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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)
Kelainan Fungsi /
Jumlah Sel Genetik
Tipe I (Autoimun)
Faktor Lingkungan
Sistim imun
(Ab anti pankreas)
Marker :
Insulin auto Ab
Islet cell auto Ab
Glutamic acid
dicarbosaflase
Au Ab (GAD. Abs)
Ideopatik
INSUFISIENSI
INSULIN
Virus
Diet
Obesitas
Hamil
Symptoms :
Polyuria
Polydipsia
Weight loss
Sometimes polyphagia
Blurred vision
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
5
mg/dl
mmol/l
Fasting
95
5.3
1-h
180
10.0
2-h
155
8.6
3-h
140
7.8
mg/dl
mmol/l
Fasting
95
5.3
1-h
180
10.0
2-h
155
8.6
Keluhan klasik -
>126
<126
>126
>200
<200
>200
110-<126
<110
mg/dl
GDS
110-200
mg/dl
<126
TTGO 2 jam
<200
>200
DIABETES MELLITUS
140-200
TGT
GDPT
<140
NORMAL
D. Endokrinopati
Acromegali, sindroma
Cushing, Feokromositoma,
hipertiroidisme
E. Karena obat/zat kimia
Vacor, pentamidin, asam
nikotinat, Glukokortikoid,
hormontiroid, tiazid, Dilantin,
interferon alfa
F. Infeksi : rubellakongenital, CMV
G. Sebab imunologi yang jarang :
Antibodi anti insulin
H. Sindroma genetik lain:
Sindroma Down, Klinefelter,
Turner dll.
4. Diabetes Gestasional
10
Type 1 Diabetes
Type 2 Diabetes
Combination of :
Serological evidence of
autoimmune process
in the pancreatic islet
Genetic markers
11
Insulin prandial
(glukosa uptake/utilzation
Insulin
puasa
Makanan
Glukagon
Glukosa
puasa
Glukosa darah puasa
Glukosa
prandial
Glukosa darah prandial
Glycemic Control
16
HbA1c
cross-sectional, median values
}0.9%
Conventional
8
HbA1c (%)
UK
S
D
P
Intensive
7
6.2% upper limit of normal range
6
0
6
9
12
Years from randomisation
15
17
UKPDS Group Lancet 1998;352:837-53
UK
S
D
P
Glycemic Control
p=0.010
p = 0.046
16 % myocardial infarction
p = 0.052
p=0.015
p=0.00005418
Conclusion
The UKPDS has shown that intensive blood glucose
control reduces the risk of diabetic complications, the
greatest effect being on microvascular complications
(and less on macrovascular complications)
Observational Study using the updated mean HbA1c in
the UKPDS population reveales that the rate of
increase of risk for microvascular disease with
hyperglycemia is greater than that for macrovascular
disease
The lower the glycemia the lower the risk of
complications
Management
A. Aim
Short term :
Eliminate symptoms
Maintain general well being
Longer term :
Prevent complications
Reduce morbidity
and mortality
Strategy :
Normalizing glucose,
lipid, and insulin levels
Activities :
Management with holistic
approach and self care
principles
20
Treatment Modalities
21
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 hasil pengelolaan
22
A D A and B D A
10-15%
30%
60-70%
Carbohydrate
Fat
10-15%
55%
Protein
Carbohydrate
Fat
Protein
23
PERENCANAAN MAKAN
KOMPOSISI :
Karbohidrat : 60 70 %
Protein
: 10 15 %
Lemak
: 20 25 %
JUMLAH KALORI :
Hitung BMI ( IMT ) = BB ( kg ) / TB ( m )2
IMT wanita ( normal ) = 18,5 23,5 kg/ m2
IMT laki ( normal )
= 22,5 25 kg / m2
Status gizi : BB Idaman = ( TB 100 ) 10%
BB kurang : < 90% BBI
BB Normal : 90 120% BBI
BB lebih
: 110 120 % BBI
Gemuk
: > 120% BBI
24
Exercise
30 minutes: 3 - 4 times / week
Continuous
Rhytmical
Interval
Progressive
Endurance training
25
26
GLYCOGENOLYSIS
3. Metformin
TZD
HGP
1. Insulin
GLUCOSEN
4. Acarbose
GLUCONEO
GENESIS
Intestine
+
+
Adipose tissue
3. Metformin
TZD
27
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
28
LIVER
GLYCOGENOLYSIS
Insulin
HGP
GLUCOSE N
GLUCONEO
GENESIS
ADIPOSE TISSUE
29
LIVER
GLYCOGENOLYSIS
Insulin
HGP
GLUCONEO
GENESIS
GLUCOSE N
G L UC O S E
Glucose
Uptake
FFA
+
ADIPOSE TISSUE
G LYCOGEN
Lipogenesis
30
LIVER
GLYCOGENOLYSIS
Insulin
HGP
G LYCOGEN
GLUCOSE N
G L UC O S E
Glucose
Uptake
GLUCONEO
GENESIS
ADIPOSE TISSUE
31
Advantage
Disadvantage
Intraperitoneal
Portal absorption
Good bioavailability
Physiologic profiles
Pump equired
Catheter blockage
Infection risk
Risk of large insulin
reservoir
Intravenous
Good bioavailability
Physiologic Profiles
Pump required
Catheter blockage
Phlebitis
Hyperinsulinemia
Nasal
Physiologic profiles
Easy use
No device required
Nasal irritation
Low bioavailability
Interference by resp.
infection 32
Advantage
Disadvantage
Pulmonary
Physiologic profiles
Simple device
Easy use
Low bioavailability
Variable absorption
Oral
Easy use
Acceptable
Low bioavailability
Variable absorption
33
34
35
Lispro Aspart
Regular
NPH
0.10-0.25
0.10-1.0
1.0-3.0
Peak
(h)
0.75-2.0
1.0-4.0
5.0-7.0
Yes w RI
+/- w lispro
Minimal
Moderate
High
Lente
Ultra lente
Glargine
1.5-4.0
2-6
2-4
4.0-8.0
8.0-12
None
13-20
18-30
-24
+/+/NO !!!
precipitate
High
Very High
Moderate to
high
1 b. Insulin Analogues
Genetic engineering
Main aim : Solubility reduction
Substitution/addition of amino acid residue of
insulin
Short acting :
Lispro: B28-lysine, B29-proline
X14
: B28-aspartate
Long acting:
B31-B32 arginine, A21-glycine
Immunogenicity
38
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
39
40
Sulphonylureas
Have been a mainstay of type 2 diabetes treatment for >
40 years
Bind to an SU receptor (SUR) on the-cell which leads
to depolarisation of -cell membrane and stimulates
insulin secretion
First generation : chlorpropamide
Second generation
: glibenclamide, glipizide,
gliclazide
Third generation
: glimepiride
Attention : Hypoglycemia (less in glipizide GITS and
glimepiride)
41
ATP Sensitive
K+ Channel
Ca 2+
Voltage Dependent
Ca 2+Channel (VDCC)
SU
Islet cell
SUR
Closed
ATP
ADP
Glucose
Glucokinase
Metabolism
Am. acid
Open
Ca 2+
Proinsulin
INSULIN
C-PEPTIDE
42
SS 01
Metformin
43
44
45
Specific
Non-specific
Reduced carbohydrate
intake
Spreading carbohydrate
intake
Carbohydrate according
to 24 hr blood
glucose profile
Dietary fibres
Low glycemic index food
Acarbose
Repaglinide
Nateglinide
Insulin lispro
Nasal/pulmonary
insulin
Glucagon-like
peptide-1
Amylin analogues
Sulphonylurea
glipizide GITS
glimepiride
Metformin
Thiazolidinediones
Long acting insulin
49
Insulin Secretagogues :
* Adipo Q-Raiser*)
1 ATHEROPROTECTIVE 3
4 5
Ciglitazone
Englitazone
Troglitazone (R/ Resulin)
Novel PGR
4
5
6
* Tsunekawa et al 2004
Adiponectin, TNF
* HOMA-R, MCR-g
1 METFORMIN : Glucophage
2 3-GUANIDINOPROPIONIC-ACID
** Aroda 2004
50
Maximal dose
mg/day
Sulphonylurea
Glibenclamide
Gliclazide
Glipizide :
Glipizide GITS
Gliquidone
Chlorpropamide
Glimepiride
2,5
80
5
5
30
50
0,5
15-20
240
20
20
120
500
6
Meglitinide
Repaglinide
Nateglinide
1.5 mg
120 mg
8 mg
360 mg
Metformin
500
3000
300
Frequency of
administration /day
1-2 X
1-2 X
2-3 X
1-2 X
1X
1X
1X
3X
3X
1-3 X
3 X51
Normal
Average Preprandial
<110
Fasting Glucose (mg/dL)
Average Postprandial
Glucose (mg/dL)
HbA1C (%)
Goal
Further Action
Required*
80 to 120
<80
>140
<140
<160
>180
<6
<7
>8
52
HbA1c 7- 8 %
Add
insulin sensitizer
or secretagoque
Target not Met
HbA1c > 8 %
Add
insulin sensitizer
and secretagoque
Target not Met
Start Insulin or
53
add Third oral agent
Complications :
Acute :
Ketoacidosis
Nonketotic Hyperosmolar
syndrome
Lactic asidosis
Hypoglikemi/koma.
Chronic :
Microangiopathy
Macroangiopathy
Retinopathy
Nephropathy
Neuropathy
CAD
PVD
Stroke
55
Penyulit Menahun
KOMPLIKASI DM
56
HYPERGLYCEMIA
Glucose
Autoxidation
Polyol
Pathway
Polyol
Pathway
Oxidative Stress
Antioxidant
Defence
NO dependent Vasolidation
Ca2+
VSMC Proliferation
LDL
Oxidation
Hemorheologic alternations
Coagulation activation
Hipoxia
Vasculopathy
Oxidative
Factors
O2 / NO
Retinopathy
Heparan
Sulphate
NVC
Endoneural
Blood Flow
Neuropathy
Nephropathy
Category
Normal
Micro Albuminuria
Clinical Albuminuria
Macro Albuminuria
Eight Causes
Elevated AER
< 30
< 20
< 30
30 - 299
20 - 199
30 - 299
> 300
> 200
> 300
GLICLAZIDE
GLICLAZIDE
INSULIN RESISTANCE
-CELL DYSFUNCTION
60
G: Glycation
O: Oxidants
S : Sorbitol
C : Cytokines
Patogenesis
Ketoacidosis
Diabetik
Diet bebas
Infeksi
Lemak (Lipolisis)
Protein
(Proteolisis)
Pelepasan FFA
Karbohidrat
Menuju hepar
Pelepasan A.A
Glukoneogenesis
hiperglikemia
Menuju hepar
Esterifikasi
HiperTrigliseridemia
Oksidasi
Partial
Ketoanemia
Ureum naik
Glukosuria
Diurese Osmotik Poliuiria
Ketosuria
Muntah
Dehidrasi
Asidosis
Ekskresi H+
Pernafasan
Kussmaul
Syok
AA : Asam Amino
G : Glukosa
FFA : Free Fatty Acid
62
METABOLIC
HAEMODYNAMIC
Glucose
Advanced
glycation
Flow
PKC
Vasoactive
Hormones
(eg. AH, endothelin)
CYTOKINES
TGF
VEGF
ECM
Cross-linking
ECM
ECM Accumulation
Vascular
permeability
Proteinuria
63
DESCRIPTION
CLINICAL FEATURES
At in creased risk
12
Kidney Damage
Microalbuminuria :
Diabetes duration 5 10 years, retinopathy,
rising BP
Albuminuria :
Diabetes duration 10 15 years, retinopathy,
HBP
34
Decreased GFR
Kidney Failure
64
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.
65
DIABETIK KETOASIDOSIS
Essentials of Dx :
Symtom + Sign :
3 P and marked fateque, nausea, vomiting
mental stupor coma.
Dehydrasi, stupor, rapid deep breathing
Fruity breath odor of acitone.
66
Laboratory Finding
Tx :
Glucose (mg/dL)
2 (Na ) +
18
+
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
69
( CHO )
70
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
71
Erithrosit
Otot
Kulit
Otak
Asam Lactat
Hati
Ginjal
Glukose
72
73
PERIODONTAL disease
CARIES
75
76
Treatment Priority
of Type 2 DM
Glucose control as
near to normal as
reasonably possible
Microvascular
disease
Macrovascular
disease
77
Hypertension
Intervention/Control
Cardiovascular
disease
Obesity
Pro-coagulant State
PAI-1,Factor VII, Fibrinogen
78
79
Age 45 years
2.
3.
4.
5.
Member of a high-risk ethnic population (e.g., AfricanAmerican, Latino, Native American, Asian-American,
Pacific Islander)
6.
7.
8.
9.
10. PCOS
11. History of vascular disease.
80
Fissured tongue
Kandidiasis
Lichenplanus Reticuler
Lichenplanus Erosive
95