DIABETES MELLITUS

Epidemiologi dan
Permasalahannya
Dr. SUHAEMI, SpPD, FINASIM

Diabetes Mellitus
Suatu Sindroma kelainan metabolik,
ditandai adanya hiperglikemia, akibat
defek sekresi insulin, defek kerja
insulin, atau kombinasi keduanya.

Definition of Type 2 Diabetes

Type 2 diabetes is characterised by:

chronic hyperglycaemia with disturbances of
carbohydrate, fat and protein metabolism
defects in insulin secretion (-cell
dysfunction) and insulin action (insulin
resistance)

Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Department of
Noncommunicable Disease Surveillance, World Health Organization, Geneva 1999.

Diabetes care 2004

Diabetes Care 2004 27:1047-53

Diabetes in the World

31.7
India

Year
2000

20.8
China

17.7
USA

8.4
Indonesia

6.8

millions

Japan

Reference: Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Diabetes Care. 2004; 27(5): 1047-1053.

Viva la Vida con Salud!

Diabetes in the World

79.4
India

21.3
Indonesia

Year
2010

42.3
China

30.3
USA

8.9

millions

Japan

Reference: Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Diabetes Care. 2004; 27(5): 1047-1053 .

Viva la Vida con Salud!

Fast Food and Obesity

200% fast-food visits 1977-1995
30% of US children (4-19 yrs)
consume fast food daily

Fast Food and Obesity

Fast-foods fat and energy
Big Mac + medium fries = 83% daily fat intake

Adversely affects dietary quality

Less fiber, fruits, vegetables and milk
Mega-meals

Mega Meals

Super Size
Each 12 oz soda has
10 tsp sugar (150 cal)
One can of soda/day
childs risk obesity
60%
Most popular
Canadian drink
> 110 L/ person/yr

1942-1998:
US production
increased 9X

Diabetes Today: An
Epidemic

Relative risks associated with

obesity

Greatly increased (>3)

Moderately increased (2-3)

Slightly increased (1-2)

DM tipe 2

CHD

CANCER
breast cancer (in post
menopausal women),
endometrial, colon

Gallbladder disease

Hypertension

Reproductive hormone
abnormalities

Dyslipidaemia

Osteoarthritis

Polycystic ovary
syndrome

Insulin Resistance

Hyperuricaemia and
gout

Impaired fertility

Breathlessness
Sleep apnoea

Table 4.1 WHO TRS 894 Obesity: Preventing and

Managing the Global Epidemic

Low back pain

Anaesthesia complications
Fetal defects in maternal
obesity

Traffic patterns in the blood

Inflammation

VLDL

Endothelial function

Glucose

IDL

Hb A1C
LDL
Receptor

Chylomicron
Remnants

LDL

Triglycerides

HDL2

Liver

Lp(a)

HDL3

Proteins
Homocysteine
Hs-CRP
Apo-A
Apo-B
Endothelial cells

Calcium
Macrophage

Intimal thickening

Lp-pla2

Diabetes Melitus
Definisi :
- gangguan metabolisme
- kenaikan kadar glukosa darah kronis
- disebabkan oleh adanya gangguan produksi insulin akibat kerusakan
sel beta pankreas dan atau kerja insulin.

Kerusakan sel
Beta pankreas

Diabetes
Tipe 2

Resistensi
Insulin

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

Resistensi Insulin & Defisiensi Insulin:

2 mekanisme yang saling berhubungan
Evolusi diabetes

Resistensi
Resistensi
Insulin
Insulin
Glukosa darah
Puasa
Sekresi
Sekresi
Insulin
Insulin

Normal

Fase
Kompensasi

Diabetes

DeFronzo R.A. et al., Diabetes Care (1998)

Pada saat diagnosis ditegakkan,

sudah ada defek pada kedua-nya

History of DM

Diabetes

Mellitus

Latin for
Greek for
sweetened
passing water
with honey
like a siphon

Ebers Papyrus

(Egyptian, 1500 B.C.)

first depiction of diabetes
mellitus
- urination of excess
amounts
- manipulation of diet
therapy

Sudah dikenal sejak zaman Ebers Papyrus 1550 SM

Willis : mencatat ada rasa manis pada urine
IBNU SINA : Gangren Diabetic
Matthew Dobson : Rasa manis karena gula
1815 : Chevreul (ahli Kimia) membuktikan bahwa
gula dalam urine adalah glukosa
1921 : Frederic Grant Banting, Charles Best
berhasil mengekstraksi insulin pertama kali dari
pankreas anjing
11 Jan 1922 : Leonardo Thompson, remaja
merupakan pasien pertama yang mendapat insulin
di RS Toronto Kanada
1979 : Goedde menghasilkan human insulin
dengan rekayasa genetik

Faktor Resiko untuk Terjadinya

DM

Kelompok Usia > 45 tahun

Gemuk : BB > 120% BBI (IMT > 27 kg/m2)
Hypertensi
Riwayat Keluarga DM
Riwayat melahirkan bayi > 4 kg.
Riwayat DM pada waktu hamil (DM Gestasi)
Dislipidemia : HDL < 35 mg/dl, Trigliserida >
250 mg/dl
Pernah mengalami gangguan toleransi glukosa

Etiologi
Herediter, diperlukan faktor lain yang disebut
faktor risiko atau faktor pencetus
Virus
Pada DM tipe 1 dijumpai HLA gen yang rentan
terhadap infeksi virus tertentu.
Virus yang selalu menimbulkan insulitis adalah :
Coxackie, Mumps, Rubella, Cytomegalovirus, Herpes,
dll.

Obesitas
Kadar Insulin cukup tetapi tidak efektif (Resistensi
Insulin )

Memakai obat-obatan yang menyebabkan Kadar

Gula Darah meningkat

Causes of Mortality in Diabetic

Patients
Myocardial
infarction
Stroke

34.7
22

Tumors

10

Infections
Diabetic coma

6.7
3.1

Renal insufficiency

2.9
2.7

Gangrene
Accident / suicide

2.1
0.9

Tuberculosis
Others
Not specified

11.4
3.4
0

% deaths in diabetics
10

Panzram G. Diabetologia 1987; 30: 120-31

20

30

40

Pankreas

Terletak dibelakang lambung

Berat : 200 250 gram
Bentuk : Kerucut terbaring
Bagian yang lebar : Kepala (Caput)
Bagian yang kecil : Ekor (Cauda)
Terdapat kumpulan sel disebut pulau-pulau
Langerhans yang berisi sel Beta dan mengeluarkan
hormon Insulin.
Disamping sel Beta terdapat sel Alfa yang
mengeluarkan Glukagon yang bekerja berlawanan
dengan insulin yaitu meningkatkan kadar gula darah.
Juga ada sel Delta yang mengeluarkan Somatostatin

INSULIN
Definisi :
Insulin adalah hormon yang
dikeluarkan oleh sel beta
pankreas yang berperanan
dalam mengatur kadar glukosa
darah
Insulin diibaratkan sbg anak
kunci yang membuka pintu
masuknya glukosa ke dalam sel

KERJA FISIOLOGIS INSULIN

& PENGLEPASAN INSULIN

Insulin dibentuk dari pro insulin distimulasi dg pe

glukosa darah menghasilkan insulin & C-peptide yg
akan masuk ke dlm aliran darah & akan me kan kadar
glukosa darah
Insulin membantu meningkatkan sintesa protein,
meningkatkan penyimpanan lemak, menstimulasi
mesuknya glukosa ke dlm sel utk sumber energi dan
membantu penyimpanan glikogen dlm lemak dan hati
Insulin : endogen & eksogen

Resting -cell
Normal glycemia

Fasting

Glu t-2

In the unstimulated bcell, KATP channels are

open and the outward
movement of K+ ions
holds the membrane
potential at a negative
level.

Insulin

K+
+

proinsulin

- -

Ca2+

cell

Stimulated -cell
Glycemia

Postprandial

Glu t-2

The flux of K+ is regulated

by intracellular ATP.
A surge in blood glucose
leads to increased
production of ATP.

Glucose
GK

G-6-P
PK
Pyruvate

K+

ATP

- ++
- + Depolarization
-

Ca2+

cell
Krebs
cycle Insulin

Insulin
NORMAL
Pintu
terbuka

Insulin

Insulin

Insulin
Insulin

Insulin

Tenaga
Glukosa dibakar
Glukosa darah

Pintu masuk sel

pembawa glukosa

Insulin
DIABETES

Glukosa darah

Pintu
tertutup

Tenaga
Tak ada yang dibakar
Glukosa darah

Pintu masuk sel

Pembawa glukosa

60 ng/ml
Individu normal
Insulin
plasma

F AS E 1
3-5 mnt

F AS E - 2
50-60 menit

waktu

Penderita DM tipe-2
Insulin

(Tumpul)

plasma
F AS E - 1

(Lebih tinggi dan lama)

F AS E - 2

(Delayed Insulin secretion)

Waktu

Loss of the early peak of insulin

secretion
Insulin
secretion

Type 2
diabetic
Non-diabetic

IV Glucose stimulus

time

Why does the -cell Fail?

Oversecretion of
insulin to
compensate for
insulin resistance1,2

Glucotoxicity2

Chronic
hyperglycemia

Lipotoxicity3

High
circulating
free fatty acids

Pancre
as

-cell
dysfunction
Boden G & Shulman GI. Eur J Clin Invest 2002; 32:1423.

Kaiser N, et al. J Pediatr Endocrinol Metab 2003; 16:522.

Finegood DT & Topp B. Diabetes Obes Metab 2001; 3 (Suppl. 1):S20S27.

Beta-Cell Function (%)

Beta-Cell Function in the UKPDS

100
80
60
40
20

Diagnosis

-12 -10
4
6

-8

-6

-4

-2

Years from Diagnosis

KERJA FISIOLOGIK INSULIN

MEMASUKKAN GLUKOSA DARI DALAM DARAH KE:
Hati:
Glukosa di robah jadi glikogen (Glikogenesis)
Glikogen hati menjadi cadangan gula dalam tubuh

Otot:
Glukosa di robah jadi Glikogen (Glikogenesis)
Glikogen otot dibakar menjadi sumber kalori.

Adiposa:
Glucosa dirobah (?) jadi trigliserida
Mencegah pemecahan lemak (Antilipolisis)

Mengaktifkan Lipoprotein Lipase di sel sel endotel P.darah

Jaringan lain: Meningkatkan sintesa protein dari A.Amino

INSULIN MENURUNKAN KADAR GLUKOSA DARAH

UKPDS :

Natural Deterioration of -Cell Function

Beta Cell Function (%)

100

75

50

Facts

25

SlametS

Th/Expectation

-12

10 -6 -2
0 2
Years from Diagnosis

10

14

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

37

DEFEK GANDA PADA DIABETES TIPE-2

PENANGAN SASARAN YANG JELAS
Resistensi
Insulin
In
su
lin

Ac
tio
n

Diabetes
Tipe-2

Disfungsi
Sel Beta

ia
em
a
yc
l
rg
e
yp
H
-cell Failure

Insulin
Concentration

Insulin
Resistance

Euglycaemia
Normal

IGT Obesity Diagnosis of Progression of

type 2 diabetes type 2 diabetes
DeFronzo et al. Diabetes Care 1992;15:318-68

Insulin Release: Normal & Type 2 DM

1st phase
Normal
Type 2 DM

2nd phase
Basal
minutes
0

Insulin release in vitro in response to glucose stimulation

100

Insulin Secretion Profiles in Type 2 Diabetic

Patients and Healthy Persons
Insulin secretion (pmol/min)

800

Healthy
Type 2 diabetes

700
600
500
400
300
200
100

6 a.m. 10 a.m. 2 p.m.

6 p.m. 10 p.m. 2 a.m.

Time
Polonsky et al., 1988b

6 a.m.

Hyperglycemia

AGE formation

Glucose autoxidation

Sorbitol pathwayr
Antoxidants

Oxidative Sress

Lipid peroxidation Endothelial dysfunction

Leukocyte adhesion NO Endothelin
Foam cell formation
Prostacyclin
TNF
TXA2

Hypercoagulability
Fibrinolysis
Coagulability
Platelet reactivity

Vascular complications
Retinopathy
SlametS

Nephropathy

Neuropathy
41

Effect of
Hyperglycemia
Sorbitol
pathway

DAG-PKC
pathway

Hexosamine
pathway

AGE
pathway

Oxidative stress
Increase of :

Extracellular
matrix
Collagen
Fibronectin

Increase of procoagulant proteins

von Willebrandt
factor
tissue factor

Decrease of
proliferation,
migration,
and
fibrinolytic
potential

Vascular complications

Increase of
apoptosis

Stehouwer CDA et al. 20

RESISTENSI INSULIN
INSULIN DALAM JUMLAH YANG NOR
MAL TIDAK DAPAT BEKERJA SECARA
OPTIMAL DI JARINGAN SASARAN NYA
SEPERTI DI OTOT, HATI DAN
ADIPOSA.
Sel sel pancreas mengkompensasi
keadaan
ini
dengan meningkatkan
produksi insulin
dan
me
nyebabkan
HIPERINSULINEMIA

Insulin Resistance

Evolution of Type 2 Diabetes

When do the Complications Begin ?
Birth
NGT

Death
IGT

Normal

Insulin resistance

IFG
Prediabetes

Insulin resistance

DM

Early

Late

Clinical Diabetes

Insulin resistance

Glucotoxicity
Lipotoxicity
Macrovascular complications :
present at different stages in the evolution of DM,
often before DM is establish
Insulin resistance, glucotoxicity and lipotoxicity :
arise during prediabetic phase

Insulin secretion

Insulin resistance
Lipotoxicity

Gluconeo
genesis

Hyperinsulinemia

Glucos
e
Islet -cell degranulation;
toxicity
Reduced insulin content
Amyloid deposit

Reduced plasma
insulin

Increased hepatic
glucose output

Hyperglycemia (Type 2 DM)

Increase Lipolysis
Decrease Lipogenesis

Elevated
Plasma
FFA

Elevated
TNF-

decreased
glucose uptake

Adipose tissue
(Obesity)

Efek pada RESITENSI INSULIN

SEBELUM metformin
insulin

glukosa
glucose
transporter

SESUDAH metformin
11/03/15

Dr Risa Anwar -Glucophage

Page 48

Action of Insulin on the Cell

Metabolism

Glucose Transporters

GLUT
GLUT
GLUT
GLUT
GLUT

1
2
3
4
5

:
:
:
:

: Endothelium
Liver, B-cells of Pancreas
Neurons
Muscle, Adipose Tissue
Intestine

Insulin Action
Insulin
Insulin
receptor

PPAR

transloca

Glucos
e

tion

RXR

Synthesis GLUT 4
mRNA

PPRE

transcription
promoter

Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.

Insulin Resistance

Glucos
e

Insulin

Insulin
receptor

Translocation

X Synthesis GLUT 4
mRNA

PPAR +RXR

PPRE

promoter

Muscle
Cells

transcription
Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.

Plasma insulin ( U/ml)

Physiological Serum Insulin

Secretion Profile
Breakfast Lunch

Dinner

50

25

4:00

8:00

12:00

16:00

Time

20:00

24:00

4:00

8:00

Perjalanan Klinis D.M Tipe-2

DM
GTG
I

II

Insulin
KGD pp

III

IV

KGD p.

Type 2 Diabetes is NOT a

mild
disease
Macrovascular
Microvascular
Stroke
Diabetic
retinopath
y
Leading
cause
of blindness
in working-age
adults1

1.2- to 1.8-fold
increase in stroke3

Cardiovascular
disease

75% diabetic
patients
die from CV events4

Diabetic
nephropathy
Leading cause of
end-stage renal
disease2

Diabetic
neuropathy
Leading cause of
non-traumatic lower
extremity
amputations5

Fong DS, et al. Diabetes Care. 2003; 26 (Suppl. 1): S99S102. 2Molitch ME, et al. Diabetes Care. 2003; 26
(Suppl. 1): S948.
3
4
Kannel WB, et al. Am Heart J. 1990; 120: 6726. Gray RP & Yudkin JS. In Textbook of Diabetes 1997.
5
Mayfield JA, et al. Diabetes Care. 2003; 26 (Suppl. 1): S78S79.

Type 2 Diabetes:
A Complex Metabolic Disorder
Impaired
insulin
secretion

Insulin
resistance

Macrovascular INSULIN
complications RESISTANCE Microvascular
complications
SYNDROME
Central
obesity

Hypertension
Dyslipidaemia

Anti-atherosclerosis Therapy in
T2DM
and the Metabolic Syndrome
Dyslipidaemia
Statins
Fibrates
Nicotinic Acid

Hypertension

Atherosclerosis

Hyperglycemia
Insulin
resistance
Insulin
Metformin
Sulfonylureas
Thiazolidinediones

Obesity
Orlistat
Sibutramine
Rimonabant

ACE inhibitors
ARBs
Beta blockers
Calcium-channel blocke
Diuretics

Platelet
activation
and
aggregation
Aspirin
Clopidogrel

Adapted from Beckman JA et al. JAMA. 2002; 287:

2570- 81

Endocrine System Control Feedback

Regulation of Blood Sugar

insulin

body
liver stores reduces
cells take sugar
appetite
up sugar
from blood

pancreas
high

liver

blood sugar level

(90mg/100ml)

low

liver
triggers releases
hunger sugar

liver

pancreas
glucagon

Glucose regulation

Bila insulin tidak ada sama sekali (DM tipe 1) atau :

Insulin tidak cukup atau efisiensi kerjanya rendah
(DM tipe 2)
PEMASUKAN GLUKOSA
KE HATI, OTOT,
ADIPOSA
AKAN TERGANGGU
GLIKOGENOLISIS &
GLUKONEOGENESIS
TIDAK
DIHAMBAT
GANGGUAN
SINT.PROTEIN
LIPOLISIS TAK
DIHAMBAT
BERAT MAKIN
MENURUN

HIPERGLIKEMIA

GLUKOSURIA
POLIURI POLIDIPSI
LEMAS /MUDAH
LELAH

Klinis Diabetes Melitus :

Polifagia : sel mengalami starvasi karena cadangan
KH,Lemak, Protein berkurang ( tdk ada pengisian depot
yg biasanya dilakukan oleh Insulin )
Polidipsia : glukosuria (diuresis osmotik) dehidrasi
intraselular dan stimulasi pusat haus di hipotalamus)
kompensasi: penderita banyak minum
Poliuria : glukosuria (diuresis osmotik) penderita
banyak kencing
Penurunan BB : cairan tubuh berkurang karena diuresis
osmotik, protein dan lemak berkurang karena dipecah
sbg sumber energi.
Lelah : Metabolisme tdk berjalan sebagaimana
mestinya.

KLASSIFIKASI DIABETES
MELLITUS
1. DM tipe-1 (Autoimun dan Idiopatik)
2. DM tipe-2
Gemuk : Resistensi Insulin > Disfungsi sel
Tak gemuk : Disfungsi sel > Resistensi
Insulin

3. DM tipe lain : MODY; Peny.Eksokrin

pancreas,Cushing S dll
4. DM Gestasi (Kalau hamil DM, tak hamil
DM nya sembuh).

Pathogenesis of Type II DM
cell defect
Genetic
Abnormal Secretion

Environment
Obesity ???
Insulin resistance

Relative Insulin Def.

cell
exhaustion

Type II DM

IDDM

H AT I

OTOT

Non Sugar

Glycogen

G
L

Glycogen

(+)

C
O
S

(+)

(-)
Glucose

cell pancreas
Adipose Tissue

Blood Glucose
Absorbed

Intestine

Insulin

Glucose
Insulin

Antilipolysis
Trigliserida

+
L.P.L

Asam Lemak
NORMAL /PHYSIOLOGIC CARBOHYDRATE METABOLISM

NORMAL /PHYSIOLOGIC CARBOHYDRATE METABOLISM

H AT I

OTOT
Glycogen

Non Sugar
Intestine
G
L
U
C
O
S
E

(+)

Glycogen

Glucose
(-)
Insulin

(+)
Glucose

Insulin

Absorbed
Blood Glucose

cell pancreas
Adipose Tissue
Antilipolysis
Trigliserida

+
LPL

Asam Lemak

Liver glucose output responds to multiple hormonal signals

AntonioVidalPuig&StephenO'rahilly(2001)Nature413,125126.

GEJALA KLASIK DM
4P

1.
2.
3.
3.

POLI DIPSIA
POLIFAGIA
POLI URIA
PENURUNAN BERAT BADAN

Kriteria Diagnosa DM
Gejala Klasik DM + Kadar Gula Darah
Sewaktu > 200 mg/dl
Gejala Klasik DM + Kadar Gula Darah Puasa
> 126 mg/dl
Kadar Gula Darah 2 jam TTGO > 200 mg/dl
Puasa diartikan tidak mendapat kalori
tambahan sedikitnya 8 jam TTGO dengan
standar WHO, menggunakan beban glukosa
yang setara dengan 75 gram glukosa
anhidrous yang dilarutkan dalam air

OGTT 1

TEST TOLERANSI GLUKOSA ORAL

(T.T.G.O)
1. Makan minum seperti biasa 3 hari sebelum
pemeriksaan
2. Kegiatan jasmani dilakukan seperti biasa
3. Berpuasa 10-12 jam sebelum pemeriksaan
4. Pagi diperiksa KGD puasa
5. Minum larutan 75 gr glukosa dalam 250cc air (5
menit)
6. Pasien menunggu selama 2 jam dan tidak merokok
7. Diperiksa KGD 2 jam sesudah minum larutan glukosa
TGT

KGD puasa normal. KGD 2 jam paska pembebanan

75 gram glukosa antara 140-200 mg%

GDPT

KGD Puasa 110-126 mg%,KGD 2 j PG Normal.

GEJALA KLINIS DIABETES MELLITUS

TIPE-2
GEJALA KHAS
Poliuria
Polidipsia
Polifagia
BB turun cepat

GEJALA TIDAK KHAS

Kesemutan
Gatal di daerah genital
Keputihan
Infeksi sukar sembuh
Bisul hilang timbul.
Penglihatan kabur
Cepat lelah
Mudah mengantuk

Complications of Diabetes
Mellitus
Chronic
Complications of
Diabetes Mellitus
Microvascular
Retinopathy
(nonproliferative/proliferati
ve)
Nephropathy
Neuropathy
Sensory and motor (monoand polyneuropathy)
Autonomic

Macrovascular
Coronary artery disease
Peripheral vascular disease
Cerebrovascular disease

Acute
Complications of
Diabetes Mellitus
Hyperglycemia
crisis
Diabetic ketoacidosis
Hyperglycemia
hyperosmolar State
Lactic acidosis

Hypoglycemia

GAMBARAN KLINIS DM TIPE-1 DAN

DM TIPE-2
GEJALA
2

DM tipe-1

Poliuria dan Polidipsia

++
Lemas dan mudah lelah
Kuat makan tapi tambah kurus
Penglihatan sering berulang kabur +
Gatal /radang kemaluan
Neuropati periferal (kebas/kesemutan)
Selalu ngompol malam (Enuresis Noct)
Sama sekali tanpa gejala

DM tipe+

++
++

+
++

+
+
++
-

++
++
++

KARAKTERISTIK
DM TIPE 1DAN DM TIPE 2

DM TIPE 1

Mudah terjadi ketoasidosis

Pengobatan harus dgn insulin
Onsetnya akut
Biasanya kurus /Umur muda
Terkait dgn HLA-DR3 & DR4
ICA; GADA; & IAA selalu (+)
Riwayat keluarga (+) pd 10%
30-50% kembar identik
terkena

DM TIPE 2
Jarang ketoasidosis (HONK
bisa)
Tidak mesti diberi insulin
Onsetlambat (pelan-pelan)
Gemuk atau tak gemuk / > 45
thn
Tak ada kaitan dengan HLA
Tak ada autoantibodi
Riwayat keluarga (+) pada
30%
100% kembar identik
terkena

Kriteria Pemantauan Diabetes

Mellitus
KGD puasa
KGD 2 jam pp
HbA1c*
Kolesterol total*
Kolest. LDL (PJK-)*
Kolest.LDL (PJK+)*
Trigliserida (PJK-)*
Trigliserida (PJK+)*

BAIK
LUMAYAN
BURUK
80-109
110-139
> 140
110-159
160-199
> 200
4 - 5.9%
6 8%
> 8%
< 200
200-239
> 240
< 130
130-159
> 160
< 100
100-129
> 130
< 200
200-249
> 250
< 150
150-199
> 200

* = diperiksa tiap 3 hingga 6 bulan

Glycated Hemoglobin
(HbA1c) 1

PADA TIAP KUNJUNGAN HARUS

DIPANTAU
KGD Sewaktu
Tekanan darah (diukur dalam keadaan duduk)
Indeks Massa Tubuh = BB (kg) / TB (M) 2

PEMERIKSAAN
BURUK
TD sistolik (mmHg)
TD diastolik
IMT Pria (Kg/M2)
atau >27
IMT wanita (Kg/M2)
>25

BAIK
< 130
< 80

LUMAYAN

130-150
80-85
>85
20-24.9
25- 27

18.5-22.9

23- 25

>150
< 20

< 18.5 atau

ACUTE COMPLICATION OF
DIABETES
Diabetic ketoacidosis (DKA)
Hyperosmolar nonketotic (HONK)
Hypoglycemia

Hyperglycemia
Drowsy
Flushed
Thirsty

Diabetic Emergencies
According
to Blood Glucose Level

Signs of Diabetic Coma

Kussmaul respirations
Dehydration
Fruity breath odor
Rapid, weak pulse
Normal or slightly low blood pressure
Varying degrees of unresponsiveness

Hypoglycemia
Weak, sweaty
Confused/irritable
/ disoriented

Hypoglycemia
Symptoms of hypoglycemia
Neurogenic (autonomic)

Neuroglycopenia

Trembling
Palpitations
Sweating
Anxiety
Hunger
Nausea
Tingling

Difficulty concentrating
Confusion
Weakness
Drowsiness
Vision changes
Difficulty speaking
Headache
Dizziness
tiredness

Drugs associated with

Hypoglycemia

ACE inhibitors
Alcohol
Antimalarials
Beta-blockers (non-cardioselective)
Disopyramide
Fluoroquinolones (e.g. gatifloxacin)
Quinidine
Salicylates (high doses only)

Baseline Vital Signs

Hypoglycemia
Respirations = normal to rapid
Pulse = normal to rapid
Skin = pale and clammy
Blood pressure = low

Hyperglycemia
Respirations = deep and rapid
Pulse = normal to fast
Skin = warm and dry
Blood pressure = normal

Tujuan Pengelolaan
Diabetes Mellitus

Menghilangkan gejala
Mempertahankan rasa sehat
Memperbaiki kualitas hidup
Mencegah komplikasi (akut dan kronis)
Mengurangi laju komplikasi yang sudah
ada
Menurunkan jumlah kematian

Edukasi
Tujuan:
Pencegahan Primer
Pencegahan Sekunder
Pencegahan Tertier

Diabetes Mellitus
Complications of chronic hyperglycemia
Macrovascular complications
Cardiovascular disease (heart attack)
Cerebrovascular disease (strokes)

Microvascular
Blindness (retinal proliferation, macular
degeneration)
Amputations
Diabetic neuropathy (diffuse, generalized, or focal)
Erectile dysfunction

Microvascular
Complications

Pathophysiology of diabetic
retinopathy
Hyperglycemia
Pericyte
loss

Hyperperfusion

Capillary/
Endothelial
damage
Capillary
occlusion

Loss of
autoregulation
Vasoactive
factors

Loss of tight
junction

Retinal
ischemia
Growth
factors
New vessels
-Low resistance
- No pericyte/autoregulation

Macular
oedema

Diabetic retinopathy
Two types of diabetic retinopathy:
Nonproliferative diabetic retinopathy
(NPDR)
Early stage diabetic retinopathy

Proliferative diabetic retinopathy (PDR)

Later stage diabetic retinopathy
94

Treatment Eye Disease

Cataract removal
Laser surgery for
retinopathy

Nonproliferative
diabetic retinopathy
(NPDR)
Also called background
diabetic retinopathy.
Earliest stage of diabetic
retinopathy.
Damaged blood vessels in
the retina leak extra fluid
and small amounts of blood
into the eye.
Cholesterol or other fat
deposits from blood, called
hard exudates, may leak
into retina.
96

Top: Healthy retina

Bottom: Retina with NPDR,
containing hard exudates

Diabetic nephropathy

Pathophysiology of diabetic
nephropathy
Hyperglycemia

Renal
vasodilatation
Increased glomular
filtration rate

Protein glycation

Increased
intraglomerular
capillary pressure
Hypertension
Increased
protein excretion

Microalbuminuria or
macroalbuminuria

Glomurular
damage

Nephropathy

Treatment - Nephropathy
ACE inhibitors
MNT protein
restriction

Diabetic neuropathy

Mechanism of nerve damage in

diabetes
METABOLIC

myoinositol

VASCULAR

glucose

Altered membrane
potensial

Slow nerve
conduction

sorbitol

nerve
oedema

AGE
formation

Arterial
narrowing
vasoconstriction

NO
production

Impairing
axonal transport

Vessel
occlusion

H2O

Burning, feeling like the feet are on fire

Stabbing, like sharp knives

Freezing, like the feet are on ice,

although they feel warm to touch

Lancinating, like electric shocks

Autonomic Neuropathy

Case 4

Assessment

Infected Ulcers
How do you know if the ulcer is infected then?
Assessing foot ulcers for the presence of infection is
vital. All open wounds are likely to get colonised with
microorganisms, such as Staphylococcus aureus, and
not necessarily infected. Therefore, the presence of
infection needs to be defined clinically rather than
microbiologically.

Page 105 of
67

Signs suggesting
infection include;
1. purulent
secretions
2. presence of friable
tissue
3. undermined edges
4. foul odour
An infected ulcer

Autonomic Neuropathy
DM-related autonomic neuropathy can involve multiple
systems, including the cardiovascular, gastrointestinal,
genitourinary, sudomotor, and metabolic systems.
Autonomic neuropathies affecting the cardiovascular
system cause a resting tachycardia and orthostatic
hypotension.
Gastroparesis and bladderemptying abnormalities are
often caused by the autonomic neuropathy seen in DM
(discussed below).
Hyperhidrosis of the upper extremities and anhidrosis
of the lower extremities result from sympathetic
nervous system dysfunction.
Anhidrosis of the feet can promote dry skin with
cracking, which increases the risk of foot ulcers.
Autonomic neuropathy may reduce counterregulatory
hormone release, leading to an inability to sense
hypoglycemia appropriately ((hypoglycemia
unawareness)

Macrovascular
complications

Atherothrombosis Has Multiple

Manifestations
Ischemic stroke

Myocardial
infarction

Transient ischemic attack

Angina:
Stable
Unstable

Peripheral arterial disease:

Intermittent claudication
Rest pain
Gangrene
Necrosis
Adapted from: Drouet L. Cerebrovasc Dis 2002;13(suppl 1):16

Diabetes and Macrovascular

Disease

Libby and Plutsky. Circulation. 2002.

Hubungan kegagalan terapi dg Stadium pada DM

Tipe 2 dan Fungsi Sel Beta Pankreas
100
75
Fungsi sel
Beta (%)

50
25

TGT

Hiperglikemi
Postprandial

-12 -10

-6

Fase I
DM tipe 2

-2

Fase II
DM tipe 2

Tahun Sejak Diagnosis

Fase III
DM tipe 2

10

14

Matching Pharmacology to
Pathophysiology
Glucose influx
Alpha-glucosidase
inhibitors
Biguanides
Hepatic (TZD)

glucose
output

Sulfonylureas
Meglitinides
Nateglinide

Hyperglycemia
TZD
(Biguanides)

Peripheral
glucose uptake

Insulin
secretion

Sejarah Insulin

1921 Insulin ditemukan

oleh Banting dan Best

1922 Leonard Thompson

adalah pasien pertama yang
mendapat suntikan insulin

1923 Novo Nordisk mulai

produksi Insulin Hewan
(Sapi dan Babi)

1973 Insulin Hewan

Monokomponen

1987
1990

Insulin Human
Insulin Analog

INDIKASI PENGGUNAAN INSULIN

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

DM tipe 1
Penurunan berat badan yg cepat
Hiperglikemia yg berat disertai dg ketosis
Ketoasidosis diabetik
Hiperglikemia hiperosmolar non ketotik
Hiperglikemia dg asidosis laktat
Gagal dg kombinasi OHO dosis hampir max
Stress berat
Kehamilan dg DM atau DM Gestasional
Gangguan fs. ginjal atau hati yg berat
Kontraindikasi dan atau alergi thp OHO

KEGUNAAN METABOLIK TERAPI INSULIN

Menurunkan kadar GD puasa & pp

Supresi produksi glukosa oleh hati
Stimulasi utilisasi glukosa perifer
oksidasi gluk / penyimpanan di otot
Perbaiki komposisi lipoprotein abnormal
Mengurangi glucose toxicity
Perbaiki kemampuan sekresi endogen
Mengurangi glycosilated end products

KAPAN INSULIN DIPERLUKAN?

Data UKPDS :
50% DMT2 perlu insulin setelah 6
tahun
Fungsi B-cell yg rendah pd saat
diagnosis risiko kegagalan OHO lebih
tinggi
Marre M. Int J Obesity (2002) ; 26 (Suppl 3) : S25-S30

Modern "Aggressive" Rx of
Type 2 DM from Time of
Diagnosis

HbA1c > 10 %
or

FPG >260 mg/dl

or

Symptomatic
or

Ketotic

IMMEDIATE
INSULIN

Modern "Aggressive" Rx 4
HbA1c not < 7% by
6 months

Start
Insuli
n

DM Treatment Steps
(OLD THEORY)
+
+
3

medicine

exercise

5 Insulin

Oral plus
insulin

Combination of
oral medicines

2 One oral
1 Diet &

HUMAN INSULIN
A chain
Gly

Phe

II
e

Val Glu Gln Cys Cys Thr Ser

Ile Cys

Ser Leu

10

Tyr Glu Leu

15

B chain

Val Asn Gln His Leu Cys

Glu Asn Tyr Cys Asn

21

S
Gly Ser His Leu Val Glu

10

Ala Leu Tyr Leu Val Cys Gly

Glu

15

20

Arg Gly

25

30 The Lys

Human insulin

A chain 21 amino acids

B chain 30 amino acids

Phe
Phe

Phe
Tyr
Pro Thr

JENIS INSULIN
Natural (animal) insulin : ekstraksi dari
pankreas hewan
Semisynthetic human insulin : insulin dari
hewan yg dimodifikasi secara enzimatik
Biosynthetic human insulin : dibuat dengan
DNA rekombinan menggunakan ragi atau
bakteri
Insulin analog : biosynthetic human insulin
yg direkayasa dgn mempertukarkan posisi
asam amino atau menambahkan satu atau
lebih asam amino/asam lemak pada rantai
molekul insulin

Tipe insulin berdasarkan puncak dan

jangka waktu kerjanya :
1.
2.
3.
4.
5.

Insulin kerja sangat cepat : NovoRapid , Humalog ,

Apidra
Insulin kerja pendek : Actrapid , Humulin R
Insulin kerja sedang : Insulatard , Humulin N
Insulin campur : Mixtard , Humulin 30/70 , NovoMix
30 , Humalog 25
Insulin kerja panjang : Levemir , Lantus

Kendala Terapi Insulin

Adanya anggapan :

Sekali dimulai, tidak pernah bisa berhenti

Akan membatasi aktivitas sehari-hari
Memulai terapi Insulin berarti:
Saya telah gagal
DM-nya sudah menjadi serius
Suntikan insulin akan sangat sakit/nyeri
Suntikan insulin menyebabkan kebutaan
Franks story: Jika anda tidak bekerja keras, anda
akan saya suntik insulin lho

Prinsip Terapi
Insulin Basal menurunkan gula darah
puasa
Insulin Bolus menurunkan gula darah
post prandial (setelah makan)
Insulin Premixed menurunkan GD
puasa dan GD 2 jam PP

Macam-macam Rejimen Insulin

Basal Bolus
4 suntikan per hari (3 bolus dan 1 basal)
Satu kali suntikan insulin basal pada malam
hari ditambah dengan obat oral
Premixed Insulin, sekali sampai 3 kali sehari,
sebelum makan.
Premixed dikombinasi dengan short acting

Insulin
in blood

4 Suntikan per Hari

3 Short + 1 Intermediate/Long Acting
(Basal Bolus)

7 8
time

Breakfast

10

11

12

Lunch

Evening Meal

10

11

12

Sleep

Insulin
in blood

Dua kali Suntikan Premixed Insulin Per

Hari

8 9
time

Breakfast

10

11

12

Lunch

Evening Meal

10

11

12

Sleep

Tempat Penyuntikan Insulin Subkutan :

Searah Jarum Jam

75 -90

1 -15

61 -75

16 -30

45 -60

31 -45

Efek Samping Insulin

Hipoglikemia (kadar glukosa darah terlalu
rendah)
Peningkatan berat badan
Reaksi Alergi (kemerahan, gatal-gatal di tempat
penyuntikkan)
Lipodistrofi

Diabetes

dan Peran Insulin Dalam Penanganannya

Dr. SUHAEMI, SpPD, FINASIM

Leonard Thompson

1922 1923

Meninggal tahun 1935

Perkembangan Terakhir Injeksi Insulin

Non-Injectable Insulin

Trans-dermal insulin delivery

Oral insulin delivery

Pulmonary insulin delivery

Buccal insulin delivery

Insulin Delivery Devices 3

Inhaled Insulin
Exubera

Inhaled Insulin
1-1-08
voluntary
discontinuation
4-6-08
Cancer Warning

Other Injectable Drugs 1

Exenatide (Byetta)
insulin
secretagogue
peptide
gila monster saliva
use with other
drugs
no hypoglycemia
bid

Other Injectable Drugs 1

Pramlintide (Symlin)
analogue of hormone
amylin
polypetide
slows gastric
emptying
induces satiety
opposes glucagon
reduces posprandial
BG
give with meals

used with insulin

Glycated Hemoglobin
(HbA1c) 2

SMBG
Value in Type 2
DM not
established
Useful for titrating
insulin