
embe
r
Novem
ber
0
2
4
6
8
10
![Page 38: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/38.jpg)
February March September October
Mean peaks (°C)
6.5 14.7 25.3 16.3
Maximum peak(°C)
19 24 31 25
Why do we consider March and September a warm month? [4]
![Page 39: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/39.jpg)
1. Antibiotic resistance values seem to be increasing on a year to year basis [5]
2.In case of CIP/LEV the increase of resistance during the last few years has almost tripled
Conclusion
P significant P not significant due to lack of cases
P not significant but cannot be excluded yet
AMP GN NOR
LEV/CIP NA
SXT
![Page 40: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/40.jpg)
3. E. coli strains do not show signs of time/season dependent resistances for individual antibiotics, but as a whole, they seem to increase gradually during the warmer months, peaking in September.
Conclusion
![Page 41: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/41.jpg)
4. Due to the aforementioned results Antibiotic Sensitivity Tests need to be performed on every case of UTI, especially during summer because:
A. High probability of resistance B. Avoid creating more resistant strains C. Improper Antibiotic treatment and long lasting
UTIs can lead to multiple serious complications ( ascending spreading, nephritis…etc.)
D. Ever increasing number of people with risk factors [6]
Conclusion
![Page 42: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/42.jpg)
5. In order to guarantee the precision and efficacy of further studies and evaluations we encourage the continuation of regular AST testing and registration.
Conclusion
![Page 43: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/43.jpg)
Thank you for your attention
![Page 44: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/44.jpg)
Special thank you to: Dr. Teodora Chigir – carried out the urine
cultures and AST tests during 2012-2013 Dr. Barabás Hajdu Enikő - coordinator
The entire County Hospital Laboratory department
![Page 45: Author: Sándor Szabolcs - student Coordinator: Dr. Barabás Hajdu Enikő – Assistant Professor.](https://reader036.fdocuments.us/reader036/viewer/2022062518/56649e685503460f94b642c2/html5/thumbnails/45.jpg)
[1] - Dr. Mártha Orsolya – Urológia, 2008 – pp. 64-65 [2] -Dumitru Buiuc,Marian Negut - Tratat de
microbiologie Clinica,2009 – pp. 255 [3] - Dumitru Buiuc,Marian Negut - Tratat de
microbiologie Clinica,2009 – pp. 263 [4] -http://www.accuweather.com/ro/ro/bucharest [5] -
http://www.sciencedirect.com/science/article/pii/S0924857906001063
[6] - http://www.diabetes.org/diabetes-basics/statistics/
References