CV

Mataram 19 Februari 1979

Tinggal di Jl Dodokan 2/26 BTN Kekalik

Bagian Ilmu Penyakit Dalam

RSUP NTB/FK UNRAM

Riwayat Pendidikan:
SD, SMP 2 di Mataram
SMA 8 Jogja ,S1 FK UGM
S2 FK UGM
Internist FK UGM

Terima Kasih

Joko Anggoro
Bagian Penyakit Dalam
FK UNRAM/RSUP NTB

P EN ATA LA K S A N A A N
TER K IN I D IA B ETES
M ELITU S TIP E 2

Fokus bahasan
Panduan terapi DM2 yang terbaru

PERKENI 2011
Mengapa memilih metformin sebagai
terapi lini pertama?
Kapan harus memakai insulin?
Panduan terapi DM2 ADA/EASD 2012

PATHOGENESIS OF TYPE 2 DIABETES

Diabetes
diseases

mellitus is a group of metabolic

characterized by hyperglycemia

defect of insulin action,

insulin secretion or both
resulting

from

Insulin
resistance

Type 2 diabetes

cell
dysfunction

DeFronzo et al. Diabetes Care 1992;15:318-68

Pathogenesis of Type 2 diabetes:

The om inous octet
Decreased incretin
effects
Decreased insulin
secretion

Increased
lipolysis

Islet-cell

HYPERGLYCEMIA
Increased
glucagon
secretion

Increased
HGP
DeFronzo RA. Diabetes 2009; 58: 773-795

Increased
glucose
reabsorption
Decreased glucose
uptake
Neurotransmitter
dysfunction

Fisiologic Insulin Response to

Constant Glucose stimulus
Level of insulin
secretion

Stimulation by
glucose
First(acut
e) Phase
on
release
Secon
d
Phase
Insulin basal

Baseline

Time

Diabetes Care 1984;7:491-502

Kenaligejala diabetes

Pada diabetes tipe 2, gejala tersebut bisa ringan bahkan hampir tidak ada
KELUHAN KLASIK

CRITERIA FOR THE DIAGNOSIS OF

DIABETES MELLITUS
1. Symptoms of diabetes
Casual plasma glucose concentration 200
mg/dl
or

2. Fasting plasma glucose > 126 mg/dl.

FPG, no caloric intake for at least 8 hours

or

3. 2-h post-OGTT > 200 mg/dl

75 gram glucose dissolved in water

or

4. HbA1C 6,5%

Konsensus Pengelolaan & Pencegahan DM 2 di Indonesia, PERKENI, 2

ADA 2010

K A D A R G LU K O S A D A R A H S EW A K TU D A N
P U A S A S EB A G A I PATO K A N P EN YA R IN G D A N
D IA G N O S IS D M (M G /D L)

Bukan DM
Kadar glukosa
Plasma vena< 100
Darah sewaktu
(mg/dl)
Darah kapiler < 90
Kadar glukosa
Plasma vena< 100
Darah puasa
(mg/dl)
Darah kapiler < 90

Belum DM
100-199
90-199
100-125
90-99

DM
200

200
126
100

Konsensus Pengelolaan & Pencegahan DM 2 di Indonesia, PERKENI, 2

Keluhan klinik diabetes

Keluhan klinis diabetes (+)

Keluhan klasik (-)

GDP 126
<126
Atau - - - - - - --GDS 200
<200

GDP
Atau
GDS

126
100-125 < 100
-- - - - - - - - - - - - - - - - - 200
140-199 < 140

Ulang GDS atau GDP

GDP
Atau
GDS

126
126
-------- 200
<200

TTGO
GD 2 Jam

200

DIABETES MELITUS

TGT

Evaluasi status gizi

Evaluasi penyulit DM
Evaluasi perencanaan makan
Sesuai kebutuhan

GDP = Glukosa darah puasa

GDS = Glukosa Darah Sewaktu
GDPT = Glukosa darah puasa terganggu
TGT = Toleransi glukjosa terganggu

140-199

<140
GDPT Normal

Nasihat umum
Perencanaan makan
Latihan jasmani
Berat idaman
Belum perlu obat
glukosa

Konsensus Pengelolaan & Pencegahan DM 2 di Indonesia, PERKENI, 2

Langkah2 diagnostik DM dan gangguan toleransi glu

Algoritme Pengelolaan DM tipe-2 Tanpa Dekompensasi

Kadar HbA1c
<7%
GHS
Gaya Hidup
Sehat
Penurunan
berat badan
Mengatur diet
Latihan
Jasmani teratur

7-8%

8-9%

>9%

9-10%

>10%

GHS
+
Monotera
pi
Met, SU,
AGI,
Glinid,
TZD, DPPIV

Catatan :
1. Dinyatakan gagal bila
Dengan terapi 2-3 bulan
Tidak mencapai target
HbA1c <7%
2. Bila tidak ada pemeriksaan
HbA1c dapat digunakan
Pemeriksaan glukosa darah
Rata-rata glukosa darah
Sehari dikonversikan ke
HbA1c menurut kriteria ADA
2010

GHS
+
Kombinasi
2 Obat

GHS

Met, SU,
AGI,
Glinid,
TZD, DPPIV

Kombinasi
3 Obat

Met, SU,
AGI,
Glinid,
TZD, DPPIV

GHS
+
Kombinasi
2 Obat
Met, SU,
AGI,
Glinid,
TZD
+
Basal
Insulin

GHS
+
Insulin
Intensif*

Konsensus Pengelolaan & Pencegahan DM 2 di Indonesia, PERKENI, 2

Correlation of A1C with average glucose

Mean plasma glucose
A1C (%)

mg/dl

mmol/l

6
7
8
9
10
11
12

126
154
183
212
240
269
298

7.0
8.6
10.2
11.8
13.4
14.9
16.5

These estimates are based on ADAG data of 2,700 glucose measurements over 3 months
per A1C measurement in 507 adults with type 1, type 2, and no diabetes. The correlation
between A1C and average glucose was 0.92 (51). A calculator for converting A1C results
into estimated average glucose (eAG), in either mg/dl or mmol/l, is available at http://
professional.diabetes.org/eAG. ADA, 2011

R elative contribution of FPG and PPG to overallhyperglycem ia

The Journal of Family Practice April 2006

Step One: Lifestyle and Metformin

Lifestyle interventions:
- Weight loss, exercise,
- Diet should be implemented by registered dieticians

Nathan DM et al. Diabetes Care 2009; 32(1) : 194-203

Efek pada R ESITEN SI

IN SU LIN
Sebelum
metformin

insulin

Sesudah
metformin

glukosa
glucose
transporter

Efek Reseptor

meningkatkan jumlah reseptor insulin fungsional (LORD -BMJ 1983)

Efek Post-Reseptor

memulihkan sensitivitas insulin pada sel otot,sel hati, & sel lemak, translokasi Glut 4 & 2 ke
tepi membran
(BAILEY - Diab. Med. 1988)

METFORMIN WITH PLEIOTROPIC

EFFECTS
INSULIN
RESISTANCE
Apn
28
SMC Fibroblast 27
Oxidative Stress 26
Capillary Perm. 25
Periph. A Blood Flow
Erytthrocyte Deform.
Platelet Aggregation
Hyperinsulinemia 21
HDL-Chol.
20
TG
19
LBK 1
18
VAT, plaque regres.
PAI-1
16
Factor-XIIIa.
15
AMPK

24
23
22

29. ADMA
2. Glucose Absorption
3. FBS
4. 2h PP
5. Glycogenesis
6. Insulin Receptor Binding
7. GUT :GLUT-5 Exp
8. Post-Receptor efc
9. Gluco & Lipo-toxicity
10. Tot-Chol, LDL-Chol
11. DPP-4 GLP-1
12. AGE, FFA
13. Fibrinogen
14. Factor VII

METFORMI
N
With
Broad
Spectrum
effects

17

30

31
32

-Endorphin

VASPIN

Tjokroprawiro, 2009

TITRATIO N D O SE O F
M ETFO RM IN

ONTRAINDIKASI METFORMIN: KREATININ >2 mg/dl atau LFGe < 30ml/m

SEPSIS,SYOK, GAGAL JANTUNG KLAS F IV
ADA 2009

Metabolic Control in Type 2 Diabetes

by Thiazolidinediones (PPAR
AGONIST)
PIOGLITAZONE
Muscle

Glucose uptake
& utilisation

Adipose

Thiazolidinediones
(pioglitazone)

Fat storage
Lipolysis
Free fatty acids

Euglycaemia
Normolipidaemia

Liver
Glucose uptake
VLDL synthesis

D PP-4 Inhibitor & G LP-1 Agonis

Makanan
DM GLP-1
Glucagon LP-1
Sel L- mukosa usus

Enzim Dipeptidyl peptidase-4

DPP-4 Inh
(vildagliptin,sitagliptin,saxagliptin)
Metabolit GLP-1 (9,36) -amide

pelepasan insulin, sekresi glukagon

RESUME MECHANISM OF
ACTION OF OAD

INSULIN

FFA release
rel
e

as
e

e etion
v
i
t
r
fec n sec
e
D uli
ins

re
il n
su
n
i
Pancreas Insulin secretagogues

Im

d
re
i
pa

Circulation

Glucose
FFA
se
a
le

gl

se
o
uc

ke
a
t
up

G
lu
co
se

TZD

Muscle

ke

Adipose

Biguanide

GLP-1
DPP IV INHIBITOR

Promotes

up
ta

Liver

Glu
co
se

Blocks

Biguanide

TZD

FFA absorption

Glucose
absorption
AGI

Intestinal lipase inhibitor

Fat

Carbohydrates

Intestines

Perbandingan obat-obatan DM
Cara kerja
utama

Efek samping
utama

Reduks
i
A1C

Keuntungan

Kerugian

Sulfonilurea

Meningkatkan
sekresi insulin

BB Naik
hipoglikemia

1,02,0%

Sangat efektif

Meningkatkan berat badan,

hipoglikemia (glibenklamid dan
klorpropamid)

Glinid

Meningkatkan
sekresi insulin

BB naik
hipoglikemia

0,51,5%

Sangat efektif

Meningkatkan berat badan, pemberian

3x/hr, harganya mahal dan
hipoglikemia

Metformin

Menekan
produksi glukosa
hati dan
menambah
sensitifitas
terhadap insulin

Dispepsia diare,
asidosis laktat

1,02,0%

Tdk ada kaitan dengan

berat badan

Efek samping gastroentestinal

kontraindikasipada insufisiensi renal

Penghambat
glukosidase
alfa

Menghambat
absorsi glukosa

Flatulens, tinja
lembek

0,50,8%

Tidak ada kaitan

dengan berat badan

Sering menimbulkan efek

gastroentestinal, 3x/hari dan mahal

Tiazolidindion

Menambah
sensitifitas
terhadap insulin

Edema

0,51,4%

Memperbaikiprofil lipid
(pioglitazon),
berpotensi
menurunkan infark
miokard) pioglitazon

Retensi cairan, CHF, fraktur, berpotensi

menimbulkan infark miokard, dan
mahal

DPP-4
inhibitor

Meningkatkan
sekresi insulin,
menghambat
sekresi glukagon

Sebah, muntah

0,50,8%

Tidak ada kaitan

dengan berat badan

Penggunaan jangka panjang tdk

disarankan, mahal

Inkretin
analog/mim
etik

Meningkatkan
sekresi insulin,
menghambat
sekresi glukagon

Sebah, muntah

0,51,0%

Penurunan berat badan

Injeksi 2x/hr penggunaan jangka

panjang tidak disarankan, dan mahal

insulin

Menekan
produksi glukosa
hati, stimulasi
pemanfaatan
glukosa

Hipoglikemi, BB
naik

1,53,5%

Dosis tdk terbatas

memperbaiki profil
lipid dan sangat efektif

Injeksi 1-4 kali/hr, hrs dimonitor,

meningkatkan berat badan,
hipoglikemia dan analognya mahal

Beta Cell
Function
(%)

Strategy to Prevent the

Deterioration
of Type 2 Diabetes
Life

Oral Hypo(s)
Combination

Monotherapy
Style

Insulin with
or without
Oral Hypo
Glycemic agent

Insulin

IGTPostprandial T2 DM

Hyperglycemia
phase I

-12 10

-6

-2

T2DM
phase
II

Years from Diagnosis

Lebovitz H. Diabetes Review 1999;7:139-53

T2DM phase
III

10

14

IndikasiTerapiInsulin
Indikasi mutlak: DM 1, KAD, SHH
Indikasi relatif:
1. gagal mencapai target dengan 3 kombinasi

OAD dosis optimal (3-6 bulan)

2. DM2 rawat jalan dengan :
kehamilan
infeksi paru (TBC)
kaki diabetes terinfeksi
riwayat KAD berulang
riwayat pankreotomi

Kendala dalam terapiInsulin

I dont want
it.!
It
It
hurts !
hurts !

Drug
Drug ?
addiction
addiction ?

Expensive !
Expensive !

Hypoglycemia !
Hypoglycemia !

Kendala dalam terapiInsulin

1. Sekali mulai terapi insulin, tidak bisa di stop lagi

(Persepsi yang salah, seperti kecanduan obat )

Berikan insulin dengan percobaan jangka pendek :
Cobalah suntik insulin selama 1 bulan saja, lalu kita evaluasi
lagi

2. Suntik insulin sangat merepotkan

( Pasien merasa tidak sanggup suntik sendiri)

Demonstrasikan kepada pasien betapa simple nya suntikan

insulin
Berikan insulin 1x /hari untuk mengurangi ketidaknyamanan

Polonsky WH, Jackson RA. Clinical Diabetes 2004;22:147-50.

Kendala dalam terapi Insulin

3. Kegagalan terapi adalah kesalahan saya
(suntikan insulin sebagai hukuman karena kegagalan pribadi)
Jelaskan bahwa insulin diperlukan karena perjalanan penyakit DM yg
progresif, bukan karena kegagalan pasien mengelola penyakitnya)

4. Famili saya disuntik insulin sebelum diamputasi

kakinya
(Insulin diberikan bila Diabetes sudah berat)

Jelaskan bahwa suatu saat insulin diperlukan karena perjalanan alamiah

penyakit DM yg progresif

5. Saya tidak berani suntik insulin sendiri, karena

nyeri..!

(Anxietas terhadap suntik insulin)

Show patient that insulin injection is less painful than BG monitoring
with a glucose meter
Polonsky WH, Jackson RA. Clinical Diabetes 2004;22:147-50.

B olus W izard C alculator : m eterentered

))
)
)
)
)
)
)
)
Paradigm 512
))))

Paradigm Link

Monitor sends BG value to pump via radio

waves : No transcribing error

Enter carbohydrate intake into pump
Bolus Wizard calculates suggested dose

G lycem ic Control: R ecom m ended goals

Measurement

Normal

IDF1

ADA/EASD2

AACE3

PERKENI

A1c*

<6%

<6.5%

<7%

<6.5%

<6.5%

Fasting Gluc

<100

<110

90-130

<110

80-110

PP (2h) Gluc

<140

<155

<180

<140

80-145

Realistic Target: Lowest A1c possible without unacceptable adverse effects

IDF = International Diabetes Federation
ADA = American Diabetes Association.
AACE = American Association of Clinical Endocrinology
1. Global guideline for type 2 diabetes clinical guidelines taskforce (Brussels: IDF,2005)
2. Nathan DM et al. Diabetologia 2006;49:1711-21.
3. http://www.aace.com/pub/odimplementation/roadmap.pdf

A D A / EA S D 2012
R EC O M M EN D ATIO N

A D A -EA SD Position Statem ent: M anagem ent

of H yperglycem ia in T2D M

Patient-Centered Approach
providing care that is respectful of and
responsive to individual patient preferences, needs,
and values ensuring that patient values guide all
clinical decisions.
Gauge patients preferred level of involvement
Explore, where possible, therapeutic choices
Utilize decision aids
Shared decision making final decisions relifestyle choices ultimately lie with the patient
Level of evidence C
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM
Inzucchi SE, et al. Diabetes Care 2012 Apr 19 (Epub ahead of print)

Approach to
M anagem ent ofH yperglycem ia

Diabetes Care 2012;35:1364-79. Diabetologia 2012;55:1577-96.

(Adapted with permission from: Ismail-Beigi et al. Ann Intern Med 2011;154:554.)

Type 2 D iabetes Anti-H yperglycem ic Therapy:

G eneralRecom m endations
Healthy eating, weight control, increased physical activity
Metformin
High
Low risk
Neutral / loss
GI / lactic acidosis
Low

Initial Drug Monotherapy

Efficacy ( HbA1c)
Hypoglycemia
Weight
Side effects
Cost

Consider initial dual

If needed to reach individualized HbA target after ~3 months, proceed to two-drug combination
Begin with
these options if(order not meant to denote any specific preference):
combination therapy
Metformin +
Metformin +
Metformin +
Metformin +
when A1c >9% metformin contraindicated
1c

Two-Drug Combinations*
Efficacy ( HbA1c)
Hypoglycemia
Weight
Side effects
Cost

Consider initial
insulin therapy
when A1c>10-12%
Three-Drug Combinations

Sulfonylurea
High
Moderate
risk
Gain
Hypoglycemi
a
Low

Metformin +
Thiazolidinedio
ne
High
Low risk
Gain
Edema, FH,
FXs
High

Metformin +
Sulfonylurea
+
TZD

Metformin
Metformin +
Thiazolidinedion
DPP-4
eSU
+

DPP-4-I

or
or

Diabetes Care 2012;35:1364-79.

Diabetologia 2012;55:1577-96.

Insulin (usually
basal)
Highest
High risk
Gain
Hypoglycemia
Variable

If needed to reach individualized HbA1c target after ~ 3 months, proceed to two-drug combination
(order not meant to denote any specific preference):

or

More Complex
Insulin Strategies

GLP-1-R
Agonists
High
Low risk
Loss
GI
High

DPP-4 Inhibitor
Intermediate
Low risk
Neutral
Rare
High

GLP-1 RA
Insulin

DPP-4-I

or
or
or

GLP-1 RA
Insulin

Metformin +

Inhibitor
+
SU

GLP-1-R
Agonists
+
SU

TZD

or
or

Insulin

Metformin +
Insulin (usually
basal)
+
TZD

TZD

or
or

Insulin

DPP-4-I

or
or

GLP-1 RA

If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6
months, proceed to a more complex
insulin strategy, usually in combination with one or two non-insulin agents

Insulin (multiple daily doses)

AD A-EASD Position Statem ent:M anagem ent

ofH yperglycem ia in T2D M
4. OTHER CONSIDERATIONS
. Age: Older adults
. Reduced life expectancy

Higher CVD burden

Reduced GFR
At risk for adverse events from polypharmacy
More likely to be compromised from hypoglycemia
Less ambitious targets
HbA1c<7.58.0% if tighter targets not easily
achieved
Focus on drug safety

Diabetes Care 2012;35:1364-79.

Diabetologia 2012;55:1577-96.

Education
the person with diabetes must be his
own doctor, biochemist and dietitian
R. D. Lawrence.

Take H om e M essages
DM 2 adalah penyakit kronis yang

progresif
Pengobatan DM2 meliputi perubahan
gaya hidup ( diet, olahraga, edukasi)
Metformin tetap menjadi pilihan pertama
sebagai terapi DM2
Terapi Insulin perlu dipertimbangkan
pada pasien DM2 dengan indikasi
Terapi DM2 harus mempertimbangkan
kondisi/kebutuhan pasien