Why we do what we do

A child with diabetes before and after treatment with insulin, 1922
University Seminar at Univ.
Nebraska-Lincoln , J. C. Baker,
Eli Lilly & Company, 2/15/06

2.

DCCT , UKPDS UKPDS
UKPDS-- DCCT EDIC

STENO2 PROACTIVE ;

ADVANCE--ACCORD
ADVANCE
ACCORD--VADT
VADT--STENO

 AACE/ACE ( HbA1c 6,5%)

HbA1c 6,5% - 7,5%

TZD
DPP-4 AGl

MET

HbA1c > 9,0%

HbA1c 7,6% - 9,0%

GLP-1 DPP-4
MET + TZD

GLP-1 DPP-4

Glinide SFU

+ TZD

GLP-1 DPP-4
23

ME
T

TZD

Glinide SFU
TZD

GLP-1 DPP-4
Colesevelam

ME
T

MET + GLP-1 DPP-4

+
AGl

GLP-1 DPP-4

TZD
+ TZD

MET + GLP-1 DPP-4

TZD

+ SFU

23

23

+ SFU

MET +
GLP-1
DPP-4

TZD
+

Glinide SFU

23

Aguilar R.B. Clinical Therapeutics 2011;33(4):408-424

&
+

( )

HbA1c 22-3

()
--

( )

+


+

+

3

( )

HbA1c 22-3

()
--

()

HbA1c 22-3

+

2
+

HbA1c 22-3

HbA1c 22-3

, 2011; 36


. 0,2 / kg.

(...) . 2 / 3
. <130 mg%.
>180 mg%, 4 / 3 .

... <70 mg%,

4 .
10% >60 .

A1C 7% 22-3 ;

... <130 mg%, .., , .

2 . 4 . 2/
3 .
. 1C 3

. ,


.

, NPH

( .)

,
.

A1C 7% 22-3 ;
Statement ADA & EASD 2006;
Diabetes Care. 2006;29: 1963

2h . . .


2
2 (
())
A 2010
A1c > 8.5%
( )

A1C < 8.5%

+ 1

A1C > 9%
()

+
TZD
MET +
GLP-1 DPP-4
SU GLIN

2-3
>7%

+
TZD
MET +
GLP-1 DPP-4
SU GLIN

+ +/-

2-3
>7%

A1c<8%

A1c<8%
A1c>8%

+
TZD + SU
MET +
GLP-1 DPP-4 2 + SU
GLP-1 DPP-4 + TZD
2-3
>7%

1.

2.

3.

DPP
DPP--4 (
))

+ +

A1c>8%

2-3
>7%

- 50%
- >50% -
()

- 2/3
HbA1c
-

...

A1 C >8,5%
140mg/dl
140mg/dl
220mg/dl
220mg/dl

200mg/dl
200mg/dl

::

Multivariate analysis of the risk factors

for severe hypoglycaemic events

Albumin:creatinine ratio
>300: HR 1.74
(95% CI: 1.372.21)

African American:
HR 1.43
(95% CI: 1.201.71)

Every 1 year increase in age:

HR 1.03
(95% CI: 1.021.05)

Women:
HR 1.21
(95% CI: 1.021.43)

BMI >30 kg/m2:

HR 0.65
(95% CI: 0.500.85)
BMI, body mass index
Miller et al. BMJ 2010;340:b5444

stress (,
(, ,
, )

; (1;2,3,4;;;)
;
;
;
;

( )+

:
:

HbA1c

IDF Global Guideline for Type 2 Diabetes, 2005

O
!

A. Rubino, Journal compilation 2007 Diabetes UK. Diabetic Medicine, 24, 4121418

Adapted from: Korytkowski M. Int J Obes 2002;26(Suppl 3):S13):S1-S7

 2011:
2011:
( )*

- Humulin
Regular
- Actrapid

- (Lispro),
Humalog
-Aspart)
Novorapid
-(Glulisine),
Apidra

()

30-45 min

1 3

5 7

30 min

1 3

6 8

0-15 min

3 4

10 min

1 3

3 5

10 20 min

- 1

3 4

2 8

2 8

1.5

4 12

4 12

()
- Humulin NPH
- Protaphane

* (SPC)
(SPC)

 2011:
2011:
( )*

()

- (Glargine)
Lantus
- (Determir)
Levemir

-30/70 (30%
70% ), Mixtard30
-30/70 (30%
70% ), Humulin M3
-40/60 (40%
60% ), Mixtard40
-50/50 (50%
50% ), Mixtard50

-
Aspart 30/70, Novomix 30
- Lispro
25/75, Humanlog mix 25
- Lispro
50/50, Humanlog mix 50

1 4

24

1 4

24

30min

2 8

24

30- 40 min

1 8

14 15

30min

2 8

24

30min

2 8

24

10 min

1 - 8

24

0- 15 min

14 -16

0 15 min

14 -16

* (SPC)
(SPC)

Lispro, aspart, glulisine, 22-5 h
Regular, 66-8 h
NPH, 1313-16 h

Glargine, Detemir, ~24 h

10

12

(h)
NPH=neutral protamine Hagedorn
Hagedorn..

14

16

18

20

22

24

1.
2. ( + )
3.

10

12

14

16

18

20

22

24

10

12

14

16

18

20

22

24

 (Levemir
(Levemir Lantus
Lantus))

2

A HbA1c -
(HbA1c <7%)
(

( , , )
( Levemir
Levemir))

 ;

detemir

glargine

aspart

lispro
glulisine
regular
aspart NPA

lispro NPL

regular

30

24
2

2011

&
+

( )
+

1

()

+

(
)

HbA1c 22- 3

()

+
+

()

HbA1c
22- 3

2

+

(
)

HbA1c 22- 3

3

+

3

HbA1c 22- 3

+ 2

+

HbA1c
2- 3

 2011:

+ 1 -2

+ 3

2011

24
2

King AB, et al. Diabetes, Obesity and Metabolism 2009;11:6971

 2
detemir
0.4 U/kg

(mg/kg/min)

glargine

0.8 U/kg

3.0
2.5
2.0
1.5
1.0
0.5
0
0

10 12 14 16 18 20 22

24

(h)

Klein O. et al. Diabetes Obesity & Metabolism 2007;9:290-9

 HbA1c 3 treat-to-target

NPH
detemir

HbA1c

(kg)

glargine

*p<0.005 vs. NPH

2.5
2
1.5
1

0.5
0
0.5
1
1.5
2
Philis-Tsimikas
2006
+ OAD

Riddle
2003


24

24
(p
(p<0,001)
400

300

15

200

10

100

10

14

18

0
6

22

( )
Polonsky K, et al. N Engl J Med 1988;318:12311988;318:1231-9

(mmol
(mmol/l)
/l)

(mg/dl)

20

::

FBG

90
90
126 mg/dl HbA1c 7%

FBG PPBG >160

mg/dl

1. Woerle H. Arch Intern Med 2004;164:1627

2004;164:162732.
2. Monnier L and Colette C. Diabetes Metab 2006;32 (1):7(1):7-13.

1.
2.

,
, HbA1c

Monnier L. Diabetes Care 2002;25:737

2002;25:73741.
Monnier l & Colette C. Diabetes Met 2006;32:72006;32:7-13.

 asal
asal/Basal
/Basal plus:
plus:
Basal
Basal
bolus

,,

basal
basal--bolus.

1 3

1
+

8 10 12 14 16 18 20 22 24
(h)

 :
:

=; =;=; = .
:
1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.

 asal/Basal plus

B + OHAs
3

HbA1c

3
7%

HbA1c
<7%

7%

HbA1c
Raccah D. et al. Diabetes/Met Res & Rev 2007;23: 257-264.

 Basal-plus

asal plus

 Basal Plus 2

OPAL

OSIRIS

Basal/Basal Plus

basal bolus

18

1-2-3

1x glulisine
2x 3x

...

ELEONOR

Telecare

Basal/Basal plus

Proof-of-Concept

asal/Basal plus

All-to-Target

Basal/Basal plus

...

 , :

, :

1. basal bolus ;
2.
;
3.
;
4.
;
5. , ;
6. asal plus
;

4 , aspart
+5.7 kg/ 12 .

APOLLO ( lispro).
+3.5 kg/ 10

ACCORD , (55%
).
27.8% 10 .

30 2
1 4mg. HbA1c 7.8%
(100-110 mg%).

;
1.
2.
3.

 "asal/Basal plus" 2

FBG ,
HbA1c

FBG

HbA1c

asal bolus

asal plus

HbA1c

OHA

-
OHA=
Raccah D. et al. Diabetes/Met Res & Rev 2007;23: 257-264.

60
: 6
: 29
: 85 kg
: .
:

HbA1c: 8.1%
FBG: 140 mg/dl
90 mg/dl

5
1

1.7 g/d+
(30 IU AM 25 IU PM)

:
glargine 30 U
FBG
110 mg/dl
3 mg

HbA1c=7,2% 3
glulisine (
4 U )
( )
3
glargine 52 U/ +
1.7 g/ +
3 mg/
glulisine 10 U

HbA1c: 6.7%
FBG: 100 mg/dl

 DECODE:

(mmol/l)
(mmol/l)

(mmol/l)
(mmol/l)
, , , ,
BMI, SBP,
DECODE study 1999

51


Detemir ;


( )

(
)



()

/
(%)

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

()

/
(%)

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

 basal + oral

1:1
( )




, 3

2 ((-
)
)
1

3 *
* ((-
--)

<80

-2

80--110
80

111--140
111

+2

141--180
141

+4

>180

+6

30 2
1 4mg. HbA1c 7.8%.
(100-110 mg%).

;
(15 15
22 30/70.). .
: lispro
aspart ( - )
7 .
( ) 50:50.
.

15 15 . : 30 20 (
..) 5

2-6

, ,

()

HbA1c

HbA1c

++

++

++

+++

++

 HbA1c
+ ;

A1c
Glargine

A1c

Eliaschewitz (2006)

9.1

7.7

1.4

Fritsche (2003)

9.1

7.8

1.3

Massi (2003)

9.0

8.5

0.5

Riddle (2003)

8.6

7.0

1.6

Rosenstock (2001)

8.6
8.6-9.1

8.2

Yki-Jarvinen (2006)

9.1

7.2

1.9

Yokoyama (2006)

7.2

6.6

0.6

Hermansen 2006

8.6

6.6

Phyllis-Tsimikas (2006)

9.1

7.5

1.6

7.2

6.6-8.5

0.4

Detemir

0.4-2.0

DPP-4

08:00
08

14:00

20:00
20

24:00

detemir
glargine
Jarvinen et al, Ann. Int. Med. 130: 389389-96, 1999


ADA/EASD
:

10 U/

2 U 3 ,

(70-130 mg/dl)

Nathan DM, et al. Diabetes Care 2006;29:1963-1972

 (
( 7%)

Glargine + SU + MET (n = 367)

8.6

7.0

M. Riddle et al
Diabetes Care 2003;26:30802003;26:3080-3086

NPH + SU + MET (n = 389

8.6

7.0

M. Riddle et al
Diabetes Care 2003;26:30802003;26:3080-3086

Glargine +SU + MET (n = 177

8.8

7.2

Glargine + MET (n = 61)

9.5

7.1

NPH + MET (n = 49)

Glarine + SU + MET (n = 104)

H. U. Janka et al
Diabetes Care 2005;8:254 - 259

(n
(n = 2325 )
9.6 8,8 %7.2
HbA1C
7,0%

60 U
U
8.8
7.1

Determix x 2 + SU + MET
(n = 237)
NPH X 2 + SU + MET (n = 238)
Glargine + SU + MET (n = 121)
Determix x 1 2 + SU + MET
(n = 291)

6.8

K. Hermansen et al
Diabetes Care 2006;29:12692006;29:1269-1274

8.5

6.6

K. Hermansen et al
Diabetes Care 2006;29:12692006;29:1269-1274

8.7

6.8

H. Yki Jarvinen et al
Diabetes Care 2007;30:12007;30:1-6

7.2

J. Ronenstock et al
Diabetologia 2008;51:4082008;51:408-416

8.6
10

H. Yki Jarvinen et al
Diabetologia 2006;494422006;49442-451

8.6

8.6

Glargine x 1 + SU + MET
(n = 291)

H. Yki Jarvinen et al
Diabetologia 2006;494422006;49442-451

J. Ronenstock et al
Diabetologia 2008;51:4082008;51:408-416

7.1
9

HbA1c (%)

 (1)

.


(Glargine
(Glargine Detemir
Detemir))

Detemir Glargine

 (2)

2


HbA1c



,
, HbA1c

basal
basal
bolus

basal plus

 HbA1c

basal

(0.50.7 U/kg)

Premixed insulin x 1

Premixed insulin x 2

rapid +
1 rapid: Basal Plus

Premixed insulin x 3

Basalbolus
Barnett A, et al. Pract Diabetes 2003;20:97102.
Dailey G, et al. Diabetes 2004;27:23638.

 ;

detemir

glargine

aspart

lispro
glulisine
regular
aspart NPA

lispro NPL

regular


HbA1c

=290 2

FBG
PPBG (%)

110 mg/dl

70
60
50
40
30
20
10
0

>10.2

9.310.2 8.59.2

7.38.4

<7.3

HbA1c (%)
Monnier L. Diabetes Care 2003;26:8815 and Hirsch IB. Clin Diabetes 2005;23:7886.

 2
&
1 +
(SU)

2 () +

61
: 6
: 31
: 95 kg
:
:

HbA1c: 8.0%
FBG: 120 mg/dl


5
glargine 1
20 U/ 60 U/
0,7 U/kg
PPBG 190 mg/dl

glargine 60 U/ +
( )

:
glulisine
( 4 U
)

3

glargine 60 U/ +
+ +
glulisine
12 U
HbA1c: 6.5%
FBG: 110 mg/dl
PPBG : 140
mg/dl

Baseline
After Insulin

Glucose Disposal
% of Matched Control Values

100

87
80

80
60

67
57

53
40

40
20
0
Scarlett

Andrews

Garvey

Scarlett, et al. Diabetes Care.

Care. 1982;5:3531982;5:353-363; Andrews, et al. Diabetes
Diabetes.. 1984;33:6341984;33:634-642; Garvey, et al. Diabetes
Diabetes..
1985;34:222--234.
1985;34:222

 HbA1c

160

: 2
:
3

Insulin (mU/mL)

140
120
100
80
60
40
20
0
0800

1200

1600

2000

2400

NPH=neutral protamine Hagedorn.

Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc; 2002:87-112.
Bolli GB et al. Diabetologia. 1999;42:1151-1167.

0400

+ ()
+

 :
:

=; =;=; = .
:
1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.

 (Stepwise)
2

,
(Novorapid,Humalog, Apidra ) 4 IU
12 1c>7
2, 4 IU
12 1c>7
3, 4IU

Meneghini et al. Diabetes 2010;59(Suppl 1.):A199 and Data on File

 (Stepwise)
2

HbA1c 1 2
, 77%
3

(Stepwise) ,
.
(basal bolus treatment)

 :
:

=; =;=; = .
:
1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.

--:

()

M3M3
-Mixtard 30

= =

 &

Humalog Mix 2525-50

Novo Mix 30 Flex Pen
HumalogHumalog
-Apidra
Apidra-Novorapid

= =

HbA1c

, HbA1c

basalbolus

basal plus

 - 2

2
.

2
,
HbA1c <8,5%. HbA1c >8,5%
2

Basal-plus Basal -bolus

Elliott P Joslin, MD,

the first doctor in the United States to
specialize in diabetes the founder of
todays Joslin Diabetes Center

1869 -1962

Robert Turner MA,

MD, FRCP
Professor of Medicine

University of Oxford

1938-1999

Insulin is a treatment for the

wise and not for the foolish,
whether they be patients or
doctors.

We dont start insulin

early enough, or use it
aggressively enough


NHANES 1999, 2004

(57%)
(50%)

1999
(47%)

2004

(13%)

Diabetes Care 2009;32:s2172009;32:s217-s221

Glycaemic,, lipid and blood pressure control in 1998 and 2006

Glycaemic
in Greek diab
diab.. Population
[Data are shown as mean value (SD)].

1998

On target

2006

On target

HbA1c (%)

8.1 (2.0)

36.1%

7.0 (1.2)

56.1%

< 0.001

SBP (mmHg)

139.3 (17.9)

22.5%

134.9 (18.7) 35.5%

< 0.001

DBP (mmHg)

80.9 (8.7)

23.0%

77.6 (9.8)

48.2%

< 0.001

HDL-C (mmol/l)

1.2 (0.3)

50.5%

1.3 (0.4)

52.3%

0.002

LDL-C (mmol/l)

3.9 (1.1)

10.4%

2.9 (0.9)

40.2 %

< 0.001

TGL (mmol/l)

2.0 (1.3)

53.6%

1.7 (0.9)

59.9%

< 0.001

Liatis et al, Exp Clin Endocrinol Diabetes 2009

Elliott P Joslin, MD,

the first doctor in the United States to
specialize in diabetes the founder of
todays Joslin Diabetes Center

1869 -1962

Robert Turner MA,

MD, FRCP
Professor of Medicine

University of Oxford

1938-1999

Insulin is a treatment for the

wise and not for the foolish,
whether they be patients or
doctors.

We dont start insulin

early enough, or use it
aggressively enough

 2;

.




1.

160

: 2
:
3

Insulin (mU/mL)

140
120
100
80
60
40
20
0
0800

1200

1600

2000

2400

NPH=neutral protamine Hagedorn.

Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc; 2002:87-112.
Bolli GB et al. Diabetologia. 1999;42:1151-1167.

0400

 :
:

=; =;=; = .
:
1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.

 2;

.




1.


.
HbA1c >6.5% .

708 T2DM

x2

x3

(1
2
)

x3

1 HbA1c >10% >8% ( 24 )

HbA1c :
7.3%
7.2%
HbA1c <6.5%.
17.0%
23.9%,

5.7
12.0,

4.7 kg
5.7 kg

HbA1c<8.5%.

Detemir
7.6%
8.1%;
2.3;
1.9 kg.

3 .
N Engl J Med 2009;361:1736-47.

 3 :
.
Proportion taking
two types of insulin

 3 .

Median95% confidence interval

 : HbA1c 3
.
Median95% confidence interval

Proportion 6.5%
Biphasic
31.9%
Prandial
44.8%
Basal
43.2%

p=0.006
p=0.03
p=0.55

Proportion 7.0%
Biphasic
49.4%
Prandial
67.4%
Basal
63.2%

p<0.001
p=0.02
p=0.22

 3 .

Median95% confidence interval

Biphasic
prandial

Prandial
basal

Basal
prandial

 Grade 2 3
3 .
Median95% confidence interval

HbA1c 6.5%

2 .

.
2

.


detemir
3

detemir

*p<0.05

NPH

2.5

(kg)

Basal oral
TTT studies

glargine
2
*

1.5
1
0.5
0

-0.5

##

Studies in type 2 diabetes

-1
IDet (am+predinner); IDet (am+bed); # IDet (12 hourly);##IDet
(am + bed); ### IDet pm vs. IGla pm

###

2
160

Insulin (mU/mL)

140
120
100
80
60
40
20
0
0800

1200

1600

2000

2400

NPH=neutral protamine Hagedorn.

Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc; 2002:87-112.
Bolli GB et al. Diabetologia. 1999;42:1151-1167.

0400

.

( -
).
; (
.
).
.
.

"" ;

30 2
1 4mg. HbA1c 7.8%.
(100-110 mg%).

;
1.
2.
3.


( NPH Levemir , glargine ).
10 0.2 U/kg
<70 mg%
4 10% >60

A1c >7%
3 ;

.

70-130 mg%,
,
.
2 . 4

HbA1c

NPH

1.2.3 study

Basal plus .

.

.

- - (
).

( )
.


PPG

FPG

HbA1c

IDF

< 135 mg/dl

<100 mg/dl

6,5 %

ADA

< 180 mg/dl

< 90-130 mg/dl

< 7,0 %

ACE (American Association of Clinical Endocrinologists) Position Statement,

2005


: HBA1C <7%
GOAL Survey
100

12.4%
7.8%

(%)

80
60
40
20
0

63%
7%

17.0%
25.8%

37.0%

37.2%
> 8%

7%
NHANES 1999-2000
:
HbA1c <7%
<130/80 mm
Hg
<200
mg/dL

HbA1c
>10%
> 9%
> 8%
7%-8%
< 7%

=404
20-74
National Health Examination Survey (NHANES),
1999-2000.
Saydah SH et al. JAMA, 2004;291:335-342

Rubino A, et al. Diabetic Medicine 2007; 24: 14121418

 58 ,
,, 22-6 ./, :27.5
:27.5,,
8 : 850mg
850mg:: 1X2, 4mg
4mg:: 1.5
.5x1
x1,
,
: 30mg
30mg X1 6 : =
165--184
165
184mg/dl,
mg/dl, = 19
190
0-245mg/dl
45mg/dl,, HbA1c
HbA1c=
=9,6% 9,8
9,8%
%

1
;

1. ,
2. /
/
4. DDP
DDP--4
5.
6.
7.

100

(511)
(=159)

-
(%, HOMA)

(=110)
80
60

40
20

UKPDS

0
10 8

Adapted from: UKPDS 16. Diabetes 1995;44:1249

1995;44:12491258.

4
6
UKPDS

HOMA: homeostasis model

assessment. n=4209

 (ADA-EASD)
1:

/
/

1o BHMA 1o

3o BHMA

2o BHMA

2:

+
+

+
+

+
+

GLP--1
GLP


/

Diabetes Care, Vol 31, 12, Dec 2008

 HbA1c

A1C

0.5 - 2.0%

1.0 - 2.0%

0.5--1.5%
0.5

1.0 - 2.0%

0.5 0.8%

DDP--4
DDP

0.5--0.8%
0.5

0.5-- 1.4%
0.5

0.5--1%
0.5

1.5--3.5%
1.5


;

:





(well being)

+
(;)

(mU/l)

50

( )

40

(Basal Insulin)

30
20

10
0
0800

1200

1600

2000

2400

0400

Y Kruszynska et al. Diabetologia 1987;30:16.

0800

290 .. 2
110 mg/dl

(%)

100

70%
50

30%
0

<7.3

7.38.4
7.3
8.4

8.59.2
8.5
9.2

9.3
9.3
10.2

HbA1c (%) quintiles

ADA=American Diabetes Association; OHA=oral hypoglycaemic agent; PG=plasma glucose.
Adapted from Monnier L, et al. Diabetes Care 2003;26:881
2003;26:8815.

>10.2

.



.

 NPH (Protaphane
(Protaphane,, Humulin NPH)
glargine (Lantus
Lantus))
detemir (Levemir
Levemir))



14
12
10

8
6

N.P.H.
Detemir

Glargine

2
0
0

10

12

14

16

18

20

22

24


;
Glargine vs. NPH

Detemir vs. NPH

HbA1c

HbA1c

(RR:
(RR: 0.84
(0.75--0.95)
(0.75

(RR:
(RR: 0.66
0.66
(0.5
(0.
55-0.
0.80
80))

(RR:
(RR: 0.56
0.56
(0.42
(0.
42--0.
0.74
74))

(RR:
(RR: 0.62
0.62
(0.52
(0.
52--0.
0.76
76))

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


2


.


.

.

 &
H Lantus
.
Levemir
Levemir,,
,
.


.
Levemir
.


(0.1--0.2 U/kg).
(0.1

850mg:
850mg: 1X2,
1X2, 4mg 1x1,
1x1,
(Lantus
(Lantus):
): 10 .

 ;
1. (15(15-20 )
2.
3.


ADA/EASD
:
:

10 U/
U/

2 U 3 ,
,

(70
(70--130 mg/dl)

Nathan DM, et al. Diabetes Care 2006; 29: 19631963-1972

 GLARGINE:
AT.LANTUS: 4.961 2.
glargine:

(%)

1.00

HbA1c (%)

1.05
1.10

30

1.08

1.15
1.20
1.25
1.22
p<0,001

Davies M, et al. Diabetes Care 2005;28:12822005;28:1282-8.

29,7
26,3

25
20
15
10
5
0

 1 80
80--110
110mg/dl
mg/dl
HbA1c:7..4% : 850
HbA1c:7
850mg
mg:: 1X2, 3mg 1x1,
1x1,
: 44 UI :220:220-260
260mg/dl
mg/dl..

2
;

1.
2.
3. /

(ADA-EASD)
1:

/
/

3o BHMA
1o BHMA 1o

2o BHMA

2:

+
+

+
+

+
+

GLP--1
GLP


/

Diabetes Care, Vol 31, 12, Dec 2008

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

Actrapid
Humulin Regular

HbA1c

..
4. .
Humalog//Novorapid
Humalog
Novorapid//Apidra

::

: 40U

:
4U
: 40
40U
U


(Mixtard 30, 40, 50, Humulin M3)

NovoMix30, Humalog Mix 25, 50

 2
70/30

Snack

Regular
NPH

!
!


NOVO MIX 30/ HUMALOG MIX25

Novomix30
Humalog Mix25

30/70

0-15
,

1 h

30 - 60

2 - 3 h

10 14
h

10 14 h


(25/75
30/70)
: 1:1
:: 50%

:: 50%

1-2 /.
( )


- 3

<80 mg/dL

-2 .

80-109 mg/dL

110-139 mg/dL

+2 .

140-179 mg/dL

+4 .

180 mg/dL

+6 .

 HbA1c6,5% 11-2-3

NovoMix 30

NovoMix 30

NovoMix 30 ,

Humalog Mix 50

Humalog Mix 50

Schernthaner G. Horm Metab Res 2004; 36: 188-193

.
.

Results of a three-year experience of

continuous subcutaneous insulin infusion
in type 1 diabetes patients
A. Kamaratos, S. Iraklianou, A. Sereti, M. Meletiadou, A.
Koutsovasilis, K. Fakatseli, A. Nikolaou,
G. Panoutsopoulos, A. Melidonis.

Tzanio General Hospital

Hospital,, Diabetes Center
Center,, Athens
Athens,, Greece

4/12/2011