kuliah dm semester 8 tahun 2007

8/10/2019 Kuliah DM Semester 8 Tahun 2007

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Dr. PANDJI MOELJONO, Sp.PD

SUBDEP PENYAKIT DALAMFK. UNIV. HANG TUAH

RUMKITAL Dr. RAMELAN

Diabetes Mellitus

The Disease and Its Management


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Definisi

Diabetes mellitus is a group of metabolicdiseases 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


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INSUFISIENSI

INSULIN

Kelainan Fungsi /

Jumlah Sel Genetik

Kelainan Aktifitas Insulin

o.k. Reseptor

Faktor Lingkungan

Virus

Diet

Obesitas

Hamil

Tipe I(Auto imun)

Sistim imun(Ab ant i pankreas)

Marker :

Insulin auto Ab

Islet cell auto Ab

Glutamic aciddicarbosaflase

Au Ab (GAD. Abs)

Ideopatik


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Symptoms :

Polyuria

Polydipsia

Weight lossSometimes polyphagia

Blurred vision


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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


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TableDiagnosis of GDM with a 100 g Oral Glucose Load (ADA-

2003)

mg/dl mmol/l

Fasting 95 5.3

1-h 180 10.0

2-h 155 8.63-h 140 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 unlimitedphysical activity. The subject should remain seated and should not

smoke throughout the test.


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TableDiagnosis of GDM with a 75 g Oral Glucose Load

(ADA-2003)

mg/dl mmol/l

Fasting 95 5.3

1-h 180 10.0

2-h 1558.6

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.


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DIABETES vs PRE-DIABETES

Fasting

Blood

Glucose

2 hours post

prandial (mg/dl)

Normal < 100 * < 140

Pre-Diabetes 100 *125 140199

Diabetes 126 200

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

developing DM in next 7 years.


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Dual Defect of T2DM (IR and Impaired AIR) :Treating a Moving Target

-cellDysfunction

InsulinResistance T2DM

Euglycaemia

Insulin

Concentration

-Cell Failure

Insulin

Action

Normal IGT+Obesity or IFG Dx T2DM Progression to T2DM


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Insulin Resistance

Coronary heartdisease

Hyperinsulinemia

Glucoseintolerance

Increasedtriglyceride

Increased bloodpressure

Decreased HDL -Cholesterol

Small dense LDL

cholesterol

Increased

Uric acid

Increased

PAI - 1


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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.


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Keluhan Klinis Diabetes

Keluhan klasik + Keluhan klasik -

GDP >126 126 110-126 200 200 140-200


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III. Klasifikasi Etiologis DM

1. Diabetes Tipe-1 (destruksisel beta)

Auto imun

Idiopatik

2. Diabetes Tipe-2 ( resistensiinsulin disertai defek sekresiinsulin atau sebaliknya)

3. Diabetes Tipe lainA. Defek genet ik fun gsi sel beta

MODY 1,2,3. DNA

mitokondria

B. Defek genet ik ker ja insu l in

C. Penyakit eksok r in pankreas;

Pankreatitis, tumor pankreas,pankreatektomi, pankreopati

fibrokalkulus

D. Endokr inop ati

Acromegali, sindroma

Cushing, Feokromositoma,

hipertiroidisme

E. Karena obat/zat kim ia

Vacor, pentamidin, asam

nikotinat, Glukokortikoid,hormontiroid, tiazid, Dilantin,

interferon alfa

F. Infeksi : rubellakon geni tal, CMV

G. Sebab imunolog i yang jarang :

Antibodi anti insulinH. Sindroma genet ik lain:

Sindroma Down, Klinefelter,

Turner dll.

4. Diabetes Gestasional


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FASTING GLUKOSA BERBEDA SECARA

METABOLIK HORMONAL DENGAN

PRANDIAL

Insulin

puasa

Glukosa

puasa

Glukagon

Glukosa darah puasa

Insulin prandial

(glukosa uptake/utilzation

Glukosa

prandial

Makanan

Glukosa darah prandial


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SEKRESI INSULIN NORMAL


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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


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Pola Sekresi Insulin DM Tipe I

Sekresi insulin tergantung sisa masa sel


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Glycemic Control


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Longer term :Prevent complications

Reduce morbidityand mortality

anagement

Short term :Eliminate symptoms

Maintain general well being

Strategy :

Normalizing glucose,

lipid, and insulin levels

Activities :Management with holistic

approach and self careprinciples

A. Aim


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Treatment Modalities

Diet/Medical nutrition therapy

Exercise

Anti hyperglycemic agents Education

Pancreas transplantation

Cloning treatment (experiment)


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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 hasilpengelolaan


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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%


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PERENCANAAN MAKANKOMPOSISI :

Karbohidrat : 6070 %

Protein : 1015 %

Lemak : 2025 %

JUMLAH KALORI :Hitung BMI ( IMT ) = BB ( kg ) / TB ( m )2

IMT wanita ( normal ) = 18,523,5 kg/ m2

IMT laki ( normal ) = 22,525 kg / m2

Status gizi : BB Idaman = ( TB100 )10%

BB kurang : < 90% BBI

BB Normal : 90120% BBI

BB lebih : 110120 % BBI

Gemuk : > 120% BBI


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Exercise

30 minutes: 3 - 4 times / week

Continuous

Rhytmical

Interval

Progressive

Endurance training


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Anti Diabetic Agents

Hypoglycemic Agents

Anti Hyperglycemic Agents


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Pilihan Terapi DM Tipe 2

Berdasarkan Target Organ

PANKREAS

SEKRESI INSUL INSulfonylureas

Meglitinides ; RepaglinideInsulin

ABSORBSI

GLUKOSA

alpha-glucosidase inhibitorsSAL. CERNA

Sonnenberg and Kotc hen. Curr Opin Nephrol Hypertens1998;7(5):5515

OTOT

AMBILAN GLUKOSAPERIFER

ThiazolidinedionesBiguanides

(Metformin)

JARINGAN

LEMAK

PRODUKSI

GLUKOSA

Biguanides

(Metformin)

Thiazolidinediones

HATI

Sites of Action of Antihyperglycemic Agents


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Adipose tissue

Sites of Action of Antihyperglycemic AgentsPancreas

1. Insulin

GLUCOSE

GLUCONEO

GENESIS

HGP-

N

Intestine

2. Insulin

secretagogue

4. Acarbose

3. Metformin

TZD

3. Metformin

TZD

+

GLYCOGENOLYSIS

+

-

+

+


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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

h S i ti Gl d ti


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LIVER

ADIPOSE TISSUE

The Suppression Hepatic Glucose ProductionPancreas

Insulin

GLUCOSE

GLUCONEO

GENESIS

HGP

GLYCOGENOLYSIS

-

N

Th Sti l ti f Li i i Adi Ti


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LIVER

ADIPOSE TISSUE

The Stimulation of Lipogenesis in Adipose TissuePancreas

Insulin

GLUCOSE

GLUCONEO

GENESIS

HGP-

GLYCOGENOLYSIS

G LYCOGEN

G L UC O S E

+

GlucoseUptake

Lipogenesis+

N

FFA


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Indications of Insulin Treatment

Indication for the use of insulin inType 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


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The Pharmacology of Insulin

Lispro Aspart

Regular

NPH

LenteUltra lente

Glargine

0.10-0.25

0.10-1.0

1.0-3.0

1.5-4.02-6

2-4

0.75-2.0

1.0-4.0

5.0-7.0

4.0-8.08.0-12

None

4.0-5.0

4.0-10

13-18

13-2018-30

-24

Yes w RI

+/- w lispro

+/-+/-

NO !!!

precipitate

Minimal

Moderate

High

HighVery High

Moderate to

high

Onset(h)

Peak(h)

Duration(h)

Miscibility withLispro or

Reg. insulin

Variability inabsorption

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

Buse BB Diabetes Spectrum 2000


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Insulin available in Indonesia

Short acting insulin Long acting insulin

Actrapid Human U 40, U100 PZI U40

Humulin R U40, U100 Ultratard U100

Regular Insulin U40

Intermediate acting insulin Penfil

Monotard U40, U100 Actrapid penfil

Insulatard U40, U100 Insulatard penfil

Humulin N U40, U100 Mixtard 30/40 penfil

NPH U40 Humulin R penfil

Humulin 30/70 penfil


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1 b. Insulin Analogues

Genetic engineering

Main aim : Solubility reduction

Substitution/addition of amino acid residue ofinsulin

Short acting :

Lispro: B28-lysine, B29-proline

X14 : B28-aspartateLong acting:

B31-B32arginine, A21-glycine

Immunogenicity

Proactive management of glycemia:


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OAD

+ basal insulin OAD + multiple daily

insulin injections

OAD

monotherapy

OAD

combinations

Proactive management of glycemia:

early combination approach

OADsuptitration

7

6

9

8

10

Diet

and exercise

Duration of diabetes

HbA1c= 7%

*OAD = oral antidiabetic

HbA1c= 6.5%

Del Prato S, et al. Int J Clin Pract2000; 7:625631.

HbA1c

(%)

OHO


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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


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Insulin Secretagogues (cont.)

ATP-sensitive Potassium Channel Inhibitors

Long acting:Sulphonylureas

Short acting :

Repagl inide : Benzoic acid derivative

Nategl inide : Phenyl alanine derivative


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Sulphonylureas

Have been a mainstay of type 2 diabetes treatmentfor > 40 years

Bind to an SU receptor (SUR) on the-cell whichleads to depolarisation of -cell membrane andstimulates insulin secretion

First generation : chlorpropamide

Second generation : glibenclamide, glipizide,gliclazide

Third generation : glimepiride

Attention : Hypoglycemia (less in glipizide GITS andglimepiride)

Mode of Action of S lphon l reas


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Depola-

risation Ca2+

Voltage DependentCa 2+Channel (VDCC)

Proinsulin

Closed

ATP SensitiveK+ 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


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3. Insulin Sensitizers (1)

Metformin Anti hyperglycemic not hypoglycemic

Do not target -cell

Suppress HGP (hepatic glucose production)

Enhance tissue sensitivity to insulin topromote uptake of glucose into muscle

Cardioprotective effect on obesepatients(UKPDS)

Often used in combination with Sus Little effect on post prandial hyperglycemia

Gastrointestinal discomfort


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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 andmetabolism by muscle and fat

Suppression of hepatic glucose production Reduce plasma triglycerides

Pioglitazone

Rosiglitazone

Insulin Sensitizers (2)


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4. Inhibition of CHO digestion

and absorption Alpha glucosidase inhibitors

acarbose Plant fibre supplements

guar gum

bran


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Ingested with meals

Delay the digestion of complexcarbohydrate

Competitive inhibition of alpha

glucosidase in the intestine

Blunting postprandial glucose spikes

Gastrointestinal side effects

Alpha Glucosidase Inhibitors

(Acarbose)


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C bi ti Th i T2DM


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Combination Therapy in T2DM:

Insulin Plus Oral Hypoglycemic Agents

Insulin Plus Sulphonylurea - BIDSSome 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 InsulinReduces peripheral insulin resistance

Reduces insulin requirement

Must balance TZD and insulin carefully to minimize

weight gain


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O l H l i D A il bl i I d i


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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

Glipizide GITS 5 20 1-2 XGliquidone 30 120 1 X

Chlorpropamide 50 500 1 X

Glimepiride 0,5 6 1 X

Megl i t in ide

Repaglinide 1.5 mg 8 mg 3XNateglinide 120 mg 360 mg 3X

Metformin 500 3000 1-3 X

Alpha glucosidase inhibitor

Acarbose 50 300 3 X

ADA Treatment Goals for Glycemic Control


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ADA Treatment Goals for Glycemic Control

Glycemia Normal Goal Further Action

Required*

Average Preprandial


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Proposed New Treatment Paradigm

for Type 2 Diabetes

Medical Nutrition Therapy, Exercise , Education and SMBG

HbA1c< 7 % HbA1c7- 8 % HbA1c > 8 %

Consider oral

monotherapy

Add

insulin sensitizer

or secretagoque

Add

insulin sensitizer

and secretagoque

Target not Met Target not Met Target not Met

Start Insulin or

add Third oral agent

Full Insulin therapy

With Or without Oral agent(s)


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PADA DM TIDAK TERKONTROL


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Stres Oksidatif EndothelHYPERGLYCEMIA

Polyol

Pathway

Antioxidant

Defence

Glucose

Autoxidation Polyol

Pathway

Oxidative

Factors

Oxidative Stress

O2/ NO

LDL

Oxidation

NOdependent Vasolidation

Ca2+

VSMC Proliferation

Hemorheologic alternations Coagulation activation

Hipoxia

NVC

Endoneural

Blood Flow

Heparan

Sulphate

Vasculopathy Retinopathy Neuropathy Nephropathy

Hiperglikemia

Oxidative Stress

Komplikasi vaskular menahun(Giugliano et al 1996, Modifikasi)

R dik l B b & Di b t M llit


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Radikal Bebas & Diabetes Mellitus

DIABETES MELLITUS

HYPERGLYCEMIA

D I R C G O S

Efek Toksik Hiperglikemia : 2 Trisula dan 1 Tombak

Rangkuman : Askandar Tjokroprawiro 1999

Keterangan :

D : Direct Effect G : Glycation C : Cytokines

I : Immunology O : Oxidants

R : Rheology S : Sorbitol

f iTidak Suntik Insulin

iPatogenesis


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Lemak (Lipolisis)

Pelepasan FFA

Menuju hepar

Esterifikasi

Hiper-

Trigliseridemia

Oksidasi

Partial

Ketoanemia

Ketosuria

Muntah

Asidosis

Pernafasan

Kussmaul

Defisiensi insulin akut

Karbohidrat

Pembakaran glukosa turun

Glukoneogenesis

hiperglikemia

Glukosuria

Diurese Osmotik -

Poliuiria

Dehidrasi

Ekskresi H+

Protein

(Proteolisis)

Pelepasan A.A

Menuju hepar

Ureum naik

Syok

InfeksiTidak Suntik Insulin

Tipe IDiet bebasKetoacidosis

Diabetik

AA : Asam Amino

G : Glukosa

FFA : Free Fatty Acid


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STAGE DESCRIPTION CLINICAL FEATURES

At in creased risk Diabetes Mellitus, HBP, family history

12 Kidney Damage Microalbuminuria :

Diabetes duration 510 years, retinopathy,

rising BP

Albuminuria :

Diabetes duration 1015 years, retinopathy,

HBP

34 Decreased GFR HBP, retinopathy, CVD, other diabetic

complications

5 Kidney Failure Retinopathy, CVD, other diabetic

complications, uremia

Stages and Clinical Features of Diabetic Kidney Disease


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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.


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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.


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Tx :


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Tentukan osmolality (N = 280300 m Osm/kg)

Fluid and electrolyte replacement

- NaCl 0,9%

45 liter (o.k. dehidrasi)

- pH darah 7,1 Bikarbonat kontra indikasi

- pH darah 6,97 Bikarbonat 1 amp (+ 200 cc

steril aqua dalam 1 jam)

- pH darah < 6,9 2 amp Bikarbonat (+ 400 cc

steril aqua 2 jam)

= 2 (Na+) + Glucose (mg/dL)18

Setiap penambahan 1 amp bicarbonat ditambahkan

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


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Setelah glukose < 250 mg/dL

D5 (dengan insulin tetap R/)

Untuk pertahankan glucose

200300 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


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HYPERGLYCEMIC HYPEROSMOLAR STATE ( CHO )

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.

LACTIC ACIDOSIS


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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 HendersonHasselbach :

pH = 6.10 + LogCO2content meq/L

pCO2mmHg x 0,03


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Normal sumber asam lactat :

Erithrosit

Otot Kulit

Otak

Asam LactatHati

GinjalGlukose

Symtom and Sign :

Terutama hipervent i lasi, bila penyebabhipoksia/kolap vaskuler, klinis variabel ~ penyulit

dasar.

Tensi normal, sirkulasi perifer baik, sianosis (-).

Treatment Priority


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Treatment Priority

of Type 2 DM

Glucose control as

near to normal asreasonably possible

Microvasculardisease

Control of Insulin resistance:

Hyperinsulinemia, Obesity,

Glucose intolerance,

Dyslipidemia, Hypertension,Procoagulant state

Macrovasculardisease

Control of Insulin Resistance


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Insulinresistance

PAI-1,Factor VII, Fibrinogen

Hyperglycemia

Hypertension

Pro-coagulant State

Obesity

Dyslipidemia

Cardiovasculardisease

Intervention/Control

Control of Insulin Resistance

Tabel. Definitions of the Metabolic Syndrome


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ATP III (American Heart

Association) (2005)

World Health

Organisation 1999

International Diabetes Federation

(2005)

Minimal

requirements

Any 3 or mor of the

following criteria

Diabetes, IFG, IGT, or

insulin resistance + any2 or more of the

following criteria

Central obesity (see under) + any 2

or more of the following criteria

Waist

circumference

In men < 102 cm

In women < 88 cm

In men 94 cm

In womwn 80 cm

Waist to hip

ratio

< 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

> 20 mg/min

Serum glucose 6.1 (5.6) mmol/l 5.6 mmol/l (100 mg/dl)

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)

Modified NCEP ATP III 2001


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Modified NCEP-ATP III 2001

80 cm

90 cm 150mg/dL

< 50mg/dL

< 40mg/dL

130/85mmHg

110mg/dL. (sekarang > 100)

1.Lingkar perut

wanita

pria2. Trigliserida

3.HDLkolesterol

wanita

pria

4. Tekanan Darah

5.Gula Darah Puasa

3 Kriteria dari variabel dibawah ini

"The Cumulative Metabolic Syndrome"


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Insulin ResistanceHyperinsulinemia2

1

Visceral Obesity

"The Black Goat"

4 Atherogenic Dyslipidemia

TriglyceridesHDL-CholesterolApolipoprotein-BSmall Dense LDL

Inflammatory Markers

(CRP, TNF, IL - 1, IL - 6)

8

Hyperuricemia 9

7Vascular Abnormalities

- Urinary Albumin Excretion- Endothelial Dysfunction

IFGIGT DM3

5

Hypertension

LVHCHF

Prothrombotic State

PAI-1 (Esp. Omental Fat)Factor VIIFibrinogenvWF

Adhesion Molecules

6

ACTH, Cortisol( Salivary Cortisol)

10

VISCERALADIPOSE TISSUE

GABRA-6 ?

The Cumulative Metabolic Syndrome A Cluster of 10 Possible Metabolic and CV Risk Factors

(Visceral Obesity is the Culprit)(Summarized : Tjokroprawiro 2002, 2003)


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Pencegahan Diabetes Mellitus

1. Primer, untuk orang yang resiko tinggi.

2. Sekunder, mencegah/menghambat

komplikasi.

3. Tertier, mencegah kecacatan


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kuliah dm semester 8 tahun 2007

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