DIABETES MELLITUS

Abdul Rahman

SMF ILMU PENYAKIT DALAM

RSUD BANTEN

Definition
Diabetes mellitus is a group of metabolic
diseases characterized by hyperglycemia
resulting from defects in insulin secretion,
insulin action, or both (Expert Committee on the
Diagnosis and Classification of Diabetes mellitus 2002)

Long-term damage, dysfunction, and failure

of various organs especially the eyes, kidneys,
nerves, heart, and blood vessels

Diabetes- What is it?

Body is not producing or has lost sensitivity
to insulin.
Insulin is a hormone that is needed to
convert sugar, starches and other food into
energy.
Insulin is produced in the body by the
pancreas.

How Does Insulin Work?

A person normally secretes insulin in
response to an elevated blood sugar level.
It does this by accelerating blood sugars
movement out of the blood and into the
cells.
Cells will not allow blood sugar in without
insulin. - this can cause a problem.

Clinical Impact of Diabetes Mellitus

Diabetes

A 2- to 4fold
increase in
cardiovascular
mortality

The leading
cause of
new cases of
end stage
renal
disease

The leading
cause of new
cases of
blindness in
workingaged adults

The leading
cause of
nontraumatic
lower
extremity
amputations

The diabetes epidemic:

171 million in 2000 to 366 million people in 2030
2000
Ranking
1
2
3
4
5
6
7
8
9
10

Country
India
China
USA
Indonesia
Japan
Pakistan
Russian Fed.
Brazil
Italy
Bangladesh

2030
People with
diabetes
(millions)
31.7
20.8
17.7
8.4
6.8
5.2
4.6
4.6
4.3
3.2

Country
India
China
USA
Indonesia
Pakistan
Brazil
Bangladesh
Japan
Philippines
Egypt

People with
diabetes
(millions)
79.4
42.3
30.3
21.3
13.9
11.3
11.1
8.9
7.8
6.7

Wild S et al. Diabetes Care 2004;27:104753

Status of diabetes management

Symptoms :
Polyuria
Polydipsia
Weight loss
Sometimes polyphagia
Blurred vision

Current recommendations
Diabetes must be diagnosed earlier. And once
diagnosed, all types of diabetes must then be managed
much more aggressively
Canadian Diabetes Association

Therefore, the results of the UKPDS mandate

that treatment of type 2 diabetes include
aggressive efforts to lower blood glucose levels
as close to normal as possible
American Diabetes Association
Canadian Diabetes Association. Can J Diabetes 2003; 27 (Suppl 2): 1163;
American Diabetes Association. Diabetes Care 2003; 26: S2832.

ADA definition of hyperglycaemic states

Criteria for the diagnosis of diabetes
Symptoms of diabetes plus casual plasma glucose 200 mg/dl (11.1 mmol/l)
or
FPG
< 100 mg/dl (5.6 mmol/l)

normal fasting glucose

100125 mg/dl (5.66.9 mmol/l)

impaired fasting glucose

126 mg/dl (7.0 mmol/l)

diabetes

or
OGTT 2-h post-load glucose
< 140 mg/dl (7.8 mmol/l)
140199 mg/dl (7.811.1 mmol/l)

normal glucose tolerance

impaired glucose tolerance

200 mg/dl (11.1 mmol/l)

diabetes

or
HbA1c > 6,5 %
ADA = American Diabetes Association

Adapted from American Diabetes Association. Diabetes Care 2004; 27:S5S10.

50% of type 2 diabetes patients have

complications at the time of diagnosis
MICROVASCULAR

MACROVASCULAR

Retinopathy,
glaucoma or
cataracts

Cerebrovascular
disease

Nephropathy

Neuropathy

Coronary
heart
disease

Peripheral
vascular
disease

UKPDS Group. UKPDS 33. Lancet 1998; 352:837853.

PENJARINGAN DM
TIPE 2
1. Idealnya untuk mendeteksi DM tipe 2 harus dilakukan
skrining populasi, kenyataan sulit oleh karena, biaya
mahal
2. Oleh karena itu penjaringan hanya dilakukan pada
mereka dengan resiko tinggi DM

KELOMPOK RESIKO
TINGGI DM
Umur diatas 45 tahun
Kegemukan > 120% BB idaman atau IMT > 27 kg/m2),
Hipertensi >140/90 mmHg,
Riwayat keluarga DM,
Pernah melahirkan anak BB lahir bayi >4000 gram,
Riwayat DMG,
Dislipidemi, HDL <35 mg/dl atau trigliserid >250 mg/dl,
Pernah TGT atau GPPT
Riwayat Penyakit kardiovaskuler

III. Klasifikasi Etiologis DM

1. Diabetes Tipe-1 (destruksi
sel beta)
Autoimun
Idiopatik

2. Diabetes Tipe-2 ( resistensi

insulin disertai defek sekresi
insulin atau sebaliknya)

3. Diabetes Tipe lain

A. Defek genetik fungsi sel beta
MODY 1,2,3. DNA
mitokondria
B. Defek genetik kerja insulin
C. Penyakit eksokrin pankreas;
Pankreatitis, tumor pankreas,
pankreatektomi, pankreopati
fibrokalkulus

D. Endokrinopati
Acromegali, sindroma
Cushing, Feokromositoma,
hipertiroidisme
E. Karena obat/zat kimia
Vacor, pentamidin, asam
nikotinat, Glukokortikoid,
hormontiroid, tiazid, Dilantin,
interferon alfa
F. Infeksi : rubellakongenital, CMV
G. Sebab imunologi yang jarang :
Antibodi anti insulin
H. Sindroma genetik lain:
Sindroma Down, Klinefelter,
Turner dll.

4. Diabetes Gestasional

GAMBARAN KLASIK DM TIPE 2

GEMUK
DENGAN RESISTENSI INSULIN

The Pathophysiology of Type 2 DM

Pancreas
LIVER

GLYCOGENOLYSIS

Insulin supply or action

GLUCONE
O
GENESIS

HGP

G LYCOGEN

GLUCOSE

FFA

LIPOLYSIS

ADIPOSE TISSUE

Lactic Acid

G L UC O S E

Management
A. Aim
Short term :
Eliminate symptoms
Maintain general well being

Longer term :
Prevent complications
Reduce morbidity
and mortality

Strategy :
Normalizing glucose,
lipid, and insulin levels

Activities :
Management with holistic
approach and self care
principles

Prinsip Dasar Terapi Diabetes Mellitus

1

PENGATURAN MAKAN

OBAT HIPOGLIKEMIK /
INSULIN

LATIHAN

PENYULUHAN

PEMANTAUAN GD SENDIRI
Konsensus Perkeni, 1998

Lifestyle intervention
Represents the first step in treating type
2 diabetes
In the Belfast Diet Study, dietary management was initially
associated with reductions in FPG and weight
However, after 6 years, a progressive rise in FPG was
observed, associated with declining
-cell function
Most patients required oral pharmacotherapy within a few
years of diagnosis

Levy J et al. Diabet Med 1998; 15: 2906.

Exercise
30-50 minutes: 3 - 4 times / week
Continuous
Rhytmical
Interval
Progressive
Endurance training

Diet/Nutrition Therapy/Meal planning

Nutrient Composition of Diabetic Diet
PERKENI

A D A and B D A

(Indonesian Soc.of Endoc.)

20-25%

10-15%
60-70%

30%

10-15%

55%

OBAT
HIPOGLIKEMIK
ORAL

Sites of Action of Antihyperglycemic Ag

Pancreas
2. Insulin
secretagogue

GLYCOGENOLYSIS

3. Metformin
TZD
HGP

1. Insulin

GLUCOSEN

4. Acarbose

GLUCONEO
GENESIS

Intestine

+
+

Adipose tissue

3. Metformin
TZD

Oral Hypoglycemic Drugs Available in Indonesia

Initial dose
mg/day

Maximal dose
mg/day

Frequency of
administration /day

Sulphonylurea
Glibenclamide
Gliclazide
Glipizide :
Gliquidone
Chlorpropamide
Glimepiride

2,5
80
5
30
50
0,5

15-20
240
20
120
500
6

1.5 mg
120 mg

8 mg
360 mg

1-2 X
1-2 X
2-3 X
1X
1X
1X

Meglitinide
Repaglinide
Nateglinide

Metformin
500
Alpha glucosidase inhibitor

3000

Acarbose
50
Derivat Thiozolidindiones
Pioglitazone
Roziglitazone

300

Fix Dose ( Campuran )

Glucovance
1,25/250

2,5/500

3X
3X

1-3 X
3X

1-2 x

Sulphonylureas
Have been a mainstay of type 2 diabetes treatment
for > 40 years
Bind to an SU receptor (SUR) on the-cell which
leads to depolarisation of -cell membrane and
stimulates insulin secretion
First generation
: chlorpropamide
Second generation
: glibenclamide, glipizide,
gliclazide
Third generation
: glimepiride
Attention : Hypoglycemia

The Suppression Hepatic Glucose Production

Pancreas

LIVER
GLYCOGENOLYSIS

Insulin
HGP

GLUCONEO
GENESIS

ADIPOSE TISSUE

GLUCOSE N

The Stimulation of Glucose Uptake

Pancreas

LIVER
GLYCOGENOLYSIS

Insulin
HGP

G LYCOGEN

GLUCOSE N
Glucose
Uptake

GLUCONEO
GENESIS

ADIPOSE TISSUE

G L UC O S E

The Stimulation of Lipogenesis in Adipose Tis

Pancreas

LIVER
GLYCOGENOLYSIS

Insulin
HGP

GLUCONEO
GENESIS

GLUCOSE N
Glucose
Uptake

FFA

+
ADIPOSE TISSUE

G LYCOGEN

Lipogenesis

G L UC O S E

1a. Insulin
Insulin actions include :
Ability of insulin to lower circulating glucose
concentrations
Suppress glucose production : liver
Stimulate glucose utilization : muscle plus fat
Additional metabolic, vascular & mitogenic actions

Insulin Injection

TYPE OF INSULIN
Type Insulin

Onset
( hour)

Peak
( hour )

Effective
Duration

Maximal
Duration

0,5 2,5
13

<5
35

45

0,5 1,0

23

46

57

24
34

4 10
4 12

10 16
12 18

14 18
16 20

6 10
2-4

14 24
Peakless

18 20
20 -24

20 - 36

Rapid Acting

Human Lyspro
0,25-0,5
Human Aspart
<0,20
Human Glulisine
Short Acting

Human Regular
Intermediate Acting

Human NPH
Human Lente
Long Acting

Human Ultralente
Insulin Glargine
Combinations
Mixtard
Novomix

Indications of Insulin Treatment

Indication for the use of insulin in
Type 2 DM
In severe metabolic decompensation
Ketoacidosis
Hyperosmolar non ketotic coma
Lactic acidosis
Severe stress :
Systemic infection
Major surgery
Weight loss within a short period of time
Pregnancy if diet does not succeed to control
glycemia
OHA failure or contra-indication of OHA

ADA Treatment Goals for Glycemic Control

Glycemia

Normal

Average Preprandial
<110
Fasting Glucose (mg/dL)
Average Postprandial
Glucose (mg/dL)
HbA1C (%)

Goal

Further Action
Required*

80 to 120

<80
>140

<140

<160

>180

<6

<7

>8

Further Action Required = Get off your rear and DO something

Adapted from the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
Diabetes Care 1999;22:S32-S41

Current ADA treatment targets

HbA1c

< 7%

Blood pressure < 130/80 mmHg

LDL-cholesterol

< 100 mg/dl (2.6 mmol/l)

HDL-cholesterol
Men > 40 mg/dl (1.1 mmol/l)
mg/dl (1.3 mmol/l)
Triglycerides

Women

> 50

< 150 mg/dl (1.7 mmol/l)

American Diabetes Association. Diabetes Care 2004; 27 (Suppl 1): S1535.

Proposed New Treatment Paradigm

for Type 2 Diabetes
Medical Nutrition Therapy, Exercise , Education and SMBG
HbA1c < 7 %
Consider oral
monotherapy

Target not Met

HbA1c 7- 8 %
Add
insulin sensitizer
or secretagoque
Target not Met

Full Insulin therapy

With Or without Oral agent(s)

HbA1c > 8 %
Add
insulin sensitizer
and secretagoque
Target not Met
Start Insulin or
add Third oral agent

Complications :
Acute :

Ketoacidosis
Nonketotic
Hyperosmolar syndrome

Chronic :
Microangiopathy

Macroangiopathy

Retinopathy
Nephropathy
Neuropathy

CAD
PVD
Stroke

KOMPLIKASI AKUT
1. Metabolik
Ketoasidosis diabetik
Koma hiperglikemik hiperosmoler non-ketotik
Hipoglikemi
Asidosis laktat
2. Infeksi berat

KETOASIDOSIS DIABETIK (1)

DIAGNOSIS

1. Klinis
- Dehidrasi, kesadaran menurun sampai koma,
hipotensi-syok, pernafasan Kussmaul, panas
2. Laboratorium
- Hiperglikemi, GDS > 300 mg/dl
- Asidosis, pH arteri <7.35 atau bikarbonas serum <15 meq/l
- Ketonemi, keton total serum >3 mM
3. Pada DM tipe 2 faktor pencetus biasanya infeksi
Catatan: Setiap penderita DM dengan kesadaran menurun
dan panas harus di curigai ketoasidosis

KETOASIDOSIS DIABETIK (2)

PENATALAKSANAAN

1. Cairan
- Infus NaCl 0.9% sebanyak 500 ml selama 15 menit pertama,
diteruskan sesuai kebutuhan
- Bila GDS < 250 mg/dl, NaCl 0.9% diganti Dextrose 5%
2. Insulin
- Pada awal diberikan 10 U insulin kerja singkat i.v secara
bolus (Actrapid, Humulin R) diteruskan dengan insulin
drips 6 U/jam
3. Potassium
- Pada pemberian insulin biasanya kalium plasma menurun
oleh karena itu perlu diberikan tambahan potassium
4. Antibiotik bila ada infeksi

KETOASIDOSIS
DIABETIK (3)
Komplikasi
1. Infeksi
2. Gagal ginjal akut

KOMA HIPERGLIKEMIK

HIPEROSMOLER NON-KETOTIK (KHHNK) (1)

DIAGNOSIS
1. Klinis
- Dehidrasi, koma, hipotensi-syok.
- Beda dengan ketoasidosis, oleh karena tanpa asidosis
tidak ada Kussmaul
- Orang tua > 60 tahun
2. Laboratorium
- Hiperglikemi, GDS > 400 mg/dl
- Osmolalitas plasma >= 315 mmol/kg

KOMA HIPERGLIKEMIK

HIPEROSMOLER NON-KETOTIK (KHHNK) (2)

PENATALAKSANAAN
1. Cairan
Sama dengan ketaosidosis, hanya biasanya penderita
dalam keadaan syok sehingga perlu pemberian NaCl 0.9%
cepat. Untuk seterusnya diberikan cairan NaCl 0.45%
2. Insulin sama dengan ketoasidosis
3. Potassium
4. Antibiotik kalau perlu

HIPOGLIKEMI (1)
Pada DM reaksi hipoglikemi terjadi bila GDS
< 50 mg/dl
Penyebab : Insulin berlebihan, OHO berlebihan,
gagal ginjal kronik mendapat OHO
Gambaran klinis
Keringat dingin, takhikardi, rasa lapar, pusing,
penglihatan kabur, kesadaran menurun sampai
koma

HIPOGLIKEMI (2)
PENATALAKSANAN
1.
2.
3.

Segera hentikan insulin atau OHO

Bila masih sadar segera berikan teh gula
Dalam keadaan koma berikan Dextrose 40% sebanyak
50 ml i.v langsung
4. Dilanjutkan dengan infus Dextrose 10% selama 48 jam

KOMPLIKASI KRONIK
Komplikasi vaskuler
Makrovaskular
Penyakit jantung koroner, strok, pembuluh darah perifer
Mikrovaskular
Retinopati,nefropati

Komplikasi neuropati
Neuropati sensorimotorik,Neuropati otonomik
Gastroparesis, diare diabetik, buli-buli neurogenik, Impotensi,
gangguan refleks kardiovaskular

Campuran vaskuler-neuropati
Ulkus kaki

Komplikasi pada kulit

RETINOPATI
DIABETIK (1)

Dikenal empat bentuk yaitu :

1. Tipe background
2. Tipe pre-proliferatif
3. Tipe proliferatif
4. Makulopati

Tipe background adalah paling ringan, sedang

tipe proliferatif penyebab kebutaan

RETINOPATI DIABETIK (2)

RETINOPATI
DIABETIK (3)

RETINOPATI
DIABETIK (4)

Pengobatan

1. Kendali glukosa darah sebaik mungkin

(HbA1c < 7%)
2. Pengobatan terhadap hipertensi, dislipidemia
bila ada
3. Hentikan merokok
4. Aspirin

NEFROPATI
DIABETIK (1)
1. Merupakan penyebab utama gagal ginjal
terminal di negara maju
2. Diperkirakan 40% DM tipe 1 menjadi nefropati
diabetik setelah menderita DM 20 tahun dan
5-10% pada DM tipe 2 dengan riwayat DM 20
tahun

NEFROPATI DIABETIK (2)

Pengertian
Normo-albuminuri
(Albustix negatif)
proteinuri

Ekskresi albumin per menit < 20 ug atau jumlah albumin

< 30 mg/24 jam

Mikro-albuminuri (Albustix negatif)

Ekskresi albumin per menit 20-200 ug atau jumlah
albumin 30-300 mg/air seni 24 jam
Makro-albuminuri = proteinuri klinik (Albustix positif)
Ekskresi albumin per menit > 200 atau jumlah albumin >
300 mg/air seni 24 jam

NEFROPATI DIABETIK (3)

Diagnosis
1. Adanya proteinuri menunjukkan nefropati diabetik
2. Nefropati diabetik klinik bila tes Albustix posistif
sedikitnya 3 kali dengan interval beberapa mili
3. Nefropati diabetik dini bila ditemukan mirkroalbuminuri
2 sampai 3 kali pemeriksaan dalam 6 bulan

NEFROPATI DIABETIK (4)

Pengobatan
1. Kendali glukosa darah sebaik mungkin
(HbA1c < 7%)
2. Pengobatan terhadap hipertensi, dislipidemia
bila ada
3. Obat anti hipertensi sebaiknya ACE inhibitor
4. Hentikan merokok
Catatan : TD sistolik < 135 mmHg, diastolik
=< 80 mmHg

KAKI
DIABETIK
INFEKSI

KAKI DIABETIK INFEKSI

(1)
Lebih dari 50% kasus amputasi nontraumatik diakibatkan oleh kaki
diabetik infeksi (gangren)
Oleh karena itu pencegahan terjadinya
ulkus kaki sangat penting

KAKI DIABETIK INFEKSI

(2)
Klasifikasi
Wagner
Derajat 0 Kaki risiko tinggi, tanpa ulkus

Derajat 1 Ulkus permukaan tanpa infeksi

Derajat 2 Ulkus dalam, sering dengan selulitis,
tanpa abses, atau infeksi tulang
Derajat 3 Ulkus dalam dengan kelainan tulang
atau adanya abses
Derajat 4 Gangren lokal (ibu jari, atau telapak
kaki)
Derajat 5 Gangren seluruh kaki

KAKI DIABETIK INFEKSI (3)

Penatalaksanaa
1. Pengobatan terpadu, internis, dan ahli bedah
n2. Pengobatan medik (internis)
Kendali glukosa darah sebaik mungkin dengan
insulin
Debridemen tiap hari
Antibiotik broad spektrum
Amputasi kecil
3. Pengobatan bedah, bedah vaskuler, amputasi