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VASCULAR COMPLICATION
IN TYPE 2 DIABETES

Prof Darmono, MD, PhD, Internist, Endocrinologist

Div of Endocrinology, Dept of Medicine, Med Fac, Diponegoro Univ, Kariadi Hospital

SCIENTIFIC MEETING INSPIRE NOVO

INDONESIAN SOCIETY OF ENDOCRINOLOGY
SEMARANG, MAY, 2014

Gangguan
Metabolik

Karbohidrat
Lemak
Protein

Diabetes
Mellitus

Glukosa
tolok ukur status metabolik
Kriteria diagnosis
Klasifikasi WHO

Menurunkan kualitas hidup

& life expectancy
Makroangiopati
Jantung

Kerusakan
Vaskular

P. darah perifer
Mikroangiopati
Mata
Ginjal
Saraf

Silent Long-Term
complications

Kerusakan
jaringan & organ

Kebutaan 30% DM (Retinopati)

Komplikasi P. Darah perifer
40 x non-DM

MORBIDITAS
&
MORTALITAS

Amputasi tungkai 10% DM

Kematian 2-5 x non-DM
Penyakit Jantung
Gagal Ginjal Kronik
Penyakit Serebro Vaskular
Life Expectacy (5 - 10 th)

Mata
Ginjal
Saraf

Mikroangiopati
(Protrombotik)

Penebalan mb Basalis
P. Darah Kapiler

Perubahan
Viskositas darah
& fungsi trombosit

Gangguan
Hemodinamik

Glukosa
normal

Aldose reduktase
Reduksi

Glucosa

Glikosilasi
non-enzimatik

Long-lived
Protein
Memb. Basalis
Kolagen

Sorbitol

Sorbitol dehidrogenase
Oksidasi

Sugar alcohol
Osmotic polyol

Sorbitol
Amadori
product

Fruktosa

Water uptake
Advanced Glycosilated
End Product (AGEP)

Otooksidasi

Free radicals
Oxidizing intermediate
highly reactive oxidants
Sitotoksik

Denaturasi
Agregasi

Glikosilasi
Non Enzimatik

3 deoxyglucosone
( 3 DG )
Highly Reactive Intermediate
Perubahan
Phenotype

Disfungsi
Endotel

AGEP

+
Receptor AGEP
Membran sel target

Angiopati
DM

Glukosa

Aktifitas
enzim
protein kinase

Post prandial

(Sel endotel)

Adesi
lekosit - endotel

Angiopati

Permeabilitas
endotel

Glukose stimulated
Vascular changes
(disfungsi endotel)

Albumin
LDL

IgG

Elastisitas
Penebalan
Penyempitan
Vaskular

Imunologik
Mb Basalis
Glikosilasi
non-enzimatik

AGEP

Binding
capacity
Anion proteoglikan
mb basalis

Sitotoksik

Permeabilitas
kapiler

Gangguan
hemodinamik

GFR ekskresi protein

Retina
Aliran darah
Tekanan i.v
Dilatasi
Ekstremitas
Aliran darah
Transportasi prot. plasma trans. kapiler

Critical
Vaskular Beds

Penyempitan
kapiler

Retina
Glomeruli
Vasa nervorum

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Produksi
prostasiklin

( vasodilator &
anti platelet
agregating agent )

Produksi
aktivator
fibrinolisis

Viskositas
Mikrotrombus
Penyempitan
vaskular

Produksi
thromboxane A2

Deformabilitas
eritrosit

( vasokonstriktor &
platelet agregating
agent )

Hambatan
aliran darah

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MAKROANGIOPATI

Jantung
P drh perifer
Otak

( Protrombotik )
Atherosclerotic
Occlusive disease
Aktifitas
trombosit

Fibrinolisis

Koagulabilitas
plasma

Disfungsi
endotel
Produksi
prostasiklin

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DM
Hiperglikemia
Hiperinsulinemia

Vasc. growth
promoting factor
Diabetic serum
growth factor 1

Proliferasi
otot polos
p darah

Insulin-like
Growth factor
Penyempitan

AGEP
Ateroma
LDL

Aterosklerosis

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Faktor risiko

CRP
Fibr
Homocyst
APO-L-B
L-A
Visk Plasma

Atherosclerotic
Occlusive disease

+
Usia
DM
Neuropati perifer

Reseptor
di
endotel
(marker inflamasi)

Procoagulant tissue factor

Leucocyte
adhession molecules
Chemostatic substances
Compounds impairing
fibrinolysis
(Plasminogen activator)

Endothelial cell
nitric oxyde
Stimulator vasodilatasi
Inhibitor Inflamasi
Proliferasi
Trombosit

Gangguan regulasi
Tonus vaskular

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Pengendalian defek metabolik

seawal mungkin

Diit
Olahraga
OHO
Inslin

Glukosa
Lipid

Proteksi thd produk

oksidatif-sitotoksik
(dari reaksi glikosilasi protein)

ANTIOKSIDAN
Preparat / obat
me pembentukan
antioksidan
koreksi disfungsi endotel

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Supresi fungsi trombosit

Stimulasi sintesis
prostaglandin I2
di dinding P. darah

Gliclazide
( OHO sulfonilurea )

Stimulasi aktifitas
fibrinolisis

Menekan glukosa & insulin

post prandial
Tidak memacu
sekresi insulin
Me trigliserid

Acarbose
Memperlambat
absorbsi glukosa
di intestinal

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METFORMIN
Hepatik
glucose production
Muscle
glucose uptake
Afinitas
insulin reseptor

Glukosa
Insulin

Status glikemi
terkendali
Vaskular growth factor

Metformin
Aman jangka panjang
(tidak ada gangguan perfusi)

Angiopati

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Koreksi Gangguan hemorheologik

Viskositas plasma
Agregasi sel

Medikamentosa
Pentoxyfilline
Aspirin
Clopidogrel
Cilostazol

Deformabilitas eritrosit

Gagal

Operasi

Neuropati
perifer
Sensorik
Motorik

Infeksi
Ulkus
Nekrosis
Gangren

Conduction velocity
Axonal atrophy

Neurofilament
( Prot Axon )
Elektrofisiologi
Morfologi
Hemorheologik

Koreksi
Gangguan fungsi
jar saraf

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