HELLENIC DIABETES ASSOCIATION

2017

2016-2017

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ADA (American Diabetes Association). To ADA
, , C
1.
-
SIGN (Scottish Intercollegiate Guidelines Network). To SIGN
6
, C, ,
, 2.

vii
 1. ADA

-
, , , ,

- ,

.




(cohort studies),
(case-control studies)
O


,
C (case reports)
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(consensus)



consensus

2. SIGN

a -

b
IIa

Ib -


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,
IV /
C

viii
 ,
(-SPC - Summary of
Product Characteristics). ,
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SPC .
-
,
SPC ,
.

.
SPC -
. SPC ,
:
http://www.ema.europa.eu/ema/index.

28/02/2017

ix
 M

AGEs Advanced Glycosylation Endproducts

Ankle-Brachial Index

ADA American Diabetes Assosiation

BBE Basal Energy Expediture

Body Mass Index

CGM Continuous Glucose Monitoring

dl Deciliter
(100 )

DPP-4 Dipeptyl-peptidase-4
--4

DSA Digital Substractive Angiography

EMA European Medicines Agency

g Gram

GFR Glomerular Filtration Rate

GLP-1 Glucagon Like Peptide-1

-1

HbA1c Glycosylated Haemoglobin A1c

A1c

IDF International Diabetes Federation

IFG Impaired Fasting Glucose

x
IGT Impaired Glucose Tolerance

IRMA Intra Retinal Microvascular Abnormalities

IU International Units

Kcal Kilocalorie
()

kg Kilogram

L Liter

m Meter

mEq/L Milliequivalent per Liter

/

mg Milligram

mg/dl Milligram per Deciliter

/

min Minute

ml Milliliter

mmHg Millimeter Mercury

mmol/L Millimole per Liter

MODY Maturity Onset Diabetes in the Young

msm Milliosmole

MUFA Monounsaturated Fatty Acids

xi
NGSP National Glycohemoglobin Standardization Program

NGT Normal Glucose Tolerance

OGTT Oral Glucose Tolerance Test

PUFA Polyunsaturated Fatty Acids

RCT Randomized Controlled Trial

SAFA Saturated Fatty Acids

SBGM Self Blood Glucose Monitoring

SPC Summary of Product Characterstics

STEMI ST Elevated Myocardial Infarction

ST

SU Sulfonylurea

TcpO2 Transcutaneous Pressure of Oxygen

TIA Transient Ischemic Attack

TZD Thiazolidinediones (Glitazones)

()

TG Triglycerides

TSPI Toe Systolic Pressure Index

VEGF Vascular Endothelial Growth Factor

xii


1 1

xiii


1 1

2 2

xiv


1. ,  1
2.  9
3. .
 13
4.  17
5.  27
6. 231
7.
1 39
8.
2 41
9.
 49
10. . 55
11.  59
12.  65
12.1.  65
12.2.  69
12.3.
 71
13. 77
13.1.  77
13.2.  78
14.  81
14.1.  81
14.2.  83

xv
15.  85
16.  89
17.  95
18.  99
19. 2
103
20. 109
21. 111
22.  113
23.  119
24. 123
25. 129
26. . Charcot 139
27. 145
28. 151
29. 157
30. 2
161
31. 167
32. 171

xvi
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ADA HbA1c 6.5%. -

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150 .

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110-125 mg/dL (IFG)1

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2IGT: Impaired Glucose Tolerance ( ).
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(IFG) 100-125 mg/
dL. (EASD) ,
100 mg/dL, 110 mg/dL.
.

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IGT), .

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7
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11
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13
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14
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:
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HbA1c < 7.0%
( ), -
<130 mg/dL <180 mg/dL
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24 140 mg/dL
110 mg/dL
HbA1c , -

-

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15
 , ,
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16
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A, B, C E ADA. 2

17
 ,


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( 4.1) 25 kg/m2
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.
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(BBE: Basal Energy Expediture)
Harris-Benedict B ( kg), Y ( cm)
H ( ). :
BEE = 6.55 + (9.6 B) + (1.8 Y) - (4.7 H)
BEE = 6.6 + (13.7 ) + (5 ) - (6.8 )

18
  C

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 C

(18.5 - 25 kg/m2), -
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19
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g/kg /)
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21
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22
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23
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24
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(Lyon Heart Study) -
OEM
,
(PREDIMED),
50% , -
(
- extra virgin oil) , -
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OEM )
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2

, -

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25
5.


2,
IGT
( 5.1), -
30 ( -
), 5 .

5.1.

50-70%
10 *

>70%





* : = 220

. = 205 (0.5 )

( 5.2) -
, .
( )
2-3 .
8-10 8-10
.
2-3 , -
3-5 . ,
10-15  A

27
 5.2. (, )

2-3
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o .

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. 75-90
. 3
, 2  A
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HbA1c

1
1,
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(>250 mg/dL)

(<100 mg/dL)
, -

28

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Charcot. , -
20
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2 >10


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30
6. 2
2

( )

2.

-

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()
()
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Peptide-1) DPP-4 (--4)

- ()

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(
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31


o




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)


,
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bA1c
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2 (-
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(500mg),
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( 6.1 - 6.1, 6.2).
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DPP-4 (,
), SGLT2 ()
(
).
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,
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, , ,

32
 , -
, , -
.
HbA1c.

.
-

(
HbA1c) -
, , -
( 6.1 - 6.1,
6.2).
: GLP-1 .
,
,
/ GLP-1 .

(.. SGLT2). -

,
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( )
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()

DPP-4 GLP-1


SGLT2 .
, HbA1c ( -
>8.5%
), , ,
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, ( 6.1)
, (
HbA1c >9%),
(, ,

33
 ),
( 6.1 - 6.1, 6.2).
( ), -
,


( -
, , , -
).
10-15 , ,
4 .
DPP-4


-
,


()
HbA1c 3 -


2 , -
, -

.

34
 6.1.

HbA1c

HbA1c > 9%
HbA1c < 8.5% HbA1c > 8.5% (

)

+ +
+
+
+
+


( )

HbA1c > (.. 7%)

+
+ + HbA1c

(.. >8.5%)

HbA1c > (.. 7%)

+ + +
( GLP-1
+ ).
+ +
+ :
GLP-1
GLP-1. ,
,

HbA1c > (.. 7%)

.
: ( + )

35
 6.1. 2
2


(+++)


,

(UKPDS)
(SU) (PIO) DPP-4i SGLT2i GLP-1 (BI)
(+++) (+++) (++) (++) - (++++) (++++)
HbA1c


, , .,
.

36

(- (LEADER, (RIGIN)
(PROACTIVE, IRIS) () SUSTAIN-6)
) (EMPAREG). (ELIXA)
+ SU MET + PIO MET + DPP-4i MET+SGLT2i MET + GLP-1 MET + BI
+ DPP-4i + SU + SU + SU + SU + SGLT-2i
+ PIO + DPP-4i + SGLT2i + DPP-4i + PIO + DPP-4i
+ SGLT2i + SGLT2i + PIO + PIO, dapa- + SGLT2 + GLP-1
+ GLP-1 ( dapa-) + BI + GLP-1 + BI + PIO
+ BI + GLP-1 + BI
+ BI
, ( GLP-1
). .
GLP-1
.
GLP-1 .
(.. PIO, SGLT2i)
DPP-4i , dipeptidyl peptidase-4 inhibitors, SGLT-2i Sodium-glucose co-transporter 2 inhibitors
 6.2.
2 ( )
-

. .
. . 12.
.
. . eGFR<30 ml/min.
.

(UKPDS)
- . ( -
(- ( - , . ,
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) ) eGFR

37
.
-
.


(, .
)
, -
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.
(
. ).

(PROACTIVE, IRIS)
 6.2. ()
2 ( )
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DPP-4 .
. (
( ).
).
(TECOS, SAVOR, EXAMINE)
-
.
GLP-1 (, ).
.
( ( ).
LR , eGFR<50 ml/min
LEADER).
30 ml/min

38
GLP - (, )
.
() .
( ELIXA )
( ).
eGFR<50 ml/min.

eGFR 30 ml/min
SGLT
(
.

HbA1c) .
() :
eGFR >60 ml/min,

eGFR 45-60ml/min
7.

1

,
,

, 24, ,
( )

. ,
,

(basal)

( ),
, ,
, .
,

(bolus)
( ).





( ),
,
,

2-3
80-130 mg/dL.

39
 ,

80-130 mg/dL 140
160 mg/dL

1, , ..
,
..

,

24 .
.

40
8.

2

,
6, .

2:

: ,
, 8.1.
:
( ,
)
( -
).

( , )
( ,
)
.
, -

HbA1c -
, -
, ,
.

: 10 (International Units, IU) -
.
: 80-130 mg/dL.
:
.

41
 8.1. 2.

&
+

+
M


( )

HbA1c
3
GLP-1



HbA1c
3

1 3

+ ()
-
+ +




( )
( )




HbA1c

HbA1c
3
3

()
-
+

HbA1c 2
3


+

+

3


( )

42
( < 70 mg/dL).

:
180 mg/dL 4
130 - 180 mg/dL 2
80 - 130 mg/dL
<80 mg/dL
2 - 4

.
-
, ,
( . 6).

,
HbA1c .

2

,
HbA1c,
( 1),
.
, -
GLP-1 ( GLP1).
, DPP-4.

, , 1, 2 3.

8.1
1:
(-
) -
(, ).
(
HbA1c >7.0%) 2 3

2:

43
 ,
( ) ,
, , .
3:
()
. -
HbA1c >7.0%,
(
) 3 .

1, 2 3

1 2
,
( ).
1-3 -
( )
( )
,
.
.

, .
: <130 mg/dL
<180 mg/dL.

3
: -
, ,
2/3 1/3
.
: 80-
130 mg/dL.
:
.
:
-

44

-

3 : -
, -

.
>130 mg/dL: 2 - 4
80 - 130 mg/dL:
< 80 mg/dL: 2 - 4

.
,

.
-
:
-

-



,

( ).

2 ( 1, 2 8.1).

2-3 ,
.

,
, , -
,
8.1.
-

45
 8.1.

+ 1-2 + 3

+

+

+ +

+ +

+ +


+ +

( , ),


, 8.2.
,
, .

46
 8.2. ( )*
-

()

Humulin Regular 30 min 1-3 5-7 5-7
Actrapid 30 min 1-3 6-8 5-7

(Lispro), 0-15 min 1 3.5-4 3-4
Humalog 100
Humalog 200

(Aspart) Novorapid 10 min 1-3 3-5 3-5

(Glulisine) Apidra 10-20 min -1 3-4 3-4

()
Humulin NPH 1 2-8 16-18 10-16
Protaphane 1.5 4-12 24 10-16

100 IU/ml

(Glargine) Lantus**, 1-4 24

(Biosimilar Glargine) Abasaglar

(Detemir) Levemir*** 1-4 24
(Degludec) Tresiba** 30-90 min >24

300 IU/ml
(Glargine) Toujeo** 1-4 >24

30/70 (30% -70% ), Mixtard 30 30 min 2-8 24 10-16

30/70 (30% -70% ), Humulin M3 30 min 1-8 10-15

14-15

Aspart 30/70, Novomix 30 10 min 1-8 24 10-16

Lispro 25/75, Humalogmix 25 0-15 min 1 14-16 10-16

Lispro 50/50, Humalogmix 50 0-15 min 1 14-16 10-16

* (spc), ** ,
*** 1 2 .
.

47
9.

1 (1) 90%

2 (2) -
, -

-

1, 2
-
. 1 , 2
2 , -
, , .

. 1

:
HbA1c 9.1.

9.1.

HbA1c % < 7.5% 7.0%
(mg/dL) 90-145 80-130
(mg/dL) 90-180* 80-150
(mg/dL) 120-180 120-150


* SPAD, -
90-150.

49
 -

(
)

-
1
-
,
(basal-bolus) -
,

-




,


. -

-



-
.

: -
,

:
( )
, ( )

50
 ( -
) -

(basal)
(bolus): 40-60% -
-
( ),
. ,
glargine, detemir, degludec ,
. H -

,
,
: -
, . -
( )
(basal) -
(bolus).
.

HbA1c
(bA1c >9%)


-
/ -

( <6 )




(
/ )

51
 , -

.

-
-


:
-
, -
,

,
(.. -
)

, -

-

, -
.
lispro aspart
2 , glulisine -
6
, glargine levemir, -
2 . degludec
>1 . glargine levemir

-


-
8.2 8.

52
. 2

2
2 ,
, -
, , ,
, 2 1
2 -
,
2 -
,
2
1 3 -

bA1c <6.5%.

:
,



,

:
/ .

. ,
-
. (bA1c <9%, -
) 500
mg 1 1.000 mg .
bA1c >9% , -
.
.

-
.

53
 9.1. 2

> 250 mg/dl, HbA1c > 9%,

,

: 80-130 mg/dL /, : 80-130 mg/dL
/
: < 140 mg/dL : < 140 mg/dL
HbA1c < 7 % HbA1c < 7 %

HbA1c
2-3

: 80-130 mg/dL /

: < 140 mg/dL
HbA1c < 7 %

HbA1c HbA1c
2-3 2-3

/,
: 80-130 mg/dL ,
: < 140 mg/dL
HbA1c < 7 %

HbA1c
2-3

54
10.
.

-
.
:

24, ( 8
), (2 -
) (
).
24

-
2-3 HbA1c.
-
( -
, Self Blood Glucose Monitoring-SBGM)
(-
),


, . -
-
/ 
-
, :

,

-

.
:

55


.
,
/ , .
-

/
, ,
-


-
, ,
/
-
,


,
, -

:
1 2
(basal) -
(bolus) , 3-7 -
24 (, , ,
)
2
24,
. ,
, HbA1c 2-3

2
-

2, -

56
 , 3 -
(, ,
)
, , 4-7

( 2
, 2-3 ..), -
, :





.

(, Continuous Glucose Monitoring
- CGM) ,
-
.
2-4 ,

, -
(Real time),

.
:
1 25
( -
) 
-

1, -
,
 C

57
11.


.
.

-
70 mg/dL .

.
<70 mg/dL.

. : -
( )
, , , , ,
, .
. :
.
, , ,
, , , , .
, ,
.

: ( <40 mg/dL)

, -

:
70 mg/dL
- : 70 mg/
dL -

59
 -

:

: ,

>70 mg/dL. -



: 60 mg/dL. -
. -
. 50 mg/dL
.
.

1
1
.

.
2
2.
2 -
(,
, ), 2.
2 1

.
, -
. -
.

, -

60
 -

.
-
.
(lispro, aspart, glulisine),

(glargine, detemir, deglutec)
.

1 2.
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,
.
.
-
1.
,
-
,
.

. -
(, , ),
(, ). -
,
.
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61
 .
-

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.

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,

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.

62


-
 C
60-70 mg/dL -
,
.
-
10-20 g
.

. 15
< 80 mg/dL 10-20 g.


, ,

, , ,
.
1
1 mg .

.
,

-
10-30 g , 35% (calorose)
. ,

, -
( 10%).
-
,
.
5% 12-72
. 2 -
, .



63
 -



1 2 -
1 ( ,
..)
,
,


-
, ( )
(CGM),
.
CGM -
, ,

. , -


-
CGM
.

64
12.
12.1.
() -
1 (
), 2


, -
, ,


(- )

pH .

. -
. ,
, , ,
( ). -
, ,
, , ,
, (
Kussmaul) ,
, .

>250 mg/dL
pH < 7.30
< 18 mEq/L
> 3 mmol/L
/

65


1 (1)
1 (
, )

(, , , -
), -
, , ,
.
.

(mg/dL) >250 >250 >250

(mEq/L) 15 - 18 10 - <15 <10
pH 7.25 - 7.30 7.00 - <7.24 <7.00
>10 >12 >12
> 1.5 mmol/L > 3 mmol/L > 3 mmol/L
2+ 3+ >3+
/ /

: : [Na+] - [Cl-+ HCO3-]
123 mEq/L. >14 mEq/L ,
. , -
,
).

66


,
, .
1.000 ml
NaCl , 15-20 ml/kg
2 1.000 ml -
NaCl , 8-10 ml/kg
4 1.000 ml
NaCl , 4-5 ml/kg
< 250 mg/dL,
5% NaCl -

, 6-12
24.

.
, -

( , bolus) 10 -
0.15 /kg.
5-10
/ (100 250 ml NaCl 0.9%,
12.5-25 ml/, )

50-70 mg/dL/
50-70 mg/dL 1 ,

67
 250 mg/dL, NaCl -
5% 150-250 ml/. -
2-4 /,
150-200 mg/dL.

.
,
. , -
, ,
,
.
, :
>5.2 mEq/L, 2
: 3.3-5.2 mEq/L, 20-30 mEq/L KCl, -
, , +

<3.3 mEq/L: 40 mEq/L KCL, ,
, + -
. ,
,
(>3.5 mEq/L).

pH 6.9-7.0 HCO3- < 5 mEq/L, 50

mmol NaHCO3 + 10 mmol KCl
pH < 6.9, 100 mmol NaHCO3 + 20
mmol KCL . pH >7.

, 2-3 , -
, ,
, ,
.

68



20-30
(. , , , )
20-30
( )

1
, , pH, 0, 2, 6, 10, 24
HCO3-, PaO2, 2, PCO2, 2-4
0, 2, 24
0, 4, 8, 12, 18.24
0, 6, 12, 24

12.2.
() -
,
,
2, ,
.

, , ,
..

:
( >600 mg/dL)
(1 + 2+ , --
<3 mmol/L ) pH >7.30
( * >320 mosm/L)

o.
* (mosm/l)= 2[Na (mEq/L)] + (mg/dL)/18 + (mg/dL)/6].

69

,
. -
(, , ,
Babinski ..). , 40%.

9-10 . -
,

. NaCl (0.9%), -
Na [ a = -
a + 0.016 * ( 100) ,
NaCl (0.45%). -
0.45% NaCl
(water for injection)
< 300 mg/dL,
5% NaCl 0.45%
, -
-
.

, ,
. 3-5
( -
150 mg/dL ) -
.

. -
, -
. , -
, ,

70
 ,
.
>5.5 mEq/L, 2.
3.5-5.5 mEq/L, 20-30 mEq/L KCL,
, ,

<3.5 mEq/L 40 mEq/L KCl, ,
, -
.

,
, -
, , ..

, -
-
, .. .

, :

( -
)
.

12.3. -


.

.

71

.
.
.
5-7%
7-10%.
:
5% : >1.5-2 sec, -
,
>5%: , , ,
,
>10%: , , .

( Holliday-Segar)
10 kg: 100 ml/kg/24
11-20 kg: 1.000 ml+ 50 ml/kg/24
> 20 kg: 1.500 ml + 20 ml/kg/24

.

shock:
NaCl 0.9 % Ringers lactate: 20 ml/kg
(15 min-1h)
. Levin -
.

shock:
NaCl 0.9%: 10 ml/kg/ 1-2
.
:
NaCl 0.9% 4-6 NaCl 0.45%
5%
250-300 mg/dL (NaCl 0.9%/DW 5% NaCl 0.45%/DW 5%)

72
 -
,
.
-
:
48 , . 24 -
50% , -
. -

24-48 -
/
NaCl 0.9%
-
.

(bolus),

iv 1-2
, -

0.05-0.1 /kg/
(pH
>7.3 HCO3 >15 meq/L) /
5% -
250-300 mg/dL
(>100 mg/dL/
),
5%, 10%
,
.
>300 mg/dL

0.05 /kg/
,
.

73
 0.05 /kg/
0.03 /kg/
,

,
.
: 0.3 /kg . 1 , -
0.1 /kg/L 0.15-0.2 /kg/2
200 mg/
dL . -
, -
5% .

,
-
, . 20 meq/L -

,
-

: 0.5 mEq/kg/h (amp 13.9 mEq/10 ml)



.

- ;
. ,
, ,

.

.

74


0.5-0.9% -
21-24%. 4-12
.
, ,
, -
( ,
,
4 ). ,
, ,
.

75
13. A N
13.1.

,
. ,
-
, -
 C

180 mg/dL. -
140-180 mg/dL. -
,
 C

-
/ ,



-
,
-
.
, -
. , ,
, -

, 80% -
, ,

. -
. 1
2 (
, >5 ..)

77
 -
, 
, -
, , -

, -
48 ,
. -



 C
-
.
,
-
-
. ,
. -
, , -
,


-




13.2.

.

-

-
,
( HbA1c), (, ) -
(e-GFR)

78
 -
,

, 12 , -
.
, ,

, -
110 180 mg/dL. -

(>250 mg/dL) ,
.
, ,
,
1 2
( 2 ,
>5 ..) -

-

-



. -
30 min

.

79
14.

14.1.
(.. , -
, , , ..)
, -
(, , ). ,
-
, -

, (
1 2),
,
.
,

-
, ,
( ),
/

, ( 1
2),
, -
. , -
- , -
, -
( <0.6 mM/L) -
(.. Ketostix).
<0.6 mml/L ,
>1.5 mmol/L <3 mmol/L -
>3 mmol/L .
-
.
.

81
 -
(.. 1 (+), 2 .. 4 )
-
.
( )
.
:
1. ( ) -
.
(, ),
( ) .
1.
2. -
.
3. 1 ( )
4-6 ( ).

( -
)
250 mg/dL.
4.
( 80-180 mg/dL)
,

.
5. ( [100-150 ml]
). .
6. . .
7.
,
.
,
-
, -
. -
,
. , ,
>200 mg/dL ,
,

82
 , / -

.

:
1.
.
2.
6 , , .
> 3 mmol/L
>250 mg/dL
.
3. .

14.2.
-
.

.
.
.
>250 mg/dL
, .
>0.6 mmol/L
.

0.1 /kg -
( )
2


(lmora, Dexrolyte ..)
<30 kg 1
>30 kg
T
-

83


( ,
..)
.
-
,

.
,
. -

.

-
, -
<70 mg/dL


,

-
, ,
-

, -
, .

84
15.
-
. , -
.
(Body Mass Index, ) 30
kg/m2, 25 29.9 kg/m2

=
[ ]2

-
.
,
. ,
,
,
.
. , -
,
,
,
(), ,
2, . , -
2 ( >40 kg/m2)
93 42
. , 2
80 85%
, -
.

-
,
, -
500-1.000 kcals .
. -

85
 -
, ,
.
:
, .
, -
. ,
. ,
-
, .
-
. ,

-
.

.
,

: -
/ (3 mg).
>30 kg/
m2 3-6
(5-10% ).
, -
, .
5% -
,
.
/
-

.
( )
3 mg
.
-
()
.
,

86
 ( -
, )
( )
( ).
2 BMI >35 kg/m2
/ (
95% , 80%
58% .

.

:
BMI >35 kg/m2


,

18-60
(<5 ).
:
(
)


O (.. )

.
-
,
.

.

87
16.

2 ()

2
HDL ,
.
LDL , -
LDL
2

H LDL
LDL, HDL

2
1 -
,
2



LDL

LDL
Friedewald: LDL = (/5)
HDL , -
<400 mg/dL
LDL :
) , )
(GFR <60 ml/min), ) - (.. ),
) >40 >10
(,
, HDL ,

89
 ): -
LDL <70 mg/dL LDL
50% 
( 4 -
) C
,
, - :
LDL <100 mg/dL LDL
50% 
LDL-
non-HDL- (non-HDL- = -
[HDL-]). non-HDL-
LDL- + 30 mg/dL.
non-HDL-
LDL-, HDL-

<150 mg/dL HDL
>40 mg/dL >50 mg/dL , -

 C

LDL -


trans

-3


,


2
/

90
 ( 16.1)

-
, , -

, ,
LDL :
, -
- (.. )
,
- :
>40 >10 -
(, -
, HDL ,
)
<40 2 
LDL >100 mg/dL, -
:
>40
<40 1 
LDL

16.1. LDL
30% - 40%
(mg) LDL%

10 39
40 31
40 34
5 39
20 35
40 25
2 37

LDL
6%

91
 ,

,

LDL , 10 mg/
LDL-

-
,

LDL , 10 mg/
LDL-
 E
,
-


PCSK9,
50-60% LDL .


-
,

, 

~10% -
.
. , -

.
( - ) ,



HDL

-
HDL -

92
 (>500 mg/dL),
/ -
-3 -

(200-500 mg/dL) -

(>200
mg/dL) HDL (<35 mg/
dL), -

. -

(eGFR <60
mL/min/1.73m2).
HDL
, -
-3 

93
17.

()
,
( ),
-
() 140 mm Hg /
() 85 mm Hg

()
,


:
<140 mm Hg
<130 mm Hg
 C
<85 mm Hg
<80 mmHg



.

-
, :
. 1 kg -
, ,

95
 ~5 mm Hg. = [ + (2*)] / 3
<1.5
g, 3.5 g . -
1 g
4 mm Hg 2 mm Hg.
. .. -
30-45 4

20 g/
10 g/
-
, ,
.

-

()
(1), -


( 1)
, 1 .
, , , ,
-
(estimated-Glomerular Filtration Rate - eGFR),
, MDRD CKD-EPI, >30 ml//1.73 m2
*
eGFR <30 ml//1.73 m2 -
>1.5 mg/dL

, 2
,
-
-
, .

96
 -
-

-
. -
, ,


,
-
( dableducational.org)
24
24
1
. 6-8
30% /
5.5 mEq/L,
,
1 -
 C


(,
).

97
18.

()

() -



(20-30%), ,
1, 2,
-
() , (

), -
-
, -
( 18.1)

/ -

24/
, -
2,
2
, , ,
, -

18.1.
()
mg/g
< 30

30-300*
> 300
* 2 3
3-6

99
 . 1, 5


(eGFR)

e GFR
( 18.2).
18.2. e-GFR*
GFR ml/min/1.73 m2*
G 1 ** GFR > 90
G 2 GFR 60 - 89
G 3 GFR 45 - 59
G 3 GFR 30 - 44
G 4 GFR 15 - 29
G 5 < 15
* eGFR MDRD CKD-EPI.
** ,
, >3 .

. ( 18.3).
18.3. GFR
() (KDIGO 2012)
()

3 . - 1 2 3
GFR -
()
<30 mg/g 30-300 mg/g >300 mg/g
<3 mg/mmol 3-30 mg/mmol >30 mg/mmol
G1 90
G2 60-89

(ml/min/1.73m2)
GFR

G3a 45-59

G3b 30-44

G4 15-29
G5 <15
: ( , ). :
. : . : .
KDIGO (Kidney Disease Improving Global Outcomes) 2012

100

:
<140/85 mmHgB

<130/80 mmHg C
<110
mmHg C
-
(-)
(1)
1, ,
()

2, , 1 -

2, , -
( >1.5 mg/dL), 1

-

1 -

- 4 ( ) - -
-
1.

1
 C
, 1
,
-
(SPC).
.

101

HbA1c <7% -
-
, HbA1c <6.5%
2, -
, -
(, ). -
.

(GFR <60 ml/min/1.73
m2) 0.8 g/kg  C

4 -
, -
.

( , ,
[ 1],
eGFR , , -
).

102
19.
2


(GFR) -
, , -

. 3
()
.

(eGFR <45 mL/min/1.73 m2)
.
,
-
. eGFR
<45 mL/min/1.73 m2 1.000 mg ,
eGFR <30 mL/min/1.73 m2 -
, ,
GFR, -
eGFR <60 mL/min/1.73 m2 B

. ,
,
, , -
, ,
1-4 .
. -

eGFR <30 mL/min/1.73 m2.
(..
) .
-
. (60 mg 3 )

103
 (eGFR <15 mL/min/1.73 m2).
eGFR <20 - 40 mL/min/1.73 m2
0.5 mg .

.
, eGFR: 10-50 mL/min /1.73 m2
25% eGFR <10 mL/min/1.73 m2 50%.
-
. -
, ,
.
, ,
-
, .
,
-
 B

-
, , ,
,
.
DPP-4
,
placebo,
.
DPP-4 , -
, -

. eGFR >50 mL/min/1.73 m2
, : eGFR 30-50 mL/min/1.73 m2 -
(50 mg/), eGFR <30 mL/min/1.73 m2
(25 mg/) -
. -
.
(eGFR 50 ml/min/1.73 m2)
, 50 mg
. (3%
3-4 4 ). -
(eGFR 50

104
 ml/min/1.73 m2), 2.5 mg
.
.
25 mg eGFR 50 ml/min/1.73 m2,
(6,25 mg). -

, -
.
, -
.
GLP1,
(eGFR 30
ml/min/1.73 m2), ,
(5 mg
) (30-50 ml/min)
,
eGFR <30 ml/min/1.73 m2. -

.

, -


SGLT2 , -
eGFR <60 ml/min/1.73 m2.
e-GFR
45-60 ml/min/1.73 m2,
10 100 mg .
- () -
, -
, eGFR
<45 ml/min/1.73 m3 50 mg 3 .

1. -


.
.

105
2. ( , -
, ,
- ),
.
.
3. -
, ,
.
4. , -

SPC .
5. -
, / .
/
.

1
.
1 1
- .
1 . -
.
(eGFR <60 ml/min/1.73 m2) -
1
( >5.5 mEq/L) -
.
-
1/3 1/2
( 4-7 ) .

. -
30% . -

1.
,
.
eGFR >30 mL/min/1.73 m2.

106
 (..
). ,

(, ,
..) C
-
,
-
.
- (, )
,
. -
(, ) -
.
, -

.

107
20.
()
.
.
( , ).
20-60
6%.
,
25 1 90%
2 .
:

( - - ),
,
, ,

(
) (Intra Retinal Microvascular
Abnormalities-IRMA)
( - - ),



,
,
,
.

:
2 
1 10 ,

,
, 2 ,

109



.
,
,


,

,

,


LASER :



.


,
(Vascular Endothelial
Growth Factor-VEGF)

(: )



.

110
21.


-
(macro=, -
macroangiopathy )
, ,

:
( )
( )
.
, -
()
,

.
, -
( Mnckeberg).

.
2-8 -


, ,
,
.

,
2 -

1

111
 ( 70%)
-
.

-

:
( LDL- -
, HDL-
)




, -
HbA1c -


( )

,

-
.
, , -
, -
- .

:
, ,



-

, .

112
22.

()

()
-

40-50%.
, 2-4 5

2 ,
IFG IGT -


. 8 - 10 ,


-
, , -
3 .

-
-

, -
(
)
,
,
(stress echo) ( )
/
,

113
 (
triplex , ..) (
)
( ).
-

-


-
-
:

-

-
:
) , -

) >40
)
)
) >30 :
1 >15
2 >10


.

() -


-

114
 1,


b1c

.

, ,
, ,
AGEs ( -
) .
-

OM
()
-
.
( ,
) , -
.

, , , -
.
ST,
STEMI (ST Elevated Myocardial Infarction)
ST,
NON-STEMI .

(CABG)
(PCI) SYNTAX score >22.
PCI ( ) -
STEMI.
H - , ,
, ,

115

.
-

140-180 mg/dL



.
-
, , -
-

.


:
(100 mg/) A

P2Y12, -
prasugrel ticagrelor B

-
,  C
-
 B
-
 C
H ,
-
 C

116
 , -

(RCT) -
HbA1c
(ADVANCE, ACCORD, VADT) PROACTIVE (
), -
(, , ). UKPDS, 342


RCTs
, DPP-4 GLP-1
(ORIGIN, EXAMINE, SAVOR, TIMI-53, TECOS, ELIXA) -
( -

)
RCT -
SGLT-2 ( ) -
( EMPA-REG),
(14%), (32%)
(38%)
(35%) .

.
GLP-1 :
(
LEADER), 13%,
( 22%) ( 15%)
,
,
. SUSTAIN 6 ,
( GLP-1)
26% , 39%
. -
.


-
-
(DCCT-EDIC UKPDS). ADVANCE, ACCORD

117
 VADT,
, ,
ACCORD -
VADT
( , ,
, , ),
ADVANCE
,
. -


.

118
23.

()
-
24
24,
, CT , -
( -Transient Ischemic Attack)
( , -
- 80% ) (-
- 20%)
:
( [] -
[ ]) -
, . -

, ( -
) -
(40% )

(
)
(20% )
,
,
(-lacunar)
(20% )
(.. ,
, , , -
, .. - 20%).

, , -
, . -

119
 ( 4% 2% -
), 50 .
4% -
5%
-
, -
, .


30%
20% 10%


-

-

, -
(lacunar) .

-
: , , , -

, -
,
() -
.

, , -
, ,

(
triplex , ..) (
)
.

120

-



, (penumbra)
-
.

CT -


(
) 6



-
,
-
( 140-180 mg/dL
). -


220 mm Hg 130 mm Hg

70-99% -
.

121
24.

() ,
.
, -
-
, .
, .
-
-
,
,
(, )
( ,
, 4% )
Mnckeberg -

. ,
, ,
.

(IFG IGT)
, -
, ,
.

,

,
2 . -

123
 Fontaine ( ) -
4 :
1:
2:
2: >200
2: <200
3:
4: ( , ).
3 4
-
.
.

. :
,
, , ,
, ,
.

(Ankle-Brachial Index: ),
( 24.1),
.
ABI 0.90
1.30 (-
Mnckeberg)
, -
Mnckeberg, , -
ABI >1.30,

124
 24.1. *

>0.90
0.90 - 0.71
0.70 - 0.41
0.40 ( )
>1.30 nckeberg
*

Doppler
(5-10 MHz)
, .

. ABI .
(
) (-
).

ABI, , -
:
50 ( ABI -
, 5/)
,
10 ,
-
, .

-

,
(treadmill test) .
20 mm
Hg ABI
.
(treadmill test)

.

(US

125
 riplex) -
-
.

Mnckeberg, ABI
, -
-

(Toe Systlic Pressure
Index, TSPI)

(Transcutaneous Pressure of
Oxygen, TcPO2)
(DSA), -
-
, , DSA
.

.
(..
30-45 /, 3 )


, ,


-


.
, -
.
3, cAMP.


, -

126

.
-
, -

-

,
,

, ,
.

127
25.

()
/

,
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, .. ,
), 10%.



,
. ,
20-50% .

-

:
,
:
()
()
.




.
,
,

,
,
.

129

,
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,

, ,
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, .

:
( 85% ).
.
O
.
.
( ) :





()

.

.


( )
( 10 )
( )
130
 (
128 Hz)
-
( )

,
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2 5 1




(
) (
128 Hz).
10


,
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.
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.
( ,
, ) (
, , )

,

131
 .
3 . ,
.

(, ),
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(.. )
,



.
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6-12
.

,
,
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2, 60

.
6-12 .

, ,
,
.
, 30
1 2
50

132
 .
6-12 .

,
,

,


.
6-12 .

2,
5 1

.

.


1 

2
2
,



/ 2
,

133



,
,


,

,
,

: 60 mg, ,
. 120
mg . 1

: 150 mg/,
2-3 . 2-4 300
mg. 1
: 300 mg/
, 2-3 ,
3.600 mg/ ,



0.025-0.075% -
.

.
29% .
:
(>100 )

.

134


, ,
, ,
, .

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.
: , ,
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(
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,

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.

135
 .




(),
/


 C

()



(
)



1
. >20 mm Hg.
.

,
<10 (
>15) R-R / <1.17

136

R-R
30 15 (30:15
index). <1.04.

Valsalva (Valsalva index)

R-R
R-R .
/ R-R
<1.2.




/
. ,

.

1

,
2 C

,
.

,
.

,
, .

137
 ,
.

5 (, ).
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138
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() ( -
-
) ,

( ),
/ .

-


-
,
, -
,

-
,
,
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.

-
.
1.0% 15.0% -

-
:

139


-

, -
-




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, , , ,
, , 1 -
, .

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:
( -
)
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)




:

-
( ..), 

140

(
).
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,


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Charcot, )

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,
 C
/
-
(,
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,

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-
(, , , )
(, )
,
,
().

.

.
.
:
: , , -


141
 .
.
, -
. -

( ),
,


.

. , ,
, , , ,
,


-
, , -
,
-

()
-

, -
, Gram
(+) , 
-
, -
. -
-
. ,
,
-

142


-
.
, -
(,
CRP, ).

Charcot
H Charcot ( - , Charcot,
, ) -
-
, , -

,
,


, , ..
0.1-0.4% . -
1
, , -
, ,
,
. -

.

-

, .
, , -



,
.

143
 :
, -

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,

-
.
:
,

,

-
(, ..)
-
, .

144
27.
1 2
.

().

-

HbA1c <6.5%,
.
HbA1c <6.5% 70-100 mg/
dL, 90-140 mg/dL



. -
, 1
. -

:

(GFR <30 ml/min)

.

, ,
.

60-100 mg/dL

145
 1 100-130 mg/dL
-

HbA1c % <6.0%. .

:
: 35-45% ( ),
20-25%, 30-40%


(25 kcal/kg ), 1.800 ,,
27.1.

27.1.

(kg) 2 3
(kg/)

< 18.5 12.5 - 18.0 0.5 (0.5 - 0.6)

18.5 - 24.9 11.5 - 16.0 0.5 (0.4 - 0.5)
25.0 - 29.9 7.0 - 11.5 0.3 (0.25 - 0.3)
30.0 5.0 - 9.0 0.25 (0.2 - 0.3)

-

, Lispro Aspart -

EMA , detemir, glargine,
-
.
-
:

146
 :
1-3 , ,
3
( )
.
. -
6-7 ( -
),
, 2-4 ..


(CGMS)

.

80-110 mg/dL. :


1-2 -
.
, -
, -

.

()
-

>92 mg/dL,

2 ( >126 mg/dL)
OGTT 24-28
18%
:

147
 (
)
(, , , -
..)
( 2)


2 .


HbA1c.
, >126 mg/dL, -

92 mg/dL, <126 mg/dL,

<92 mg/dL,
24 28

.
75 g
60 120

-

92 mg/dL
60 180 mg/dL
120 153 mg/dL

, 8

3
-
( >150 g/) -
.

148


70-95 mg/dL
1 90-130 mg/dL
2 80-120 mg/dL.

: 35-45% ( ),
20-25%, 30-40%


(25 kcal/kg -
), 1.800 -
27.1
, (.. -
10 ) .

b1c

2 .


6 -
( ) 4 (
).

-
, -
. -
,


,
.

149


-
-
27.2

27.2.

1-3
2-3 OGTT
1 OGTT

3 OGTT
OGTT
OGTT =

150
28.

20% (>65
)
-
. ,
2,
1 ,

. ( :
, : , -
: , )
( , , -
, , )
-


, , -
, .

.



( , , )
-
( -
), -
. .

, ( ), -
,
( , , ..)
-

151

-
, .
, (
)
. -
(, ) (,
),

,

,
, 



,
( 28.1).
28.1.
HbA1c 2
(%)
(mg/dL) (mg/dL)

( 7.0-7.5 90-130 < 180

,
)

(
, / , < 8.0 150 180
, (> 5 )
)

( - < 8.5* < 180 < 200
, / ) (< 5 )
*HbA1c: 8.5% ~200 mg/dL ()
, ,
, .

152
 -
, ,
, -
-
,
.

( -
) (
) , -
.

, ,




-

, :
6-7




,
(0.8-1.0 g/kg )
.

. . -
,
, ,

:


153



.
,
. ,
, -
(GFR).

, -

, HbA1c, -
, ,

-
2, -
( -
, ).


. ,
. -
-
, .
DPP-4 ,

, -
. GLP-1

>75 .
SGLT-2
. -

,
.
.


, -
,

154
 (, )
.
,
, , ,


-


155
29.

() -
. 2
, - (-
- ) 1/3

-
( , , , -
, , )
, , . -
,
, . -
,
. -
, , -
(Child-Pugh, MELD ..),

, -
,
.
, -
. , -
,
. ,
-
,
( -
)

157

-
.
,
, -

.

2
,
/ -
(.. -
-
3 -
)
-
-

.
, ,
-
,
2

GLP-1 -
( )
, ,

-
DPP-4, GLP-1 SGLT-
2, . -
DPP-4
SGLT-2,
. GLP-1

-

158
 , -

-
/ ,
.
, -
,


159
30.
2

()
. 6,
2.4 ( Framingham)
10 22%, 2
4
, , -
(29%) -
(41%)
,
( ), ,
. -

HbA1c ( bA1c
1% 8% )
.
: , , -


( )
-

( )


. -
.

( -

161
 , , , -
) -
/
(
BNP (NT-pro-BNP).
-
.
-
.
( ) <40%,
40% 49%,
( 50%).


,
-
( ,
, ). 45-50%

, , -
, .
30.1 -
.

30.1.

() ( )
3
( )



, -

( ) ( )
, , , ( ),
, (>2 , , , -
/), , ,
, ..

162
 30.2

.

.

( 7 8%)
: -
( ).
1)
. : -
( ),
.

30.2.

BNP/NT-proBNP BNP/NT-proBNP

NT-proBNP NT-proBNP NT-proBNP NT-proBNP
< 300 pg/mL 300 pg/mL 125 pg/mL < 125 pg/mL

BNP < 100 pg/mL BNP 100 pg/mL BNP 35 pg/mL BNP < 35 pg/mL

163
 eGFR<30 ml/min.
-
eGFR 30 60 ml/min.


( ,

).
2) (
IV NYHA).



-
.
3) DPP-4 -
.
TECOS -

( ) -
.
 A

, SAVOR-
TIMI
EXAMINE ( -
) -
( ). .
( -
).
4) GLP-1 (GLP-1 ) -
ELIXA () LEADER
() .

.
5) EMPA-REG (
2: SGLT-2)
2

164
 ( ).

. (,
) .
eGFR<60 ml/min
(
).
, 10 mg 1 45-60 ml/min A
-
eGFR 30-60 ml/min -
.
eGFR <45 ml/min.

1. 7-7.5% (
).
2. eGFR >60 ml/min: 2
. :
100 mg 1 (
). 3 , 2
.
3. eGFR 30-60 ml/min,
1 . ( -
eGFR <45 ml/min). 2
50 mg 1 (10 mg 1)
. ( eGFR < 45 ml/min).
4. eGFR <30 ml/min ,
25 mg 1 .
.

,
5 mg 1 50 mg 1 (

).

165
31.

, ,
.
,
,
,

, 3-6 ,

, (HbA1c
%),
,






( /
)

167
 o: , /
, .



(, ,
, , , )


: ,



.

, .

,



, , .

, (,
o, , , ), , ,
, , .
:
, , BMI

( ,
)

( , ,
)

168
 (
, ,
,
: , , , , , , ,
, , , )

( , ,
, , )

:
/ .

, 2
,
3-6 HbA1c %
( ):
,
: , , HDL, LDL
, , ,
(eGFR) MDRD CKD-EPI
(AST, ALT), , GT, CPK
(TSH) 1,
, 50
(
)

/ .

1 :
(TSH, anti-TPO,
anti-TG, ) (
, anti-TTG).

:
2

169
 1 10 ,

,
, ,


,
.

6
.
19 64 23
(PPSV23)
> 65 , ,
13 (PCV13)
PPSV23 6-12 .
> 65 , PPSV23,
PCV13 12 .
.
19 59
60 ,
(
anti-HBs).

170
32.

(Diabetes Self-management
Education)
-

,
. ,




. -

-
, , , -
,


. -
.
-
. .
-

-
, -
, , ,
-

.



. ,

171
 -




. -
-
( ).

,
,
,
.

1
1, . -

. ,


, .



. -
.
,
, -
,
:
-
,


-

.

172