, 27.11.

2013

 2

[]
[]

 - (%)

OADs
+ GLP-1

Detemir
add on to
Liraglutide2

Basal

Premix
Insulin
Basalbolus
Type 2 diabetes

2
1.
2.

Nathan DM et al. Diabetes Care 2009:32:193203

SmPC Levemir

;
;


2;
HbA1C >7%
HbA1c > 8.5%
2
3

(
)

(>1.8)

2013

Diabetes Care, Diabetologia.

19 April 2012 [Epub ahead of print]


2.....

....

Low socioeconomic
Status

What is your highest educational degree?

Are you a manual worker?

Work and family stress

Do you lack control over how to meet the demands

at work?
Is your reward inappropriate for your effort?
Do you have serious problems with your spouse?

Social isolation
Are you living alone?
Do you lack a close confidant?

Depression
Do you feel down, depressed, and hopeless?
Have you lost interest and pleasure in life?

Anxiety
Do you frequently feel nervous, anxious, or on edge?
Are you frequently unable to stop or control worrying?

Hostility
Do you frequently feel angry over little things?
Do you often feel annoyed about other peoples habits?

Type D personality

European Guidelines on cardiovascular disease

prevention in clinical practice (version 2012)

In general, do you often feel anxious, irritable, or

depressed?
Do you avoid sharing your thoughts and feelings with
other people?

ADA-EASD:
2

HbA1c < 7.0% ( 150-160 mg/dl)

<130 mg/dl

<180 mg/dl

(6.0 - 6.5%) ,

(7.5 - 8.0%+) - ,

,
...

Diabetes Care, Diabetologia. 19 April 2012

(0.2-0.4 IU/kg)


&
:

detemir
glargine

aspart

lispro
glulisine
regular
aspart NPA

lispro NPL

regular


Lispro (Humalog)
~ 4 hr

Aspart
Glulisine

(Regular Actrapid,)

36 hr

(NPH, Protaphane)

814 hr

Detemir ~ 14-18 hr
Glargine ~24 hr

10

12

14

16

18

20

22

24

()
. Rosenstock J. Clin Cornerstone. 2001; 4: 50-64

Lyspro (Humalog)

5-15

30-90

3-5

Aspart (Novorapid)

5-15

30-90

3-5

Glulysine* (Apidra)

5-15

30-90

3-5

30-60

2-3

5-8

2-4

4-10

10-16

glargine (Lantus)

2-4

20-24

detemir* (Levemir)

2-4

6-14

16-20

(Regular, Actrapid)
()
(Humulin ...,
Protaphane)

: glargine,
detemir, NPH ( NPH
)

: HbA1c

IDF Global Guideline for Type 2 Diabetes, 2005

(1) + A1c>9% +

(2)
+ 1c>8.5%

(3) 2 +
A1c > 8.5%

www.ede.gr

(4) 3

 1
61
2 2

(--,
5 kg 2 )
: 102 kg, : 32,1 kg/m2,

HbA1c: 11,2%, : 275 mg/dl

 ;
1.

2. 2

3.

4.
5. GLP-1

www.ede.gr

 ;
1.

2. 2

3.

4.
5. GLP-1

vs.
382


2

(
/)

Weng J et al. Lancet 2008;371:1753

( )

850 mg/d -> 1000mgx2

3 :
5 kg
HbA1c: 7.6%, FPG: 120-140 mg/dl
:


;

:

(well being)

DPP-4 GLP-1

DPP-4

: (
)

.

H

HbA1c 24

SAXA 5 mg + INS
(N=300)

PBO + INS
(N=149)

HbA1c (%)

0
-0.1
-0.2
-0.3
-0.4

-0.32 0 .07

-0.5

-0.41 0.09

-0.6
-0.7
-0.73 0.05

-0.8
-0.9

p<0.0001

, -9.1% (95% CI [-18,7, 0,7]) 24.
SAXA= , BO= , INS=

Barnett AH, Charbonnel B, Donovan M, Fleming D.

Curr Med Res Opin. 2012 Feb 8

 GLP-1 RA

detemir liraglutide
metformin ,
.

16 2012 ( European Medicine Agencies) .....

BYETTA
/
.

Glargine + exenatide

Ann Intern Med. 2011;154

08:00

14:00

20:00

24:00

 ;
Glargine vs. NPH

Detemir vs. NPH

HbA1c

(RR: 0.84
(0.75-0.95)

(RR: 0.66
(0.55-0.80)

HbA1c

(RR: 0.56
(0.42-0.74)

(RR: 0.62
(0.52-0.76)

Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005613.

 ;
Glargine vs. NPH

Detemir vs. NPH

Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005613.

(~

 Glargine Detemir

Glargine

Detemir

T. Heise and T. Pieber. Diab Obes Metab 2007

1.
2.
3. = FBG

4.
5. !
6. +

.


.

2-3 U 3 ,
(90-130 mg/dl)

0,2 /Kg

61
: 10
: 28.5
:

HbA1c: 8.7%, 8.8%

FBG: 165-181 mg/dl,

195-274 mg/dl)

1. ,
2-3
2. ,
3.

4. DDP-4 /
5.

850mg 2
30mg: 3X1

8.8 7= 1.8

58
: 12
: 28.5
:

1. ,
2-3
2. ,

HbA1c: 8.5%, 8.8%

FBG: 185-191 mg/dl,

199-264 mg/dl)

3.
4. DDP-4 /
5.

(4)
: 1000mg 2
: 4mg X1

8.5/8.8 7= 1.5/1.8

63
: 7
: 29
:

HbA1c: 7.5%, 7.8%

FBG: 167-188 mg/dl,

175-264 mg/dl)
GFR: ~31ml/min

;
1. ,
2-3

2.
3.
4. /
5.

M: 1000X2
DPP-4 : 1X1
: 41

7.5/7.8 7= 0.6/0.8

 4
73
2 x12 , : 91 kg, : 30,1 kg/m2
(1000 mgx2) + DPP-4
:
( )
( )

HbA1c: 10,3% (8,4-10,6% 3 )

3-5x/, (..: 185

mg/dl)

 HbA1C

HbA1C (%)
5
6
7
8
9
10
11
12

(mg/dL)
97
126
154
183
212
240
269
298

eAG (mg/dl) = (28.7 x HbA1c) 46.7

2 + A1c > 8.5%

www.ede.gr


(08.00)

2hrs

175

214

(14.00)

2hrs

162

158

3
4

204

202

8
9

2hrs

174

188

188

264

177

280

176

6
168

168

5
7

(21.30)

154
198

228


(08.00)

2hrs

(14.00)

2hrs

230
: 216

(21.30)

2hrs

10
10

210

207

14

198

14

5
6
7
8
9

175
182
152
162
146

: 185

10

14
18

: 153

18
18

500

27.8

400

22.2

16.7

300

200

11.1

5.6

100

0
08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00 02:00 04:00 06:00 08:00

Reaven G. Diabetes 1988;37:10204.

(mmol/l)

(mg/dl)


& (1/):

,
.

,
.

60-80%
6 & .
SANNE G., DIABETES CARE, VOLUME 32, SUPPLEMENT 2, NOVEMBER 2009; S253-259

 :



stress

/

DF 2007 pp 6-11, DIS Study, DECDE, Framingham,J Clin Endocrinol Metab 2009; 94:1595-1601

IDF Clinical Guidelines Task Force: Guidelines for the Management of Postmeal Glucose. IDF 2007

 HbA1c

( ) .
;

1.

2. .
3. .
4. GLP-1 .

Insulin Strategies in T2DM

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

:
: 40U

: 4U

Lispro (Humalog)
Aspart (Novo
Rapid)
Glulisine (Apidra)

Actrapid
Humulin Regular

HbA1c


2STEPWISE
3

4U

HbA1c >7%

4U
2

HbA1c >7%

4U
3

Pfutzner et al. 2009

:
, 4

Data from Skyler JS: Insulin Treatment. In Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders. 3 rd ed. American Diabetes
Association, 1998:186-203.

 basal-bolus

~ 0,5 1,0 IU / kg , 24
~ 40% - 50%
0,8 1,5 IU / 1
(10)

 12

1 .

 1500

1500

.
1

.

 1800

1800

.
1

.


&
:


:
850mg: 12
:
4mg: 1.5X1
ns. Glargine: 44 U (11)
: 28.6

,

,
: 571.

2.

7
3. /
b1C: 7.7-7.7.8%
4. GLP-1
:

: 90110mg/dl
: 130140mg/dl
: 220265mg/dl

, ,
: ..

 (4)
73
2 x12 , : 91 kg, : 30,1 kg/m2
(1000 mgx2) + DPP-4
:
( )

( )
/

HbA1c: 10,3% (8,4-10,6% 3 )

3-5x/, (..: 185

mg/dl)

 (3)
(08.00)

2hrs

110

114

97

(14.00)

2hrs

8
9

2hrs

47
47
47

5
7

(21.30)

 (2)

10 / -> 47 /
(1000 mgx2) + DPP-4

3 6
: 91 -> 94 kg
HbA1c: 10,3 -> 8,9 -> 8,0% (8,4-10,6% 3
)
5-10x/,
(..: 185 mg/dl)

 (4)
(08.00)

2hrs

115

144

(14.00)

276

188

6
8

202

108

188

148

5
7

184

104

2hrs

258

3
4

162

2hrs

(21.30)

264

134

198

238

187

280

 (3)
47 /

8 /
->

2hrs <140-145 mg/dl

(1000 mgx2).
DPP-4

 (2)
(08.00)

2hrs

115

184

(14.00)

276

188

6
8

202

108

188

198

5
7

184

104

2hrs

258

3
4

162

2hrs

(21.30)

264

234

198

238

187

280

()

/
(%)

Mixtard 30
(Novo Nordisk)

70/30

10ml

Humulin M3
(Eli Lilly)

70/30

10ml

Mixtard 30 Penfill
(Novo Nordisk)

70/30

3 ml

Mixtard 40 Penfill
(Novo Nordisk)

60/40

3 ml

Mixtard 50 Penfill
(Novo Nordisk)

50/50

3 ml

Humulin M3 cart
(Eli Lilly)

70/30

3 ml

--: ()

M3-Mixtard 30

= =

()

/ (%)

NovoMix 30
(Novo Nordisk)

70/30

Aspart

3ml

Humalog mix 25
(Eli Lilly)

75/25

Lispro

3 ml

Humalog mix 50
(Eli Lilly)

50/50

Lispro

3 ml

 &

Humalog Mix 25-50

Novo Mix 30 Flex Pen

Humalog-Apidra-Novorapid

= =

( 2013)
Humalog Mix 25 NovoMix 30

2-4 U
3

2-4 U
3



HbA1c
8.5
(%)

FPG
9.6
(mmol/l)

PPG
12.6
(mmol/l)

Weight
85.8
(kg)

Hypoglycaemia
grade 2 or 3
(events/patient/year)
25
20
15
10
5
0

p<0.001

p<0.001

P<0.001

p<0.001

p=0.04

20
10
0
-10
-20
-30
-40

N Engl J Med 2007; 357: 1716-30

Levit S et al. Horm Int J Clin Pract 2011 65:165-171

.

.

.

,


.

 HbA1c,

Conventional*
Glibenclamide
Metformin
Insulin

HbA1c (%)

8.5
8
7.5
7

Recommended treatment
target <7.0%

6.5
6

6.2% upper limit of normal range

0

Years from randomisation

*Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L
ADA clinical practice recommendations. UKPDS 34, n=1704

UKPDS 34. Lancet 1998:352:85465; Kahn et al. NEJM 2006;355(23):242743

10

. A1 C 9%.
40 6 -128 , ,
.
8

;
1.
2.
3.

4. 6

 .
.

1 .
2.

3.

4.


10 :

HbA1c

10

7% ( )

7,9% ( )

-25%

HbA1c
.

Adapted from UKPDS 80 . New Engl J Med, 2008. 359(15):1577-89.

95