Diabetes Mellitus

The Disease and Its Management

Dr. PANDJI MOELJONO, Sp.PD
SUBDEP PENYAKIT DALAM FK. UNIV. HANG TUAH
RUMKITAL Dr. RAMELAN

Definisi
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

Kelainan Fungsi /
Jumlah Sel Genetik
Tipe I (Autoimun)
Faktor Lingkungan

Sistim imun
(Ab anti pankreas)

Marker :
Insulin auto Ab
Islet cell auto Ab
Glutamic acid
dicarbosaflase
Au Ab (GAD. Abs)

Ideopatik

INSUFISIENSI
INSULIN

Kelainan Aktifitas Insulin

o.k. Reseptor

Virus
Diet
Obesitas
Hamil

Symptoms :
Polyuria
Polydipsia
Weight loss
Sometimes polyphagia
Blurred vision

Diagnosis
Symptoms of diabetes plus glucose > 200 mg/dl
or
Fasting plasma glucose > 126 mg/dl
or
2-h plasma glucose > 200 mg/dl during an OGTT

Table Diagnosis of GDM with a 100 g Oral Glucose Load (ADA2003)

Fasting
1-h
2-h
3-h

mg/dl

mmol/l

95
180
155
140

5.3
10.0
8.6
7.8

Two or of the venous plasma concentrations must be met or exceeded

for a positive diagnosis. The test should be done in the morning after
an overnight fast of between 8 and 14 h and after least 3 days of
unrestricted diet ( 150 g carbohidrate per day) and unlimited
physical activity. The subject should remain seated and should not
smoke throughout the test.

Table Diagnosis of GDM with a 75 g Oral Glucose Load

(ADA-2003)

Fasting
1-h
2-h

mg/dl

mmol/l

95
180
155
8.6

5.3
10.0

Two or of the venous plasma concentrations must be met or

exceeded for a positive diagnosis. The test should be done in the
morning after an overnight fast of between 8 and 14 h and after
least 3 days of unrestricted diet ( 150 g carbohidrate per day)
and unlimited physical activity. The subject should remain seated
and should not smoke throughout the test.

DIABETES vs PRE-DIABETES
Fasting
Blood
Glucose
Normal
< 100 *
Pre-Diabetes 100 * 125
Diabetes
126

2 hours post
prandial (mg/dl)
< 140
140 199
200

If FBG is > 100, have a 10-15% chance of

developing DM in next 7 years.

UKPDS :

Progressive Deterioration of -Cell Function

Beta Cell Function (%)

100

75

Th/Expectation
Postprandial
Hyperglycemia

50

25

IFG
IGT

Facts
T2 DM
phase I

T2DM phase III

T2DM
phase II

-12 10 -6 -2 0 2
Years from Diagnosis

10

14

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

Dual Defect of T2DM (IR and Impaired AIR) :

Treating a Moving Target
Insulin
Resistance

T2DM

-cell
Dysfunction

-Cell Failure
Insulin
Concentration
Insulin
Action
Euglycaemia
Normal

IGT+Obesity or IFG

Dx T2DM

Progression to T2DM

Insulin Resistance
Hyperinsulinemia

Glucose
intolerance

Increased
triglyceride

Small dense LDL

cholesterol

Decreased HDL Cholesterol

Increased
Uric acid

Coronary heart
disease

Increased blood
pressure

Increased
PAI - 1

The glycemic targets for GDM should be

at the following levels :
1. Fasting Plasma Glucose (FPG) 105
mg/dl.
2. 1-h Postprandial Plasma Glucose (1-h PP)
< 155 mg/dl.

3. 2-h Postprandial Plasma Glucose (2-h PP)

< 130 mg/dl.

Keluhan Klinis Diabetes

Keluhan klasik +
GDP

Keluhan klasik -

>126

<126

>126

>200

<200

>200

110-<126

<110

mg/dl

GDS

110-200

mg/dl

ulang GDS atau GDP

>126
>200

<126

TTGO 2 jam

<200
>200

DIABETES MELLITUS

140-200

TGT

GDPT

<140

NORMAL

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 1 Diabetes

Type 2 Diabetes

Absolute insulin deficiency

identified by :

Combination of :

Serological evidence of
autoimmune process
in the pancreatic islet
Genetic markers

Insulin resistance and

Inadequate compensatory
insulin secretory response

FASTING GLUKOSA BERBEDA SECARA

METABOLIK & HORMONAL DENGAN
PRANDIAL

Insulin prandial
(glukosa uptake/utilzation

Insulin
puasa

Makanan

Glukagon
Glukosa
puasa

Glukosa darah puasa

Glukosa
prandial
Glukosa darah prandial

SEKRESI INSULIN NORMAL

Sekresi Insulin Pada DM Tipe II

Gambar. Variabilitas
responsi insulin
terhadap OGTT
pada NIDDM

Untuk mengatasi resistensi insulin, sel harus mampu

sekresi insulin lebih banyak dan sepanjang mampu DM,
GTG (-) maka DM tipe II sekresi insulin bervariasi

Pola Sekresi Insulin DM Tipe I

Sekresi insulin tergantung sisa masa sel

Glycemic Control

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

Treatment Modalities

Diet/Medical nutrition therapy

Exercise
Anti hyperglycemic agents
Education
Pancreas transplantation
Cloning treatment (experiment)

Education
Tujuan :
Perubahan perilaku pasien dan keluarganya
Cara :
Berikan dukungan dan nasehat positif
Berikan informasi secara bertahap
Mulai dengan hal hal yang sederhana
Gunakan alat bantu
Lakukan pendekatan dan simulasi
Berikan pengobatan sesederhana mungkin
Jangan terlalu memaksakan kehendak kita
Berikan motivasi, penghargaan dan diskusikan hasil
pengelolaan

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%

30%

60-70%

Carbohydrate

Fat

10-15%

55%

Protein

Carbohydrate

Fat

Protein

PERENCANAAN MAKAN
KOMPOSISI :
Karbohidrat : 60 70 %

Protein

: 10 15 %

Lemak

: 20 25 %

JUMLAH KALORI :
Hitung BMI ( IMT ) = BB ( kg ) / TB ( m )2
IMT wanita ( normal ) = 18,5 23,5 kg/ m2
IMT laki ( normal )

= 22,5 25 kg / m2

Status gizi

: BB Idaman = ( TB 100 ) 10%

BB kurang

: < 90% BBI

BB Normal

: 90 120% BBI

BB lebih

: 110 120 % BBI

Gemuk

: > 120% BBI

Exercise
30 minutes: 3 - 4 times / week

Continuous
Rhytmical
Interval
Progressive
Endurance training

Anti Diabetic Agents

Hypoglycemic Agents
Anti Hyperglycemic Agents

Pilihan Terapi DM Tipe 2

Berdasarkan Target Organ
HATI

PANKREAS

PRODUKSI
GLUKOSA

Biguanides
(Metformin)
Thiazolidinediones

JARINGAN
LEMAK

OTOT

SEKRESI INSULIN
Sulfonylureas

AMBILAN GLUKOSA
PERIFER

Meglitinides ; Repaglinide

Thiazolidinediones

Insulin

Biguanides
(Metformin)

SAL. CERNA
alpha-glucosidase inhibitors
ABSORBSI
GLUKOSA

Sonnenberg and Kotchen. Curr Opin Nephrol Hypertens 1998;7(5):5515

Sites of Action of Antihyperglycemic Agents

Pancreas
2. Insulin
secretagogue

GLYCOGENOLYSIS

3. Metformin
TZD

1. Insulin

HGP

GLUCOSE N

+
4. Acarbose

GLUCONEO
GENESIS

Intestine

Adipose tissue

3. Metformin
TZD

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

The Suppression Hepatic Glucose Production

Pancreas

LIVER
GLYCOGENOLYSIS

Insulin

HGP

GLUCOSE N

GLUCONEO
GENESIS

ADIPOSE TISSUE

The Stimulation of Lipogenesis in Adipose Tissue

Pancreas

LIVER
GLYCOGENOLYSIS

Insulin

G LYCOGEN

HGP

GLUCOSE N

GLUCONEO
GENESIS

Glucose
Uptake

FFA

+
ADIPOSE TISSUE

Lipogenesis

G L UC O S E

The Stimulation of Glucose Uptake

Pancreas

LIVER
GLYCOGENOLYSIS

Insulin

G LYCOGEN

HGP

GLUCOSE N
Glucose
Uptake

GLUCONEO
GENESIS

ADIPOSE TISSUE

G L UC O S E

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

The Pharmacology of Insulin

Onset
(h)

Lispro Aspart
Regular
NPH

0.10-0.25
0.10-1.0
1.0-3.0

Peak
(h)

0.75-2.0
1.0-4.0
5.0-7.0

Duration Miscibility with Variability in

(h)
Lispro or
absorption
Reg. insulin
4.0-5.0
4.0-10
13-18

Yes w RI
+/- w lispro

Minimal
Moderate
High

Pre-mixed (70/30,50/50,lispro mix 75/25) equivalent to sum of above components

Lente
Ultra lente
Glargine

1.5-4.0
2-6
2-4

4.0-8.0
8.0-12
None

13-20
18-30
-24

+/+/NO !!!
precipitate

High
Very High
Moderate to
high

Buse BB Diabetes Spectrum 2000

Insulin available in Indonesia

Short acting insulin
Actrapid Human U 40, U100
Humulin R U40, U100
Regular Insulin U40
Intermediate acting insulin
Monotard U40, U100
Insulatard U40, U100
Humulin N U40, U100
NPH U40

Long acting insulin

PZI U40
Ultratard U100

Penfil
Actrapid penfil
Insulatard penfil
Mixtard 30/40 penfil
Humulin R penfil
Humulin 30/70 penfil

1 b. Insulin Analogues
Genetic engineering
Main aim : Solubility reduction
Substitution/addition of amino acid residue of
insulin
Short acting :
Lispro: B28-lysine, B29-proline
X14 : B28-aspartate
Long acting:
B31-B32 arginine, A21-glycine

Immunogenicity

Proactive management of glycemia:

early combination approach

HbA1c (%)

Diet
and exercise
OAD
monotherapy
10
OAD
combinations
9

OADs
uptitration

OAD
+ basal insulin

OAD + multiple daily

insulin injections

8
HbA1c = 7%
7
HbA1c = 6.5%

Duration of diabetes
*OAD = oral antidiabetic

Del Prato S, et al. Int J Clin Pract 2000; 7:625631.

OHO
(Obat Hipoglikemic Oral)
2. Insulin Secretagogues
Induce insulin secretion
Potentiate nutrient-induced insulin
secretion
Antagonize inhibitors of insulin secretion
Calcium, Cyclic AMP and Adrenoreceptor
Manipulator
Other Insulin secretagogues

Insulin Secretagogues (cont.)

ATP-sensitive Potassium Channel Inhibitors
Long acting :Sulphonylureas

Short acting :
Repaglinide : Benzoic acid derivative
Nateglinide : Phenyl alanine derivative

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)

Mode of Action of Sulphonylureas

Depolarisation

ATP Sensitive
K+ Channel

Ca 2+

Voltage Dependent
Ca 2+Channel (VDCC)

SU

Islet cell
SUR

Closed

Open

Ca 2+
ATP
ADP
Glucose

Glucokinase

Metabolism

Am. acid

Proinsulin
INSULIN
C-PEPTIDE
SS 01

3. Insulin Sensitizers (1)

Metformin

Anti hyperglycemic not hypoglycemic

Do not target -cell
Suppress HGP (hepatic glucose production)
Enhance tissue sensitivity to insulin to
promote uptake of glucose into muscle
Cardioprotective effect on obese
patients(UKPDS)
Often used in combination with Sus
Little effect on post prandial hyperglycemia
Gastrointestinal discomfort

Insulin Sensitizers (2)

Thiazolidinediones
Anti hyperglycemic not hypoglycemic
Increase expression of transmembrane glucose
transporters (GLUT 1 and GLUT 4)
Increase insulin-stimulated glucose disposal
Increase insulin-stimulated glucose uptake and
metabolism by muscle and fat
Suppression of hepatic glucose production
Reduce plasma triglycerides
Pioglitazone
Rosiglitazone

4. Inhibition of CHO digestion

and absorption
Alpha glucosidase inhibitors
acarbose
Plant fibre supplements
guar gum
bran

Alpha Glucosidase Inhibitors

(Acarbose)
Ingested with meals
Delay the digestion of complex
carbohydrate
Competitive inhibition of alpha
glucosidase in the intestine
Blunting postprandial glucose spikes
Gastrointestinal side effects

Oral Anti Hyperglycemic Agents that Have Potential

Effect of Overcoming Peaks and Valleys
Pharmacological
Dietetic

Specific

Non-specific

Reduced carbohydrate
intake
Spreading carbohydrate
intake
Carbohydrate according
to 24 hr blood
glucose profile
Dietary fibres
Low glycemic index food

Acarbose
Repaglinide
Nateglinide
Insulin lispro
Nasal/pulmonary
insulin
Glucagon-like
peptide-1
Amylin analogues

Sulphonylurea
glipizide GITS
glimepiride
Metformin
Thiazolidinediones
Long acting insulin

Combination Therapy in T2DM:

Insulin Plus Oral Hypoglycemic Agents
Insulin Plus Sulphonylurea - BIDS
Some insulin is endogenous, with natural
secretory pattern
Biguanide Plus Insulin
Reduces hepatic insulin resistance
May achieve better control with less insulin
Can reduce weight gain
Alpha Glucosidase Inhibitor Plus Insulin
Reduces posotprandial glucose level
Thiazolidinedione Plus Insulin
Reduces peripheral insulin resistance
Reduces insulin requirement
Must balance TZD and insulin carefully to minimize
weight gain

Benefits of Insulin and Oral Agents Combination

Improves glycemic control
Treats multiple physiologic abnormalities
Less insulin is needed to achieve good glycemic
control
Reduces potensial for weight gain
Patients:
more practical and less frightening
improved psychological acceptance, patients
continue the oral drugs
less / minimal education is needed
treatment can be started in an
outpatients-setting
better compliance, and cost may be less

Oral Hypoglycemic Drugs Available in Indonesia

Initial dose
mg/day

Maximal dose
mg/day

Sulphonylurea
Glibenclamide
Gliclazide
Glipizide :
Glipizide GITS
Gliquidone
Chlorpropamide
Glimepiride

2,5
80
5
5
30
50
0,5

15-20
240
20
20
120
500
6

Meglitinide
Repaglinide
Nateglinide

1.5 mg
120 mg

8 mg
360 mg

Metformin

500

3000

Alpha glucosidase inhibitor

Acarbose
50

300

Frequency of
administration /day

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

3X

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

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 :
Infeksi

Acute :

Chronic
Neuropathy

Ketoacidosis
Nonketotic Hyperosmolar
syndrome
Lactic asidosis
Hypoglikemi/koma.

Microangiopathy

Macroangiopathy

Retinopathy
Nephropathy
Neuropathy

CAD
PVD
Stroke

Penyulit Menahun

KOMPLIKASI DM

How have these foot lesions possibly developed in this

woman with neglected type 2 diabetes?

PADA DM TIDAK TERKONTROL

Stres Oksidatif Endothel
HYPERGLYCEMIA

Glucose
Autoxidation

Polyol
Pathway

Polyol
Pathway

Oxidative Stress
Antioxidant
Defence

NO dependent Vasolidation
Ca2+
VSMC Proliferation

LDL
Oxidation

Hemorheologic alternations
Coagulation activation
Hipoxia

Vasculopathy

Oxidative
Factors

O2 / NO

Retinopathy

Heparan
Sulphate

NVC
Endoneural
Blood Flow

Neuropathy

Nephropathy

Hiperglikemia Oxidative Stress Komplikasi vaskular menahun (Giugliano et al 1996, Modifikasi)

Radikal Bebas & Diabetes Mellitus

DIABETES MELLITUS

HYPERGLYCEMIA

Efek Toksik Hiperglikemia : 2 Trisula dan 1 Tombak

Rangkuman : Askandar Tjokroprawiro 1999

Keterangan :
D : Direct Effect
I : Immunology
R : Rheology

G : Glycation
O : Oxidants
S : Sorbitol

C : Cytokines

Patogenesis
Ketoacidosis
Diabetik

Diet bebas

Infeksi

Tidak Suntik Insulin

Tipe I

Defisiensi insulin akut

Lemak (Lipolisis)

Protein
(Proteolisis)

Pelepasan FFA

Karbohidrat

Menuju hepar

Pembakaran glukosa turun

Pelepasan A.A

Glukoneogenesis
hiperglikemia

Menuju hepar

Esterifikasi

Oksidasi

Ureum naik
HiperTrigliseridemia

Partial
Ketoanemia

Glukosuria
Diurese Osmotik Poliuiria

Ketosuria
Muntah

Dehidrasi

Asidosis

Ekskresi H+
Pernafasan
Kussmaul

Syok

AA : Asam Amino
G : Glukosa
FFA : Free Fatty Acid

Stages and Clinical Features of Diabetic Kidney Disease

STAGE

DESCRIPTION

CLINICAL FEATURES

At in creased risk

Diabetes Mellitus, HBP, family history

12

Kidney Damage

Microalbuminuria :
Diabetes duration 5 10 years, retinopathy,
rising BP
Albuminuria :
Diabetes duration 10 15 years, retinopathy,
HBP

34

Decreased GFR

HBP, retinopathy, CVD, other diabetic

complications

Kidney Failure

Retinopathy, CVD, other diabetic

complications, uremia

KOMA PADA DM
1. Hipoglikemi o.k. over Tx. Insulin, OHO.
2. Hipoglikemi
Severe defisiensi insulin Ketoasidosis
Mild / moderate hiperglikemi, hiper osmolar.
Laktik asidosis pada severe infekti,
cardiovaskuler collaps.

DIABETIK KETOASIDOSIS
Essentials of Dx :

Hyperglycemia > 250 mg/dl.

Acidosis with blood pH < 7,3
Serum bicarbonat < 15 meq/L
Serum (+) for ketones.

Symtom + Sign :
3 P and marked fateque, nausea, vomiting
mental stupor coma.
Dehydrasi, stupor, rapid deep breathing
Fruity breath odor of acitone.

Laboratory Finding

Urin reduksi, ketonuria.

Kimia darah : Hiperglikemia, Ketonemia.
pH darah rendah
Bikarbonate plasma rendah
K+
Azotemia lebih baik ~ status ginjal dibanding
serum creatinine.
Lekositosis > 25000 / uL left shift ada / tidaknya
infeksi, o.k. DM ketoasidosis hipotermi tanpa
infeksi.

Tx :

Tentukan osmolality (N = 280 300 m Osm/kg)

=

(Na+)

Glucose (mg/dL)
+
18

Fluid and electrolyte replacement

-

NaCl 0,9% 4 5 liter (o.k. dehidrasi)

pH darah 7,1 Bikarbonat kontra indikasi
pH darah 6,9 7 Bikarbonat 1 amp (+ 200 cc
steril aqua dalam 1 jam)
pH darah < 6,9 2 amp Bikarbonat (+ 400 cc
steril aqua 2 jam)

Setiap penambahan 1 amp bicarbonat ditambahkan

pula 15 mEq/L KCl selama K+ tidak lebih dari 5,5 mEq/L.

Setelah glukose < 250 mg/dL D5 (dengan insulin tetap R/)

Untuk pertahankan glucose 200 300 mg/dL
Cegah hipoglikemi

cerebral edema.

Insulin :
Regular insulin bolus 0,1 unit/kg dilanjutkan 0,1 unit/kg/jam
infus/i.m.
Bila resistensi insulin (+) dosis dapat dinaikkan
2 x setiap 2-4 jam
Antibiotika ~ dengan indikasi

HYPERGLYCEMIC HYPEROSMOLAR STATE

ESS DX :

Hyperglikemia > 600 mg/dL

Serum osm > 310 mOsm/kg
Acidosis (-) pH > 7,3
Serum bicarbonat > 15 meq/L
Normal aniopgam (< 14 eq/L)

Symtom and Sign :

3P, ***, vomiting
Lethargy, confusion convulsion,
deep coma tanpa Kusmaull resp.

( CHO )

LACTIC ACIDOSIS
ESS DX :
Severe acidosis with hyperventilation
pH darah < 7.30
Serum bicarbonat < 15 meq/l
Anion gap > 15 meq/l
Absent serum keton
Serum lactat > 5 mmol/l

ANION GAP

N = (Na+ + K+) (Cl + HCO3) = 16 7

(unnaeasua red anion)

pH rumus Henderson Hasselbach :

pH = 6.10 + Log

CO2 content meq/L

pCO2 mmHg x 0,03

Normal sumber asam lactat :

Erithrosit
Otot
Kulit
Otak

Asam Lactat

Hati
Ginjal

Glukose

Symtom and Sign :

Terutama hiperventilasi, bila penyebab
hipoksia/kolap vaskuler, klinis variabel ~ penyulit
dasar.
Tensi normal, sirkulasi perifer baik, sianosis (-).

Treatment Priority
of Type 2 DM

Glucose control as
near to normal as
reasonably possible

Control of Insulin resistance:

Hyperinsulinemia, Obesity,
Glucose intolerance,
Dyslipidemia, Hypertension,
Procoagulant state

Microvascular
disease

Macrovascular
disease

Control of Insulin Resistance

Hyperglycemia

Intervention/Control
Dyslipidemia
Insulin
resistance

Hypertension
Obesity
Pro-coagulant State

PAI-1,Factor VII, Fibrinogen

Cardiovascular
disease

Tabel. Definitions of the Metabolic Syndrome

ATP III (American Heart
Association) (2005)
Minimal
requirements

Any 3 or mor of the

following criteria

Waist
circumference

In men < 102 cm

In women < 88 cm

Waist to hip
ratio

World Health
Organisation 1999

International Diabetes Federation

(2005)

Diabetes, IFG, IGT, or

insulin resistance + any
2 or more of the
following criteria

Central obesity (see under) + any 2

or more of the following criteria

In men 94 cm
In womwn 80 cm
< 0,90 in men
< 0,85 in womwn

Reduced HDL
cholesterol

< 1.00 mmol/l in men

< 1.30 mmol/l in women

< 0.90 mmol/l in men

< 1.00 mmol/l in women

< 1.03 mmol/l (40 mg/dl) in men

< 1.29 mmol/l (50 mg/dl) in women

Elevated
Triglycerides

> 1.70 mmol/l

> 1.70 mmol/l

1.70 mmol/l (150 mg/dl)

Elevated Blood
Pressure

> 130 / >85

140 / 90

130 / 85

Urinary Albumin
Excretion

Serum glucose

> 20 mg/min

6.1 (5.6) mmol/l

ATP III (Expert panel etc, 2001)

American Heart Association (Grundy et al, 2005)
World Health Organisation (World Health Organisation, 1999)
International Diabetes Federation (Alberti et al, 2005)

5.6 mmol/l (100 mg/dl)

Modified NCEP-ATP III 2001

3 Kriteria dari variabel dibawah ini

1. Lingkar perut
wanita
pria

80 cm
90 cm

2. Trigliserida
3. HDLkolesterol

150mg/dL

wanita
pria

< 50mg/dL

4. Tekanan Darah
5. Gula Darah Puasa

< 40mg/dL
130/85mmHg
110mg/dL. (sekarang > 100)

"The Cumulative Metabolic Syndrome"

A Cluster of 10 Possible Metabolic and CV Risk Factors
(Visceral Obesity is the Culprit)
(Summarized : Tjokroprawiro 2002, 2003)
Visceral Obesity
"The Black Goat"

ACTH, Cortisol
( Salivary Cortisol)

Insulin Resistance
2 Hyperinsulinemia

VISCERAL
ADIPOSE TISSUE

10
Hyperuricemia 9
Inflammatory Markers 8
(CRP, TNF, IL - 1, IL - 6)
Vascular Abnormalities 7
- Urinary Albumin Excretion
- Endothelial Dysfunction

GABRA-6 ?

6
Prothrombotic State
PAI-1 (Esp. Omental Fat)
Factor VII
Fibrinogen
vWF
Adhesion Molecules

IFG
IGT

DM

4 Atherogenic Dyslipidemia
Triglycerides
HDL-Cholesterol
Apolipoprotein-B
Small Dense LDL

5
Hypertension
LVH
CHF

Pencegahan Diabetes Mellitus

1. Primer, untuk orang yang resiko tinggi.

2. Sekunder, mencegah/menghambat
komplikasi.
3. Tertier, mencegah kecacatan

Monitor Pengelolaan Diabetes

Terbaik
1. HbA1c (A1C)
2. Fructosamine

Table Risk Factors for Type 2 Diabetes Mellitus

(ADA-2003)
1.

Age 45 years

2.

Over weight (BMI 25 kg/m2)

3.

First = degree relative with diabetes

4.

Habitual physical inactivity

5.

Member of a high-risk ethnic population (e.g., AfricanAmerican, Latino, Native American, Asian-American,
Pacific Islander)

6.

Previously identified pre-diabetes (IFG or IGT)

7.

History of GDM or delivery of a baby weighing > 9 lbs

8.

Hypertensive ( 140/90 mmHg)

9.

HDL cholesterol level 35 mg/dl (0.90 mmol/l) and/or a

Triglyceride level 3 250 mg/dl (2.82 mmol/l).

10. PCOS
11. History of vascular disease.