:

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&
. . .

16
17 - 19 2014

,
,


/ ,
.
(American Diabetes Association,
Consensus Statement, San Antonio, 1988).

()

()
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ADA Statement, Diabetes Care 2005, 28: 956

30%


20-40%


(20-40%)

, Charcot

Abbott et al, Diabetes Care July 2011


()

HIV

0.1

0.2

0.3

0.4

0.5

0.6

2.0

2.1

( . )

Bennet 1998

(
): , ,
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( ):


:

:



:
, ( , ,
)
A
,


(1)

,
HBA1c


(2)

Boulton A et al, Diabet Med

2002, 19: 870

. 12

CIPD

, Charcot,

Diabetologia 1998, 41: 416-423

Steno-2: treatment conditions

Conventional group

Aim: to modify CV risk

factors to conventional
targets:

Systolic BP < 160

Diastolic BP < 95
HbA1c < 7.5%
Fasting serum total
cholesterol: 250 mg/dl
Fasting serum
triglycerides: 195 mg/dl
Aspirin for those with
known ischaemia

Intensive group
Aim: to modify CV risk
factors to strict targets:

Slide No. 20

Steno-2: N Engl J Med 2003;348:38393

Steno-2: Lancet 1999;353:61722

Systolic BP < 140

Diastolic BP < 85
HbA1c < 6.5%
Fasting serum total
cholesterol 190 mg/dl
Fasting serum triglycerides
150 mg/dl
Aspirin for those with
known ischaemia or
peripheral vascular disease
Automatic treatment with
ACE inhibitor

Slide No. 21

A
ne ut
ur o n
o p om
at ic
hy

op
Re
t in

hr
N
ep

CV
D

Relative risk reduction for intensive

vs conventional treatment (%)

op
at

at
hy

hy

Steno-2: relative risk reduction with

intensive treatment

* p < 0.05
** p < 0.01

*
**

Adapted from: N Engl J Med 2003;348:38393

**

, Charcot,

stress

PKC

PKC-
(
)

2 NGF

ADA Statement, Diabetes Care 2005, 28: 956

Efforts for aetiologic treatment

ADA consensus, Diabetes Care 2005; 28: 956

, Charcot,

Amitriptyline
Imipramine
SSRIs
Paroxetin
Citalopram
SNRIs
Venlafaxin
Duloxetin

Saroten (25, 75 mg) 25-150
Anafranil (10, 25, 75 mg)

Seroxat (20 mg)

Seropram (20 mg)

40
40

(mg/d)
NNT
2.7 (2.1-3.9)
25-150
2.7 (2.1-3.9)

Efexor (75, 150 mg) 75-300

Cymbalta (60 mg)
60

Carbamazepine
Gabapentin
Pregabalin
Topiramate

Tegretol (200 mg)

200-400
Neurontin (300-800 mg)
Lyrica (25-300 mg) 150-600
Topamac (25-200 mg)
Lacosamide (200-600 mg)

1.9 (1.4-2.8)
900-1800 2.7 (2.2-3.4)
3.7
25-400
9
400-600

Tramadol
Codein CR

50-400
10-60

7.8
-

ADA Statement, Diabetes Care 2005, 28: 956

/ / C

C, A

27

Baron R et al. Lancet Neurol 2010;9: 80719.

,
,

28

.


.

2-1 2

15 35%

Taylor CP, et al. Epilepsy Res. 2007;73(2):137-50/ Dooley et al. J Pharmacol Exp Ther. 2000;295:1086-93/ Mico JA
& Prieto R. CNS Drugs 2012; 26 (8): 637-648/ Tuchman, M. et al. J. Pain 11, 12411249

30

Raphe

2-1

(,
)

,
,
,

(Petit mal)

(Grand mal)

,


Mico JA & Prieto R. CNS Drugs 2012; 26 (8): 637-648/Stahl SM et al. Trends in Pharmacological Sciences 2013; 34: 33239/Melrose et al Neurosci Lett (2007) 417(2):187-92/Tanabe, M., et al., J Neurosci Res, 2008. 86(15): p. 325831
64./Tuchman M et al. The Journal of Pain, 2010;11:1241-9

(mg/.)

**

(mg/.)

***
***

***

***

***

**P<0,01, ***P<0,001 placebo

~ 6,5

, 6 , 5
Data on file, Pfizer Inc

***P<0,001 placebo
~ 6,6

5-12




(mg/.)

***
***
***

***P<0,001 placebo
~ 5,1

, 6 , 5
Data on file, Pfizer Inc

 (
30%) 10

***P0,001 placebo
***
***

60%

51%

***
40%
30%

(mg/.)
* 30%

, 6 , 5
Data on file, Pfizer Inc

 (
50%)* 10

***P0,001 placebo

***
47%

***
34%

***
26%
19%

(mg/.)
* 50%

Data on file, Pfizer Inc


(%
)
Placebo
(n=764)

(mg/.)

150
(n=427)

300
(n=509)

600
(n=459)

(n=1556)

(n=1556)

6,4

13,3

25,5

29,6

21,7*

3,1

3,8

9,8

15,9

17,6

13,8*

2,6

1,8

5,2

12,0

13,5

9,5*

0,8

4,8

6,6

7,1

3,9

6,2

0,1

1,8

4,7

5,3

8,1

5,9*

0,3

*P<0,05 placebo

5%
, placebo
Data on file, Pfizer Inc

 COMBODN:




, , ,

DPNP

Tesfaye et al. Pain 2013; online pub May 2013

 COMBO-DN
:

<30% BPI-

. &

1
1: Group
Dx 120

2
2: Group
Dx+Pb

Dx 30

60

Dx 30

60

. 300

Pb150

3
3: Group
Pb+Dx

Group 4

. .
. .
DPNP

1-2

1
-1 -2

120

IV

Dx 60

Dx 30

Dx 60 +
Pb 150 Dx 60 + Pb 300

Dx 30+
Pb 150

Dx 30 +
Pb 150

Pb 300
+Dx 30

Pb 300 + Dx 60

Pb 150
+Dx 30

Pb 150
+Dx 30

Pb
450

. 600

Pb 300

Pb 150

Dx 90

Pb150

. 300

4: Pb 600
, .

12

16

18

Tesfaye et al. Pain 2013; online pub May 2013

 COMBO-DN :
BPI-

LS BPI-
(MMRM)

8 ( )

DPNP

(120 DLX 300 PGB)

(60 DLX + 300 PGB)

p = 0,098
p = 0,370

Tesfaye et al. Pain 2013; online pub May 2013

 COMBO-DN

. 8 .
60 . 300

- - -

. 8

BPI

HADS
*

//
//

CGI-I
PGI-I
-1.4

-1.2

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

-0.8

-0.6

-0.4

-0.2

0.0

0.2

0.4

LS (MMRM) 95% CI
* : , HADS-

DPNP

Tesfaye et al. Pain 2013; online pub May 2013

0.6

 DPNP:
12

>1% ,

(%)

*p<0,05

* *
*

DPNP

Robinson et al. Poster presented at the 8 th International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP); San
Francisco, CA; Nov 5, 2005.

BMJ 2014;349:g4658 doi: 10.1136/bmj.g4658 (Published 31 July 2014)

Ioanna Eleftheriadou , Nicholas Tentolouris , Edward B Jude


(E)
.

, ,

-


1,
2& 3 2-4

NNT

Vinik & Casselini Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2013:6 57
78

44