DIABETES MELITUS

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
3
The diabetes epidemic:
171 million in 2000 to 366 million people in 2030
India
China
USA
Indonesia
Pakistan
Brazil
Bangladesh
Japan
Philippines
Egypt
Country
2030
79.4
42.3
30.3
21.3
13.9
11.3
11.1
8.9
7.8
6.7
People with
diabetes
(millions)
India
China
USA
Indonesia
Japan
Pakistan
Russian Fed.
Brazil
Italy
Bangladesh
Country
2000
31.7
20.8
17.7
8.4
6.8
5.2
4.6
4.6
4.3
3.2
People with
diabetes
(millions)
1
2
3
4
5
6
7
8
9
10
Ranking
Wild S et al. Diabetes Care 2004;27:104753
Status of diabetes management
Symptoms :
Polyuria
Polydipsia
Weight loss
Sometimes polyphagia
Blurred vision
50% of type 2 diabetes patients have
complications at the time of diagnosis
Retinopathy,
glaucoma or
cataracts
Nephropathy
Neuropathy
MICROVASCULAR
MACROVASCULAR
Cerebrovascular
disease
Coronary
heart
disease
Peripheral
vascular
disease
UKPDS Group. UKPDS 33. Lancet 1998; 352:837853.
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.
Current recommendations
ADA definition of hyperglycaemic states
ADA = American Diabetes Association
OGTT 2-h

post-load glucose
< 140 mg/dl (7.8 mmol/l) normal glucose tolerance
140199 mg/dl (7.811.1

mmol/l)

impaired glucose tolerance
200 mg/dl (11.1 mmol/l) diabetes
Adapted from American Diabetes Association. Diabetes Care 2004; 27:S5S10.
Criteria for the diagnosis of diabetes
Symptoms of diabetes plus casual plasma glucose 200 mg/dl (11.1 mmol/l)
126 mg/dl (7.0 mmol/l) diabetes
FPG
< 100 mg/dl (5.6 mmol/l) normal fasting glucose
100125

mg/dl (5.66.9 mmol/l) impaired fasting glucose
or
or
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
Umur diatas 45 tahun
Kegemukan > 120% BB idaman atau IMT > 27 kg/m
2
),
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
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
Type 2 diabetes: a growing problem
A serious, progressive disease
Characterised by two fundamental defects:
insulin resistance
-cell dysfunction
Accounts for 90% of diabetes cases worldwide

Associated with serious microvascular and
macrovascular complications

Represents a significant disease burden
Represents a considerable economic burden
Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. World Health Organization, 1999.
Diabetes Mellitus. Fact Sheet No 138. World Health Organization, 2002.
LIVER
ADIPOSE TISSUE
Pancreas
Insulin supply or action
GLUCOSE
-
GLYCOGENOLYSIS
HGP
+
G L UC O S E
G LYCOGEN
GLUCONEO
GENESIS
The Pathophysiology of Type 2 DM
LIPOLYSIS
FFA
+
Lactic Acid
Longer term :
Prevent complications
Reduce morbidity
and mortality
Management
Short term :
Eliminate symptoms
Maintain general well being

Strategy :
Normalizing glucose,
lipid, and insulin levels
Activities :
Management with holistic
approach and self care
principles
A. Aim
Prinsip Dasar Terapi Diabetes Mellitus
1
PENGATURAN MAKAN
LATIHAN
OBAT HIPOGLIKEMIK
PENYULUHAN
CANGKOK PANKREAS
Konsensus Perkeni, 1998
2 3
5 4
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 minutes: 3 - 4 times / week


Continuous
Rhytmical
Interval
Progressive
Endurance training
Nutrient Composition of Diabetic Diet

PERKENI A D A and B D A
(Indonesian Soc.of Endoc.)

Carbohydrate Fat Protein
20-25%
10-15%
60-70%
Diet/Nutrition Therapy/Meal planning
Carbohydrate Fat Protein
30%
10-15%
55%
OBAT HIPOGLIKEMIK ORAL
Adipose tissue
Sites of Action of Antihyperglycemic Agents
Pancreas
1. Insulin
GLUCOSE
GLUCONEO
GENESIS
HGP
-
N
Intestine
2. Insulin
secretagogue
4. Acarbose
3. Metformin
TZD
3. Metformin
TZD
+
GLYCOGENOLYSIS
+
-
+
+
Oral Hypoglycemic Drugs Available in Indonesia
Initial dose Maximal dose Frequency of
mg/day mg/day administration /day
Sulphonylurea
Glibenclamide 2,5 15-20 1-2 X
Gliclazide 80 240 1-2 X
Glipizide : 5 20 2-3 X
Gliquidone 30 120 1 X
Chlorpropamide 50 500 1 X
Glimepiride 0,5 6 1 X
Meglitinide
Repaglinide 1.5 mg 8 mg 3X
Nateglinide 120 mg 360 mg 3X
Metformin 500 3000 1-3 X
Alpha glucosidase inhibitor
Acarbose 50 300 3 X
Derivat Thiozolidindiones
Pioglitazone
Roziglitazone
Fix Dose ( Campuran )
Glucovance 1,25/250 2,5/500 1-2 x
Monotherapy
Insulin therapy
Combination oral therapy
Lifestyle modification
Expected HbA
1c

(time allotted)
1% (3 months)
1 to 2%
(13 months)
1 to 2% fall per
additional OHA
(13 months)
Unlimited
T2DM treatment strategies*
*Individualise
Adapted from Bergenstal RM. In: De Fronzo RA, et al (eds). International Textbook of Diabetes Mellitus.
3rd ed. Chichester, New York: John Wiley & Sons; 2004:9951015.
Diet/
exercise
Oral
monotherapy
Oral
combination
Insulin
Early aggressive
combination therapy
Stepwise treatment
Oral
+/- insulin
New treatment paradigms for
type 2 diabetes
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 (less in glipizide GITS and
glimepiride)
Depola-
risation
Ca
2+
Voltage Dependent
Ca
2+
Channel (VDCC)
Proinsulin
Closed
ATP Sensitive
K
+
Channel
SS 01
Islet cell
Open
Ca
2+
INSULIN
C-PEPTIDE
SU
SUR
ATP
ADP
ATP
ADP
Glucose
Am. acid
Glucokinase
Metabolism
Mode of Action of Sulphonylureas
LIVER
ADIPOSE TISSUE
The Suppression Hepatic Glucose Production
Pancreas
Insulin
GLUCOSE
GLUCONEO
GENESIS
HGP
GLYCOGENOLYSIS
-
N
LIVER
ADIPOSE TISSUE
The Stimulation of Glucose Uptake
Pancreas
Insulin
GLUCOSE
GLUCONEO
GENESIS
HGP
-
GLYCOGENOLYSIS
G LYCOGEN
N
G L UC O S E
+
Glucose
Uptake

LIVER
ADIPOSE TISSUE
The Stimulation of Lipogenesis in Adipose Tissue
Pancreas
Insulin
GLUCOSE
GLUCONEO
GENESIS
HGP
-
GLYCOGENOLYSIS
G LYCOGEN
G L UC O S E
+
Glucose
Uptake

Lipogenesis
+
N
FFA
ADA Treatment Goals for Glycemic Control
Glycemia Normal Goal Further Action
Required*
Average Preprandial <110 80 to 120 <80
Fasting Glucose (mg/dL) >140
Average Postprandial <140 <160 >180
Glucose (mg/dL)
HbA
1C
(%) <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
American Diabetes Association. Diabetes Care 2004; 27 (Suppl 1): S1535.
Current ADA treatment targets
HbA
1c
< 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)
Women > 50 mg/dl (1.3 mmol/l)
Triglycerides < 150 mg/dl (1.7 mmol/l)
Treatment Priority
of Type 2 DM
Glucose control as
near to normal as
reasonably possible
Microvascular
disease
Control of Insulin resistance:
Hyperinsulinemia, Obesity,
Glucose intolerance,
Dyslipidemia, Hypertension,
Procoagulant state
Macrovascular
disease
Insulin
resistance
PAI-1,Factor VII, Fibrinogen
Hyperglycemia
Hypertension
Pro-coagulant State
Obesity
Dyslipidemia
Cardiovascular
disease
Intervention/Control
Control of Insulin Resistance
KOMPLIKASI AKUT
1. Metabolik
Ketoasidosis diabetik
Koma hiperglikemik hiperosmoler non-ketotik
Hipoglikemi
Asidosis laktat
2. Infeksi berat
KETOASIDOSIS DIABETIK (1)
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
DIAGNOSIS
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)
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
DIAGNOSIS
KOMA HIPERGLIKEMIK
HIPEROSMOLER NON-KETOTIK (KHHNK) (2)
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
PENATALAKSANAAN
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 (1)
HIPOGLIKEMI (2)
1. Segera hentikan insulin atau OHO
2. Bila masih sadar segera berikan teh gula
3. Dalam keadaan koma berikan Dextrose 40% sebanyak
50 ml i.v langsung
4. Dilanjutkan dengan infus Dextrose 10% selama 48 jam
PENATALAKSANAN
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)
1. Kendali glukosa darah sebaik mungkin
(HbA1c < 7%)
2. Pengobatan terhadap hipertensi, dislipidemia
bila ada
3. Hentikan merokok
4. Aspirin
RETINOPATI DIABETIK (4)
Pengobatan
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 proteinuri
Normo-albuminuri (Albustix negatif)
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
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
NEFROPATI DIABETIK (4)
NEFROPATI DIABETIK (5)
1. Hemodialisa

2. Transplantasi ginjal
Pengobatan gagal ginjal terminal :
We are not getting
older

We are getting better