Penatalaksanaan Terkini Diabetes Mellitus

Dr. Nanang Miftah F, SpPD

Diabetes
Mellitus
Suatu penyakit metabolik yang ditandai oleh
hiperglikemia (Gula darah tinggi) akibat :
gangguan pada sekresi insulin,
kerja insulin tidak optimal
atau keduanya.
American Diabetes Association, 2010

Diabeinein = pancuran air,

= Rasa Manis

Mellitus

Kencing Manis

Faktor Resiko Diabetes

Mellitus

Umur > 45 tahun

Obesity
Physical inactivity
First -degree relative with diabetes
Wanita yang melahirkan bayi 4 kg atau
terdiagnosa gestasional DM
Hypertensi (Tekanan Darah 140/90mmHg)
Dyslipidemia ( TG> 250, HDL < 35mg/dL)
IFG (impaired fasting glucose) or IGT (impaired
glucose tolerance) on previous testing
Riwayat coronary heart disease
Riwayat polycystic ovarial syndrome (PCOS)

Diabetes care 32,suppl1,2009

Indonesian Diabetes Prevalence

(Guestimate for 2003 / 2005)- BPS& CIA

Tahun
2003

2030

BPS
l Rural

5,548,869

8,076,613

l Urban

8,248.601

12,006,186

13,797,470

20,082,799

l of DM patients
CIA facts book
l Rural
l Urban

* 2006

l of DM patients

6,379,735 *

9,031,326

9,432,108 *

13,352,348

15,881,843

22,383,674

Total population BPS = 214 juta (est.) & Total population 20 years = 133 juta ;
urban = 56 juta , rural = 77 juta
- Total population CIA = 245 juta (est.) & Total population 20 years = 152juta ;
urban = 64 juta, rural = 88 juta
4
-

Kriteria Diagnosis DM
Normal

Prediabetes
IFG

FPG
(mg/dL)
2-h PG
(mg/dL)

DM

IGT

< 100

100-125

<100

> 126

< 140

< 140

140-199*

> 200

FPG : Fasting Plasma Glucose

2-h PG : 2- hour Plasma
Glucose
IFG : Impaired Fasting
Glucose
IGT : Impaired Glucose
Tolerance
OGTT : Oral Glucose

* OGTT : post load 75 g

Kriteria Diagnosis Diabetes Mellitus

ADA Diabetes.org diabetes basics

Classification of Diabetes
Type 1

Cells
destruction
absolute insulin
deficiency

Type 2

Progressive insulin
secretory defect on
background of
insulin resistance

Other specific type of

diabetes due to other
causes

Genetic defect on
cell function
Genetic defects in
insulin action
Disease of the
exocrine pancreas
Drug or chemical
induced diabetes

Gestational

Diabetes
diagnosed during
pregnancy

Patogenesa DM Tipe2
Genetic
susceptibility,
obesity, Western
lifestyle

Insulin
resistance

IR

Type 2 diabetes

-cell
dysfunction

Rhodes CJ & White MF. Eur J Clin Invest 2002; 32 (Suppl.

3):313.

Management of Type 2 DM
1. Life Style Modification :
Diit
Excercise

2. Blood Glucose Controle

Oral Anti Diabetic
Insulin
Both

3. Prevent Complication
4. Eliminate Complication
Anti Hypertension
Anti lipidemia agent

Terapi non
Farmakologis Pada DM
Tipe 2

Langkah Perencanaan
Untuk Diit
Composition
Calculate Daily
Calorie Intake

Carbohydrate
Counting

Macronutrien
Recommendation
Category

Recommendation

CH (% of energy)
4 kcal/gram

45-65% total energy,

simple CH <10% of total energy
Total CH 130 g/d is recommended and
<130 g/d for obese patients

Polysaccharides

Emphasizes whole grains, legumes,

vegetables: containing fibers

Mono- & disaccharides

As flavour

Glycemic index

Incorporate into exchange and teaching

material

Fiber

25 g/d or 14g/1000 cal

Nutrition Recommendation and Intervention in type 2 diabetes, Diabetes Care

Nutrition Recommendation
Category
Protein (% of energy) 4
kcal/gram
Total fat (% of energy) 9
kcal/gram
- SAFA/trans (% of energy)
- MUFA (% of energy)
PUFA (% of energy)
Cholesterol (mg/d)
Salt (g/d)
Sugar alcohols and nonnutritive sweeteners

Recommendation
15-20% total energy
20-25% total energy
<7% total energy
12-15% total energy
<10% total energy
<200mg
<6 g/d
safe in daily intake
levels by FDA

Fat
20%

Prot
20%

CHO
60
%

The Plate
Method

http://www.tops.org/images/plate

Hand Method

Management of Type 2 DM : Longterm

Challenges
-Glycemic control
Prevent
microvascular
complications
Prevent
macrovascular
complications

-A1C : 6,5 7%
-GDP < 100 mg/dl
-GD 2 jam pp < 140 mg/dl

- Glycemic control:
-A1C : 6,5 7%
-GDP < 100
-GD 2 jam pp < 140

- Improve dyslipidemia
-LDL < 100 mg/dl, cardiac risk
< 70 mg/dl

- Control blood
pressure
- 130/80 mmHg
- Control other risk
factors :
Stop merokok
Kurangi berat badan

Makna Klinis dari Penurunan HbA1C

sebagai
Target Terapi
Reduced
Every 1%
reduction in
Risk*
HBA1c
- 21%

Deaths from diabetes

- 14%

Heart attacks

- 37%

Microvascular complications
Peripheral vascular disorders

- 43%

1%

*p<0.0001
UKPDS 35 BMJ 2000;321:405-412

Correlation between A1c with Glucose Level

Mean Plasma
A1c (%)

Glucose

mmol/L

mg/dL

3.5
5.5
7.5
9.5
11.5
13.5
15.5
17.5
19.5

65
100
135
170
205
240
275
310
345

4
5
6
7
8
9
10
11
12

Rohlfing et al. Diabetes Care 25: 275-278, 2002

Treatment Type 2
Diabetes

Pedoman Penggunaan Obat Antidiabetic

Oral
Dimulai dengan monoterapi metformin
Jika target (HbA1C) tidak tercapai dalam 2-3 bulan :
Dosis bisa ditinggkatkan
Mulai dengan Kombinasi OAD :
MET + SU
MET + TZD
MET + Acarbose
MET + DPP IV inhib
MET + GLINID

Target (A1c) diharapkan tercapai dalam 3-6 bulan

Insulin bisa ditambahkan bila perlu untuk mencapai
target terapi

Keuntungan Terapi Kombinasi

Dua /lebih OAD dengan mekanisme kerja

yang berbeda bisa diberikan kepada pasien
Kombinasi 2 macam obat lebih
direkomendasi daripada monoterapi
dengan dosis maximal
Kombinasi terapi OAD memiliki efek
samping yang minimal daripada
monoterapi dengan menggunakan dosis
maximal

Penggolongan Obat Diabetes Oral

A. Insulin Secretagogues :

Sulfonylureas: Glipizide, Glymepiride, Gliclazide,glyquidone,

glybenclamide
Glinides: Nateglinide, Repaglinide

B. Insulin Sensitizers:

Thiazolidinediones : Pioglitazone, Rosiglitazone

Biguanide : Metformin

C. Alpha Glucosidase Inhibitors

Acarbose
Miglitol
D. Incretin Enhancers:

GLP-1 analog : exenatide, liraglutide

Dipeptidyl-Peptidase 4 Inhibitors : Sitagliptin,
Vidagliptin, saxagliptin

AACE Diabetes Melllitus Guidelines, Endocr Pract. 2007; 13 (suppl 1) 2007

Major Targeted Sites of Oral Drug

Classes
Pancreas
Beta-cell
dysfunction

Muscle and
fat

Liver

Hepatic glucose
overproduction

Glucose level

Insulin resistance

Gut

Glucose
absorption

DPP-4=dipeptidyl peptidase-4; TZDs=thiazolidinediones.

DeFronzo RA. Ann Intern Med. 1999;131:281303.
Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:14271483.

Major Targeted Sites of Oral Drug

Classes
Pancreas
Beta-cell
dysfunction

Sulfonylureas
Glinides

Liver

Hepatic glucose
overproduction

Biguanides

DPP-4
inhibitors/
GLP-1 analog

Glucose level
Gut

TZDs
DPP-4 inhibitors/
GLP-1 analog

Muscle
and fat
Insulin
resistance

TZDs
Biguanid
es

Glucose
absorption

Alphaglucosidase
inhibitors

DPP-4=dipeptidyl peptidase-4; TZDs=thiazolidinediones.

DeFronzo RA. Ann Intern Med. 1999;131:281303.
Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:14271483.

Overview of conventional therapeutic

agents for
type 2 diabetes

Pengelolaan Diabetes Mellitus

dengan Insulin

Pengendalian Kadar Gula

Darah
200 mg/dL

130 mg/Dl

GLUCOSE

NORMAL
70-126 mg/dL

70 mg/dL

INSULIN

Glukosa Tidak Terkontrol Bila

Insulin Terganggu
200 mg/dL

GLUCOSE
130 mg/Dl

NORMAL
70-126 mg/dL

70 mg/dL

INSULIN

HYPERGLYCEMIA
Terjadi ketika produksi insulin
berkurang
Defek pada kualitas insulin
Resistensi insulin

Blood insulin
level

Natural insulin
pattern

bolus

basal

Br
ea

kf
a

st

Lu
nc
h

Te
a
33

Normal Insulin Secretion

The Basal-Bolus Insulin Concept
Endogenous Insulin

Insulin Efect

Bolus Insulin
Basal Insulin

HS

Time of Administration

B, breakfast; L, lunch; D, dinner; HS, bedtime.

Adapted from:
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.

Hyperglycemia
and Insulin Type

Fasting (basal = post absorbtive)

hyperglycemia
Prandial hyperglycemia

Deficiency Insulin

Basal insulin

Prandial
insulin

Basal
hyperglycemi
a

Prandial
hyperglycemia

Tujuan Terapi Insulin

Terapi insulin eksogen bertujuan
untuk meniru profil insulin endogen
sehingga kadar glukosa darah dapat
dipertahankan senormal mungkin
Diabetes tipe 1: memerlukan
penggantian insulin mutlak untuk
bertahan hidup
Diabetes tipe 2: insulin sebagai
suplemen untuk meningkatkan kontrol
glikemik ketika OHAs tidak lagi efektif.
37

Basal vs Bolus Insulin

BASAL INSULIN
Menekan produksi
glukosa dari hati
(malam dan intermeal)
Mencegah katabolisme
(lipid dan protein)
ketosis
gluconeogenesis

mengurangi
glucolipotoxicity
Proporsinya 50-60%
dari kebutuhan insulin
harian

BOLUS INSULIN
Menekan produksi
glukosa saat kita
makan
Penyimpanan nutrisi
Membantu menekan
produksi glukosa
hepatik antar-makan
Proporsinya 10 -20 %

Sediaan Insulin yang Ada di Pasaran

(ASKES)
Rapid acting
Human Insulin

Regular :
Actrapid
Humulin R

NPH :
Insulatard
Humulin N

Mixed (70/30):
Mixtard

Analog
Insulin
aspart (Novorapid)
glulisine (Apidra)
lispro (Humalog)

Mixed
Humalog 50/50,
Humalog 75/25
Novomix 70/30

Long acting
glargine (Lantus)
detemir (Levemir)

Overview of Insulin and Action

Penggunaan OAD dan

Insulin Menurut Guideline

LIFESTYLE MODIFICATION

A1C 7.6-9.0%

A1C 6.5-7.5%
Monotherapy
MET

GLP1

DPP4

TZD

Dual Therapy
AGI
MET

GLP1 or
DPP4 or
TZD

GLP-1 or DPP4

Glinide or SU
TZD
MET

Triple Therapy

GLP-1 or DPP4

GLP1
or
DPP4

Colesevelam

AGI

MET

Triple Therapy
MET +
GLP1 or
DPP4

TZD
+

Triple Therapy
GLP1
or
DPP4
MET

TZD

Drug nave,
No symptoms

SU or
Glinides

Dual Therapy
MET

A1C >9%

GLP1
or
DPP4

+SU

TZD
GLP1
or
DPP4

+TZD

+TZD

+SU

Symptoms or
under treatment

TZD

Glinides
or SU

Adapted from AACE

December 2009
update with
permission

Insulin + other agents

ADA EASD Recommendation 2012

Inzucchi et al 2012,Diabetologia,DOI 10.1007/s00125-012-2534-0

RINGKASAN PENGELOLAAN
DM

Ringkasan Pengelolaan DM
1. Tentukan Diagnosis DM
2. Tentukan Klasifikasi DM
3. Tentukan Komplikasi MICRO dan MACRO
vaskulaer

Tx:

1. Lifestyle modification :
DIIT
Excercise
2. Pharmaco Terapi :
Berdasarkan Guideline
Berdasarkan Pathofisiologi
Individual
Mengacu pada Target
3. Pengobatan Penyakit Penyerta / Komplikasi :
Hipertensi
Dislipidemia
CKD
4. Pencegahan Komplikasi :
Pemeriksaan berkala kaki dan mata
Evaluasi Laboratorium
5. Edukasi

DM
Deficiency Insulin
Basal insulin
Basal
hyperglycemia
Sulfonil Urea
TZD
DPP 4 Inhibitor
Metformin
Insulin Basal

Prandial
insulin

Prandial hyperglycemia

Acarbose
Glinides
Insulin Short
Acting

Terima Kasih