NAMA : DR.

DJOKO MARYONO,DSPD,DSJP,FIHA,FASE
LAHIR ; surabaya 27-03-47
DOKTER UMUM; AIRLANGGA SBY 1974
DOKTER AHLI PENYAKIT DALAM : AIRLANGGA SBY 1978
DOKTER AHLI JANTUNG : AIRLANGGA SBY 1985
KONSULTAN CARDIOLOGY : UNIV ALABAMA,USA I986
MEMBERSHIP:
AMERICAN COLLEGE OF CARDIOLOGY
AMERICAN INVASIVE CARDIOLOGY
INTERNATIONAL ATHEROSCLEROSIS SOCIETY
ASIA-PASIFIC ATHEROSCLEROSIS SOCIETY
KOSULTANT CARDIOLOGY DI
RS PERTAMINA
RS PONDOK INDAH
RS SILOAM
DIABETES DAN PENYAKIT
JANTUNG KORONER
DR.DJOKO MARYONO,SPPD,SPJP,FIHA,FACC

SPESIALIS PENYAKIT DALAM,SPESIALIS PENYAKIT

JANTUNG
Global Projections for the Diabetes related
to Coronary art diss and Stroke
26.5
32.9
14.2 24%
17.5
23%
84.5
132.3
9.4 57%
14.1
15.6 50%
22.5
44%
1.0
1.3
World 33%
2000 = 151 million
2015 = 230 million
Increase of 60%
Zimmet P et al. Adapted with permission from Nature 2001; 414: 782–7. www.nature.com
Aboriginal Canadians Oji-Cree
Genes and environment in metab syndrome
and atherosclerosis
 PRIMARY CAUSE OF HEART
DISSEASE AND STROKE IN ASIA
PASIFIC AREA
• 1.GLICO-LIPO
TOXICITY(KEBANYAKAN
• GULA DAN LEMAK)

• 2.IN ACTIVITY HABIT(MALAS

BERGE-
• RAK/OLAH RAGA)

• 3.TO MUCH FREE

RADICAL(TERLALU
• BANYAK POLUSI)
MODERNIZATION
WESTERNIZATION
Soft Drink Maniac
 Progression Rate of DM from IGT Related
to Soft Drink Consumption
Re-Tested OGTT

0.193

0.1
0.085

Time 2 years
Ekowati etal, Preliminary Report 2002
 Assessment of Abdominal Visceral Fat
WC (waist circumference)

Mid axillary line

Lowest rib

Iliac crest

Men Women
At risk High risk At risk High risk
WHO (cm) 94-102 > 102 80-88 > 88

Asia-Pacific (cm)  90  80
SINDROMA METABOLIK PENYEBAB
JANTUNG KORONER DAN STROKE
 ERECTILE
DYSFUNTION
NORMAL ATHERO-
SCLEROSIS

STROKE HEART
ATTACK
Problems in Managing Type 2 Diabetes

1. We diagnose late …

2. Cardiovascular risk begins earlier,

even before diabetes onset

3. We don’t reach glycemic targets ...

 Type 2 Diabetes Mellitus
• We diagnose late ……

Early diabetes is detected by  PPG

- FPG is frequently normal
- case in point is IGT

Later diabetes is characterised by  FPG

Late Diagnosis of Type 2 Diabetes

100

80
Percentage with

Onset of
Retinopathy

60 Type 2
Diabetes Diagnosis
40

20

0
-6.5 0 5 10 15
Time since Diagnosis of Diabetes (Years)
 Type 2 Diabetes Mellitus

• Cardiovascular Risk begins earlier ……

…… before Diabetes onset
 Atherosclerosis in Diabetes

• ~80% of all diabetic mortality

– 75% from coronary atherosclerosis
– 25% from cerebral or peripheral vascular
disease

• >75% of all hospitalizations for diabetic

complications

• >50% of patients with newly diagnosed

type 2 diabetes have CHD

National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995.

 2
Criteria for the Diagnosis of Pre-DM (IGT & IFG) and DM
(ADA-2003,2004*, Summarized : Tjokroprawiro 2003, 2004)
Normal Pre - Diabetes Diabetes Mellitus
(mg/dl) (mg/dl) (mg/dl)
FPG < 110 IGT IFG T2DM
2-h PG < 140

IGT FPG FPG > 126

Impaired Glucose Tolerance 2h-PG 110-125 2-h PG > 200
IFG 140-199 New IFG*: CPG > 200
Impaired Fasting Glucose 100-125 with Classical Symptoms

A Dx of Diabetes must be confirmed on a subsequent day by any one of the 3 Methods.

Fasting means : No Calorie intake for at least 8 hours *IGT by OGTT; *IFG by FPG
* New Criterion by ADA (Fall 2003). Glucose Load : 75g Anhydrous Glucose in Water
INTOLERANCE GLUCOSE TEST[
I.G.T]
GANGGUAN TOLERANSI GULA[G.T.G]
PREDIABETES STAGE
BERBAKAT DIABETES

BILA KADAR GULA SEWAKTU

150-200 mg% !!!!!

 KENAPA DEMIKIAN?

FAKTA : pancreas baik

produksi hormon INSULIN normal
KELAINAN:
RESEPTOR INSULIN jumlah berkurang diotot
rangka,akibat terhalang oleh sel2 lemak->hor
insulin tdk dpt masuk sel->gula tdk dpt masuk
sel->sel lapar dan cepat rusak,terutama sel2
pembuluh darah.

5- 10 thn lagi->
DIABETES tipe II
 SIAPA YANG BERBAKAT
DIABETES?

1.ORANG TUA DIABETES

2.KEGEMUKAN
SENTRAL,PINGGANG>90
CM PRIA,>80CM WANITA

3.MELAHIRKAN BAYI >

4,5KG
4.GULA DARAH PUASA
100-125 MG%,ATAU GULA
SEWAKTU 140-199MG%
 35%
20%
PENDERITA IGT KEDOKTER KARENA

55
%
Type 2 Diabetes Mellitus Complications

MICROVASCULAR MACROVASCULAR
Retinopathy,
glaucoma or Cerebrovascular
cataracts disease

Cardiomyopathy Coronary
heart
Nephropathy disease

Peripheral
Neuropathy vascular
disease

Erectile dysfunction
 Intracellular HYPERGLYCEMIA

Protein kinase C Oxidative

Polyol pathway Protein glycation pathway
pathway

1 2 3 4

Diabetic Angiopathy
 Oxidative Pathway
• Oxidative stress occurs when:

 Free
radical
scavenger
 Free system
radical
production
 Oxidative Pathway
• High oxidative stress status in
diabetes:

– Increased production of free

radicals:
• Auto-oxidation of glucose
• Accumulation of AGE
– Reduced antioxidant defenses
 Oxidative pathways
Polyol pathway
HYPERGLYCEMIA

Glucose auto-oxidation  capacity

of
regeneration
of anti-
AGE
 oxygen free radicals
(imbalance of free radical
oxidants
production and free radical
scavenging)

Vascular In vitro
complications and in vivo evidences
Management of Diabetes Mellitus
The Earlier the Better
(prevention of Complications)
Early Diagnosis
Early Treatment
Early Combination
Early Insulin Therapy
Art of Treatment, Have to be Very Delicate,
Individualize, Start Low Go Slow
(avoid side effects)
 Management of T2DM
Long-term Challenges
Prevent Microvascular Complications
- Glycemic control

Prevent Macrovascular Complications

- Glycemic control
- Improve dyslipidemia
- Control blood pressure
- Control other risk factors (smoking etc.)

Prevent Long-term Deterioration of Glucose

Homeostasis
ALGORITHM for COMBINED TREATMENT in T2DM
Meal Planning and Exercise
TNA

Insulin Metformin Acarbose Glitazone

Secretagogues
TNA

Add 2nd Oral Drug: Oral Combination Therapy

TNA

Add 3rd Oral Drug DAY TIME Oral Drug +

BED TIME INSULIN
TNA
TNA
Add 4th Oral Drug DAY TIME Oral Drug+
BED TIME INSULIN Insulin
TNA
TNA
TNA
DAY TIME Oral Drug+ TNA
BED TIME INSULIN Insulin Target Not Achieved
 Proposed New Treatment Paradigm
for Type 2 Diabetes
Medical Nutrition Therapy, Exercise, Education and SMBG

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

Consider oral Add Add

monotherapy insulin sensitizer insulin sensitizer
Or secretagoque And secretagoque

Target not Met Target not Met Target not Met

Full Insulin therapy Start (add) Insulin Or

With Or without Oral agent(s) Add Third oral agent
 Good Glycaemic Control Reduces
the Incidence of Complications
Risk Reduction by Decrease in A1c (%)
Complications DCCT1,2 Kumamoto3 UKPDS4
of diabetes mellitus (9% 7%) (9% 7%) (8% 7%)

Retinopathy –63% –69% –21%

Nephropathy –54% –70% –34%
Neuropathy –60% – –
Macrovascular
disease –41%* – –16%*
*Not statistically significant

1DCCT Research Group. N Engl J Med 1993; 329: 977–86. 2DCCT Research Group. Diabetes 1995; 44: 968–83.
3Ohkubo Y et al. Diabetes Res Clin Pract 1995; 28: 103–17. 4UKPDS Group. Lancet 1998; 352: 837–53.
Surveillance Necessary for
Prevention of Diabetes Complications
Retinopathy : regular fundal (photo) examination
Nephropathy: regular urine check for
microalbuminuria – proteinuria
Cardiovascular: regular check for ECG/
Treadmill-exercise test or
whenever any positive complaint
Foot Problems: Regular foot check and
simple foot education
Neuropathy: symptoms of neuropathy. EMG ??
Lung : regular chest X ray or whenever any chronic
cough
Treatment Strategies for
Management of Diabetic Complications
Retina : Photocoagulation, vitrectomy, endolaser treatment
CKD: Conservative management with diet and medication
Replacement therapy:
Dialysis : hemodialysis
peritoneal dialysis
Renal transplantation
CAD: Management of CHF
Management of MCI
Conservative – medicamentosa
Operative: Angioplasty
CABG
PVD : Conservative Foot-care podiatric – foot clinic
Vascular control, Debridement, wound control
and infection control
Neuropathy: symptomatic treatments: Neurotropic ?
Local – capsaicin ?
 Penyakit jantung,stroke,merupakan penyebab
kematian tertinggi sedunia ¹†

AIDS 5.1

Penyakit paru 6

Injuries 9

INFEKSI 18

PENYAKIT KANKER 19
JANTUNG ,STROKE* 28
0 5 10 15 20 25 30
Kematian (%)
*Ischemic heart disease, cerebrovascular disease, inflammatory heart disease and hypertensive heart disease
†Worldwide defined as Member States by WHO Region (African, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific)

1 . The World Health Report, 2002, WHO Geneva, 2002.

Terima kasih
 Hiperglikemia

Jalur Poliol Autooksidasi Glikasi Protein

Defens
Antioksidans
Glukosa Faktor
/ NO Oksidatif
Stres Oksidatif

O2
NO dependent
Vasodilatation Oksidasi LDL Heparan
Proliferasi Otot Sulfat
Polos
Perubahan Hemoreologis
Aktivasi Koagulasi NCV
Hipoksia Drh Endoneural

Vaskulopati Retinopati Neuropati Nefropati

Mekanisme Terjadinya Berbagai Komplikasi Vaskular pada DM
 Risk Factors for Diabetic
Vascular Complications

Hyperglycemia

Dyslipidemia

Micro- and
Hypertension macroangiopathy

Insulin resistance
Hyperinsulinemia