CURICULUM VITAE

Nama : DR.dr. Sugiarto, Sp.PD-KEMD, FINASIM

TTL : Surakarta, 22 Mei1962
Alamat: Banyuagung 002/005 Kadipiro Solo
Pendidikan: S1 FK UNS 1988
S2 Spesialis Peny. Dlm FK UGM 2003
S3 FK Unair 2010
Subspesialis FK UGM 2015
Pekerjaan : Kapuskes Larangan, Brebes 1989-1998
Staf Pengajar Bagian Peny. Dlm FK UNS 2003-
sekarang
KPS Penyakit Dalam FK UNS 2015- sekarang
 PERAN AGEN HAEMOREOLOGI PADA
NEUROPATI DIABETIC

Sugiarto
Devisi Endokrin, Metabolik dan Diabetes Ilmu Penyakit Dalam FK / RSUD
Dr Moewardi Universitas Sebelas Maret Surakarta

Best western Solo baru 22-23 -Oktober -2016

PENDAHULUAN

• Diabetes mellitus adalah

• suatu sindroma klinik yang di tandai adanya gangguan
metabolisme karbohidrat, protein dan lemak yang
• Ditandai
• Hiperglikemia akibat defisiensi insulin dan atau resistensi
insulin di berbagai sel tubuh.

Puasa ≥ 126 mg/dl atau

2 jam OGTT ≥ 200 mg/dl
Sewaktu ≥ 200 mg/dl
disertai gejala klinis klasik
 DIAGNOSIS
350 Post-meal
300 glucose Fasting
Glucose 250 glucose
(mg/dl) 200
150
100
50
250 Insulin resistance
Relative 200
-cell 150 Insulin
level
function 100
(%) 50 -cell failure
0
Obesity IGT T2DM
Uncontrolled
hyperglycaemia

Clinical
features Risk for diabetes complications

Years −10 −5 0 5 10 15 20 25 30

IGT = impaired glucose tolerance

Adapted from Bergenstal RM. In: Int. Textbook of Diabetes Mellitus, third edition: John Wiley & Sons; 2004: p995―1015.
 THE GOAL OF DIABETES MANAGEMENT IS TO SECURE OPTIMAL
GLYCEMIC CONTROL TO AVOID COMPLICATIONS
Microvascular Macrovascular
Stroke
Diabetic
retinopathy 1.2- to 1.8-fold
(20-60%) increase in
stroke3
Leading cause
of blindness
Cardiovascular
in working-age
disease
adults1
75% diabetic patients
Diabetic die from CV events4
Nephropathy
(30-40%)
Diabetic
Leading cause of neuropathy(60-70%)
end-stage renal Leading cause of
disease2 non-traumatic lower
extremity
Erectile Dysfunction
amputations5
The most secretive
Complication of DM Diabetic Foot
1Fong DS, et al. Diabetes Care 2003;e 26 (Suppl.1):S99–S102. 2Molitch ME, et al. Diabetes Slide 5 26 (Suppl.1):S94–S98. 3Kannel WB, et al. Am Heart J 1990; 120:672–676. 4Gray RP & Yudkin JS. Textboo
Care 2003;
Diabetes 1997. Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl.1):S78–S79.
5
 PREVALENCE OF MACROVASCULAR AND
MICROVASCULAR COMPLICATIONS OF DIABETES

† ‡

Macrovascular Microvascular
*In NHANES, “chronic kidney disease" refers to people with microalbuminuria (albumin:creatinine ratio >30 µg/mg).
†In the NHANES analysis, "foot problems" includes foot/toe amputations, foot lesions, and numbness in the feet.
‡"Eye damage" includes a positive response by NHANES participants to the question, "Have you been told diabetes has affected your eyes/had retinopathy?"

Retinopathy is damage to the eye's retina. In NHANES, people without diagnosed diabetes were not asked this question, therefore, prevalence information for
nondiabetics is not available.
CHD = coronary heart disease; CHF = congestive heart failure.
American Association of Clinical Endocrinologists. State of Diabetes Complications in America Report. Available at:
http://www.aace.com/newsroom/press/2007/images/DiabetesComplicationsReport_FINAL.pdf. Accessed March 9, 2009.
 ~ 66% Diabetic
Neuropathy

Chen H, Lamer TH, Rho RH et al. Mayo Clin Proceed. 79; 2004
Boulton AJM, Mailik RA, ArezzoJC, Sosenko JM. Diab.Care 27, 2004
Wendling Patrice. 45% of Diabetic Patients Not Reaching HbA1C Target. Internal Medicine News. July 15 2007;40(No.14):1, 20.
 NEUROPATI DIABETIK
• Definisi :
• Adanya gejala atau tanda disfungsi syaraf perifir
pada pasien diabetes mellitus
• setelah mengeksklusi penyakit lainnya
• seperti malignansi, alkoholis kronik, defisiensi
nutrisi, infeksi, iatrogenic, dll
 Pathogenesis of diabetic neuropathy
Diabetes mellitus,
Microvascular
Autoimmunity genetics/environments
Smoking, alcoho, diet inefficiency

Poor Glycaemic
control

Physiological Mediators
Metabolic initiators +
Endothelial function
oxidative stress

Nerve damage Nerve damage

Diabetic neuropathy,
leakage of antigens with
further damage
Sachdev, 2009 ,Clinical Endocrinology dan Diabetes Mellitus
 Impact of Diabetic Neuropathy

• 15% of diabetics will develop

an ulcer.

• One in six of those with ulcers

will have an amputation.

• Half of those will have an ulcer

on the opposite foot within
three years.

Gordois et al. Diabetes Care 26:1790-1795, 2003

 KLASIFIKASI NEUROPATI (SACHDEV, 2009)
• Length-dependent diabetic neuropathy.
• Distal symmetrical sensorimotor polyneuropathy.
• Small fibre painful neuropathy.
• Acute painful neuropathy
• Chronic painful neuropathy
• Long fibre neuropathy.
• Autonomic neuropathies
• Focal and multifocal neuropathies.
• Cranial neuropathies.
• Limb neuropathies.
• Proximal neuropathy of the lower limb.
• Truncal neuropathies.
• Other
• Pressure or entrapment palsies.
• Acquired inflammatory demyelinating polyneuropathy
 Classification of diabetic neuropathy (as per pattern of nervous system involvement)
Diabetic neuropathy

Peripheral Autonomic

Sensory Sensosrimotor Motor Parasympathetic Sympathetic

Small fibre Long fibre Proxima L, Focal and

asymmetrical multifocal

Cranial Thoracolumbar Limb mononeuropathy

Sachdev, 2009 ,Clinical Endocrinology dan Diabetes Mellitus

 DIABETIC NEUROPATHIES

III VI

Truncal

Ulnar

Median
Lateral
popliteal

Large-fiber Small-fiber Proximal motor Acute mono

Entrapment
neuropathy neuropathy neuropathy neuropathies
Sensory loss: 0 – +++ Sensory loss: 0 – + Sensory loss: 0 – + Sensory loss: 0 – + Sensory loss in nerve
(touch vibration) (thermal allodynia) distribution: + – +++
Pain: + – +++ Pain: + – +++ Pain: + – +++ Pain: + – +++ Pain: + – ++
Tendon reflex: Tendon reflex: N –  Tendon reflex:  Tendon reflex: N Tendon reflex: N
N – 
Motor deficit: 0 – +++ Motor deficit: 0 Proximal motor Motor deficit: + – +++ Motor deficit: + – +++
deficit: + – +++

N, normal Vinik A et al. Clin Geriatr Med. 2008;24:407.

 SIGNS AND SYMPTOMS OF DIABETIC PERIPHERAL
NEUROPATHY

Distal symmetrical sensorimotor polyneuropathy

is the most common form of DPN. Signs and symptoms
may progress from distal to proximal over time.

SIGNS SYMPTOMS
•Diminished vibratory perception • Numbness, loss of feeling, prickling,
tingling
•Decreased knee and ankle reflexes
•Reduced protective sensation, such • Aching pain
as pressure, hot and cold, pain • Burning pain
•Diminished ability to sense position • Lancinating pain
of toes and feet • Unusual sensitivity or tenderness
when feet are touched (allodynia)
Boulton AJ, et al. Diabetes Care. 2005;28(4):956-962.
 Neuropathic Pain

Disebabkan kerusakan myelin sheet, yang

berakibat :
1. impuls yang lewat akan menyebar
ke sel saraf lainnya,
sehingga timbul nyeri
2. penghantaran implus ke sel saraf
berikutnya menjadi terhambat
 timbul gangguan sensorik.
 HEMOREOLOGI
• Hemoreologi ilmu yang mempelajari tentang aliran
pembuluh darah dan interaksinya dengan eritrosit terhadap
sistem vaskuler yang meliputi: sel-sel, plasma, viskositas
darah dan shear rate.

• Komponen :
• 1. Vaskuler (sistem kardiovaskuler ke sistem makrosirkulasi
selanjutkan ke mirkosirkulasi diameter < 100 mm).
• 2. Komponen darah
• eritrosit, leukosit dan trombosit
KOMPONEN VASKULER DAN ERITROSIT
INTERAKSI ERITROSIT DI VASKULER
AGEN HEMOREOLOGI

Annals New York Academy of sciences

 KOMPONEN YG MENINGKATKAN RESISTENSI
MIKROVASKULER
• Deformitas dan agregasi eritrosit.
• Deformitas leukosit.
• Hiperaktifitas dan agregasi trombosit.
• Peningkatan viskositas plasma:
• acute-phase reactions (infeksi atau trauma pos
pembedahan),
• plasma protein (fibrinogen dan globulin)
 DEFORMITAS ERITROSIT PADA DIABETES
• Penurunan kadar C-peptide dan insulin
• Penurunan aktifitas NA+,K+-ATPase.

Forst dan Kunt, 2004

 GANGGUAN HEMOREOLOGI PADA DM
(HIPERGLIKEMIA)
• Endotel :
• Inflamsi
• Disfungsi endotel dan penebalan arteria.
• Penebalan membrane basalis dan perubahan struktur pada kapiler
• Komponen sel sel darah :
• Peningkatan hematokrit
• Deformitas dan agregasi eritrosit.
• Agregasi dan hiperaktifitas trombosit.
• Plasma darah:
• Peningkatan protein plasma ( fibrinogen dan globulin).
• Penurunan albumin
• Peningkatan viskositas darah.
ERYTHROCYTE DEFORMABILITY AND AGGREGABILITY
(HAMLIN DAN BENEDIK, 2014).
PENINGKATAN VISKOSITAS DARAH

• Mikroangiopati diabetik,
• Gangguan mikrosirkulasi.
• Defisiensi nutrisi di jaringan.
MICROANGIOPATHY DAN NEUROPATHY ENDONEURAL
• Hiperplasi dan hipertropi endotelial  ukuran lumen mengecil
•  Aliran darah endoneural menurun.
•  Degenerasi pericyte cell .
•  Kerusakan nerve fiber atau C fiber
• --> kerusakan axon reflek.
• Agregasi trombosit dan fibrinogen.
• Aktifitas von Willebrand factor
• Cell adhesion molecules
• Perubahan transfortasi dan nutrisi.
• penurunan fungsi dan perbaikan jaringan.
Malik and Veves
(Forst dan Kunt, 2004) .
PATHOGENESIS OF DIABETIC NEUROPATHY.
Management of diabetic neuropathy

Evaluation

Standart methodology
(10 gm monofilament, modified NDS system)

Treatment

Glycaemic control,
lipid control
insulin therapy
IGF-I, IGF-II, Laminin B,
Nerve growth factor(NGF)

Nerve regeneration
+
Restoration of nerve function
Sachdev, 2009 ,Clinical Endocrinology dan Diabetes Mellitus
 KESIMPULAN
• Diabetes mellitus suatu sindroma yang di tandai adanya
gangguan metabolisme karbohidrat, protein dan lemak yg
ditandai hiperglikemia kronik.
• Perubahan hemoreologi akibat hiperglikemia menyebabkan
komplikasi neuropati, retinopati dan nefropati DM.
• Agen hemoreologi meliputi: endotel, komponen darah dan
plasma.
• Hemoreologi berhubungan dengan mikroangiopati dan
neuropati endoneural
• Terapi pertama neuropati perifir diabetic adalah pencegahan
WAALAIKUM SALAM WR WB