KOMPLIKASI DIABETES

Dr. PANDJI MOELJONO, Sp.PD,KEMD,FINASIM

SUBDEP PENYAKIT DALAM
FK. WIJAYA KUSUMA FK. 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

Genetic determinants of
individual susceptibility

Repeted changes
in cellular metabolism

hyperglicemia

Cummulative long term

changes
in
stable
macromolecules

Diabetic tissue
damage

Independent accelerating
factors (e.g hypertension,
hyperlipidemia

FIG. 1. General features of hyperglycemia-induced tissue damage.

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

MECHANISM OF CHRONIC
COMPLICATIONS

Pathobiology of Diabetic Vacsular Complication

The Role of Oxidative Stress
(Michael Brownlee, Banting Lecture 2004)

1. Polyol Pathway (1966)

2. AGE Pathway (1980)
3. PKC Pathway (early 1990)
4. Hexosamine Pathway (late 1990)

Power AC (2006) : Diabetes Mellitus.

Harrisons Endocrinology

Hyperglycemia

Intracellular
Glucose
Aldose
reductase

AGEs

Abnormal
protein
Function

Altered Cell
Function

Circulating
AGEs

Renal
,Vascular,
Connective
tissue effect
Cytokines,
Growth Factor

Sorbitol

Alterations
in redox
potential ,
ROS
Altered
Cell
function

Fruc-6-P

DAG

Altered
Enzyme
function
(Cpla2),
eNOS

Complication
of Diabetes

Flux in
hexosamin
e pathway

PKC
activatio
n

Altered
gene
expressio
n

Growth
Factors

PAI-1,
growth
factors

FIG. 2. Hyperglycemia increases flux through the polyol pathway. From Brownlee M:
Biochemistry and molecular cell biology of diabetic complications.
Nature 414:813820, 2001.

FIG. 3. Increased production of AGE precursors and its pathologic consequences.

From Brownlee M: Biochemistry and molecular cell biology of diabetic complications.

Nature 414:813820, 2001.

Hyperglicemia

Consequences of hyperglycemiainduced activation of PKC.

DAG
PKC
and isoform

+eNOS

ET -1

VEGF

TGF -

Collagen

PAI -1

NAD(P)H

NF -B

Fibrinolysis

ROS

Fibronectin
Pro inflammatory

Blood flow
abnormalities

Gene expression

Vascular
Permeability
angiogenesis

Capillary
occlusion

Vascular
occlusion
Multiple effect

FIG. 5. Hyperglycemia increases flux through the hexosamine pathway.

From Brownlee M: Biochemistry and molecular cell biology of diabetic complications.

Nature 414:813820, 2001.

Oxidative Damage

Diseases Induced by Atherosclerosis

Eye
Hypertensive
retinopathy Amaurosis
fugax

Kidney
Albuminuria
Renal
Disorder
Renal Failure
Dialysis

Brain
Cerebral hemorrhage
Cerebral infarction
Transient ischemic attack

Heart
Angina pectoris
Myocardial Infarction

Peripheral Artery
Arteriosclerosis plaque
Aorta detachment

PAD

Klasifikasi Lain
Jenis Serabut Saraf
Neuropati Sensorik
Neuropati Otonom
Neuropati Motorik

Respons terhadap Terapi

Fenomena Reversibel Cepat
Manifestasi yang telah Menetap
Thomas PK. International Textbook of Diabetes Mellitus, 2004

SIGNS AND SYMPTOMS OF NEUROPATHY

(Apfel 1999)

Small-fiber sensory
Large-fiber sensory
Autonomic
--------------------------------------------------------------------------------------------------------Burning pain
Loss of vibration sense Heart rate abnormalities
Hyperesthesia
Loss of proprioception Postural hypotension
Paresthesias
Loss of reflexes
Abnormal sweating
Lancinating pain
Slowed NCVs
Gastroparesis
Loss of pain & temp.
Neuropathic diarrhea
Foot ulceration
Impotence
Loss of visceral pain
Retrograde ejaculation

How have these foot lesions possibly developed in this

woman with neglected type 2 diabetes?

HIPOGLIKEMI

HIPOGLIKEMI

Kadar gula darah < 60 mg/dl

Koma gula darah < 30 mg/dl

Penyebab Hipoglikemi pada DM :

OHA induce
Insulin induce

CEREBRAL CORTEX
Neuroglycopenic
symptoms
Hypoglycaemia
Hypothalamus

Parasympathetic
nervous system

Sympathetic
nerves

Adrenal
medulla
Adrenaline
Tremor

Heart
Pounding heart

Autonomic
symptoms

Sudomotor
eccrine
sweat glands
Sweating

Perception
interpretation
and action

MEKANISME TERJADINYA HIPOGLIKEMI

(Dikutip dari : Service, 1995)

Gejala dan Tanda Hipoglikemi :

1. Neuroglikopeni :

Daya
berpikir menurun
Sulit
berbicara
Nyeri
kepala

Mata kabur

Kesadaran menurun sampai

koma

Kejang

Gejala dan Tanda Hipoglikemi :

2. Adanya Rangsangan

Adrenergik
:
Takhikardi

Palpitasi

Gemetar

Berkeringat dan pucat

Rasa lapar

Mual

Cemas

Hipoglikemi dibagi 3
derajat :
I.

Ringan
II. Sedang
III. Berat

TERAPI HIPOGLIKEMI
1. Pisang / roti / KH lain
2. gula , tetesi gula kembali atau madu dibawah lidah
3. Injeksi D 40% i.v 25 cc dilanjutkan infus D 10% atau
Martos 10% dapat diulang tiap 1/2 jam sampai
sadar
4. Injeksi efedrin 25 - 50 mg atau glukagon 1 mg i.m.

Bila kadar gula darah diketahui

Kadar gula darah D 40%

<30 mg/dl 3 f
30 - 60 mg/dl 2 f
60 - 100 mg/dl

1f

(Askandar Tj., 1996)

KETO ASIDOSIS
METABOLIK

PENCETUS KAD :

Infeksi
Penghentian insulin atau terapi
insulin yang tidak adekuat
Penderita baru
IMA
Obat steroid
20% tidak diketahui

Decreased Insulin & Increased Counterregulatory Hormones

(Glucagon, Catecholamines, & Cortisol)
INCREASED LIPOLYSIS
AND TG BREAKDOWN

INCREASED GLUCOSE PRODUCTION

&
DECREASED GLUCOSE UPTAKE

Increased Plasma
Amino Acids

Increased FFA
in Plasma
Increased FFA
to Liver

INCREASED
PROTEOLYSIS

Stimulate
Gluconeogenesis

HYPERGLYCEMIA

Precursors for
Gluconeogenesis

Increased
Amino Acids
to Liver

Glucosuria
Increased
Ketogenesis
Ketonemia & ketonuria
Decreased Alkali
Reserve
Acidosis

PATOFISIOLOGI KAD

Osmotic Diuresis
Loss of Electrolytes
Cellular Dehydration
Volume Depletion
Impaired Renal Function

(Dikutip dari : Kitaochi, 1994)

KRITERIA DIAGNOSIS KAD

1. Klinik : Poliuria, polidipsia, mual / muntah,
pernafasan kussmaul (dalam dan frekuen),
lemah, dehidrasi, hipotensi sampai syok,
kesadaran terganggu sampai koma.
2. Darah : hiperglikemi lebih dari 300 mg/dl
(biasanya melebihi 500 mg/dl), bikarbonat
kurang dari 20 mEg/l (dan pH<7.35),
ketonemia
3. Urin

glukosuria dan ketonuria

KLASIFIKASI KAD

Stadia KAD
I.

Ringan

II. Sedang

Macam KAD
KAD ringan

PH darah Bikarbonat darah

7.30-7.35

15-20 mEq/l

Prekoma diabetik 7.20-7.30

III. Berat Koma diabetik 6.90-7.20

IV. Sangat berat Koma diabetik berat

12-15

8-12
< 6.90

<8

TERAPI KAD
Protokol terapi KAD terdiri dari 2 fase yaitu :
Fase I (fase gawat)
Fase II (fase rehabilitasi)
Dengan batas kadar glukosa darah antara kedua fase tersebut sekitar 250
mg/dl.
FASE I :
1. Rehidrasi : Na cl 0.9% atau RL 2 liter/2 jam pertama, lalu 80 tetes/menit
selama 4 jam, lalu 30-50 tetes/menit selama 18 jam (4-6 liter/24 jam),
diteruskan sampai 24 jam berikutnya.
2. Insulin dosis rendah intravena : 4-8 unit/jam I.v sampai fase II.
3. Infus K : 75 mEq (bila K <2.5 mEq/l), 50 mEq (K = 2.5 -3.0 mEq/l) dan 25
mEq (K = 3.0 - 3.5 mEq/l) per 24 jam
4. Infus bikarbonat : bila pH <7.20 atau bikarbonat <12 mEq/l : 50-100 mEq
langsung drip dalam 2 jam, bolus 50-100 mEq diberikan bila pH kurang
dari 7.0
5. Antibiotika up to date dan dosis adekuat.

TERAPI KAD
FASE II :
1. Maintenance : Nacl 0.9%, atau potakol R (IR 4-8 U),
maltosa 10% (IR 8-12 U) bergantian 20 tetes/menit
2. Kalium : p.e (bila K < 4 mEq/l) atau per os (air
tomat
atau kaldu 1-2 gelas)
3. Insulin reguler : 3 x 8-12 U s.c
4. Makanan lunak Karbohidrat kompleks peroral

HIPER OSMOLAR NON KETOTIK

KOMA HIPEROSOMOLER NON

KETOTIK (KHONK)

Hiperglikemi

Dehidrasi berat

Tanpa asidosis metabolik dan

ketosis

Privalensi lebih jarang 1/5 - 1/6 KAD

DM tipe-2 usia tua

Mortalitas 30.4% kasus KHONK

FAKTOR PENCETUS :
Faktor pencetus KHONK yang paling penting
adalah infeksi dan penyakit kardiovaskuler.
Namun dapat juga disebabkan o.k. iatrogenik
seperti hiperalimentasi parenteral, peritoneal
dialysis hipertonik, pembedahan dan pemberian
obat-obat kortikosteroid dan diuretic.

(Kuzuya T, 1999)

KRITERIA DIAGNOSIS KHONK

Diagnosis klinik KHONK bila Didapatkan :
1. Glukosa darah >800 mg/dl
2. Anamnesis DM tidak ada atau meragukan
3. Pernafasan Kussmaul tidak ada
4. Ketonuri dan ketonemia negatif atau positif
ringan.

KRITERIA DIAGNOSIS KHONK

Faktor penunjang diagnosis klinik HONK
1. pH darah >7.3
2. Adanya prerenal azotemia
3. Hipernatremi (>150 mEq/l)
4. Gangguan kesadaran
5. Gejala neurologik (konvulsi)
Diagnosis Pasti KHONK : Diagnosis klinik +
Osmolaritas > 325.
Osm/l = 2X (Na + K) + Glukosa (mg/dl) + BUN
18
2.8

TERAPI

= KAD
Bila Na <150 mEq/l
Na > 150 mEq/l
hipotonik
Tanpa Nabic.

cairan Nacl 0.9%

cairan

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 (-).

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

Correlation Between AIC level and

Mean Plasma Glucose
AIC (%)

Mean Plasma Glucose

mg%

mmol/L

133

7.5

170

9.9

205

11.5

240

13.5

10

275

15.5

11

310

17.5

345

19.5

12

Rohlfing CL et al. Diabetes Care 25; 275:, 2002

Terima Kasih...

Diagnosis for PAD

ABI
ABI (Ankle
(Ankle Brachial
Brachial Index)
Index)
Lower Leg BP

ABI = Upper Arm BP

Normal leg
PAD

Above
1.0
Below
0.9

(Above1.3 need caution)

Diagnosis for PAD

ABI
ABI (Ankle
(Ankle Brachial
Brachial Index)
Index)
Lower Leg BP

ABI = Upper Arm BP

Normal leg
PAD

Above
1.0
Below
0.9

(Above1.3 need caution)

Diagnosis for PAD

Diagnosis
Diagnosis at
at Bedside
Bedside
Interview
Interview
1.

Any cold or numbness

2.

Any intermittent
claudication Many patient
come to hospital due to
claim intermittent
claudication. Important
point is to distinguish from
other nerve disorders.

3.

Any ulcer or gangrene at

arms and legs

4.

Need more precaution to

patient with hypertension,
hyperlipidemia,
ischemic
heart disease, diabetes.

Observe change of skin color

Pale Cyanosis, etc
Observe skin temperature decline
Palpate arteries
Elevation test
Elevate both legs. Compare both
legs color change after flexing leg
joint for 15 seconds. Patient legs
color become
pale test
compared to
Dropping
normal legs.
After elevation test, drop both legs
to compare the color change.
Patient legs need longer time to
become red
compared to normal
Stethoscope
legs.

Any bruit at Vascular or not

Supersonic wave doppler

Diagnosis for PAD

ABI
ABI (Ankle
(Ankle Brachial
Brachial Index)
Index)
Lower Leg BP

ABI = Upper Arm BP

Normal leg
PAD

Above
1.0
Below
0.9

(Above1.3 need caution)

Diagnosis for PAD

Points for artery palpation

Dorsalis pedis artery

Posterior tibial artery

Femoral artery

Popliteal artery

Diagnosis for PAD

Elevation
Elevation test
test

Drop
Drop test
test

Elevate both legs as highest, flexing (leg joint

exercise) for 15 seconds. No color changes
are observed at normal legs, but legs with
obstruction artery colors become pale.

After elevation test, rise body and drop both

legs. At normal legs color returned to normal
rapidly. But legs with obstruction artery
become red very slowly . If there is difference
between right and left leg, we can see the
difference very clear.